Genere e demenze
Amalia C Bruni
Centro Regionale di Neurogenetica
Lamezia Terme
ASP CZ
Padova 27 novembre 2017
2
Global world challenges
Increasing world population
Feeding the population withsafer healthier higherndashquality
food through a sustainableagriculture
Ageing population
Functional and cognitive decline
Diet-related diseases
Metabolic Disorders Allergies Obesityhellip
Depression
Life expectancy and gender difference
Popolazione residente per condizione di salute malattie croniche dichiarate negli ultimi due giorni precedenti lrsquointervista classe di etagrave sesso
Anno 2013 (per 100 persone della stessa classe di etagrave e sesso)
ANNICLASSI DI ETArsquo
1 malattia cronica o piugrave
2 malattie croniche o piugrave
Diabete Ipertensione Malattie del cuore
2009 388 203 48 158 26
2010 386 201 49 160 37
2011 384 200 49 159 36
2012 386 204 55 164 35
2013 379 200 54 167 37
2013 ndash Per classi di etagrave e sessoMASCHI
60-64 610 304 130 330 69
65-74 728 422 160 452 116
75 e oltre 828 587 207 504 198
2013 ndash Per classi di etagrave e sessoFEMMINE
60-64 664 394 77 319 32
65-74 781 544 143 447 67
75 e oltre 886 739 201 576 144
Istat 2013
Dementia subtypes
Nel mondo un caso di demenza ogni tre secondi
TIMELINE DEMENZE
LEWY
VASCULAR
AD
Podcasy and Epperson Dialogues in Clinical Neuroscience - Vol 18 No 4 2016
Un soggetto su nove ha la malattia di Alzheimer e le donne sono il doppio
(gt65 anni)
Studio ILSA Incidenza della malattia di Alzheimer e della demenza vascolare per sesso e classi di etagrave
0
3
6
9
12
15
18
65-69 70-74 75-79 80-84
Classi di etagrave
Inci
denz
a pe
r 100
0
0
3
6
9
12
15
18
65-69 70-74 75-79 80-84
Classi di etagrave
Inci
denz
a pe
r 10
00
Uomini Donne
AD VaD
Metanalysis 12784 ALS patients
Higher female prevalence of C9orf72 hexanucleotide repeat expansions in ALS and GRN mutations in FTD suggest that sex-related risk factors might moderate C9orf72 and GRN mediatedphenotypic expression
Curtis et al Neurologyreg 2017891ndash10
A cosa DOBBIAMO QUESTE DIFFERENZE
DIFFERENTE PESO DEI FATTORI DI RISCHIO
DIFFERENTI CONNESSIONI E NETWORK
DIFFERENTE BACKGROUND ORMONALE
DIFFERENTE ESPRESSIONEASSETTO GENETICO
Gender differences in behavioraland cognitive functioning
bull The brain can be considered as a large-scale network of interconnected nodes within the human connectome
bull Small world network (network di connessione tra nodi))
Gender differences in brain connectome mayprovide an important foundation to delineate thepathophysiological mechanisms underlying sexdifferences in neuropsychiatric disorders and to potentially guide the development of sex specifictreatments
Differenti comunicazioni maschi in blu (percezione-azione coordinata)donne in arancio (analitico-intuitivo)
Ingalhalikar et al 2013
Mosconi et al Neurology 2017
Differenze ormonali
These results indicate progressively increased risk of AD as women undergo menopausal changes suggesting that endocrine aging accelerates chronologic aging in the female brain several years if
not decades prior to emergence of possible clinical symptoms of AD
AD
Ris
k
40yrs
OVARIECTOMY
Timing hypothesis
50yrs
Rocca et al 2011
Approximately 650 genes
(~ 14 of all genes in mouse
tissue) are expressed
differentially in the brains of
males and females The
morphology of the brain may
be sexually differentiated
because of epigenetic
mechanisms
Yang X et al (2006) Tissue-specific expression and regulationof sexually dimorphic genes in mice Genome Research 16 (8) 995-1004
Murray E K et al (2009) Epigenetic Control of SexualDifferentiation of the Bed Nucleus of the Stria Terminalis Endocrinology 150 (9) 4241-4247
Genes differences
Diversa espressione dei geni nei cervelli di maschi e femmine
Sex differences in metabolic aging of the brain insights into female susceptibility to Alzheimerrsquos disease
bull Gene expression profiles revealed substantial differences in the trajectory of aging changes between female and male brains
bull In female brains 442 of genes were significantly changed from 6 months to 9 months and two-thirds showed downregulation
bull In contrast in male brains only 54 in the same period
Zhao et al Neurobiol Aging 2016 June 42 69ndash79 doi101016jneurobiolaging201602011
Conclusions female and male brains follow profoundly dissimilar trajectories as they age female brains undergo age-related changes much earlier than male brains early changes in female brains signal the onset of a hypometabolicphenotype at risk for AD
These findings provide a mechanistic rationale for female susceptibility to AD and suggest a potential window of opportunity for AD prevention and risk reduction in women
Differente espressione di SRY in aree cerebrali
HLoke et al The International Journal of Biochemistry amp Cell Biology 65 (2015) 139ndash150
Male and female brains are neurochemicallydistinct concerning dopaminergic serotonergic and gamma-aminobutyric acid (GABA)ergic markers
Cosgrove KP et al Biol Psychiatry 2007 Oct 1562(8)847-55 Epub 2007 Jun 4
Sex-specific differences in neuromediators
Serotonin sexually differentiated multiple levels
Risk factors
Female sex early-onset hypertension and risk of dementia
Gilsanz et al Neurologyreg 2017891ndash8
Mid-adulthood hypertension wasassociated with 65 (95confidenceinterval [CI]125ndash218) increased dementia risk amongwomen but not men
Onset of hypertension in mid-adulthood predicted 73 higherdementia risk in women (95 CI 124ndash240) compared to stablenormotensive
Midlife hypertension was more common in men however itwas associated with dementia risk only in women
APOE4 effect is more pronounced in women than in men
HZ carrier APOEe4 earlier age at onset of AD
3-4 times more likely to develop AD
FARRER ET AL 1997
Fattori di rischio geneticihanno pesi diversi
ApoE4 strongly promotes amyloid-β deposition in the brain
Liu et al Nat Rev Neurol 2013
Risk gender for dementia or AD
In all three examples women experienced a higher risk of dementia or AD attributable to the specific risk factors (bigger red oval) Panel A APOE E4 allele is equally frequent in men and women (equal boxes) but has a stronger effect in women (thicker red arrow) Panel B low education has the same effect on the risk of dementia or AD in both men and women (equal strength of the blue and red
Rocca et al Maturitas 2014 October 79(2) 196ndash201 doi101016jmaturitas201405008
Men blueWomen red
APOE Meta analysis
JAMANeuroldoi101001jamaneurol20172188 PublishedonlineAugust282017
Increased risk in womenbetween 65-75 yrs
Risk factors in 1925 AD patients
Notaro P doctoral thesis 2017Unical
Le demenze sono molto variabili nei loro fenotipi
female patients with DLB having a higher frequency of VH symptoms
Chiu et al Int J Geriatr Psychiatry 2017
Women show an advantage in verbal memory despite evidence of moderate hippocampalatrophy This advantage may represent a sex-specific form of cognitive reserve delaying verbal memory decline until more advanced disease stages
lrsquoanalisi dei gruppi evidenziache queste donne hanno piugrave di 15 anni di
scolaritagrave
Cognitive reserve
IN SINTESIhellip
bull Le donne sono maggiormente a rischio per demenza e specie per malattia di Alzheimer tutto sembra concorrere a farle ammalare di piugrave dei maschi
bull Lrsquo assetto genetico e ormonale il modo di connettere informazioni a livello cerebrale le tante malattie in piugrave il piugrave basso livello di scolaritagrave e la minore attivitagrave laquosocialeraquo rispetto ai maschihelliphellip
Take home messages
bull Le differenze di genere osservate nelle demenze ( per tipo sintomied espressione fenotipica) originano dale profonde differenzecerebrali (genetiche ormonali e di connessioni) che esistono tra I due sessi
bull La consapevolezza e la ricerca in questa direzione potrebberoportare in futuro ad avere trattamenti genere - specifici non solo per gli aspetti cognitivi ma ancora di piugrave per quelli comportamentali
Il ogni caso il futuro egrave disegnatohellip studiare di piugrave avere una maggiore vita sociale fare attivitagrave fisica combattere le malattiehelliphellip
Anno 1791 giorno 29 Dicembre helliphelliphelliphellip Magnifica Eleonora Miceli helliphelliphelliphelliphelliphelliphellipanni sei sopra cento helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellipin giusto ragionamento ed intelligenza dei sensihelliphelliphelliphelliphelliphellip
Serrastretta Parish Archives
She does not recognize anybody she does not understand anything she does not answer any questions and she is emotionally flat She stays in bed all day moving her eyes around without any kind of thoughts driving her mind or triggering any movements of her limbs She mumbles incomprehensible words She seems astonished and scaredrsquorsquo
She died of marasmus at the age of 40 yearsin 1905helliphellip
2
Global world challenges
Increasing world population
Feeding the population withsafer healthier higherndashquality
food through a sustainableagriculture
Ageing population
Functional and cognitive decline
Diet-related diseases
Metabolic Disorders Allergies Obesityhellip
Depression
Life expectancy and gender difference
Popolazione residente per condizione di salute malattie croniche dichiarate negli ultimi due giorni precedenti lrsquointervista classe di etagrave sesso
Anno 2013 (per 100 persone della stessa classe di etagrave e sesso)
ANNICLASSI DI ETArsquo
1 malattia cronica o piugrave
2 malattie croniche o piugrave
Diabete Ipertensione Malattie del cuore
2009 388 203 48 158 26
2010 386 201 49 160 37
2011 384 200 49 159 36
2012 386 204 55 164 35
2013 379 200 54 167 37
2013 ndash Per classi di etagrave e sessoMASCHI
60-64 610 304 130 330 69
65-74 728 422 160 452 116
75 e oltre 828 587 207 504 198
2013 ndash Per classi di etagrave e sessoFEMMINE
60-64 664 394 77 319 32
65-74 781 544 143 447 67
75 e oltre 886 739 201 576 144
Istat 2013
Dementia subtypes
Nel mondo un caso di demenza ogni tre secondi
TIMELINE DEMENZE
LEWY
VASCULAR
AD
Podcasy and Epperson Dialogues in Clinical Neuroscience - Vol 18 No 4 2016
Un soggetto su nove ha la malattia di Alzheimer e le donne sono il doppio
(gt65 anni)
Studio ILSA Incidenza della malattia di Alzheimer e della demenza vascolare per sesso e classi di etagrave
0
3
6
9
12
15
18
65-69 70-74 75-79 80-84
Classi di etagrave
Inci
denz
a pe
r 100
0
0
3
6
9
12
15
18
65-69 70-74 75-79 80-84
Classi di etagrave
Inci
denz
a pe
r 10
00
Uomini Donne
AD VaD
Metanalysis 12784 ALS patients
Higher female prevalence of C9orf72 hexanucleotide repeat expansions in ALS and GRN mutations in FTD suggest that sex-related risk factors might moderate C9orf72 and GRN mediatedphenotypic expression
Curtis et al Neurologyreg 2017891ndash10
A cosa DOBBIAMO QUESTE DIFFERENZE
DIFFERENTE PESO DEI FATTORI DI RISCHIO
DIFFERENTI CONNESSIONI E NETWORK
DIFFERENTE BACKGROUND ORMONALE
DIFFERENTE ESPRESSIONEASSETTO GENETICO
Gender differences in behavioraland cognitive functioning
bull The brain can be considered as a large-scale network of interconnected nodes within the human connectome
bull Small world network (network di connessione tra nodi))
Gender differences in brain connectome mayprovide an important foundation to delineate thepathophysiological mechanisms underlying sexdifferences in neuropsychiatric disorders and to potentially guide the development of sex specifictreatments
Differenti comunicazioni maschi in blu (percezione-azione coordinata)donne in arancio (analitico-intuitivo)
Ingalhalikar et al 2013
Mosconi et al Neurology 2017
Differenze ormonali
These results indicate progressively increased risk of AD as women undergo menopausal changes suggesting that endocrine aging accelerates chronologic aging in the female brain several years if
not decades prior to emergence of possible clinical symptoms of AD
AD
Ris
k
40yrs
OVARIECTOMY
Timing hypothesis
50yrs
Rocca et al 2011
Approximately 650 genes
(~ 14 of all genes in mouse
tissue) are expressed
differentially in the brains of
males and females The
morphology of the brain may
be sexually differentiated
because of epigenetic
mechanisms
Yang X et al (2006) Tissue-specific expression and regulationof sexually dimorphic genes in mice Genome Research 16 (8) 995-1004
Murray E K et al (2009) Epigenetic Control of SexualDifferentiation of the Bed Nucleus of the Stria Terminalis Endocrinology 150 (9) 4241-4247
Genes differences
Diversa espressione dei geni nei cervelli di maschi e femmine
Sex differences in metabolic aging of the brain insights into female susceptibility to Alzheimerrsquos disease
bull Gene expression profiles revealed substantial differences in the trajectory of aging changes between female and male brains
bull In female brains 442 of genes were significantly changed from 6 months to 9 months and two-thirds showed downregulation
bull In contrast in male brains only 54 in the same period
Zhao et al Neurobiol Aging 2016 June 42 69ndash79 doi101016jneurobiolaging201602011
Conclusions female and male brains follow profoundly dissimilar trajectories as they age female brains undergo age-related changes much earlier than male brains early changes in female brains signal the onset of a hypometabolicphenotype at risk for AD
These findings provide a mechanistic rationale for female susceptibility to AD and suggest a potential window of opportunity for AD prevention and risk reduction in women
Differente espressione di SRY in aree cerebrali
HLoke et al The International Journal of Biochemistry amp Cell Biology 65 (2015) 139ndash150
Male and female brains are neurochemicallydistinct concerning dopaminergic serotonergic and gamma-aminobutyric acid (GABA)ergic markers
Cosgrove KP et al Biol Psychiatry 2007 Oct 1562(8)847-55 Epub 2007 Jun 4
Sex-specific differences in neuromediators
Serotonin sexually differentiated multiple levels
Risk factors
Female sex early-onset hypertension and risk of dementia
Gilsanz et al Neurologyreg 2017891ndash8
Mid-adulthood hypertension wasassociated with 65 (95confidenceinterval [CI]125ndash218) increased dementia risk amongwomen but not men
Onset of hypertension in mid-adulthood predicted 73 higherdementia risk in women (95 CI 124ndash240) compared to stablenormotensive
Midlife hypertension was more common in men however itwas associated with dementia risk only in women
APOE4 effect is more pronounced in women than in men
HZ carrier APOEe4 earlier age at onset of AD
3-4 times more likely to develop AD
FARRER ET AL 1997
Fattori di rischio geneticihanno pesi diversi
ApoE4 strongly promotes amyloid-β deposition in the brain
Liu et al Nat Rev Neurol 2013
Risk gender for dementia or AD
In all three examples women experienced a higher risk of dementia or AD attributable to the specific risk factors (bigger red oval) Panel A APOE E4 allele is equally frequent in men and women (equal boxes) but has a stronger effect in women (thicker red arrow) Panel B low education has the same effect on the risk of dementia or AD in both men and women (equal strength of the blue and red
Rocca et al Maturitas 2014 October 79(2) 196ndash201 doi101016jmaturitas201405008
Men blueWomen red
APOE Meta analysis
JAMANeuroldoi101001jamaneurol20172188 PublishedonlineAugust282017
Increased risk in womenbetween 65-75 yrs
Risk factors in 1925 AD patients
Notaro P doctoral thesis 2017Unical
Le demenze sono molto variabili nei loro fenotipi
female patients with DLB having a higher frequency of VH symptoms
Chiu et al Int J Geriatr Psychiatry 2017
Women show an advantage in verbal memory despite evidence of moderate hippocampalatrophy This advantage may represent a sex-specific form of cognitive reserve delaying verbal memory decline until more advanced disease stages
lrsquoanalisi dei gruppi evidenziache queste donne hanno piugrave di 15 anni di
scolaritagrave
Cognitive reserve
IN SINTESIhellip
bull Le donne sono maggiormente a rischio per demenza e specie per malattia di Alzheimer tutto sembra concorrere a farle ammalare di piugrave dei maschi
bull Lrsquo assetto genetico e ormonale il modo di connettere informazioni a livello cerebrale le tante malattie in piugrave il piugrave basso livello di scolaritagrave e la minore attivitagrave laquosocialeraquo rispetto ai maschihelliphellip
Take home messages
bull Le differenze di genere osservate nelle demenze ( per tipo sintomied espressione fenotipica) originano dale profonde differenzecerebrali (genetiche ormonali e di connessioni) che esistono tra I due sessi
bull La consapevolezza e la ricerca in questa direzione potrebberoportare in futuro ad avere trattamenti genere - specifici non solo per gli aspetti cognitivi ma ancora di piugrave per quelli comportamentali
Il ogni caso il futuro egrave disegnatohellip studiare di piugrave avere una maggiore vita sociale fare attivitagrave fisica combattere le malattiehelliphellip
Anno 1791 giorno 29 Dicembre helliphelliphelliphellip Magnifica Eleonora Miceli helliphelliphelliphelliphelliphelliphellipanni sei sopra cento helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellipin giusto ragionamento ed intelligenza dei sensihelliphelliphelliphelliphelliphellip
Serrastretta Parish Archives
She does not recognize anybody she does not understand anything she does not answer any questions and she is emotionally flat She stays in bed all day moving her eyes around without any kind of thoughts driving her mind or triggering any movements of her limbs She mumbles incomprehensible words She seems astonished and scaredrsquorsquo
She died of marasmus at the age of 40 yearsin 1905helliphellip
Depression
Life expectancy and gender difference
Popolazione residente per condizione di salute malattie croniche dichiarate negli ultimi due giorni precedenti lrsquointervista classe di etagrave sesso
Anno 2013 (per 100 persone della stessa classe di etagrave e sesso)
ANNICLASSI DI ETArsquo
1 malattia cronica o piugrave
2 malattie croniche o piugrave
Diabete Ipertensione Malattie del cuore
2009 388 203 48 158 26
2010 386 201 49 160 37
2011 384 200 49 159 36
2012 386 204 55 164 35
2013 379 200 54 167 37
2013 ndash Per classi di etagrave e sessoMASCHI
60-64 610 304 130 330 69
65-74 728 422 160 452 116
75 e oltre 828 587 207 504 198
2013 ndash Per classi di etagrave e sessoFEMMINE
60-64 664 394 77 319 32
65-74 781 544 143 447 67
75 e oltre 886 739 201 576 144
Istat 2013
Dementia subtypes
Nel mondo un caso di demenza ogni tre secondi
TIMELINE DEMENZE
LEWY
VASCULAR
AD
Podcasy and Epperson Dialogues in Clinical Neuroscience - Vol 18 No 4 2016
Un soggetto su nove ha la malattia di Alzheimer e le donne sono il doppio
(gt65 anni)
Studio ILSA Incidenza della malattia di Alzheimer e della demenza vascolare per sesso e classi di etagrave
0
3
6
9
12
15
18
65-69 70-74 75-79 80-84
Classi di etagrave
Inci
denz
a pe
r 100
0
0
3
6
9
12
15
18
65-69 70-74 75-79 80-84
Classi di etagrave
Inci
denz
a pe
r 10
00
Uomini Donne
AD VaD
Metanalysis 12784 ALS patients
Higher female prevalence of C9orf72 hexanucleotide repeat expansions in ALS and GRN mutations in FTD suggest that sex-related risk factors might moderate C9orf72 and GRN mediatedphenotypic expression
Curtis et al Neurologyreg 2017891ndash10
A cosa DOBBIAMO QUESTE DIFFERENZE
DIFFERENTE PESO DEI FATTORI DI RISCHIO
DIFFERENTI CONNESSIONI E NETWORK
DIFFERENTE BACKGROUND ORMONALE
DIFFERENTE ESPRESSIONEASSETTO GENETICO
Gender differences in behavioraland cognitive functioning
bull The brain can be considered as a large-scale network of interconnected nodes within the human connectome
bull Small world network (network di connessione tra nodi))
Gender differences in brain connectome mayprovide an important foundation to delineate thepathophysiological mechanisms underlying sexdifferences in neuropsychiatric disorders and to potentially guide the development of sex specifictreatments
Differenti comunicazioni maschi in blu (percezione-azione coordinata)donne in arancio (analitico-intuitivo)
Ingalhalikar et al 2013
Mosconi et al Neurology 2017
Differenze ormonali
These results indicate progressively increased risk of AD as women undergo menopausal changes suggesting that endocrine aging accelerates chronologic aging in the female brain several years if
not decades prior to emergence of possible clinical symptoms of AD
AD
Ris
k
40yrs
OVARIECTOMY
Timing hypothesis
50yrs
Rocca et al 2011
Approximately 650 genes
(~ 14 of all genes in mouse
tissue) are expressed
differentially in the brains of
males and females The
morphology of the brain may
be sexually differentiated
because of epigenetic
mechanisms
Yang X et al (2006) Tissue-specific expression and regulationof sexually dimorphic genes in mice Genome Research 16 (8) 995-1004
Murray E K et al (2009) Epigenetic Control of SexualDifferentiation of the Bed Nucleus of the Stria Terminalis Endocrinology 150 (9) 4241-4247
Genes differences
Diversa espressione dei geni nei cervelli di maschi e femmine
Sex differences in metabolic aging of the brain insights into female susceptibility to Alzheimerrsquos disease
bull Gene expression profiles revealed substantial differences in the trajectory of aging changes between female and male brains
bull In female brains 442 of genes were significantly changed from 6 months to 9 months and two-thirds showed downregulation
bull In contrast in male brains only 54 in the same period
Zhao et al Neurobiol Aging 2016 June 42 69ndash79 doi101016jneurobiolaging201602011
Conclusions female and male brains follow profoundly dissimilar trajectories as they age female brains undergo age-related changes much earlier than male brains early changes in female brains signal the onset of a hypometabolicphenotype at risk for AD
These findings provide a mechanistic rationale for female susceptibility to AD and suggest a potential window of opportunity for AD prevention and risk reduction in women
Differente espressione di SRY in aree cerebrali
HLoke et al The International Journal of Biochemistry amp Cell Biology 65 (2015) 139ndash150
Male and female brains are neurochemicallydistinct concerning dopaminergic serotonergic and gamma-aminobutyric acid (GABA)ergic markers
Cosgrove KP et al Biol Psychiatry 2007 Oct 1562(8)847-55 Epub 2007 Jun 4
Sex-specific differences in neuromediators
Serotonin sexually differentiated multiple levels
Risk factors
Female sex early-onset hypertension and risk of dementia
Gilsanz et al Neurologyreg 2017891ndash8
Mid-adulthood hypertension wasassociated with 65 (95confidenceinterval [CI]125ndash218) increased dementia risk amongwomen but not men
Onset of hypertension in mid-adulthood predicted 73 higherdementia risk in women (95 CI 124ndash240) compared to stablenormotensive
Midlife hypertension was more common in men however itwas associated with dementia risk only in women
APOE4 effect is more pronounced in women than in men
HZ carrier APOEe4 earlier age at onset of AD
3-4 times more likely to develop AD
FARRER ET AL 1997
Fattori di rischio geneticihanno pesi diversi
ApoE4 strongly promotes amyloid-β deposition in the brain
Liu et al Nat Rev Neurol 2013
Risk gender for dementia or AD
In all three examples women experienced a higher risk of dementia or AD attributable to the specific risk factors (bigger red oval) Panel A APOE E4 allele is equally frequent in men and women (equal boxes) but has a stronger effect in women (thicker red arrow) Panel B low education has the same effect on the risk of dementia or AD in both men and women (equal strength of the blue and red
Rocca et al Maturitas 2014 October 79(2) 196ndash201 doi101016jmaturitas201405008
Men blueWomen red
APOE Meta analysis
JAMANeuroldoi101001jamaneurol20172188 PublishedonlineAugust282017
Increased risk in womenbetween 65-75 yrs
Risk factors in 1925 AD patients
Notaro P doctoral thesis 2017Unical
Le demenze sono molto variabili nei loro fenotipi
female patients with DLB having a higher frequency of VH symptoms
Chiu et al Int J Geriatr Psychiatry 2017
Women show an advantage in verbal memory despite evidence of moderate hippocampalatrophy This advantage may represent a sex-specific form of cognitive reserve delaying verbal memory decline until more advanced disease stages
lrsquoanalisi dei gruppi evidenziache queste donne hanno piugrave di 15 anni di
scolaritagrave
Cognitive reserve
IN SINTESIhellip
bull Le donne sono maggiormente a rischio per demenza e specie per malattia di Alzheimer tutto sembra concorrere a farle ammalare di piugrave dei maschi
bull Lrsquo assetto genetico e ormonale il modo di connettere informazioni a livello cerebrale le tante malattie in piugrave il piugrave basso livello di scolaritagrave e la minore attivitagrave laquosocialeraquo rispetto ai maschihelliphellip
Take home messages
bull Le differenze di genere osservate nelle demenze ( per tipo sintomied espressione fenotipica) originano dale profonde differenzecerebrali (genetiche ormonali e di connessioni) che esistono tra I due sessi
bull La consapevolezza e la ricerca in questa direzione potrebberoportare in futuro ad avere trattamenti genere - specifici non solo per gli aspetti cognitivi ma ancora di piugrave per quelli comportamentali
Il ogni caso il futuro egrave disegnatohellip studiare di piugrave avere una maggiore vita sociale fare attivitagrave fisica combattere le malattiehelliphellip
Anno 1791 giorno 29 Dicembre helliphelliphelliphellip Magnifica Eleonora Miceli helliphelliphelliphelliphelliphelliphellipanni sei sopra cento helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellipin giusto ragionamento ed intelligenza dei sensihelliphelliphelliphelliphelliphellip
Serrastretta Parish Archives
She does not recognize anybody she does not understand anything she does not answer any questions and she is emotionally flat She stays in bed all day moving her eyes around without any kind of thoughts driving her mind or triggering any movements of her limbs She mumbles incomprehensible words She seems astonished and scaredrsquorsquo
She died of marasmus at the age of 40 yearsin 1905helliphellip
Life expectancy and gender difference
Popolazione residente per condizione di salute malattie croniche dichiarate negli ultimi due giorni precedenti lrsquointervista classe di etagrave sesso
Anno 2013 (per 100 persone della stessa classe di etagrave e sesso)
ANNICLASSI DI ETArsquo
1 malattia cronica o piugrave
2 malattie croniche o piugrave
Diabete Ipertensione Malattie del cuore
2009 388 203 48 158 26
2010 386 201 49 160 37
2011 384 200 49 159 36
2012 386 204 55 164 35
2013 379 200 54 167 37
2013 ndash Per classi di etagrave e sessoMASCHI
60-64 610 304 130 330 69
65-74 728 422 160 452 116
75 e oltre 828 587 207 504 198
2013 ndash Per classi di etagrave e sessoFEMMINE
60-64 664 394 77 319 32
65-74 781 544 143 447 67
75 e oltre 886 739 201 576 144
Istat 2013
Dementia subtypes
Nel mondo un caso di demenza ogni tre secondi
TIMELINE DEMENZE
LEWY
VASCULAR
AD
Podcasy and Epperson Dialogues in Clinical Neuroscience - Vol 18 No 4 2016
Un soggetto su nove ha la malattia di Alzheimer e le donne sono il doppio
(gt65 anni)
Studio ILSA Incidenza della malattia di Alzheimer e della demenza vascolare per sesso e classi di etagrave
0
3
6
9
12
15
18
65-69 70-74 75-79 80-84
Classi di etagrave
Inci
denz
a pe
r 100
0
0
3
6
9
12
15
18
65-69 70-74 75-79 80-84
Classi di etagrave
Inci
denz
a pe
r 10
00
Uomini Donne
AD VaD
Metanalysis 12784 ALS patients
Higher female prevalence of C9orf72 hexanucleotide repeat expansions in ALS and GRN mutations in FTD suggest that sex-related risk factors might moderate C9orf72 and GRN mediatedphenotypic expression
Curtis et al Neurologyreg 2017891ndash10
A cosa DOBBIAMO QUESTE DIFFERENZE
DIFFERENTE PESO DEI FATTORI DI RISCHIO
DIFFERENTI CONNESSIONI E NETWORK
DIFFERENTE BACKGROUND ORMONALE
DIFFERENTE ESPRESSIONEASSETTO GENETICO
Gender differences in behavioraland cognitive functioning
bull The brain can be considered as a large-scale network of interconnected nodes within the human connectome
bull Small world network (network di connessione tra nodi))
Gender differences in brain connectome mayprovide an important foundation to delineate thepathophysiological mechanisms underlying sexdifferences in neuropsychiatric disorders and to potentially guide the development of sex specifictreatments
Differenti comunicazioni maschi in blu (percezione-azione coordinata)donne in arancio (analitico-intuitivo)
Ingalhalikar et al 2013
Mosconi et al Neurology 2017
Differenze ormonali
These results indicate progressively increased risk of AD as women undergo menopausal changes suggesting that endocrine aging accelerates chronologic aging in the female brain several years if
not decades prior to emergence of possible clinical symptoms of AD
AD
Ris
k
40yrs
OVARIECTOMY
Timing hypothesis
50yrs
Rocca et al 2011
Approximately 650 genes
(~ 14 of all genes in mouse
tissue) are expressed
differentially in the brains of
males and females The
morphology of the brain may
be sexually differentiated
because of epigenetic
mechanisms
Yang X et al (2006) Tissue-specific expression and regulationof sexually dimorphic genes in mice Genome Research 16 (8) 995-1004
Murray E K et al (2009) Epigenetic Control of SexualDifferentiation of the Bed Nucleus of the Stria Terminalis Endocrinology 150 (9) 4241-4247
Genes differences
Diversa espressione dei geni nei cervelli di maschi e femmine
Sex differences in metabolic aging of the brain insights into female susceptibility to Alzheimerrsquos disease
bull Gene expression profiles revealed substantial differences in the trajectory of aging changes between female and male brains
bull In female brains 442 of genes were significantly changed from 6 months to 9 months and two-thirds showed downregulation
bull In contrast in male brains only 54 in the same period
Zhao et al Neurobiol Aging 2016 June 42 69ndash79 doi101016jneurobiolaging201602011
Conclusions female and male brains follow profoundly dissimilar trajectories as they age female brains undergo age-related changes much earlier than male brains early changes in female brains signal the onset of a hypometabolicphenotype at risk for AD
These findings provide a mechanistic rationale for female susceptibility to AD and suggest a potential window of opportunity for AD prevention and risk reduction in women
Differente espressione di SRY in aree cerebrali
HLoke et al The International Journal of Biochemistry amp Cell Biology 65 (2015) 139ndash150
Male and female brains are neurochemicallydistinct concerning dopaminergic serotonergic and gamma-aminobutyric acid (GABA)ergic markers
Cosgrove KP et al Biol Psychiatry 2007 Oct 1562(8)847-55 Epub 2007 Jun 4
Sex-specific differences in neuromediators
Serotonin sexually differentiated multiple levels
Risk factors
Female sex early-onset hypertension and risk of dementia
Gilsanz et al Neurologyreg 2017891ndash8
Mid-adulthood hypertension wasassociated with 65 (95confidenceinterval [CI]125ndash218) increased dementia risk amongwomen but not men
Onset of hypertension in mid-adulthood predicted 73 higherdementia risk in women (95 CI 124ndash240) compared to stablenormotensive
Midlife hypertension was more common in men however itwas associated with dementia risk only in women
APOE4 effect is more pronounced in women than in men
HZ carrier APOEe4 earlier age at onset of AD
3-4 times more likely to develop AD
FARRER ET AL 1997
Fattori di rischio geneticihanno pesi diversi
ApoE4 strongly promotes amyloid-β deposition in the brain
Liu et al Nat Rev Neurol 2013
Risk gender for dementia or AD
In all three examples women experienced a higher risk of dementia or AD attributable to the specific risk factors (bigger red oval) Panel A APOE E4 allele is equally frequent in men and women (equal boxes) but has a stronger effect in women (thicker red arrow) Panel B low education has the same effect on the risk of dementia or AD in both men and women (equal strength of the blue and red
Rocca et al Maturitas 2014 October 79(2) 196ndash201 doi101016jmaturitas201405008
Men blueWomen red
APOE Meta analysis
JAMANeuroldoi101001jamaneurol20172188 PublishedonlineAugust282017
Increased risk in womenbetween 65-75 yrs
Risk factors in 1925 AD patients
Notaro P doctoral thesis 2017Unical
Le demenze sono molto variabili nei loro fenotipi
female patients with DLB having a higher frequency of VH symptoms
Chiu et al Int J Geriatr Psychiatry 2017
Women show an advantage in verbal memory despite evidence of moderate hippocampalatrophy This advantage may represent a sex-specific form of cognitive reserve delaying verbal memory decline until more advanced disease stages
lrsquoanalisi dei gruppi evidenziache queste donne hanno piugrave di 15 anni di
scolaritagrave
Cognitive reserve
IN SINTESIhellip
bull Le donne sono maggiormente a rischio per demenza e specie per malattia di Alzheimer tutto sembra concorrere a farle ammalare di piugrave dei maschi
bull Lrsquo assetto genetico e ormonale il modo di connettere informazioni a livello cerebrale le tante malattie in piugrave il piugrave basso livello di scolaritagrave e la minore attivitagrave laquosocialeraquo rispetto ai maschihelliphellip
Take home messages
bull Le differenze di genere osservate nelle demenze ( per tipo sintomied espressione fenotipica) originano dale profonde differenzecerebrali (genetiche ormonali e di connessioni) che esistono tra I due sessi
bull La consapevolezza e la ricerca in questa direzione potrebberoportare in futuro ad avere trattamenti genere - specifici non solo per gli aspetti cognitivi ma ancora di piugrave per quelli comportamentali
Il ogni caso il futuro egrave disegnatohellip studiare di piugrave avere una maggiore vita sociale fare attivitagrave fisica combattere le malattiehelliphellip
Anno 1791 giorno 29 Dicembre helliphelliphelliphellip Magnifica Eleonora Miceli helliphelliphelliphelliphelliphelliphellipanni sei sopra cento helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellipin giusto ragionamento ed intelligenza dei sensihelliphelliphelliphelliphelliphellip
Serrastretta Parish Archives
She does not recognize anybody she does not understand anything she does not answer any questions and she is emotionally flat She stays in bed all day moving her eyes around without any kind of thoughts driving her mind or triggering any movements of her limbs She mumbles incomprehensible words She seems astonished and scaredrsquorsquo
She died of marasmus at the age of 40 yearsin 1905helliphellip
Popolazione residente per condizione di salute malattie croniche dichiarate negli ultimi due giorni precedenti lrsquointervista classe di etagrave sesso
Anno 2013 (per 100 persone della stessa classe di etagrave e sesso)
ANNICLASSI DI ETArsquo
1 malattia cronica o piugrave
2 malattie croniche o piugrave
Diabete Ipertensione Malattie del cuore
2009 388 203 48 158 26
2010 386 201 49 160 37
2011 384 200 49 159 36
2012 386 204 55 164 35
2013 379 200 54 167 37
2013 ndash Per classi di etagrave e sessoMASCHI
60-64 610 304 130 330 69
65-74 728 422 160 452 116
75 e oltre 828 587 207 504 198
2013 ndash Per classi di etagrave e sessoFEMMINE
60-64 664 394 77 319 32
65-74 781 544 143 447 67
75 e oltre 886 739 201 576 144
Istat 2013
Dementia subtypes
Nel mondo un caso di demenza ogni tre secondi
TIMELINE DEMENZE
LEWY
VASCULAR
AD
Podcasy and Epperson Dialogues in Clinical Neuroscience - Vol 18 No 4 2016
Un soggetto su nove ha la malattia di Alzheimer e le donne sono il doppio
(gt65 anni)
Studio ILSA Incidenza della malattia di Alzheimer e della demenza vascolare per sesso e classi di etagrave
0
3
6
9
12
15
18
65-69 70-74 75-79 80-84
Classi di etagrave
Inci
denz
a pe
r 100
0
0
3
6
9
12
15
18
65-69 70-74 75-79 80-84
Classi di etagrave
Inci
denz
a pe
r 10
00
Uomini Donne
AD VaD
Metanalysis 12784 ALS patients
Higher female prevalence of C9orf72 hexanucleotide repeat expansions in ALS and GRN mutations in FTD suggest that sex-related risk factors might moderate C9orf72 and GRN mediatedphenotypic expression
Curtis et al Neurologyreg 2017891ndash10
A cosa DOBBIAMO QUESTE DIFFERENZE
DIFFERENTE PESO DEI FATTORI DI RISCHIO
DIFFERENTI CONNESSIONI E NETWORK
DIFFERENTE BACKGROUND ORMONALE
DIFFERENTE ESPRESSIONEASSETTO GENETICO
Gender differences in behavioraland cognitive functioning
bull The brain can be considered as a large-scale network of interconnected nodes within the human connectome
bull Small world network (network di connessione tra nodi))
Gender differences in brain connectome mayprovide an important foundation to delineate thepathophysiological mechanisms underlying sexdifferences in neuropsychiatric disorders and to potentially guide the development of sex specifictreatments
Differenti comunicazioni maschi in blu (percezione-azione coordinata)donne in arancio (analitico-intuitivo)
Ingalhalikar et al 2013
Mosconi et al Neurology 2017
Differenze ormonali
These results indicate progressively increased risk of AD as women undergo menopausal changes suggesting that endocrine aging accelerates chronologic aging in the female brain several years if
not decades prior to emergence of possible clinical symptoms of AD
AD
Ris
k
40yrs
OVARIECTOMY
Timing hypothesis
50yrs
Rocca et al 2011
Approximately 650 genes
(~ 14 of all genes in mouse
tissue) are expressed
differentially in the brains of
males and females The
morphology of the brain may
be sexually differentiated
because of epigenetic
mechanisms
Yang X et al (2006) Tissue-specific expression and regulationof sexually dimorphic genes in mice Genome Research 16 (8) 995-1004
Murray E K et al (2009) Epigenetic Control of SexualDifferentiation of the Bed Nucleus of the Stria Terminalis Endocrinology 150 (9) 4241-4247
Genes differences
Diversa espressione dei geni nei cervelli di maschi e femmine
Sex differences in metabolic aging of the brain insights into female susceptibility to Alzheimerrsquos disease
bull Gene expression profiles revealed substantial differences in the trajectory of aging changes between female and male brains
bull In female brains 442 of genes were significantly changed from 6 months to 9 months and two-thirds showed downregulation
bull In contrast in male brains only 54 in the same period
Zhao et al Neurobiol Aging 2016 June 42 69ndash79 doi101016jneurobiolaging201602011
Conclusions female and male brains follow profoundly dissimilar trajectories as they age female brains undergo age-related changes much earlier than male brains early changes in female brains signal the onset of a hypometabolicphenotype at risk for AD
These findings provide a mechanistic rationale for female susceptibility to AD and suggest a potential window of opportunity for AD prevention and risk reduction in women
Differente espressione di SRY in aree cerebrali
HLoke et al The International Journal of Biochemistry amp Cell Biology 65 (2015) 139ndash150
Male and female brains are neurochemicallydistinct concerning dopaminergic serotonergic and gamma-aminobutyric acid (GABA)ergic markers
Cosgrove KP et al Biol Psychiatry 2007 Oct 1562(8)847-55 Epub 2007 Jun 4
Sex-specific differences in neuromediators
Serotonin sexually differentiated multiple levels
Risk factors
Female sex early-onset hypertension and risk of dementia
Gilsanz et al Neurologyreg 2017891ndash8
Mid-adulthood hypertension wasassociated with 65 (95confidenceinterval [CI]125ndash218) increased dementia risk amongwomen but not men
Onset of hypertension in mid-adulthood predicted 73 higherdementia risk in women (95 CI 124ndash240) compared to stablenormotensive
Midlife hypertension was more common in men however itwas associated with dementia risk only in women
APOE4 effect is more pronounced in women than in men
HZ carrier APOEe4 earlier age at onset of AD
3-4 times more likely to develop AD
FARRER ET AL 1997
Fattori di rischio geneticihanno pesi diversi
ApoE4 strongly promotes amyloid-β deposition in the brain
Liu et al Nat Rev Neurol 2013
Risk gender for dementia or AD
In all three examples women experienced a higher risk of dementia or AD attributable to the specific risk factors (bigger red oval) Panel A APOE E4 allele is equally frequent in men and women (equal boxes) but has a stronger effect in women (thicker red arrow) Panel B low education has the same effect on the risk of dementia or AD in both men and women (equal strength of the blue and red
Rocca et al Maturitas 2014 October 79(2) 196ndash201 doi101016jmaturitas201405008
Men blueWomen red
APOE Meta analysis
JAMANeuroldoi101001jamaneurol20172188 PublishedonlineAugust282017
Increased risk in womenbetween 65-75 yrs
Risk factors in 1925 AD patients
Notaro P doctoral thesis 2017Unical
Le demenze sono molto variabili nei loro fenotipi
female patients with DLB having a higher frequency of VH symptoms
Chiu et al Int J Geriatr Psychiatry 2017
Women show an advantage in verbal memory despite evidence of moderate hippocampalatrophy This advantage may represent a sex-specific form of cognitive reserve delaying verbal memory decline until more advanced disease stages
lrsquoanalisi dei gruppi evidenziache queste donne hanno piugrave di 15 anni di
scolaritagrave
Cognitive reserve
IN SINTESIhellip
bull Le donne sono maggiormente a rischio per demenza e specie per malattia di Alzheimer tutto sembra concorrere a farle ammalare di piugrave dei maschi
bull Lrsquo assetto genetico e ormonale il modo di connettere informazioni a livello cerebrale le tante malattie in piugrave il piugrave basso livello di scolaritagrave e la minore attivitagrave laquosocialeraquo rispetto ai maschihelliphellip
Take home messages
bull Le differenze di genere osservate nelle demenze ( per tipo sintomied espressione fenotipica) originano dale profonde differenzecerebrali (genetiche ormonali e di connessioni) che esistono tra I due sessi
bull La consapevolezza e la ricerca in questa direzione potrebberoportare in futuro ad avere trattamenti genere - specifici non solo per gli aspetti cognitivi ma ancora di piugrave per quelli comportamentali
Il ogni caso il futuro egrave disegnatohellip studiare di piugrave avere una maggiore vita sociale fare attivitagrave fisica combattere le malattiehelliphellip
Anno 1791 giorno 29 Dicembre helliphelliphelliphellip Magnifica Eleonora Miceli helliphelliphelliphelliphelliphelliphellipanni sei sopra cento helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellipin giusto ragionamento ed intelligenza dei sensihelliphelliphelliphelliphelliphellip
Serrastretta Parish Archives
She does not recognize anybody she does not understand anything she does not answer any questions and she is emotionally flat She stays in bed all day moving her eyes around without any kind of thoughts driving her mind or triggering any movements of her limbs She mumbles incomprehensible words She seems astonished and scaredrsquorsquo
She died of marasmus at the age of 40 yearsin 1905helliphellip
Dementia subtypes
Nel mondo un caso di demenza ogni tre secondi
TIMELINE DEMENZE
LEWY
VASCULAR
AD
Podcasy and Epperson Dialogues in Clinical Neuroscience - Vol 18 No 4 2016
Un soggetto su nove ha la malattia di Alzheimer e le donne sono il doppio
(gt65 anni)
Studio ILSA Incidenza della malattia di Alzheimer e della demenza vascolare per sesso e classi di etagrave
0
3
6
9
12
15
18
65-69 70-74 75-79 80-84
Classi di etagrave
Inci
denz
a pe
r 100
0
0
3
6
9
12
15
18
65-69 70-74 75-79 80-84
Classi di etagrave
Inci
denz
a pe
r 10
00
Uomini Donne
AD VaD
Metanalysis 12784 ALS patients
Higher female prevalence of C9orf72 hexanucleotide repeat expansions in ALS and GRN mutations in FTD suggest that sex-related risk factors might moderate C9orf72 and GRN mediatedphenotypic expression
Curtis et al Neurologyreg 2017891ndash10
A cosa DOBBIAMO QUESTE DIFFERENZE
DIFFERENTE PESO DEI FATTORI DI RISCHIO
DIFFERENTI CONNESSIONI E NETWORK
DIFFERENTE BACKGROUND ORMONALE
DIFFERENTE ESPRESSIONEASSETTO GENETICO
Gender differences in behavioraland cognitive functioning
bull The brain can be considered as a large-scale network of interconnected nodes within the human connectome
bull Small world network (network di connessione tra nodi))
Gender differences in brain connectome mayprovide an important foundation to delineate thepathophysiological mechanisms underlying sexdifferences in neuropsychiatric disorders and to potentially guide the development of sex specifictreatments
Differenti comunicazioni maschi in blu (percezione-azione coordinata)donne in arancio (analitico-intuitivo)
Ingalhalikar et al 2013
Mosconi et al Neurology 2017
Differenze ormonali
These results indicate progressively increased risk of AD as women undergo menopausal changes suggesting that endocrine aging accelerates chronologic aging in the female brain several years if
not decades prior to emergence of possible clinical symptoms of AD
AD
Ris
k
40yrs
OVARIECTOMY
Timing hypothesis
50yrs
Rocca et al 2011
Approximately 650 genes
(~ 14 of all genes in mouse
tissue) are expressed
differentially in the brains of
males and females The
morphology of the brain may
be sexually differentiated
because of epigenetic
mechanisms
Yang X et al (2006) Tissue-specific expression and regulationof sexually dimorphic genes in mice Genome Research 16 (8) 995-1004
Murray E K et al (2009) Epigenetic Control of SexualDifferentiation of the Bed Nucleus of the Stria Terminalis Endocrinology 150 (9) 4241-4247
Genes differences
Diversa espressione dei geni nei cervelli di maschi e femmine
Sex differences in metabolic aging of the brain insights into female susceptibility to Alzheimerrsquos disease
bull Gene expression profiles revealed substantial differences in the trajectory of aging changes between female and male brains
bull In female brains 442 of genes were significantly changed from 6 months to 9 months and two-thirds showed downregulation
bull In contrast in male brains only 54 in the same period
Zhao et al Neurobiol Aging 2016 June 42 69ndash79 doi101016jneurobiolaging201602011
Conclusions female and male brains follow profoundly dissimilar trajectories as they age female brains undergo age-related changes much earlier than male brains early changes in female brains signal the onset of a hypometabolicphenotype at risk for AD
These findings provide a mechanistic rationale for female susceptibility to AD and suggest a potential window of opportunity for AD prevention and risk reduction in women
Differente espressione di SRY in aree cerebrali
HLoke et al The International Journal of Biochemistry amp Cell Biology 65 (2015) 139ndash150
Male and female brains are neurochemicallydistinct concerning dopaminergic serotonergic and gamma-aminobutyric acid (GABA)ergic markers
Cosgrove KP et al Biol Psychiatry 2007 Oct 1562(8)847-55 Epub 2007 Jun 4
Sex-specific differences in neuromediators
Serotonin sexually differentiated multiple levels
Risk factors
Female sex early-onset hypertension and risk of dementia
Gilsanz et al Neurologyreg 2017891ndash8
Mid-adulthood hypertension wasassociated with 65 (95confidenceinterval [CI]125ndash218) increased dementia risk amongwomen but not men
Onset of hypertension in mid-adulthood predicted 73 higherdementia risk in women (95 CI 124ndash240) compared to stablenormotensive
Midlife hypertension was more common in men however itwas associated with dementia risk only in women
APOE4 effect is more pronounced in women than in men
HZ carrier APOEe4 earlier age at onset of AD
3-4 times more likely to develop AD
FARRER ET AL 1997
Fattori di rischio geneticihanno pesi diversi
ApoE4 strongly promotes amyloid-β deposition in the brain
Liu et al Nat Rev Neurol 2013
Risk gender for dementia or AD
In all three examples women experienced a higher risk of dementia or AD attributable to the specific risk factors (bigger red oval) Panel A APOE E4 allele is equally frequent in men and women (equal boxes) but has a stronger effect in women (thicker red arrow) Panel B low education has the same effect on the risk of dementia or AD in both men and women (equal strength of the blue and red
Rocca et al Maturitas 2014 October 79(2) 196ndash201 doi101016jmaturitas201405008
Men blueWomen red
APOE Meta analysis
JAMANeuroldoi101001jamaneurol20172188 PublishedonlineAugust282017
Increased risk in womenbetween 65-75 yrs
Risk factors in 1925 AD patients
Notaro P doctoral thesis 2017Unical
Le demenze sono molto variabili nei loro fenotipi
female patients with DLB having a higher frequency of VH symptoms
Chiu et al Int J Geriatr Psychiatry 2017
Women show an advantage in verbal memory despite evidence of moderate hippocampalatrophy This advantage may represent a sex-specific form of cognitive reserve delaying verbal memory decline until more advanced disease stages
lrsquoanalisi dei gruppi evidenziache queste donne hanno piugrave di 15 anni di
scolaritagrave
Cognitive reserve
IN SINTESIhellip
bull Le donne sono maggiormente a rischio per demenza e specie per malattia di Alzheimer tutto sembra concorrere a farle ammalare di piugrave dei maschi
bull Lrsquo assetto genetico e ormonale il modo di connettere informazioni a livello cerebrale le tante malattie in piugrave il piugrave basso livello di scolaritagrave e la minore attivitagrave laquosocialeraquo rispetto ai maschihelliphellip
Take home messages
bull Le differenze di genere osservate nelle demenze ( per tipo sintomied espressione fenotipica) originano dale profonde differenzecerebrali (genetiche ormonali e di connessioni) che esistono tra I due sessi
bull La consapevolezza e la ricerca in questa direzione potrebberoportare in futuro ad avere trattamenti genere - specifici non solo per gli aspetti cognitivi ma ancora di piugrave per quelli comportamentali
Il ogni caso il futuro egrave disegnatohellip studiare di piugrave avere una maggiore vita sociale fare attivitagrave fisica combattere le malattiehelliphellip
Anno 1791 giorno 29 Dicembre helliphelliphelliphellip Magnifica Eleonora Miceli helliphelliphelliphelliphelliphelliphellipanni sei sopra cento helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellipin giusto ragionamento ed intelligenza dei sensihelliphelliphelliphelliphelliphellip
Serrastretta Parish Archives
She does not recognize anybody she does not understand anything she does not answer any questions and she is emotionally flat She stays in bed all day moving her eyes around without any kind of thoughts driving her mind or triggering any movements of her limbs She mumbles incomprehensible words She seems astonished and scaredrsquorsquo
She died of marasmus at the age of 40 yearsin 1905helliphellip
TIMELINE DEMENZE
LEWY
VASCULAR
AD
Podcasy and Epperson Dialogues in Clinical Neuroscience - Vol 18 No 4 2016
Un soggetto su nove ha la malattia di Alzheimer e le donne sono il doppio
(gt65 anni)
Studio ILSA Incidenza della malattia di Alzheimer e della demenza vascolare per sesso e classi di etagrave
0
3
6
9
12
15
18
65-69 70-74 75-79 80-84
Classi di etagrave
Inci
denz
a pe
r 100
0
0
3
6
9
12
15
18
65-69 70-74 75-79 80-84
Classi di etagrave
Inci
denz
a pe
r 10
00
Uomini Donne
AD VaD
Metanalysis 12784 ALS patients
Higher female prevalence of C9orf72 hexanucleotide repeat expansions in ALS and GRN mutations in FTD suggest that sex-related risk factors might moderate C9orf72 and GRN mediatedphenotypic expression
Curtis et al Neurologyreg 2017891ndash10
A cosa DOBBIAMO QUESTE DIFFERENZE
DIFFERENTE PESO DEI FATTORI DI RISCHIO
DIFFERENTI CONNESSIONI E NETWORK
DIFFERENTE BACKGROUND ORMONALE
DIFFERENTE ESPRESSIONEASSETTO GENETICO
Gender differences in behavioraland cognitive functioning
bull The brain can be considered as a large-scale network of interconnected nodes within the human connectome
bull Small world network (network di connessione tra nodi))
Gender differences in brain connectome mayprovide an important foundation to delineate thepathophysiological mechanisms underlying sexdifferences in neuropsychiatric disorders and to potentially guide the development of sex specifictreatments
Differenti comunicazioni maschi in blu (percezione-azione coordinata)donne in arancio (analitico-intuitivo)
Ingalhalikar et al 2013
Mosconi et al Neurology 2017
Differenze ormonali
These results indicate progressively increased risk of AD as women undergo menopausal changes suggesting that endocrine aging accelerates chronologic aging in the female brain several years if
not decades prior to emergence of possible clinical symptoms of AD
AD
Ris
k
40yrs
OVARIECTOMY
Timing hypothesis
50yrs
Rocca et al 2011
Approximately 650 genes
(~ 14 of all genes in mouse
tissue) are expressed
differentially in the brains of
males and females The
morphology of the brain may
be sexually differentiated
because of epigenetic
mechanisms
Yang X et al (2006) Tissue-specific expression and regulationof sexually dimorphic genes in mice Genome Research 16 (8) 995-1004
Murray E K et al (2009) Epigenetic Control of SexualDifferentiation of the Bed Nucleus of the Stria Terminalis Endocrinology 150 (9) 4241-4247
Genes differences
Diversa espressione dei geni nei cervelli di maschi e femmine
Sex differences in metabolic aging of the brain insights into female susceptibility to Alzheimerrsquos disease
bull Gene expression profiles revealed substantial differences in the trajectory of aging changes between female and male brains
bull In female brains 442 of genes were significantly changed from 6 months to 9 months and two-thirds showed downregulation
bull In contrast in male brains only 54 in the same period
Zhao et al Neurobiol Aging 2016 June 42 69ndash79 doi101016jneurobiolaging201602011
Conclusions female and male brains follow profoundly dissimilar trajectories as they age female brains undergo age-related changes much earlier than male brains early changes in female brains signal the onset of a hypometabolicphenotype at risk for AD
These findings provide a mechanistic rationale for female susceptibility to AD and suggest a potential window of opportunity for AD prevention and risk reduction in women
Differente espressione di SRY in aree cerebrali
HLoke et al The International Journal of Biochemistry amp Cell Biology 65 (2015) 139ndash150
Male and female brains are neurochemicallydistinct concerning dopaminergic serotonergic and gamma-aminobutyric acid (GABA)ergic markers
Cosgrove KP et al Biol Psychiatry 2007 Oct 1562(8)847-55 Epub 2007 Jun 4
Sex-specific differences in neuromediators
Serotonin sexually differentiated multiple levels
Risk factors
Female sex early-onset hypertension and risk of dementia
Gilsanz et al Neurologyreg 2017891ndash8
Mid-adulthood hypertension wasassociated with 65 (95confidenceinterval [CI]125ndash218) increased dementia risk amongwomen but not men
Onset of hypertension in mid-adulthood predicted 73 higherdementia risk in women (95 CI 124ndash240) compared to stablenormotensive
Midlife hypertension was more common in men however itwas associated with dementia risk only in women
APOE4 effect is more pronounced in women than in men
HZ carrier APOEe4 earlier age at onset of AD
3-4 times more likely to develop AD
FARRER ET AL 1997
Fattori di rischio geneticihanno pesi diversi
ApoE4 strongly promotes amyloid-β deposition in the brain
Liu et al Nat Rev Neurol 2013
Risk gender for dementia or AD
In all three examples women experienced a higher risk of dementia or AD attributable to the specific risk factors (bigger red oval) Panel A APOE E4 allele is equally frequent in men and women (equal boxes) but has a stronger effect in women (thicker red arrow) Panel B low education has the same effect on the risk of dementia or AD in both men and women (equal strength of the blue and red
Rocca et al Maturitas 2014 October 79(2) 196ndash201 doi101016jmaturitas201405008
Men blueWomen red
APOE Meta analysis
JAMANeuroldoi101001jamaneurol20172188 PublishedonlineAugust282017
Increased risk in womenbetween 65-75 yrs
Risk factors in 1925 AD patients
Notaro P doctoral thesis 2017Unical
Le demenze sono molto variabili nei loro fenotipi
female patients with DLB having a higher frequency of VH symptoms
Chiu et al Int J Geriatr Psychiatry 2017
Women show an advantage in verbal memory despite evidence of moderate hippocampalatrophy This advantage may represent a sex-specific form of cognitive reserve delaying verbal memory decline until more advanced disease stages
lrsquoanalisi dei gruppi evidenziache queste donne hanno piugrave di 15 anni di
scolaritagrave
Cognitive reserve
IN SINTESIhellip
bull Le donne sono maggiormente a rischio per demenza e specie per malattia di Alzheimer tutto sembra concorrere a farle ammalare di piugrave dei maschi
bull Lrsquo assetto genetico e ormonale il modo di connettere informazioni a livello cerebrale le tante malattie in piugrave il piugrave basso livello di scolaritagrave e la minore attivitagrave laquosocialeraquo rispetto ai maschihelliphellip
Take home messages
bull Le differenze di genere osservate nelle demenze ( per tipo sintomied espressione fenotipica) originano dale profonde differenzecerebrali (genetiche ormonali e di connessioni) che esistono tra I due sessi
bull La consapevolezza e la ricerca in questa direzione potrebberoportare in futuro ad avere trattamenti genere - specifici non solo per gli aspetti cognitivi ma ancora di piugrave per quelli comportamentali
Il ogni caso il futuro egrave disegnatohellip studiare di piugrave avere una maggiore vita sociale fare attivitagrave fisica combattere le malattiehelliphellip
Anno 1791 giorno 29 Dicembre helliphelliphelliphellip Magnifica Eleonora Miceli helliphelliphelliphelliphelliphelliphellipanni sei sopra cento helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellipin giusto ragionamento ed intelligenza dei sensihelliphelliphelliphelliphelliphellip
Serrastretta Parish Archives
She does not recognize anybody she does not understand anything she does not answer any questions and she is emotionally flat She stays in bed all day moving her eyes around without any kind of thoughts driving her mind or triggering any movements of her limbs She mumbles incomprehensible words She seems astonished and scaredrsquorsquo
She died of marasmus at the age of 40 yearsin 1905helliphellip
Podcasy and Epperson Dialogues in Clinical Neuroscience - Vol 18 No 4 2016
Un soggetto su nove ha la malattia di Alzheimer e le donne sono il doppio
(gt65 anni)
Studio ILSA Incidenza della malattia di Alzheimer e della demenza vascolare per sesso e classi di etagrave
0
3
6
9
12
15
18
65-69 70-74 75-79 80-84
Classi di etagrave
Inci
denz
a pe
r 100
0
0
3
6
9
12
15
18
65-69 70-74 75-79 80-84
Classi di etagrave
Inci
denz
a pe
r 10
00
Uomini Donne
AD VaD
Metanalysis 12784 ALS patients
Higher female prevalence of C9orf72 hexanucleotide repeat expansions in ALS and GRN mutations in FTD suggest that sex-related risk factors might moderate C9orf72 and GRN mediatedphenotypic expression
Curtis et al Neurologyreg 2017891ndash10
A cosa DOBBIAMO QUESTE DIFFERENZE
DIFFERENTE PESO DEI FATTORI DI RISCHIO
DIFFERENTI CONNESSIONI E NETWORK
DIFFERENTE BACKGROUND ORMONALE
DIFFERENTE ESPRESSIONEASSETTO GENETICO
Gender differences in behavioraland cognitive functioning
bull The brain can be considered as a large-scale network of interconnected nodes within the human connectome
bull Small world network (network di connessione tra nodi))
Gender differences in brain connectome mayprovide an important foundation to delineate thepathophysiological mechanisms underlying sexdifferences in neuropsychiatric disorders and to potentially guide the development of sex specifictreatments
Differenti comunicazioni maschi in blu (percezione-azione coordinata)donne in arancio (analitico-intuitivo)
Ingalhalikar et al 2013
Mosconi et al Neurology 2017
Differenze ormonali
These results indicate progressively increased risk of AD as women undergo menopausal changes suggesting that endocrine aging accelerates chronologic aging in the female brain several years if
not decades prior to emergence of possible clinical symptoms of AD
AD
Ris
k
40yrs
OVARIECTOMY
Timing hypothesis
50yrs
Rocca et al 2011
Approximately 650 genes
(~ 14 of all genes in mouse
tissue) are expressed
differentially in the brains of
males and females The
morphology of the brain may
be sexually differentiated
because of epigenetic
mechanisms
Yang X et al (2006) Tissue-specific expression and regulationof sexually dimorphic genes in mice Genome Research 16 (8) 995-1004
Murray E K et al (2009) Epigenetic Control of SexualDifferentiation of the Bed Nucleus of the Stria Terminalis Endocrinology 150 (9) 4241-4247
Genes differences
Diversa espressione dei geni nei cervelli di maschi e femmine
Sex differences in metabolic aging of the brain insights into female susceptibility to Alzheimerrsquos disease
bull Gene expression profiles revealed substantial differences in the trajectory of aging changes between female and male brains
bull In female brains 442 of genes were significantly changed from 6 months to 9 months and two-thirds showed downregulation
bull In contrast in male brains only 54 in the same period
Zhao et al Neurobiol Aging 2016 June 42 69ndash79 doi101016jneurobiolaging201602011
Conclusions female and male brains follow profoundly dissimilar trajectories as they age female brains undergo age-related changes much earlier than male brains early changes in female brains signal the onset of a hypometabolicphenotype at risk for AD
These findings provide a mechanistic rationale for female susceptibility to AD and suggest a potential window of opportunity for AD prevention and risk reduction in women
Differente espressione di SRY in aree cerebrali
HLoke et al The International Journal of Biochemistry amp Cell Biology 65 (2015) 139ndash150
Male and female brains are neurochemicallydistinct concerning dopaminergic serotonergic and gamma-aminobutyric acid (GABA)ergic markers
Cosgrove KP et al Biol Psychiatry 2007 Oct 1562(8)847-55 Epub 2007 Jun 4
Sex-specific differences in neuromediators
Serotonin sexually differentiated multiple levels
Risk factors
Female sex early-onset hypertension and risk of dementia
Gilsanz et al Neurologyreg 2017891ndash8
Mid-adulthood hypertension wasassociated with 65 (95confidenceinterval [CI]125ndash218) increased dementia risk amongwomen but not men
Onset of hypertension in mid-adulthood predicted 73 higherdementia risk in women (95 CI 124ndash240) compared to stablenormotensive
Midlife hypertension was more common in men however itwas associated with dementia risk only in women
APOE4 effect is more pronounced in women than in men
HZ carrier APOEe4 earlier age at onset of AD
3-4 times more likely to develop AD
FARRER ET AL 1997
Fattori di rischio geneticihanno pesi diversi
ApoE4 strongly promotes amyloid-β deposition in the brain
Liu et al Nat Rev Neurol 2013
Risk gender for dementia or AD
In all three examples women experienced a higher risk of dementia or AD attributable to the specific risk factors (bigger red oval) Panel A APOE E4 allele is equally frequent in men and women (equal boxes) but has a stronger effect in women (thicker red arrow) Panel B low education has the same effect on the risk of dementia or AD in both men and women (equal strength of the blue and red
Rocca et al Maturitas 2014 October 79(2) 196ndash201 doi101016jmaturitas201405008
Men blueWomen red
APOE Meta analysis
JAMANeuroldoi101001jamaneurol20172188 PublishedonlineAugust282017
Increased risk in womenbetween 65-75 yrs
Risk factors in 1925 AD patients
Notaro P doctoral thesis 2017Unical
Le demenze sono molto variabili nei loro fenotipi
female patients with DLB having a higher frequency of VH symptoms
Chiu et al Int J Geriatr Psychiatry 2017
Women show an advantage in verbal memory despite evidence of moderate hippocampalatrophy This advantage may represent a sex-specific form of cognitive reserve delaying verbal memory decline until more advanced disease stages
lrsquoanalisi dei gruppi evidenziache queste donne hanno piugrave di 15 anni di
scolaritagrave
Cognitive reserve
IN SINTESIhellip
bull Le donne sono maggiormente a rischio per demenza e specie per malattia di Alzheimer tutto sembra concorrere a farle ammalare di piugrave dei maschi
bull Lrsquo assetto genetico e ormonale il modo di connettere informazioni a livello cerebrale le tante malattie in piugrave il piugrave basso livello di scolaritagrave e la minore attivitagrave laquosocialeraquo rispetto ai maschihelliphellip
Take home messages
bull Le differenze di genere osservate nelle demenze ( per tipo sintomied espressione fenotipica) originano dale profonde differenzecerebrali (genetiche ormonali e di connessioni) che esistono tra I due sessi
bull La consapevolezza e la ricerca in questa direzione potrebberoportare in futuro ad avere trattamenti genere - specifici non solo per gli aspetti cognitivi ma ancora di piugrave per quelli comportamentali
Il ogni caso il futuro egrave disegnatohellip studiare di piugrave avere una maggiore vita sociale fare attivitagrave fisica combattere le malattiehelliphellip
Anno 1791 giorno 29 Dicembre helliphelliphelliphellip Magnifica Eleonora Miceli helliphelliphelliphelliphelliphelliphellipanni sei sopra cento helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellipin giusto ragionamento ed intelligenza dei sensihelliphelliphelliphelliphelliphellip
Serrastretta Parish Archives
She does not recognize anybody she does not understand anything she does not answer any questions and she is emotionally flat She stays in bed all day moving her eyes around without any kind of thoughts driving her mind or triggering any movements of her limbs She mumbles incomprehensible words She seems astonished and scaredrsquorsquo
She died of marasmus at the age of 40 yearsin 1905helliphellip
Un soggetto su nove ha la malattia di Alzheimer e le donne sono il doppio
(gt65 anni)
Studio ILSA Incidenza della malattia di Alzheimer e della demenza vascolare per sesso e classi di etagrave
0
3
6
9
12
15
18
65-69 70-74 75-79 80-84
Classi di etagrave
Inci
denz
a pe
r 100
0
0
3
6
9
12
15
18
65-69 70-74 75-79 80-84
Classi di etagrave
Inci
denz
a pe
r 10
00
Uomini Donne
AD VaD
Metanalysis 12784 ALS patients
Higher female prevalence of C9orf72 hexanucleotide repeat expansions in ALS and GRN mutations in FTD suggest that sex-related risk factors might moderate C9orf72 and GRN mediatedphenotypic expression
Curtis et al Neurologyreg 2017891ndash10
A cosa DOBBIAMO QUESTE DIFFERENZE
DIFFERENTE PESO DEI FATTORI DI RISCHIO
DIFFERENTI CONNESSIONI E NETWORK
DIFFERENTE BACKGROUND ORMONALE
DIFFERENTE ESPRESSIONEASSETTO GENETICO
Gender differences in behavioraland cognitive functioning
bull The brain can be considered as a large-scale network of interconnected nodes within the human connectome
bull Small world network (network di connessione tra nodi))
Gender differences in brain connectome mayprovide an important foundation to delineate thepathophysiological mechanisms underlying sexdifferences in neuropsychiatric disorders and to potentially guide the development of sex specifictreatments
Differenti comunicazioni maschi in blu (percezione-azione coordinata)donne in arancio (analitico-intuitivo)
Ingalhalikar et al 2013
Mosconi et al Neurology 2017
Differenze ormonali
These results indicate progressively increased risk of AD as women undergo menopausal changes suggesting that endocrine aging accelerates chronologic aging in the female brain several years if
not decades prior to emergence of possible clinical symptoms of AD
AD
Ris
k
40yrs
OVARIECTOMY
Timing hypothesis
50yrs
Rocca et al 2011
Approximately 650 genes
(~ 14 of all genes in mouse
tissue) are expressed
differentially in the brains of
males and females The
morphology of the brain may
be sexually differentiated
because of epigenetic
mechanisms
Yang X et al (2006) Tissue-specific expression and regulationof sexually dimorphic genes in mice Genome Research 16 (8) 995-1004
Murray E K et al (2009) Epigenetic Control of SexualDifferentiation of the Bed Nucleus of the Stria Terminalis Endocrinology 150 (9) 4241-4247
Genes differences
Diversa espressione dei geni nei cervelli di maschi e femmine
Sex differences in metabolic aging of the brain insights into female susceptibility to Alzheimerrsquos disease
bull Gene expression profiles revealed substantial differences in the trajectory of aging changes between female and male brains
bull In female brains 442 of genes were significantly changed from 6 months to 9 months and two-thirds showed downregulation
bull In contrast in male brains only 54 in the same period
Zhao et al Neurobiol Aging 2016 June 42 69ndash79 doi101016jneurobiolaging201602011
Conclusions female and male brains follow profoundly dissimilar trajectories as they age female brains undergo age-related changes much earlier than male brains early changes in female brains signal the onset of a hypometabolicphenotype at risk for AD
These findings provide a mechanistic rationale for female susceptibility to AD and suggest a potential window of opportunity for AD prevention and risk reduction in women
Differente espressione di SRY in aree cerebrali
HLoke et al The International Journal of Biochemistry amp Cell Biology 65 (2015) 139ndash150
Male and female brains are neurochemicallydistinct concerning dopaminergic serotonergic and gamma-aminobutyric acid (GABA)ergic markers
Cosgrove KP et al Biol Psychiatry 2007 Oct 1562(8)847-55 Epub 2007 Jun 4
Sex-specific differences in neuromediators
Serotonin sexually differentiated multiple levels
Risk factors
Female sex early-onset hypertension and risk of dementia
Gilsanz et al Neurologyreg 2017891ndash8
Mid-adulthood hypertension wasassociated with 65 (95confidenceinterval [CI]125ndash218) increased dementia risk amongwomen but not men
Onset of hypertension in mid-adulthood predicted 73 higherdementia risk in women (95 CI 124ndash240) compared to stablenormotensive
Midlife hypertension was more common in men however itwas associated with dementia risk only in women
APOE4 effect is more pronounced in women than in men
HZ carrier APOEe4 earlier age at onset of AD
3-4 times more likely to develop AD
FARRER ET AL 1997
Fattori di rischio geneticihanno pesi diversi
ApoE4 strongly promotes amyloid-β deposition in the brain
Liu et al Nat Rev Neurol 2013
Risk gender for dementia or AD
In all three examples women experienced a higher risk of dementia or AD attributable to the specific risk factors (bigger red oval) Panel A APOE E4 allele is equally frequent in men and women (equal boxes) but has a stronger effect in women (thicker red arrow) Panel B low education has the same effect on the risk of dementia or AD in both men and women (equal strength of the blue and red
Rocca et al Maturitas 2014 October 79(2) 196ndash201 doi101016jmaturitas201405008
Men blueWomen red
APOE Meta analysis
JAMANeuroldoi101001jamaneurol20172188 PublishedonlineAugust282017
Increased risk in womenbetween 65-75 yrs
Risk factors in 1925 AD patients
Notaro P doctoral thesis 2017Unical
Le demenze sono molto variabili nei loro fenotipi
female patients with DLB having a higher frequency of VH symptoms
Chiu et al Int J Geriatr Psychiatry 2017
Women show an advantage in verbal memory despite evidence of moderate hippocampalatrophy This advantage may represent a sex-specific form of cognitive reserve delaying verbal memory decline until more advanced disease stages
lrsquoanalisi dei gruppi evidenziache queste donne hanno piugrave di 15 anni di
scolaritagrave
Cognitive reserve
IN SINTESIhellip
bull Le donne sono maggiormente a rischio per demenza e specie per malattia di Alzheimer tutto sembra concorrere a farle ammalare di piugrave dei maschi
bull Lrsquo assetto genetico e ormonale il modo di connettere informazioni a livello cerebrale le tante malattie in piugrave il piugrave basso livello di scolaritagrave e la minore attivitagrave laquosocialeraquo rispetto ai maschihelliphellip
Take home messages
bull Le differenze di genere osservate nelle demenze ( per tipo sintomied espressione fenotipica) originano dale profonde differenzecerebrali (genetiche ormonali e di connessioni) che esistono tra I due sessi
bull La consapevolezza e la ricerca in questa direzione potrebberoportare in futuro ad avere trattamenti genere - specifici non solo per gli aspetti cognitivi ma ancora di piugrave per quelli comportamentali
Il ogni caso il futuro egrave disegnatohellip studiare di piugrave avere una maggiore vita sociale fare attivitagrave fisica combattere le malattiehelliphellip
Anno 1791 giorno 29 Dicembre helliphelliphelliphellip Magnifica Eleonora Miceli helliphelliphelliphelliphelliphelliphellipanni sei sopra cento helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellipin giusto ragionamento ed intelligenza dei sensihelliphelliphelliphelliphelliphellip
Serrastretta Parish Archives
She does not recognize anybody she does not understand anything she does not answer any questions and she is emotionally flat She stays in bed all day moving her eyes around without any kind of thoughts driving her mind or triggering any movements of her limbs She mumbles incomprehensible words She seems astonished and scaredrsquorsquo
She died of marasmus at the age of 40 yearsin 1905helliphellip
Studio ILSA Incidenza della malattia di Alzheimer e della demenza vascolare per sesso e classi di etagrave
0
3
6
9
12
15
18
65-69 70-74 75-79 80-84
Classi di etagrave
Inci
denz
a pe
r 100
0
0
3
6
9
12
15
18
65-69 70-74 75-79 80-84
Classi di etagrave
Inci
denz
a pe
r 10
00
Uomini Donne
AD VaD
Metanalysis 12784 ALS patients
Higher female prevalence of C9orf72 hexanucleotide repeat expansions in ALS and GRN mutations in FTD suggest that sex-related risk factors might moderate C9orf72 and GRN mediatedphenotypic expression
Curtis et al Neurologyreg 2017891ndash10
A cosa DOBBIAMO QUESTE DIFFERENZE
DIFFERENTE PESO DEI FATTORI DI RISCHIO
DIFFERENTI CONNESSIONI E NETWORK
DIFFERENTE BACKGROUND ORMONALE
DIFFERENTE ESPRESSIONEASSETTO GENETICO
Gender differences in behavioraland cognitive functioning
bull The brain can be considered as a large-scale network of interconnected nodes within the human connectome
bull Small world network (network di connessione tra nodi))
Gender differences in brain connectome mayprovide an important foundation to delineate thepathophysiological mechanisms underlying sexdifferences in neuropsychiatric disorders and to potentially guide the development of sex specifictreatments
Differenti comunicazioni maschi in blu (percezione-azione coordinata)donne in arancio (analitico-intuitivo)
Ingalhalikar et al 2013
Mosconi et al Neurology 2017
Differenze ormonali
These results indicate progressively increased risk of AD as women undergo menopausal changes suggesting that endocrine aging accelerates chronologic aging in the female brain several years if
not decades prior to emergence of possible clinical symptoms of AD
AD
Ris
k
40yrs
OVARIECTOMY
Timing hypothesis
50yrs
Rocca et al 2011
Approximately 650 genes
(~ 14 of all genes in mouse
tissue) are expressed
differentially in the brains of
males and females The
morphology of the brain may
be sexually differentiated
because of epigenetic
mechanisms
Yang X et al (2006) Tissue-specific expression and regulationof sexually dimorphic genes in mice Genome Research 16 (8) 995-1004
Murray E K et al (2009) Epigenetic Control of SexualDifferentiation of the Bed Nucleus of the Stria Terminalis Endocrinology 150 (9) 4241-4247
Genes differences
Diversa espressione dei geni nei cervelli di maschi e femmine
Sex differences in metabolic aging of the brain insights into female susceptibility to Alzheimerrsquos disease
bull Gene expression profiles revealed substantial differences in the trajectory of aging changes between female and male brains
bull In female brains 442 of genes were significantly changed from 6 months to 9 months and two-thirds showed downregulation
bull In contrast in male brains only 54 in the same period
Zhao et al Neurobiol Aging 2016 June 42 69ndash79 doi101016jneurobiolaging201602011
Conclusions female and male brains follow profoundly dissimilar trajectories as they age female brains undergo age-related changes much earlier than male brains early changes in female brains signal the onset of a hypometabolicphenotype at risk for AD
These findings provide a mechanistic rationale for female susceptibility to AD and suggest a potential window of opportunity for AD prevention and risk reduction in women
Differente espressione di SRY in aree cerebrali
HLoke et al The International Journal of Biochemistry amp Cell Biology 65 (2015) 139ndash150
Male and female brains are neurochemicallydistinct concerning dopaminergic serotonergic and gamma-aminobutyric acid (GABA)ergic markers
Cosgrove KP et al Biol Psychiatry 2007 Oct 1562(8)847-55 Epub 2007 Jun 4
Sex-specific differences in neuromediators
Serotonin sexually differentiated multiple levels
Risk factors
Female sex early-onset hypertension and risk of dementia
Gilsanz et al Neurologyreg 2017891ndash8
Mid-adulthood hypertension wasassociated with 65 (95confidenceinterval [CI]125ndash218) increased dementia risk amongwomen but not men
Onset of hypertension in mid-adulthood predicted 73 higherdementia risk in women (95 CI 124ndash240) compared to stablenormotensive
Midlife hypertension was more common in men however itwas associated with dementia risk only in women
APOE4 effect is more pronounced in women than in men
HZ carrier APOEe4 earlier age at onset of AD
3-4 times more likely to develop AD
FARRER ET AL 1997
Fattori di rischio geneticihanno pesi diversi
ApoE4 strongly promotes amyloid-β deposition in the brain
Liu et al Nat Rev Neurol 2013
Risk gender for dementia or AD
In all three examples women experienced a higher risk of dementia or AD attributable to the specific risk factors (bigger red oval) Panel A APOE E4 allele is equally frequent in men and women (equal boxes) but has a stronger effect in women (thicker red arrow) Panel B low education has the same effect on the risk of dementia or AD in both men and women (equal strength of the blue and red
Rocca et al Maturitas 2014 October 79(2) 196ndash201 doi101016jmaturitas201405008
Men blueWomen red
APOE Meta analysis
JAMANeuroldoi101001jamaneurol20172188 PublishedonlineAugust282017
Increased risk in womenbetween 65-75 yrs
Risk factors in 1925 AD patients
Notaro P doctoral thesis 2017Unical
Le demenze sono molto variabili nei loro fenotipi
female patients with DLB having a higher frequency of VH symptoms
Chiu et al Int J Geriatr Psychiatry 2017
Women show an advantage in verbal memory despite evidence of moderate hippocampalatrophy This advantage may represent a sex-specific form of cognitive reserve delaying verbal memory decline until more advanced disease stages
lrsquoanalisi dei gruppi evidenziache queste donne hanno piugrave di 15 anni di
scolaritagrave
Cognitive reserve
IN SINTESIhellip
bull Le donne sono maggiormente a rischio per demenza e specie per malattia di Alzheimer tutto sembra concorrere a farle ammalare di piugrave dei maschi
bull Lrsquo assetto genetico e ormonale il modo di connettere informazioni a livello cerebrale le tante malattie in piugrave il piugrave basso livello di scolaritagrave e la minore attivitagrave laquosocialeraquo rispetto ai maschihelliphellip
Take home messages
bull Le differenze di genere osservate nelle demenze ( per tipo sintomied espressione fenotipica) originano dale profonde differenzecerebrali (genetiche ormonali e di connessioni) che esistono tra I due sessi
bull La consapevolezza e la ricerca in questa direzione potrebberoportare in futuro ad avere trattamenti genere - specifici non solo per gli aspetti cognitivi ma ancora di piugrave per quelli comportamentali
Il ogni caso il futuro egrave disegnatohellip studiare di piugrave avere una maggiore vita sociale fare attivitagrave fisica combattere le malattiehelliphellip
Anno 1791 giorno 29 Dicembre helliphelliphelliphellip Magnifica Eleonora Miceli helliphelliphelliphelliphelliphelliphellipanni sei sopra cento helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellipin giusto ragionamento ed intelligenza dei sensihelliphelliphelliphelliphelliphellip
Serrastretta Parish Archives
She does not recognize anybody she does not understand anything she does not answer any questions and she is emotionally flat She stays in bed all day moving her eyes around without any kind of thoughts driving her mind or triggering any movements of her limbs She mumbles incomprehensible words She seems astonished and scaredrsquorsquo
She died of marasmus at the age of 40 yearsin 1905helliphellip
Metanalysis 12784 ALS patients
Higher female prevalence of C9orf72 hexanucleotide repeat expansions in ALS and GRN mutations in FTD suggest that sex-related risk factors might moderate C9orf72 and GRN mediatedphenotypic expression
Curtis et al Neurologyreg 2017891ndash10
A cosa DOBBIAMO QUESTE DIFFERENZE
DIFFERENTE PESO DEI FATTORI DI RISCHIO
DIFFERENTI CONNESSIONI E NETWORK
DIFFERENTE BACKGROUND ORMONALE
DIFFERENTE ESPRESSIONEASSETTO GENETICO
Gender differences in behavioraland cognitive functioning
bull The brain can be considered as a large-scale network of interconnected nodes within the human connectome
bull Small world network (network di connessione tra nodi))
Gender differences in brain connectome mayprovide an important foundation to delineate thepathophysiological mechanisms underlying sexdifferences in neuropsychiatric disorders and to potentially guide the development of sex specifictreatments
Differenti comunicazioni maschi in blu (percezione-azione coordinata)donne in arancio (analitico-intuitivo)
Ingalhalikar et al 2013
Mosconi et al Neurology 2017
Differenze ormonali
These results indicate progressively increased risk of AD as women undergo menopausal changes suggesting that endocrine aging accelerates chronologic aging in the female brain several years if
not decades prior to emergence of possible clinical symptoms of AD
AD
Ris
k
40yrs
OVARIECTOMY
Timing hypothesis
50yrs
Rocca et al 2011
Approximately 650 genes
(~ 14 of all genes in mouse
tissue) are expressed
differentially in the brains of
males and females The
morphology of the brain may
be sexually differentiated
because of epigenetic
mechanisms
Yang X et al (2006) Tissue-specific expression and regulationof sexually dimorphic genes in mice Genome Research 16 (8) 995-1004
Murray E K et al (2009) Epigenetic Control of SexualDifferentiation of the Bed Nucleus of the Stria Terminalis Endocrinology 150 (9) 4241-4247
Genes differences
Diversa espressione dei geni nei cervelli di maschi e femmine
Sex differences in metabolic aging of the brain insights into female susceptibility to Alzheimerrsquos disease
bull Gene expression profiles revealed substantial differences in the trajectory of aging changes between female and male brains
bull In female brains 442 of genes were significantly changed from 6 months to 9 months and two-thirds showed downregulation
bull In contrast in male brains only 54 in the same period
Zhao et al Neurobiol Aging 2016 June 42 69ndash79 doi101016jneurobiolaging201602011
Conclusions female and male brains follow profoundly dissimilar trajectories as they age female brains undergo age-related changes much earlier than male brains early changes in female brains signal the onset of a hypometabolicphenotype at risk for AD
These findings provide a mechanistic rationale for female susceptibility to AD and suggest a potential window of opportunity for AD prevention and risk reduction in women
Differente espressione di SRY in aree cerebrali
HLoke et al The International Journal of Biochemistry amp Cell Biology 65 (2015) 139ndash150
Male and female brains are neurochemicallydistinct concerning dopaminergic serotonergic and gamma-aminobutyric acid (GABA)ergic markers
Cosgrove KP et al Biol Psychiatry 2007 Oct 1562(8)847-55 Epub 2007 Jun 4
Sex-specific differences in neuromediators
Serotonin sexually differentiated multiple levels
Risk factors
Female sex early-onset hypertension and risk of dementia
Gilsanz et al Neurologyreg 2017891ndash8
Mid-adulthood hypertension wasassociated with 65 (95confidenceinterval [CI]125ndash218) increased dementia risk amongwomen but not men
Onset of hypertension in mid-adulthood predicted 73 higherdementia risk in women (95 CI 124ndash240) compared to stablenormotensive
Midlife hypertension was more common in men however itwas associated with dementia risk only in women
APOE4 effect is more pronounced in women than in men
HZ carrier APOEe4 earlier age at onset of AD
3-4 times more likely to develop AD
FARRER ET AL 1997
Fattori di rischio geneticihanno pesi diversi
ApoE4 strongly promotes amyloid-β deposition in the brain
Liu et al Nat Rev Neurol 2013
Risk gender for dementia or AD
In all three examples women experienced a higher risk of dementia or AD attributable to the specific risk factors (bigger red oval) Panel A APOE E4 allele is equally frequent in men and women (equal boxes) but has a stronger effect in women (thicker red arrow) Panel B low education has the same effect on the risk of dementia or AD in both men and women (equal strength of the blue and red
Rocca et al Maturitas 2014 October 79(2) 196ndash201 doi101016jmaturitas201405008
Men blueWomen red
APOE Meta analysis
JAMANeuroldoi101001jamaneurol20172188 PublishedonlineAugust282017
Increased risk in womenbetween 65-75 yrs
Risk factors in 1925 AD patients
Notaro P doctoral thesis 2017Unical
Le demenze sono molto variabili nei loro fenotipi
female patients with DLB having a higher frequency of VH symptoms
Chiu et al Int J Geriatr Psychiatry 2017
Women show an advantage in verbal memory despite evidence of moderate hippocampalatrophy This advantage may represent a sex-specific form of cognitive reserve delaying verbal memory decline until more advanced disease stages
lrsquoanalisi dei gruppi evidenziache queste donne hanno piugrave di 15 anni di
scolaritagrave
Cognitive reserve
IN SINTESIhellip
bull Le donne sono maggiormente a rischio per demenza e specie per malattia di Alzheimer tutto sembra concorrere a farle ammalare di piugrave dei maschi
bull Lrsquo assetto genetico e ormonale il modo di connettere informazioni a livello cerebrale le tante malattie in piugrave il piugrave basso livello di scolaritagrave e la minore attivitagrave laquosocialeraquo rispetto ai maschihelliphellip
Take home messages
bull Le differenze di genere osservate nelle demenze ( per tipo sintomied espressione fenotipica) originano dale profonde differenzecerebrali (genetiche ormonali e di connessioni) che esistono tra I due sessi
bull La consapevolezza e la ricerca in questa direzione potrebberoportare in futuro ad avere trattamenti genere - specifici non solo per gli aspetti cognitivi ma ancora di piugrave per quelli comportamentali
Il ogni caso il futuro egrave disegnatohellip studiare di piugrave avere una maggiore vita sociale fare attivitagrave fisica combattere le malattiehelliphellip
Anno 1791 giorno 29 Dicembre helliphelliphelliphellip Magnifica Eleonora Miceli helliphelliphelliphelliphelliphelliphellipanni sei sopra cento helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellipin giusto ragionamento ed intelligenza dei sensihelliphelliphelliphelliphelliphellip
Serrastretta Parish Archives
She does not recognize anybody she does not understand anything she does not answer any questions and she is emotionally flat She stays in bed all day moving her eyes around without any kind of thoughts driving her mind or triggering any movements of her limbs She mumbles incomprehensible words She seems astonished and scaredrsquorsquo
She died of marasmus at the age of 40 yearsin 1905helliphellip
A cosa DOBBIAMO QUESTE DIFFERENZE
DIFFERENTE PESO DEI FATTORI DI RISCHIO
DIFFERENTI CONNESSIONI E NETWORK
DIFFERENTE BACKGROUND ORMONALE
DIFFERENTE ESPRESSIONEASSETTO GENETICO
Gender differences in behavioraland cognitive functioning
bull The brain can be considered as a large-scale network of interconnected nodes within the human connectome
bull Small world network (network di connessione tra nodi))
Gender differences in brain connectome mayprovide an important foundation to delineate thepathophysiological mechanisms underlying sexdifferences in neuropsychiatric disorders and to potentially guide the development of sex specifictreatments
Differenti comunicazioni maschi in blu (percezione-azione coordinata)donne in arancio (analitico-intuitivo)
Ingalhalikar et al 2013
Mosconi et al Neurology 2017
Differenze ormonali
These results indicate progressively increased risk of AD as women undergo menopausal changes suggesting that endocrine aging accelerates chronologic aging in the female brain several years if
not decades prior to emergence of possible clinical symptoms of AD
AD
Ris
k
40yrs
OVARIECTOMY
Timing hypothesis
50yrs
Rocca et al 2011
Approximately 650 genes
(~ 14 of all genes in mouse
tissue) are expressed
differentially in the brains of
males and females The
morphology of the brain may
be sexually differentiated
because of epigenetic
mechanisms
Yang X et al (2006) Tissue-specific expression and regulationof sexually dimorphic genes in mice Genome Research 16 (8) 995-1004
Murray E K et al (2009) Epigenetic Control of SexualDifferentiation of the Bed Nucleus of the Stria Terminalis Endocrinology 150 (9) 4241-4247
Genes differences
Diversa espressione dei geni nei cervelli di maschi e femmine
Sex differences in metabolic aging of the brain insights into female susceptibility to Alzheimerrsquos disease
bull Gene expression profiles revealed substantial differences in the trajectory of aging changes between female and male brains
bull In female brains 442 of genes were significantly changed from 6 months to 9 months and two-thirds showed downregulation
bull In contrast in male brains only 54 in the same period
Zhao et al Neurobiol Aging 2016 June 42 69ndash79 doi101016jneurobiolaging201602011
Conclusions female and male brains follow profoundly dissimilar trajectories as they age female brains undergo age-related changes much earlier than male brains early changes in female brains signal the onset of a hypometabolicphenotype at risk for AD
These findings provide a mechanistic rationale for female susceptibility to AD and suggest a potential window of opportunity for AD prevention and risk reduction in women
Differente espressione di SRY in aree cerebrali
HLoke et al The International Journal of Biochemistry amp Cell Biology 65 (2015) 139ndash150
Male and female brains are neurochemicallydistinct concerning dopaminergic serotonergic and gamma-aminobutyric acid (GABA)ergic markers
Cosgrove KP et al Biol Psychiatry 2007 Oct 1562(8)847-55 Epub 2007 Jun 4
Sex-specific differences in neuromediators
Serotonin sexually differentiated multiple levels
Risk factors
Female sex early-onset hypertension and risk of dementia
Gilsanz et al Neurologyreg 2017891ndash8
Mid-adulthood hypertension wasassociated with 65 (95confidenceinterval [CI]125ndash218) increased dementia risk amongwomen but not men
Onset of hypertension in mid-adulthood predicted 73 higherdementia risk in women (95 CI 124ndash240) compared to stablenormotensive
Midlife hypertension was more common in men however itwas associated with dementia risk only in women
APOE4 effect is more pronounced in women than in men
HZ carrier APOEe4 earlier age at onset of AD
3-4 times more likely to develop AD
FARRER ET AL 1997
Fattori di rischio geneticihanno pesi diversi
ApoE4 strongly promotes amyloid-β deposition in the brain
Liu et al Nat Rev Neurol 2013
Risk gender for dementia or AD
In all three examples women experienced a higher risk of dementia or AD attributable to the specific risk factors (bigger red oval) Panel A APOE E4 allele is equally frequent in men and women (equal boxes) but has a stronger effect in women (thicker red arrow) Panel B low education has the same effect on the risk of dementia or AD in both men and women (equal strength of the blue and red
Rocca et al Maturitas 2014 October 79(2) 196ndash201 doi101016jmaturitas201405008
Men blueWomen red
APOE Meta analysis
JAMANeuroldoi101001jamaneurol20172188 PublishedonlineAugust282017
Increased risk in womenbetween 65-75 yrs
Risk factors in 1925 AD patients
Notaro P doctoral thesis 2017Unical
Le demenze sono molto variabili nei loro fenotipi
female patients with DLB having a higher frequency of VH symptoms
Chiu et al Int J Geriatr Psychiatry 2017
Women show an advantage in verbal memory despite evidence of moderate hippocampalatrophy This advantage may represent a sex-specific form of cognitive reserve delaying verbal memory decline until more advanced disease stages
lrsquoanalisi dei gruppi evidenziache queste donne hanno piugrave di 15 anni di
scolaritagrave
Cognitive reserve
IN SINTESIhellip
bull Le donne sono maggiormente a rischio per demenza e specie per malattia di Alzheimer tutto sembra concorrere a farle ammalare di piugrave dei maschi
bull Lrsquo assetto genetico e ormonale il modo di connettere informazioni a livello cerebrale le tante malattie in piugrave il piugrave basso livello di scolaritagrave e la minore attivitagrave laquosocialeraquo rispetto ai maschihelliphellip
Take home messages
bull Le differenze di genere osservate nelle demenze ( per tipo sintomied espressione fenotipica) originano dale profonde differenzecerebrali (genetiche ormonali e di connessioni) che esistono tra I due sessi
bull La consapevolezza e la ricerca in questa direzione potrebberoportare in futuro ad avere trattamenti genere - specifici non solo per gli aspetti cognitivi ma ancora di piugrave per quelli comportamentali
Il ogni caso il futuro egrave disegnatohellip studiare di piugrave avere una maggiore vita sociale fare attivitagrave fisica combattere le malattiehelliphellip
Anno 1791 giorno 29 Dicembre helliphelliphelliphellip Magnifica Eleonora Miceli helliphelliphelliphelliphelliphelliphellipanni sei sopra cento helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellipin giusto ragionamento ed intelligenza dei sensihelliphelliphelliphelliphelliphellip
Serrastretta Parish Archives
She does not recognize anybody she does not understand anything she does not answer any questions and she is emotionally flat She stays in bed all day moving her eyes around without any kind of thoughts driving her mind or triggering any movements of her limbs She mumbles incomprehensible words She seems astonished and scaredrsquorsquo
She died of marasmus at the age of 40 yearsin 1905helliphellip
Gender differences in behavioraland cognitive functioning
bull The brain can be considered as a large-scale network of interconnected nodes within the human connectome
bull Small world network (network di connessione tra nodi))
Gender differences in brain connectome mayprovide an important foundation to delineate thepathophysiological mechanisms underlying sexdifferences in neuropsychiatric disorders and to potentially guide the development of sex specifictreatments
Differenti comunicazioni maschi in blu (percezione-azione coordinata)donne in arancio (analitico-intuitivo)
Ingalhalikar et al 2013
Mosconi et al Neurology 2017
Differenze ormonali
These results indicate progressively increased risk of AD as women undergo menopausal changes suggesting that endocrine aging accelerates chronologic aging in the female brain several years if
not decades prior to emergence of possible clinical symptoms of AD
AD
Ris
k
40yrs
OVARIECTOMY
Timing hypothesis
50yrs
Rocca et al 2011
Approximately 650 genes
(~ 14 of all genes in mouse
tissue) are expressed
differentially in the brains of
males and females The
morphology of the brain may
be sexually differentiated
because of epigenetic
mechanisms
Yang X et al (2006) Tissue-specific expression and regulationof sexually dimorphic genes in mice Genome Research 16 (8) 995-1004
Murray E K et al (2009) Epigenetic Control of SexualDifferentiation of the Bed Nucleus of the Stria Terminalis Endocrinology 150 (9) 4241-4247
Genes differences
Diversa espressione dei geni nei cervelli di maschi e femmine
Sex differences in metabolic aging of the brain insights into female susceptibility to Alzheimerrsquos disease
bull Gene expression profiles revealed substantial differences in the trajectory of aging changes between female and male brains
bull In female brains 442 of genes were significantly changed from 6 months to 9 months and two-thirds showed downregulation
bull In contrast in male brains only 54 in the same period
Zhao et al Neurobiol Aging 2016 June 42 69ndash79 doi101016jneurobiolaging201602011
Conclusions female and male brains follow profoundly dissimilar trajectories as they age female brains undergo age-related changes much earlier than male brains early changes in female brains signal the onset of a hypometabolicphenotype at risk for AD
These findings provide a mechanistic rationale for female susceptibility to AD and suggest a potential window of opportunity for AD prevention and risk reduction in women
Differente espressione di SRY in aree cerebrali
HLoke et al The International Journal of Biochemistry amp Cell Biology 65 (2015) 139ndash150
Male and female brains are neurochemicallydistinct concerning dopaminergic serotonergic and gamma-aminobutyric acid (GABA)ergic markers
Cosgrove KP et al Biol Psychiatry 2007 Oct 1562(8)847-55 Epub 2007 Jun 4
Sex-specific differences in neuromediators
Serotonin sexually differentiated multiple levels
Risk factors
Female sex early-onset hypertension and risk of dementia
Gilsanz et al Neurologyreg 2017891ndash8
Mid-adulthood hypertension wasassociated with 65 (95confidenceinterval [CI]125ndash218) increased dementia risk amongwomen but not men
Onset of hypertension in mid-adulthood predicted 73 higherdementia risk in women (95 CI 124ndash240) compared to stablenormotensive
Midlife hypertension was more common in men however itwas associated with dementia risk only in women
APOE4 effect is more pronounced in women than in men
HZ carrier APOEe4 earlier age at onset of AD
3-4 times more likely to develop AD
FARRER ET AL 1997
Fattori di rischio geneticihanno pesi diversi
ApoE4 strongly promotes amyloid-β deposition in the brain
Liu et al Nat Rev Neurol 2013
Risk gender for dementia or AD
In all three examples women experienced a higher risk of dementia or AD attributable to the specific risk factors (bigger red oval) Panel A APOE E4 allele is equally frequent in men and women (equal boxes) but has a stronger effect in women (thicker red arrow) Panel B low education has the same effect on the risk of dementia or AD in both men and women (equal strength of the blue and red
Rocca et al Maturitas 2014 October 79(2) 196ndash201 doi101016jmaturitas201405008
Men blueWomen red
APOE Meta analysis
JAMANeuroldoi101001jamaneurol20172188 PublishedonlineAugust282017
Increased risk in womenbetween 65-75 yrs
Risk factors in 1925 AD patients
Notaro P doctoral thesis 2017Unical
Le demenze sono molto variabili nei loro fenotipi
female patients with DLB having a higher frequency of VH symptoms
Chiu et al Int J Geriatr Psychiatry 2017
Women show an advantage in verbal memory despite evidence of moderate hippocampalatrophy This advantage may represent a sex-specific form of cognitive reserve delaying verbal memory decline until more advanced disease stages
lrsquoanalisi dei gruppi evidenziache queste donne hanno piugrave di 15 anni di
scolaritagrave
Cognitive reserve
IN SINTESIhellip
bull Le donne sono maggiormente a rischio per demenza e specie per malattia di Alzheimer tutto sembra concorrere a farle ammalare di piugrave dei maschi
bull Lrsquo assetto genetico e ormonale il modo di connettere informazioni a livello cerebrale le tante malattie in piugrave il piugrave basso livello di scolaritagrave e la minore attivitagrave laquosocialeraquo rispetto ai maschihelliphellip
Take home messages
bull Le differenze di genere osservate nelle demenze ( per tipo sintomied espressione fenotipica) originano dale profonde differenzecerebrali (genetiche ormonali e di connessioni) che esistono tra I due sessi
bull La consapevolezza e la ricerca in questa direzione potrebberoportare in futuro ad avere trattamenti genere - specifici non solo per gli aspetti cognitivi ma ancora di piugrave per quelli comportamentali
Il ogni caso il futuro egrave disegnatohellip studiare di piugrave avere una maggiore vita sociale fare attivitagrave fisica combattere le malattiehelliphellip
Anno 1791 giorno 29 Dicembre helliphelliphelliphellip Magnifica Eleonora Miceli helliphelliphelliphelliphelliphelliphellipanni sei sopra cento helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellipin giusto ragionamento ed intelligenza dei sensihelliphelliphelliphelliphelliphellip
Serrastretta Parish Archives
She does not recognize anybody she does not understand anything she does not answer any questions and she is emotionally flat She stays in bed all day moving her eyes around without any kind of thoughts driving her mind or triggering any movements of her limbs She mumbles incomprehensible words She seems astonished and scaredrsquorsquo
She died of marasmus at the age of 40 yearsin 1905helliphellip
Differenti comunicazioni maschi in blu (percezione-azione coordinata)donne in arancio (analitico-intuitivo)
Ingalhalikar et al 2013
Mosconi et al Neurology 2017
Differenze ormonali
These results indicate progressively increased risk of AD as women undergo menopausal changes suggesting that endocrine aging accelerates chronologic aging in the female brain several years if
not decades prior to emergence of possible clinical symptoms of AD
AD
Ris
k
40yrs
OVARIECTOMY
Timing hypothesis
50yrs
Rocca et al 2011
Approximately 650 genes
(~ 14 of all genes in mouse
tissue) are expressed
differentially in the brains of
males and females The
morphology of the brain may
be sexually differentiated
because of epigenetic
mechanisms
Yang X et al (2006) Tissue-specific expression and regulationof sexually dimorphic genes in mice Genome Research 16 (8) 995-1004
Murray E K et al (2009) Epigenetic Control of SexualDifferentiation of the Bed Nucleus of the Stria Terminalis Endocrinology 150 (9) 4241-4247
Genes differences
Diversa espressione dei geni nei cervelli di maschi e femmine
Sex differences in metabolic aging of the brain insights into female susceptibility to Alzheimerrsquos disease
bull Gene expression profiles revealed substantial differences in the trajectory of aging changes between female and male brains
bull In female brains 442 of genes were significantly changed from 6 months to 9 months and two-thirds showed downregulation
bull In contrast in male brains only 54 in the same period
Zhao et al Neurobiol Aging 2016 June 42 69ndash79 doi101016jneurobiolaging201602011
Conclusions female and male brains follow profoundly dissimilar trajectories as they age female brains undergo age-related changes much earlier than male brains early changes in female brains signal the onset of a hypometabolicphenotype at risk for AD
These findings provide a mechanistic rationale for female susceptibility to AD and suggest a potential window of opportunity for AD prevention and risk reduction in women
Differente espressione di SRY in aree cerebrali
HLoke et al The International Journal of Biochemistry amp Cell Biology 65 (2015) 139ndash150
Male and female brains are neurochemicallydistinct concerning dopaminergic serotonergic and gamma-aminobutyric acid (GABA)ergic markers
Cosgrove KP et al Biol Psychiatry 2007 Oct 1562(8)847-55 Epub 2007 Jun 4
Sex-specific differences in neuromediators
Serotonin sexually differentiated multiple levels
Risk factors
Female sex early-onset hypertension and risk of dementia
Gilsanz et al Neurologyreg 2017891ndash8
Mid-adulthood hypertension wasassociated with 65 (95confidenceinterval [CI]125ndash218) increased dementia risk amongwomen but not men
Onset of hypertension in mid-adulthood predicted 73 higherdementia risk in women (95 CI 124ndash240) compared to stablenormotensive
Midlife hypertension was more common in men however itwas associated with dementia risk only in women
APOE4 effect is more pronounced in women than in men
HZ carrier APOEe4 earlier age at onset of AD
3-4 times more likely to develop AD
FARRER ET AL 1997
Fattori di rischio geneticihanno pesi diversi
ApoE4 strongly promotes amyloid-β deposition in the brain
Liu et al Nat Rev Neurol 2013
Risk gender for dementia or AD
In all three examples women experienced a higher risk of dementia or AD attributable to the specific risk factors (bigger red oval) Panel A APOE E4 allele is equally frequent in men and women (equal boxes) but has a stronger effect in women (thicker red arrow) Panel B low education has the same effect on the risk of dementia or AD in both men and women (equal strength of the blue and red
Rocca et al Maturitas 2014 October 79(2) 196ndash201 doi101016jmaturitas201405008
Men blueWomen red
APOE Meta analysis
JAMANeuroldoi101001jamaneurol20172188 PublishedonlineAugust282017
Increased risk in womenbetween 65-75 yrs
Risk factors in 1925 AD patients
Notaro P doctoral thesis 2017Unical
Le demenze sono molto variabili nei loro fenotipi
female patients with DLB having a higher frequency of VH symptoms
Chiu et al Int J Geriatr Psychiatry 2017
Women show an advantage in verbal memory despite evidence of moderate hippocampalatrophy This advantage may represent a sex-specific form of cognitive reserve delaying verbal memory decline until more advanced disease stages
lrsquoanalisi dei gruppi evidenziache queste donne hanno piugrave di 15 anni di
scolaritagrave
Cognitive reserve
IN SINTESIhellip
bull Le donne sono maggiormente a rischio per demenza e specie per malattia di Alzheimer tutto sembra concorrere a farle ammalare di piugrave dei maschi
bull Lrsquo assetto genetico e ormonale il modo di connettere informazioni a livello cerebrale le tante malattie in piugrave il piugrave basso livello di scolaritagrave e la minore attivitagrave laquosocialeraquo rispetto ai maschihelliphellip
Take home messages
bull Le differenze di genere osservate nelle demenze ( per tipo sintomied espressione fenotipica) originano dale profonde differenzecerebrali (genetiche ormonali e di connessioni) che esistono tra I due sessi
bull La consapevolezza e la ricerca in questa direzione potrebberoportare in futuro ad avere trattamenti genere - specifici non solo per gli aspetti cognitivi ma ancora di piugrave per quelli comportamentali
Il ogni caso il futuro egrave disegnatohellip studiare di piugrave avere una maggiore vita sociale fare attivitagrave fisica combattere le malattiehelliphellip
Anno 1791 giorno 29 Dicembre helliphelliphelliphellip Magnifica Eleonora Miceli helliphelliphelliphelliphelliphelliphellipanni sei sopra cento helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellipin giusto ragionamento ed intelligenza dei sensihelliphelliphelliphelliphelliphellip
Serrastretta Parish Archives
She does not recognize anybody she does not understand anything she does not answer any questions and she is emotionally flat She stays in bed all day moving her eyes around without any kind of thoughts driving her mind or triggering any movements of her limbs She mumbles incomprehensible words She seems astonished and scaredrsquorsquo
She died of marasmus at the age of 40 yearsin 1905helliphellip
Mosconi et al Neurology 2017
Differenze ormonali
These results indicate progressively increased risk of AD as women undergo menopausal changes suggesting that endocrine aging accelerates chronologic aging in the female brain several years if
not decades prior to emergence of possible clinical symptoms of AD
AD
Ris
k
40yrs
OVARIECTOMY
Timing hypothesis
50yrs
Rocca et al 2011
Approximately 650 genes
(~ 14 of all genes in mouse
tissue) are expressed
differentially in the brains of
males and females The
morphology of the brain may
be sexually differentiated
because of epigenetic
mechanisms
Yang X et al (2006) Tissue-specific expression and regulationof sexually dimorphic genes in mice Genome Research 16 (8) 995-1004
Murray E K et al (2009) Epigenetic Control of SexualDifferentiation of the Bed Nucleus of the Stria Terminalis Endocrinology 150 (9) 4241-4247
Genes differences
Diversa espressione dei geni nei cervelli di maschi e femmine
Sex differences in metabolic aging of the brain insights into female susceptibility to Alzheimerrsquos disease
bull Gene expression profiles revealed substantial differences in the trajectory of aging changes between female and male brains
bull In female brains 442 of genes were significantly changed from 6 months to 9 months and two-thirds showed downregulation
bull In contrast in male brains only 54 in the same period
Zhao et al Neurobiol Aging 2016 June 42 69ndash79 doi101016jneurobiolaging201602011
Conclusions female and male brains follow profoundly dissimilar trajectories as they age female brains undergo age-related changes much earlier than male brains early changes in female brains signal the onset of a hypometabolicphenotype at risk for AD
These findings provide a mechanistic rationale for female susceptibility to AD and suggest a potential window of opportunity for AD prevention and risk reduction in women
Differente espressione di SRY in aree cerebrali
HLoke et al The International Journal of Biochemistry amp Cell Biology 65 (2015) 139ndash150
Male and female brains are neurochemicallydistinct concerning dopaminergic serotonergic and gamma-aminobutyric acid (GABA)ergic markers
Cosgrove KP et al Biol Psychiatry 2007 Oct 1562(8)847-55 Epub 2007 Jun 4
Sex-specific differences in neuromediators
Serotonin sexually differentiated multiple levels
Risk factors
Female sex early-onset hypertension and risk of dementia
Gilsanz et al Neurologyreg 2017891ndash8
Mid-adulthood hypertension wasassociated with 65 (95confidenceinterval [CI]125ndash218) increased dementia risk amongwomen but not men
Onset of hypertension in mid-adulthood predicted 73 higherdementia risk in women (95 CI 124ndash240) compared to stablenormotensive
Midlife hypertension was more common in men however itwas associated with dementia risk only in women
APOE4 effect is more pronounced in women than in men
HZ carrier APOEe4 earlier age at onset of AD
3-4 times more likely to develop AD
FARRER ET AL 1997
Fattori di rischio geneticihanno pesi diversi
ApoE4 strongly promotes amyloid-β deposition in the brain
Liu et al Nat Rev Neurol 2013
Risk gender for dementia or AD
In all three examples women experienced a higher risk of dementia or AD attributable to the specific risk factors (bigger red oval) Panel A APOE E4 allele is equally frequent in men and women (equal boxes) but has a stronger effect in women (thicker red arrow) Panel B low education has the same effect on the risk of dementia or AD in both men and women (equal strength of the blue and red
Rocca et al Maturitas 2014 October 79(2) 196ndash201 doi101016jmaturitas201405008
Men blueWomen red
APOE Meta analysis
JAMANeuroldoi101001jamaneurol20172188 PublishedonlineAugust282017
Increased risk in womenbetween 65-75 yrs
Risk factors in 1925 AD patients
Notaro P doctoral thesis 2017Unical
Le demenze sono molto variabili nei loro fenotipi
female patients with DLB having a higher frequency of VH symptoms
Chiu et al Int J Geriatr Psychiatry 2017
Women show an advantage in verbal memory despite evidence of moderate hippocampalatrophy This advantage may represent a sex-specific form of cognitive reserve delaying verbal memory decline until more advanced disease stages
lrsquoanalisi dei gruppi evidenziache queste donne hanno piugrave di 15 anni di
scolaritagrave
Cognitive reserve
IN SINTESIhellip
bull Le donne sono maggiormente a rischio per demenza e specie per malattia di Alzheimer tutto sembra concorrere a farle ammalare di piugrave dei maschi
bull Lrsquo assetto genetico e ormonale il modo di connettere informazioni a livello cerebrale le tante malattie in piugrave il piugrave basso livello di scolaritagrave e la minore attivitagrave laquosocialeraquo rispetto ai maschihelliphellip
Take home messages
bull Le differenze di genere osservate nelle demenze ( per tipo sintomied espressione fenotipica) originano dale profonde differenzecerebrali (genetiche ormonali e di connessioni) che esistono tra I due sessi
bull La consapevolezza e la ricerca in questa direzione potrebberoportare in futuro ad avere trattamenti genere - specifici non solo per gli aspetti cognitivi ma ancora di piugrave per quelli comportamentali
Il ogni caso il futuro egrave disegnatohellip studiare di piugrave avere una maggiore vita sociale fare attivitagrave fisica combattere le malattiehelliphellip
Anno 1791 giorno 29 Dicembre helliphelliphelliphellip Magnifica Eleonora Miceli helliphelliphelliphelliphelliphelliphellipanni sei sopra cento helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellipin giusto ragionamento ed intelligenza dei sensihelliphelliphelliphelliphelliphellip
Serrastretta Parish Archives
She does not recognize anybody she does not understand anything she does not answer any questions and she is emotionally flat She stays in bed all day moving her eyes around without any kind of thoughts driving her mind or triggering any movements of her limbs She mumbles incomprehensible words She seems astonished and scaredrsquorsquo
She died of marasmus at the age of 40 yearsin 1905helliphellip
These results indicate progressively increased risk of AD as women undergo menopausal changes suggesting that endocrine aging accelerates chronologic aging in the female brain several years if
not decades prior to emergence of possible clinical symptoms of AD
AD
Ris
k
40yrs
OVARIECTOMY
Timing hypothesis
50yrs
Rocca et al 2011
Approximately 650 genes
(~ 14 of all genes in mouse
tissue) are expressed
differentially in the brains of
males and females The
morphology of the brain may
be sexually differentiated
because of epigenetic
mechanisms
Yang X et al (2006) Tissue-specific expression and regulationof sexually dimorphic genes in mice Genome Research 16 (8) 995-1004
Murray E K et al (2009) Epigenetic Control of SexualDifferentiation of the Bed Nucleus of the Stria Terminalis Endocrinology 150 (9) 4241-4247
Genes differences
Diversa espressione dei geni nei cervelli di maschi e femmine
Sex differences in metabolic aging of the brain insights into female susceptibility to Alzheimerrsquos disease
bull Gene expression profiles revealed substantial differences in the trajectory of aging changes between female and male brains
bull In female brains 442 of genes were significantly changed from 6 months to 9 months and two-thirds showed downregulation
bull In contrast in male brains only 54 in the same period
Zhao et al Neurobiol Aging 2016 June 42 69ndash79 doi101016jneurobiolaging201602011
Conclusions female and male brains follow profoundly dissimilar trajectories as they age female brains undergo age-related changes much earlier than male brains early changes in female brains signal the onset of a hypometabolicphenotype at risk for AD
These findings provide a mechanistic rationale for female susceptibility to AD and suggest a potential window of opportunity for AD prevention and risk reduction in women
Differente espressione di SRY in aree cerebrali
HLoke et al The International Journal of Biochemistry amp Cell Biology 65 (2015) 139ndash150
Male and female brains are neurochemicallydistinct concerning dopaminergic serotonergic and gamma-aminobutyric acid (GABA)ergic markers
Cosgrove KP et al Biol Psychiatry 2007 Oct 1562(8)847-55 Epub 2007 Jun 4
Sex-specific differences in neuromediators
Serotonin sexually differentiated multiple levels
Risk factors
Female sex early-onset hypertension and risk of dementia
Gilsanz et al Neurologyreg 2017891ndash8
Mid-adulthood hypertension wasassociated with 65 (95confidenceinterval [CI]125ndash218) increased dementia risk amongwomen but not men
Onset of hypertension in mid-adulthood predicted 73 higherdementia risk in women (95 CI 124ndash240) compared to stablenormotensive
Midlife hypertension was more common in men however itwas associated with dementia risk only in women
APOE4 effect is more pronounced in women than in men
HZ carrier APOEe4 earlier age at onset of AD
3-4 times more likely to develop AD
FARRER ET AL 1997
Fattori di rischio geneticihanno pesi diversi
ApoE4 strongly promotes amyloid-β deposition in the brain
Liu et al Nat Rev Neurol 2013
Risk gender for dementia or AD
In all three examples women experienced a higher risk of dementia or AD attributable to the specific risk factors (bigger red oval) Panel A APOE E4 allele is equally frequent in men and women (equal boxes) but has a stronger effect in women (thicker red arrow) Panel B low education has the same effect on the risk of dementia or AD in both men and women (equal strength of the blue and red
Rocca et al Maturitas 2014 October 79(2) 196ndash201 doi101016jmaturitas201405008
Men blueWomen red
APOE Meta analysis
JAMANeuroldoi101001jamaneurol20172188 PublishedonlineAugust282017
Increased risk in womenbetween 65-75 yrs
Risk factors in 1925 AD patients
Notaro P doctoral thesis 2017Unical
Le demenze sono molto variabili nei loro fenotipi
female patients with DLB having a higher frequency of VH symptoms
Chiu et al Int J Geriatr Psychiatry 2017
Women show an advantage in verbal memory despite evidence of moderate hippocampalatrophy This advantage may represent a sex-specific form of cognitive reserve delaying verbal memory decline until more advanced disease stages
lrsquoanalisi dei gruppi evidenziache queste donne hanno piugrave di 15 anni di
scolaritagrave
Cognitive reserve
IN SINTESIhellip
bull Le donne sono maggiormente a rischio per demenza e specie per malattia di Alzheimer tutto sembra concorrere a farle ammalare di piugrave dei maschi
bull Lrsquo assetto genetico e ormonale il modo di connettere informazioni a livello cerebrale le tante malattie in piugrave il piugrave basso livello di scolaritagrave e la minore attivitagrave laquosocialeraquo rispetto ai maschihelliphellip
Take home messages
bull Le differenze di genere osservate nelle demenze ( per tipo sintomied espressione fenotipica) originano dale profonde differenzecerebrali (genetiche ormonali e di connessioni) che esistono tra I due sessi
bull La consapevolezza e la ricerca in questa direzione potrebberoportare in futuro ad avere trattamenti genere - specifici non solo per gli aspetti cognitivi ma ancora di piugrave per quelli comportamentali
Il ogni caso il futuro egrave disegnatohellip studiare di piugrave avere una maggiore vita sociale fare attivitagrave fisica combattere le malattiehelliphellip
Anno 1791 giorno 29 Dicembre helliphelliphelliphellip Magnifica Eleonora Miceli helliphelliphelliphelliphelliphelliphellipanni sei sopra cento helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellipin giusto ragionamento ed intelligenza dei sensihelliphelliphelliphelliphelliphellip
Serrastretta Parish Archives
She does not recognize anybody she does not understand anything she does not answer any questions and she is emotionally flat She stays in bed all day moving her eyes around without any kind of thoughts driving her mind or triggering any movements of her limbs She mumbles incomprehensible words She seems astonished and scaredrsquorsquo
She died of marasmus at the age of 40 yearsin 1905helliphellip
AD
Ris
k
40yrs
OVARIECTOMY
Timing hypothesis
50yrs
Rocca et al 2011
Approximately 650 genes
(~ 14 of all genes in mouse
tissue) are expressed
differentially in the brains of
males and females The
morphology of the brain may
be sexually differentiated
because of epigenetic
mechanisms
Yang X et al (2006) Tissue-specific expression and regulationof sexually dimorphic genes in mice Genome Research 16 (8) 995-1004
Murray E K et al (2009) Epigenetic Control of SexualDifferentiation of the Bed Nucleus of the Stria Terminalis Endocrinology 150 (9) 4241-4247
Genes differences
Diversa espressione dei geni nei cervelli di maschi e femmine
Sex differences in metabolic aging of the brain insights into female susceptibility to Alzheimerrsquos disease
bull Gene expression profiles revealed substantial differences in the trajectory of aging changes between female and male brains
bull In female brains 442 of genes were significantly changed from 6 months to 9 months and two-thirds showed downregulation
bull In contrast in male brains only 54 in the same period
Zhao et al Neurobiol Aging 2016 June 42 69ndash79 doi101016jneurobiolaging201602011
Conclusions female and male brains follow profoundly dissimilar trajectories as they age female brains undergo age-related changes much earlier than male brains early changes in female brains signal the onset of a hypometabolicphenotype at risk for AD
These findings provide a mechanistic rationale for female susceptibility to AD and suggest a potential window of opportunity for AD prevention and risk reduction in women
Differente espressione di SRY in aree cerebrali
HLoke et al The International Journal of Biochemistry amp Cell Biology 65 (2015) 139ndash150
Male and female brains are neurochemicallydistinct concerning dopaminergic serotonergic and gamma-aminobutyric acid (GABA)ergic markers
Cosgrove KP et al Biol Psychiatry 2007 Oct 1562(8)847-55 Epub 2007 Jun 4
Sex-specific differences in neuromediators
Serotonin sexually differentiated multiple levels
Risk factors
Female sex early-onset hypertension and risk of dementia
Gilsanz et al Neurologyreg 2017891ndash8
Mid-adulthood hypertension wasassociated with 65 (95confidenceinterval [CI]125ndash218) increased dementia risk amongwomen but not men
Onset of hypertension in mid-adulthood predicted 73 higherdementia risk in women (95 CI 124ndash240) compared to stablenormotensive
Midlife hypertension was more common in men however itwas associated with dementia risk only in women
APOE4 effect is more pronounced in women than in men
HZ carrier APOEe4 earlier age at onset of AD
3-4 times more likely to develop AD
FARRER ET AL 1997
Fattori di rischio geneticihanno pesi diversi
ApoE4 strongly promotes amyloid-β deposition in the brain
Liu et al Nat Rev Neurol 2013
Risk gender for dementia or AD
In all three examples women experienced a higher risk of dementia or AD attributable to the specific risk factors (bigger red oval) Panel A APOE E4 allele is equally frequent in men and women (equal boxes) but has a stronger effect in women (thicker red arrow) Panel B low education has the same effect on the risk of dementia or AD in both men and women (equal strength of the blue and red
Rocca et al Maturitas 2014 October 79(2) 196ndash201 doi101016jmaturitas201405008
Men blueWomen red
APOE Meta analysis
JAMANeuroldoi101001jamaneurol20172188 PublishedonlineAugust282017
Increased risk in womenbetween 65-75 yrs
Risk factors in 1925 AD patients
Notaro P doctoral thesis 2017Unical
Le demenze sono molto variabili nei loro fenotipi
female patients with DLB having a higher frequency of VH symptoms
Chiu et al Int J Geriatr Psychiatry 2017
Women show an advantage in verbal memory despite evidence of moderate hippocampalatrophy This advantage may represent a sex-specific form of cognitive reserve delaying verbal memory decline until more advanced disease stages
lrsquoanalisi dei gruppi evidenziache queste donne hanno piugrave di 15 anni di
scolaritagrave
Cognitive reserve
IN SINTESIhellip
bull Le donne sono maggiormente a rischio per demenza e specie per malattia di Alzheimer tutto sembra concorrere a farle ammalare di piugrave dei maschi
bull Lrsquo assetto genetico e ormonale il modo di connettere informazioni a livello cerebrale le tante malattie in piugrave il piugrave basso livello di scolaritagrave e la minore attivitagrave laquosocialeraquo rispetto ai maschihelliphellip
Take home messages
bull Le differenze di genere osservate nelle demenze ( per tipo sintomied espressione fenotipica) originano dale profonde differenzecerebrali (genetiche ormonali e di connessioni) che esistono tra I due sessi
bull La consapevolezza e la ricerca in questa direzione potrebberoportare in futuro ad avere trattamenti genere - specifici non solo per gli aspetti cognitivi ma ancora di piugrave per quelli comportamentali
Il ogni caso il futuro egrave disegnatohellip studiare di piugrave avere una maggiore vita sociale fare attivitagrave fisica combattere le malattiehelliphellip
Anno 1791 giorno 29 Dicembre helliphelliphelliphellip Magnifica Eleonora Miceli helliphelliphelliphelliphelliphelliphellipanni sei sopra cento helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellipin giusto ragionamento ed intelligenza dei sensihelliphelliphelliphelliphelliphellip
Serrastretta Parish Archives
She does not recognize anybody she does not understand anything she does not answer any questions and she is emotionally flat She stays in bed all day moving her eyes around without any kind of thoughts driving her mind or triggering any movements of her limbs She mumbles incomprehensible words She seems astonished and scaredrsquorsquo
She died of marasmus at the age of 40 yearsin 1905helliphellip
Approximately 650 genes
(~ 14 of all genes in mouse
tissue) are expressed
differentially in the brains of
males and females The
morphology of the brain may
be sexually differentiated
because of epigenetic
mechanisms
Yang X et al (2006) Tissue-specific expression and regulationof sexually dimorphic genes in mice Genome Research 16 (8) 995-1004
Murray E K et al (2009) Epigenetic Control of SexualDifferentiation of the Bed Nucleus of the Stria Terminalis Endocrinology 150 (9) 4241-4247
Genes differences
Diversa espressione dei geni nei cervelli di maschi e femmine
Sex differences in metabolic aging of the brain insights into female susceptibility to Alzheimerrsquos disease
bull Gene expression profiles revealed substantial differences in the trajectory of aging changes between female and male brains
bull In female brains 442 of genes were significantly changed from 6 months to 9 months and two-thirds showed downregulation
bull In contrast in male brains only 54 in the same period
Zhao et al Neurobiol Aging 2016 June 42 69ndash79 doi101016jneurobiolaging201602011
Conclusions female and male brains follow profoundly dissimilar trajectories as they age female brains undergo age-related changes much earlier than male brains early changes in female brains signal the onset of a hypometabolicphenotype at risk for AD
These findings provide a mechanistic rationale for female susceptibility to AD and suggest a potential window of opportunity for AD prevention and risk reduction in women
Differente espressione di SRY in aree cerebrali
HLoke et al The International Journal of Biochemistry amp Cell Biology 65 (2015) 139ndash150
Male and female brains are neurochemicallydistinct concerning dopaminergic serotonergic and gamma-aminobutyric acid (GABA)ergic markers
Cosgrove KP et al Biol Psychiatry 2007 Oct 1562(8)847-55 Epub 2007 Jun 4
Sex-specific differences in neuromediators
Serotonin sexually differentiated multiple levels
Risk factors
Female sex early-onset hypertension and risk of dementia
Gilsanz et al Neurologyreg 2017891ndash8
Mid-adulthood hypertension wasassociated with 65 (95confidenceinterval [CI]125ndash218) increased dementia risk amongwomen but not men
Onset of hypertension in mid-adulthood predicted 73 higherdementia risk in women (95 CI 124ndash240) compared to stablenormotensive
Midlife hypertension was more common in men however itwas associated with dementia risk only in women
APOE4 effect is more pronounced in women than in men
HZ carrier APOEe4 earlier age at onset of AD
3-4 times more likely to develop AD
FARRER ET AL 1997
Fattori di rischio geneticihanno pesi diversi
ApoE4 strongly promotes amyloid-β deposition in the brain
Liu et al Nat Rev Neurol 2013
Risk gender for dementia or AD
In all three examples women experienced a higher risk of dementia or AD attributable to the specific risk factors (bigger red oval) Panel A APOE E4 allele is equally frequent in men and women (equal boxes) but has a stronger effect in women (thicker red arrow) Panel B low education has the same effect on the risk of dementia or AD in both men and women (equal strength of the blue and red
Rocca et al Maturitas 2014 October 79(2) 196ndash201 doi101016jmaturitas201405008
Men blueWomen red
APOE Meta analysis
JAMANeuroldoi101001jamaneurol20172188 PublishedonlineAugust282017
Increased risk in womenbetween 65-75 yrs
Risk factors in 1925 AD patients
Notaro P doctoral thesis 2017Unical
Le demenze sono molto variabili nei loro fenotipi
female patients with DLB having a higher frequency of VH symptoms
Chiu et al Int J Geriatr Psychiatry 2017
Women show an advantage in verbal memory despite evidence of moderate hippocampalatrophy This advantage may represent a sex-specific form of cognitive reserve delaying verbal memory decline until more advanced disease stages
lrsquoanalisi dei gruppi evidenziache queste donne hanno piugrave di 15 anni di
scolaritagrave
Cognitive reserve
IN SINTESIhellip
bull Le donne sono maggiormente a rischio per demenza e specie per malattia di Alzheimer tutto sembra concorrere a farle ammalare di piugrave dei maschi
bull Lrsquo assetto genetico e ormonale il modo di connettere informazioni a livello cerebrale le tante malattie in piugrave il piugrave basso livello di scolaritagrave e la minore attivitagrave laquosocialeraquo rispetto ai maschihelliphellip
Take home messages
bull Le differenze di genere osservate nelle demenze ( per tipo sintomied espressione fenotipica) originano dale profonde differenzecerebrali (genetiche ormonali e di connessioni) che esistono tra I due sessi
bull La consapevolezza e la ricerca in questa direzione potrebberoportare in futuro ad avere trattamenti genere - specifici non solo per gli aspetti cognitivi ma ancora di piugrave per quelli comportamentali
Il ogni caso il futuro egrave disegnatohellip studiare di piugrave avere una maggiore vita sociale fare attivitagrave fisica combattere le malattiehelliphellip
Anno 1791 giorno 29 Dicembre helliphelliphelliphellip Magnifica Eleonora Miceli helliphelliphelliphelliphelliphelliphellipanni sei sopra cento helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellipin giusto ragionamento ed intelligenza dei sensihelliphelliphelliphelliphelliphellip
Serrastretta Parish Archives
She does not recognize anybody she does not understand anything she does not answer any questions and she is emotionally flat She stays in bed all day moving her eyes around without any kind of thoughts driving her mind or triggering any movements of her limbs She mumbles incomprehensible words She seems astonished and scaredrsquorsquo
She died of marasmus at the age of 40 yearsin 1905helliphellip
Sex differences in metabolic aging of the brain insights into female susceptibility to Alzheimerrsquos disease
bull Gene expression profiles revealed substantial differences in the trajectory of aging changes between female and male brains
bull In female brains 442 of genes were significantly changed from 6 months to 9 months and two-thirds showed downregulation
bull In contrast in male brains only 54 in the same period
Zhao et al Neurobiol Aging 2016 June 42 69ndash79 doi101016jneurobiolaging201602011
Conclusions female and male brains follow profoundly dissimilar trajectories as they age female brains undergo age-related changes much earlier than male brains early changes in female brains signal the onset of a hypometabolicphenotype at risk for AD
These findings provide a mechanistic rationale for female susceptibility to AD and suggest a potential window of opportunity for AD prevention and risk reduction in women
Differente espressione di SRY in aree cerebrali
HLoke et al The International Journal of Biochemistry amp Cell Biology 65 (2015) 139ndash150
Male and female brains are neurochemicallydistinct concerning dopaminergic serotonergic and gamma-aminobutyric acid (GABA)ergic markers
Cosgrove KP et al Biol Psychiatry 2007 Oct 1562(8)847-55 Epub 2007 Jun 4
Sex-specific differences in neuromediators
Serotonin sexually differentiated multiple levels
Risk factors
Female sex early-onset hypertension and risk of dementia
Gilsanz et al Neurologyreg 2017891ndash8
Mid-adulthood hypertension wasassociated with 65 (95confidenceinterval [CI]125ndash218) increased dementia risk amongwomen but not men
Onset of hypertension in mid-adulthood predicted 73 higherdementia risk in women (95 CI 124ndash240) compared to stablenormotensive
Midlife hypertension was more common in men however itwas associated with dementia risk only in women
APOE4 effect is more pronounced in women than in men
HZ carrier APOEe4 earlier age at onset of AD
3-4 times more likely to develop AD
FARRER ET AL 1997
Fattori di rischio geneticihanno pesi diversi
ApoE4 strongly promotes amyloid-β deposition in the brain
Liu et al Nat Rev Neurol 2013
Risk gender for dementia or AD
In all three examples women experienced a higher risk of dementia or AD attributable to the specific risk factors (bigger red oval) Panel A APOE E4 allele is equally frequent in men and women (equal boxes) but has a stronger effect in women (thicker red arrow) Panel B low education has the same effect on the risk of dementia or AD in both men and women (equal strength of the blue and red
Rocca et al Maturitas 2014 October 79(2) 196ndash201 doi101016jmaturitas201405008
Men blueWomen red
APOE Meta analysis
JAMANeuroldoi101001jamaneurol20172188 PublishedonlineAugust282017
Increased risk in womenbetween 65-75 yrs
Risk factors in 1925 AD patients
Notaro P doctoral thesis 2017Unical
Le demenze sono molto variabili nei loro fenotipi
female patients with DLB having a higher frequency of VH symptoms
Chiu et al Int J Geriatr Psychiatry 2017
Women show an advantage in verbal memory despite evidence of moderate hippocampalatrophy This advantage may represent a sex-specific form of cognitive reserve delaying verbal memory decline until more advanced disease stages
lrsquoanalisi dei gruppi evidenziache queste donne hanno piugrave di 15 anni di
scolaritagrave
Cognitive reserve
IN SINTESIhellip
bull Le donne sono maggiormente a rischio per demenza e specie per malattia di Alzheimer tutto sembra concorrere a farle ammalare di piugrave dei maschi
bull Lrsquo assetto genetico e ormonale il modo di connettere informazioni a livello cerebrale le tante malattie in piugrave il piugrave basso livello di scolaritagrave e la minore attivitagrave laquosocialeraquo rispetto ai maschihelliphellip
Take home messages
bull Le differenze di genere osservate nelle demenze ( per tipo sintomied espressione fenotipica) originano dale profonde differenzecerebrali (genetiche ormonali e di connessioni) che esistono tra I due sessi
bull La consapevolezza e la ricerca in questa direzione potrebberoportare in futuro ad avere trattamenti genere - specifici non solo per gli aspetti cognitivi ma ancora di piugrave per quelli comportamentali
Il ogni caso il futuro egrave disegnatohellip studiare di piugrave avere una maggiore vita sociale fare attivitagrave fisica combattere le malattiehelliphellip
Anno 1791 giorno 29 Dicembre helliphelliphelliphellip Magnifica Eleonora Miceli helliphelliphelliphelliphelliphelliphellipanni sei sopra cento helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellipin giusto ragionamento ed intelligenza dei sensihelliphelliphelliphelliphelliphellip
Serrastretta Parish Archives
She does not recognize anybody she does not understand anything she does not answer any questions and she is emotionally flat She stays in bed all day moving her eyes around without any kind of thoughts driving her mind or triggering any movements of her limbs She mumbles incomprehensible words She seems astonished and scaredrsquorsquo
She died of marasmus at the age of 40 yearsin 1905helliphellip
Differente espressione di SRY in aree cerebrali
HLoke et al The International Journal of Biochemistry amp Cell Biology 65 (2015) 139ndash150
Male and female brains are neurochemicallydistinct concerning dopaminergic serotonergic and gamma-aminobutyric acid (GABA)ergic markers
Cosgrove KP et al Biol Psychiatry 2007 Oct 1562(8)847-55 Epub 2007 Jun 4
Sex-specific differences in neuromediators
Serotonin sexually differentiated multiple levels
Risk factors
Female sex early-onset hypertension and risk of dementia
Gilsanz et al Neurologyreg 2017891ndash8
Mid-adulthood hypertension wasassociated with 65 (95confidenceinterval [CI]125ndash218) increased dementia risk amongwomen but not men
Onset of hypertension in mid-adulthood predicted 73 higherdementia risk in women (95 CI 124ndash240) compared to stablenormotensive
Midlife hypertension was more common in men however itwas associated with dementia risk only in women
APOE4 effect is more pronounced in women than in men
HZ carrier APOEe4 earlier age at onset of AD
3-4 times more likely to develop AD
FARRER ET AL 1997
Fattori di rischio geneticihanno pesi diversi
ApoE4 strongly promotes amyloid-β deposition in the brain
Liu et al Nat Rev Neurol 2013
Risk gender for dementia or AD
In all three examples women experienced a higher risk of dementia or AD attributable to the specific risk factors (bigger red oval) Panel A APOE E4 allele is equally frequent in men and women (equal boxes) but has a stronger effect in women (thicker red arrow) Panel B low education has the same effect on the risk of dementia or AD in both men and women (equal strength of the blue and red
Rocca et al Maturitas 2014 October 79(2) 196ndash201 doi101016jmaturitas201405008
Men blueWomen red
APOE Meta analysis
JAMANeuroldoi101001jamaneurol20172188 PublishedonlineAugust282017
Increased risk in womenbetween 65-75 yrs
Risk factors in 1925 AD patients
Notaro P doctoral thesis 2017Unical
Le demenze sono molto variabili nei loro fenotipi
female patients with DLB having a higher frequency of VH symptoms
Chiu et al Int J Geriatr Psychiatry 2017
Women show an advantage in verbal memory despite evidence of moderate hippocampalatrophy This advantage may represent a sex-specific form of cognitive reserve delaying verbal memory decline until more advanced disease stages
lrsquoanalisi dei gruppi evidenziache queste donne hanno piugrave di 15 anni di
scolaritagrave
Cognitive reserve
IN SINTESIhellip
bull Le donne sono maggiormente a rischio per demenza e specie per malattia di Alzheimer tutto sembra concorrere a farle ammalare di piugrave dei maschi
bull Lrsquo assetto genetico e ormonale il modo di connettere informazioni a livello cerebrale le tante malattie in piugrave il piugrave basso livello di scolaritagrave e la minore attivitagrave laquosocialeraquo rispetto ai maschihelliphellip
Take home messages
bull Le differenze di genere osservate nelle demenze ( per tipo sintomied espressione fenotipica) originano dale profonde differenzecerebrali (genetiche ormonali e di connessioni) che esistono tra I due sessi
bull La consapevolezza e la ricerca in questa direzione potrebberoportare in futuro ad avere trattamenti genere - specifici non solo per gli aspetti cognitivi ma ancora di piugrave per quelli comportamentali
Il ogni caso il futuro egrave disegnatohellip studiare di piugrave avere una maggiore vita sociale fare attivitagrave fisica combattere le malattiehelliphellip
Anno 1791 giorno 29 Dicembre helliphelliphelliphellip Magnifica Eleonora Miceli helliphelliphelliphelliphelliphelliphellipanni sei sopra cento helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellipin giusto ragionamento ed intelligenza dei sensihelliphelliphelliphelliphelliphellip
Serrastretta Parish Archives
She does not recognize anybody she does not understand anything she does not answer any questions and she is emotionally flat She stays in bed all day moving her eyes around without any kind of thoughts driving her mind or triggering any movements of her limbs She mumbles incomprehensible words She seems astonished and scaredrsquorsquo
She died of marasmus at the age of 40 yearsin 1905helliphellip
Male and female brains are neurochemicallydistinct concerning dopaminergic serotonergic and gamma-aminobutyric acid (GABA)ergic markers
Cosgrove KP et al Biol Psychiatry 2007 Oct 1562(8)847-55 Epub 2007 Jun 4
Sex-specific differences in neuromediators
Serotonin sexually differentiated multiple levels
Risk factors
Female sex early-onset hypertension and risk of dementia
Gilsanz et al Neurologyreg 2017891ndash8
Mid-adulthood hypertension wasassociated with 65 (95confidenceinterval [CI]125ndash218) increased dementia risk amongwomen but not men
Onset of hypertension in mid-adulthood predicted 73 higherdementia risk in women (95 CI 124ndash240) compared to stablenormotensive
Midlife hypertension was more common in men however itwas associated with dementia risk only in women
APOE4 effect is more pronounced in women than in men
HZ carrier APOEe4 earlier age at onset of AD
3-4 times more likely to develop AD
FARRER ET AL 1997
Fattori di rischio geneticihanno pesi diversi
ApoE4 strongly promotes amyloid-β deposition in the brain
Liu et al Nat Rev Neurol 2013
Risk gender for dementia or AD
In all three examples women experienced a higher risk of dementia or AD attributable to the specific risk factors (bigger red oval) Panel A APOE E4 allele is equally frequent in men and women (equal boxes) but has a stronger effect in women (thicker red arrow) Panel B low education has the same effect on the risk of dementia or AD in both men and women (equal strength of the blue and red
Rocca et al Maturitas 2014 October 79(2) 196ndash201 doi101016jmaturitas201405008
Men blueWomen red
APOE Meta analysis
JAMANeuroldoi101001jamaneurol20172188 PublishedonlineAugust282017
Increased risk in womenbetween 65-75 yrs
Risk factors in 1925 AD patients
Notaro P doctoral thesis 2017Unical
Le demenze sono molto variabili nei loro fenotipi
female patients with DLB having a higher frequency of VH symptoms
Chiu et al Int J Geriatr Psychiatry 2017
Women show an advantage in verbal memory despite evidence of moderate hippocampalatrophy This advantage may represent a sex-specific form of cognitive reserve delaying verbal memory decline until more advanced disease stages
lrsquoanalisi dei gruppi evidenziache queste donne hanno piugrave di 15 anni di
scolaritagrave
Cognitive reserve
IN SINTESIhellip
bull Le donne sono maggiormente a rischio per demenza e specie per malattia di Alzheimer tutto sembra concorrere a farle ammalare di piugrave dei maschi
bull Lrsquo assetto genetico e ormonale il modo di connettere informazioni a livello cerebrale le tante malattie in piugrave il piugrave basso livello di scolaritagrave e la minore attivitagrave laquosocialeraquo rispetto ai maschihelliphellip
Take home messages
bull Le differenze di genere osservate nelle demenze ( per tipo sintomied espressione fenotipica) originano dale profonde differenzecerebrali (genetiche ormonali e di connessioni) che esistono tra I due sessi
bull La consapevolezza e la ricerca in questa direzione potrebberoportare in futuro ad avere trattamenti genere - specifici non solo per gli aspetti cognitivi ma ancora di piugrave per quelli comportamentali
Il ogni caso il futuro egrave disegnatohellip studiare di piugrave avere una maggiore vita sociale fare attivitagrave fisica combattere le malattiehelliphellip
Anno 1791 giorno 29 Dicembre helliphelliphelliphellip Magnifica Eleonora Miceli helliphelliphelliphelliphelliphelliphellipanni sei sopra cento helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellipin giusto ragionamento ed intelligenza dei sensihelliphelliphelliphelliphelliphellip
Serrastretta Parish Archives
She does not recognize anybody she does not understand anything she does not answer any questions and she is emotionally flat She stays in bed all day moving her eyes around without any kind of thoughts driving her mind or triggering any movements of her limbs She mumbles incomprehensible words She seems astonished and scaredrsquorsquo
She died of marasmus at the age of 40 yearsin 1905helliphellip
Serotonin sexually differentiated multiple levels
Risk factors
Female sex early-onset hypertension and risk of dementia
Gilsanz et al Neurologyreg 2017891ndash8
Mid-adulthood hypertension wasassociated with 65 (95confidenceinterval [CI]125ndash218) increased dementia risk amongwomen but not men
Onset of hypertension in mid-adulthood predicted 73 higherdementia risk in women (95 CI 124ndash240) compared to stablenormotensive
Midlife hypertension was more common in men however itwas associated with dementia risk only in women
APOE4 effect is more pronounced in women than in men
HZ carrier APOEe4 earlier age at onset of AD
3-4 times more likely to develop AD
FARRER ET AL 1997
Fattori di rischio geneticihanno pesi diversi
ApoE4 strongly promotes amyloid-β deposition in the brain
Liu et al Nat Rev Neurol 2013
Risk gender for dementia or AD
In all three examples women experienced a higher risk of dementia or AD attributable to the specific risk factors (bigger red oval) Panel A APOE E4 allele is equally frequent in men and women (equal boxes) but has a stronger effect in women (thicker red arrow) Panel B low education has the same effect on the risk of dementia or AD in both men and women (equal strength of the blue and red
Rocca et al Maturitas 2014 October 79(2) 196ndash201 doi101016jmaturitas201405008
Men blueWomen red
APOE Meta analysis
JAMANeuroldoi101001jamaneurol20172188 PublishedonlineAugust282017
Increased risk in womenbetween 65-75 yrs
Risk factors in 1925 AD patients
Notaro P doctoral thesis 2017Unical
Le demenze sono molto variabili nei loro fenotipi
female patients with DLB having a higher frequency of VH symptoms
Chiu et al Int J Geriatr Psychiatry 2017
Women show an advantage in verbal memory despite evidence of moderate hippocampalatrophy This advantage may represent a sex-specific form of cognitive reserve delaying verbal memory decline until more advanced disease stages
lrsquoanalisi dei gruppi evidenziache queste donne hanno piugrave di 15 anni di
scolaritagrave
Cognitive reserve
IN SINTESIhellip
bull Le donne sono maggiormente a rischio per demenza e specie per malattia di Alzheimer tutto sembra concorrere a farle ammalare di piugrave dei maschi
bull Lrsquo assetto genetico e ormonale il modo di connettere informazioni a livello cerebrale le tante malattie in piugrave il piugrave basso livello di scolaritagrave e la minore attivitagrave laquosocialeraquo rispetto ai maschihelliphellip
Take home messages
bull Le differenze di genere osservate nelle demenze ( per tipo sintomied espressione fenotipica) originano dale profonde differenzecerebrali (genetiche ormonali e di connessioni) che esistono tra I due sessi
bull La consapevolezza e la ricerca in questa direzione potrebberoportare in futuro ad avere trattamenti genere - specifici non solo per gli aspetti cognitivi ma ancora di piugrave per quelli comportamentali
Il ogni caso il futuro egrave disegnatohellip studiare di piugrave avere una maggiore vita sociale fare attivitagrave fisica combattere le malattiehelliphellip
Anno 1791 giorno 29 Dicembre helliphelliphelliphellip Magnifica Eleonora Miceli helliphelliphelliphelliphelliphelliphellipanni sei sopra cento helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellipin giusto ragionamento ed intelligenza dei sensihelliphelliphelliphelliphelliphellip
Serrastretta Parish Archives
She does not recognize anybody she does not understand anything she does not answer any questions and she is emotionally flat She stays in bed all day moving her eyes around without any kind of thoughts driving her mind or triggering any movements of her limbs She mumbles incomprehensible words She seems astonished and scaredrsquorsquo
She died of marasmus at the age of 40 yearsin 1905helliphellip
Risk factors
Female sex early-onset hypertension and risk of dementia
Gilsanz et al Neurologyreg 2017891ndash8
Mid-adulthood hypertension wasassociated with 65 (95confidenceinterval [CI]125ndash218) increased dementia risk amongwomen but not men
Onset of hypertension in mid-adulthood predicted 73 higherdementia risk in women (95 CI 124ndash240) compared to stablenormotensive
Midlife hypertension was more common in men however itwas associated with dementia risk only in women
APOE4 effect is more pronounced in women than in men
HZ carrier APOEe4 earlier age at onset of AD
3-4 times more likely to develop AD
FARRER ET AL 1997
Fattori di rischio geneticihanno pesi diversi
ApoE4 strongly promotes amyloid-β deposition in the brain
Liu et al Nat Rev Neurol 2013
Risk gender for dementia or AD
In all three examples women experienced a higher risk of dementia or AD attributable to the specific risk factors (bigger red oval) Panel A APOE E4 allele is equally frequent in men and women (equal boxes) but has a stronger effect in women (thicker red arrow) Panel B low education has the same effect on the risk of dementia or AD in both men and women (equal strength of the blue and red
Rocca et al Maturitas 2014 October 79(2) 196ndash201 doi101016jmaturitas201405008
Men blueWomen red
APOE Meta analysis
JAMANeuroldoi101001jamaneurol20172188 PublishedonlineAugust282017
Increased risk in womenbetween 65-75 yrs
Risk factors in 1925 AD patients
Notaro P doctoral thesis 2017Unical
Le demenze sono molto variabili nei loro fenotipi
female patients with DLB having a higher frequency of VH symptoms
Chiu et al Int J Geriatr Psychiatry 2017
Women show an advantage in verbal memory despite evidence of moderate hippocampalatrophy This advantage may represent a sex-specific form of cognitive reserve delaying verbal memory decline until more advanced disease stages
lrsquoanalisi dei gruppi evidenziache queste donne hanno piugrave di 15 anni di
scolaritagrave
Cognitive reserve
IN SINTESIhellip
bull Le donne sono maggiormente a rischio per demenza e specie per malattia di Alzheimer tutto sembra concorrere a farle ammalare di piugrave dei maschi
bull Lrsquo assetto genetico e ormonale il modo di connettere informazioni a livello cerebrale le tante malattie in piugrave il piugrave basso livello di scolaritagrave e la minore attivitagrave laquosocialeraquo rispetto ai maschihelliphellip
Take home messages
bull Le differenze di genere osservate nelle demenze ( per tipo sintomied espressione fenotipica) originano dale profonde differenzecerebrali (genetiche ormonali e di connessioni) che esistono tra I due sessi
bull La consapevolezza e la ricerca in questa direzione potrebberoportare in futuro ad avere trattamenti genere - specifici non solo per gli aspetti cognitivi ma ancora di piugrave per quelli comportamentali
Il ogni caso il futuro egrave disegnatohellip studiare di piugrave avere una maggiore vita sociale fare attivitagrave fisica combattere le malattiehelliphellip
Anno 1791 giorno 29 Dicembre helliphelliphelliphellip Magnifica Eleonora Miceli helliphelliphelliphelliphelliphelliphellipanni sei sopra cento helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellipin giusto ragionamento ed intelligenza dei sensihelliphelliphelliphelliphelliphellip
Serrastretta Parish Archives
She does not recognize anybody she does not understand anything she does not answer any questions and she is emotionally flat She stays in bed all day moving her eyes around without any kind of thoughts driving her mind or triggering any movements of her limbs She mumbles incomprehensible words She seems astonished and scaredrsquorsquo
She died of marasmus at the age of 40 yearsin 1905helliphellip
Female sex early-onset hypertension and risk of dementia
Gilsanz et al Neurologyreg 2017891ndash8
Mid-adulthood hypertension wasassociated with 65 (95confidenceinterval [CI]125ndash218) increased dementia risk amongwomen but not men
Onset of hypertension in mid-adulthood predicted 73 higherdementia risk in women (95 CI 124ndash240) compared to stablenormotensive
Midlife hypertension was more common in men however itwas associated with dementia risk only in women
APOE4 effect is more pronounced in women than in men
HZ carrier APOEe4 earlier age at onset of AD
3-4 times more likely to develop AD
FARRER ET AL 1997
Fattori di rischio geneticihanno pesi diversi
ApoE4 strongly promotes amyloid-β deposition in the brain
Liu et al Nat Rev Neurol 2013
Risk gender for dementia or AD
In all three examples women experienced a higher risk of dementia or AD attributable to the specific risk factors (bigger red oval) Panel A APOE E4 allele is equally frequent in men and women (equal boxes) but has a stronger effect in women (thicker red arrow) Panel B low education has the same effect on the risk of dementia or AD in both men and women (equal strength of the blue and red
Rocca et al Maturitas 2014 October 79(2) 196ndash201 doi101016jmaturitas201405008
Men blueWomen red
APOE Meta analysis
JAMANeuroldoi101001jamaneurol20172188 PublishedonlineAugust282017
Increased risk in womenbetween 65-75 yrs
Risk factors in 1925 AD patients
Notaro P doctoral thesis 2017Unical
Le demenze sono molto variabili nei loro fenotipi
female patients with DLB having a higher frequency of VH symptoms
Chiu et al Int J Geriatr Psychiatry 2017
Women show an advantage in verbal memory despite evidence of moderate hippocampalatrophy This advantage may represent a sex-specific form of cognitive reserve delaying verbal memory decline until more advanced disease stages
lrsquoanalisi dei gruppi evidenziache queste donne hanno piugrave di 15 anni di
scolaritagrave
Cognitive reserve
IN SINTESIhellip
bull Le donne sono maggiormente a rischio per demenza e specie per malattia di Alzheimer tutto sembra concorrere a farle ammalare di piugrave dei maschi
bull Lrsquo assetto genetico e ormonale il modo di connettere informazioni a livello cerebrale le tante malattie in piugrave il piugrave basso livello di scolaritagrave e la minore attivitagrave laquosocialeraquo rispetto ai maschihelliphellip
Take home messages
bull Le differenze di genere osservate nelle demenze ( per tipo sintomied espressione fenotipica) originano dale profonde differenzecerebrali (genetiche ormonali e di connessioni) che esistono tra I due sessi
bull La consapevolezza e la ricerca in questa direzione potrebberoportare in futuro ad avere trattamenti genere - specifici non solo per gli aspetti cognitivi ma ancora di piugrave per quelli comportamentali
Il ogni caso il futuro egrave disegnatohellip studiare di piugrave avere una maggiore vita sociale fare attivitagrave fisica combattere le malattiehelliphellip
Anno 1791 giorno 29 Dicembre helliphelliphelliphellip Magnifica Eleonora Miceli helliphelliphelliphelliphelliphelliphellipanni sei sopra cento helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellipin giusto ragionamento ed intelligenza dei sensihelliphelliphelliphelliphelliphellip
Serrastretta Parish Archives
She does not recognize anybody she does not understand anything she does not answer any questions and she is emotionally flat She stays in bed all day moving her eyes around without any kind of thoughts driving her mind or triggering any movements of her limbs She mumbles incomprehensible words She seems astonished and scaredrsquorsquo
She died of marasmus at the age of 40 yearsin 1905helliphellip
APOE4 effect is more pronounced in women than in men
HZ carrier APOEe4 earlier age at onset of AD
3-4 times more likely to develop AD
FARRER ET AL 1997
Fattori di rischio geneticihanno pesi diversi
ApoE4 strongly promotes amyloid-β deposition in the brain
Liu et al Nat Rev Neurol 2013
Risk gender for dementia or AD
In all three examples women experienced a higher risk of dementia or AD attributable to the specific risk factors (bigger red oval) Panel A APOE E4 allele is equally frequent in men and women (equal boxes) but has a stronger effect in women (thicker red arrow) Panel B low education has the same effect on the risk of dementia or AD in both men and women (equal strength of the blue and red
Rocca et al Maturitas 2014 October 79(2) 196ndash201 doi101016jmaturitas201405008
Men blueWomen red
APOE Meta analysis
JAMANeuroldoi101001jamaneurol20172188 PublishedonlineAugust282017
Increased risk in womenbetween 65-75 yrs
Risk factors in 1925 AD patients
Notaro P doctoral thesis 2017Unical
Le demenze sono molto variabili nei loro fenotipi
female patients with DLB having a higher frequency of VH symptoms
Chiu et al Int J Geriatr Psychiatry 2017
Women show an advantage in verbal memory despite evidence of moderate hippocampalatrophy This advantage may represent a sex-specific form of cognitive reserve delaying verbal memory decline until more advanced disease stages
lrsquoanalisi dei gruppi evidenziache queste donne hanno piugrave di 15 anni di
scolaritagrave
Cognitive reserve
IN SINTESIhellip
bull Le donne sono maggiormente a rischio per demenza e specie per malattia di Alzheimer tutto sembra concorrere a farle ammalare di piugrave dei maschi
bull Lrsquo assetto genetico e ormonale il modo di connettere informazioni a livello cerebrale le tante malattie in piugrave il piugrave basso livello di scolaritagrave e la minore attivitagrave laquosocialeraquo rispetto ai maschihelliphellip
Take home messages
bull Le differenze di genere osservate nelle demenze ( per tipo sintomied espressione fenotipica) originano dale profonde differenzecerebrali (genetiche ormonali e di connessioni) che esistono tra I due sessi
bull La consapevolezza e la ricerca in questa direzione potrebberoportare in futuro ad avere trattamenti genere - specifici non solo per gli aspetti cognitivi ma ancora di piugrave per quelli comportamentali
Il ogni caso il futuro egrave disegnatohellip studiare di piugrave avere una maggiore vita sociale fare attivitagrave fisica combattere le malattiehelliphellip
Anno 1791 giorno 29 Dicembre helliphelliphelliphellip Magnifica Eleonora Miceli helliphelliphelliphelliphelliphelliphellipanni sei sopra cento helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellipin giusto ragionamento ed intelligenza dei sensihelliphelliphelliphelliphelliphellip
Serrastretta Parish Archives
She does not recognize anybody she does not understand anything she does not answer any questions and she is emotionally flat She stays in bed all day moving her eyes around without any kind of thoughts driving her mind or triggering any movements of her limbs She mumbles incomprehensible words She seems astonished and scaredrsquorsquo
She died of marasmus at the age of 40 yearsin 1905helliphellip
ApoE4 strongly promotes amyloid-β deposition in the brain
Liu et al Nat Rev Neurol 2013
Risk gender for dementia or AD
In all three examples women experienced a higher risk of dementia or AD attributable to the specific risk factors (bigger red oval) Panel A APOE E4 allele is equally frequent in men and women (equal boxes) but has a stronger effect in women (thicker red arrow) Panel B low education has the same effect on the risk of dementia or AD in both men and women (equal strength of the blue and red
Rocca et al Maturitas 2014 October 79(2) 196ndash201 doi101016jmaturitas201405008
Men blueWomen red
APOE Meta analysis
JAMANeuroldoi101001jamaneurol20172188 PublishedonlineAugust282017
Increased risk in womenbetween 65-75 yrs
Risk factors in 1925 AD patients
Notaro P doctoral thesis 2017Unical
Le demenze sono molto variabili nei loro fenotipi
female patients with DLB having a higher frequency of VH symptoms
Chiu et al Int J Geriatr Psychiatry 2017
Women show an advantage in verbal memory despite evidence of moderate hippocampalatrophy This advantage may represent a sex-specific form of cognitive reserve delaying verbal memory decline until more advanced disease stages
lrsquoanalisi dei gruppi evidenziache queste donne hanno piugrave di 15 anni di
scolaritagrave
Cognitive reserve
IN SINTESIhellip
bull Le donne sono maggiormente a rischio per demenza e specie per malattia di Alzheimer tutto sembra concorrere a farle ammalare di piugrave dei maschi
bull Lrsquo assetto genetico e ormonale il modo di connettere informazioni a livello cerebrale le tante malattie in piugrave il piugrave basso livello di scolaritagrave e la minore attivitagrave laquosocialeraquo rispetto ai maschihelliphellip
Take home messages
bull Le differenze di genere osservate nelle demenze ( per tipo sintomied espressione fenotipica) originano dale profonde differenzecerebrali (genetiche ormonali e di connessioni) che esistono tra I due sessi
bull La consapevolezza e la ricerca in questa direzione potrebberoportare in futuro ad avere trattamenti genere - specifici non solo per gli aspetti cognitivi ma ancora di piugrave per quelli comportamentali
Il ogni caso il futuro egrave disegnatohellip studiare di piugrave avere una maggiore vita sociale fare attivitagrave fisica combattere le malattiehelliphellip
Anno 1791 giorno 29 Dicembre helliphelliphelliphellip Magnifica Eleonora Miceli helliphelliphelliphelliphelliphelliphellipanni sei sopra cento helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellipin giusto ragionamento ed intelligenza dei sensihelliphelliphelliphelliphelliphellip
Serrastretta Parish Archives
She does not recognize anybody she does not understand anything she does not answer any questions and she is emotionally flat She stays in bed all day moving her eyes around without any kind of thoughts driving her mind or triggering any movements of her limbs She mumbles incomprehensible words She seems astonished and scaredrsquorsquo
She died of marasmus at the age of 40 yearsin 1905helliphellip
Risk gender for dementia or AD
In all three examples women experienced a higher risk of dementia or AD attributable to the specific risk factors (bigger red oval) Panel A APOE E4 allele is equally frequent in men and women (equal boxes) but has a stronger effect in women (thicker red arrow) Panel B low education has the same effect on the risk of dementia or AD in both men and women (equal strength of the blue and red
Rocca et al Maturitas 2014 October 79(2) 196ndash201 doi101016jmaturitas201405008
Men blueWomen red
APOE Meta analysis
JAMANeuroldoi101001jamaneurol20172188 PublishedonlineAugust282017
Increased risk in womenbetween 65-75 yrs
Risk factors in 1925 AD patients
Notaro P doctoral thesis 2017Unical
Le demenze sono molto variabili nei loro fenotipi
female patients with DLB having a higher frequency of VH symptoms
Chiu et al Int J Geriatr Psychiatry 2017
Women show an advantage in verbal memory despite evidence of moderate hippocampalatrophy This advantage may represent a sex-specific form of cognitive reserve delaying verbal memory decline until more advanced disease stages
lrsquoanalisi dei gruppi evidenziache queste donne hanno piugrave di 15 anni di
scolaritagrave
Cognitive reserve
IN SINTESIhellip
bull Le donne sono maggiormente a rischio per demenza e specie per malattia di Alzheimer tutto sembra concorrere a farle ammalare di piugrave dei maschi
bull Lrsquo assetto genetico e ormonale il modo di connettere informazioni a livello cerebrale le tante malattie in piugrave il piugrave basso livello di scolaritagrave e la minore attivitagrave laquosocialeraquo rispetto ai maschihelliphellip
Take home messages
bull Le differenze di genere osservate nelle demenze ( per tipo sintomied espressione fenotipica) originano dale profonde differenzecerebrali (genetiche ormonali e di connessioni) che esistono tra I due sessi
bull La consapevolezza e la ricerca in questa direzione potrebberoportare in futuro ad avere trattamenti genere - specifici non solo per gli aspetti cognitivi ma ancora di piugrave per quelli comportamentali
Il ogni caso il futuro egrave disegnatohellip studiare di piugrave avere una maggiore vita sociale fare attivitagrave fisica combattere le malattiehelliphellip
Anno 1791 giorno 29 Dicembre helliphelliphelliphellip Magnifica Eleonora Miceli helliphelliphelliphelliphelliphelliphellipanni sei sopra cento helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellipin giusto ragionamento ed intelligenza dei sensihelliphelliphelliphelliphelliphellip
Serrastretta Parish Archives
She does not recognize anybody she does not understand anything she does not answer any questions and she is emotionally flat She stays in bed all day moving her eyes around without any kind of thoughts driving her mind or triggering any movements of her limbs She mumbles incomprehensible words She seems astonished and scaredrsquorsquo
She died of marasmus at the age of 40 yearsin 1905helliphellip
APOE Meta analysis
JAMANeuroldoi101001jamaneurol20172188 PublishedonlineAugust282017
Increased risk in womenbetween 65-75 yrs
Risk factors in 1925 AD patients
Notaro P doctoral thesis 2017Unical
Le demenze sono molto variabili nei loro fenotipi
female patients with DLB having a higher frequency of VH symptoms
Chiu et al Int J Geriatr Psychiatry 2017
Women show an advantage in verbal memory despite evidence of moderate hippocampalatrophy This advantage may represent a sex-specific form of cognitive reserve delaying verbal memory decline until more advanced disease stages
lrsquoanalisi dei gruppi evidenziache queste donne hanno piugrave di 15 anni di
scolaritagrave
Cognitive reserve
IN SINTESIhellip
bull Le donne sono maggiormente a rischio per demenza e specie per malattia di Alzheimer tutto sembra concorrere a farle ammalare di piugrave dei maschi
bull Lrsquo assetto genetico e ormonale il modo di connettere informazioni a livello cerebrale le tante malattie in piugrave il piugrave basso livello di scolaritagrave e la minore attivitagrave laquosocialeraquo rispetto ai maschihelliphellip
Take home messages
bull Le differenze di genere osservate nelle demenze ( per tipo sintomied espressione fenotipica) originano dale profonde differenzecerebrali (genetiche ormonali e di connessioni) che esistono tra I due sessi
bull La consapevolezza e la ricerca in questa direzione potrebberoportare in futuro ad avere trattamenti genere - specifici non solo per gli aspetti cognitivi ma ancora di piugrave per quelli comportamentali
Il ogni caso il futuro egrave disegnatohellip studiare di piugrave avere una maggiore vita sociale fare attivitagrave fisica combattere le malattiehelliphellip
Anno 1791 giorno 29 Dicembre helliphelliphelliphellip Magnifica Eleonora Miceli helliphelliphelliphelliphelliphelliphellipanni sei sopra cento helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellipin giusto ragionamento ed intelligenza dei sensihelliphelliphelliphelliphelliphellip
Serrastretta Parish Archives
She does not recognize anybody she does not understand anything she does not answer any questions and she is emotionally flat She stays in bed all day moving her eyes around without any kind of thoughts driving her mind or triggering any movements of her limbs She mumbles incomprehensible words She seems astonished and scaredrsquorsquo
She died of marasmus at the age of 40 yearsin 1905helliphellip
Risk factors in 1925 AD patients
Notaro P doctoral thesis 2017Unical
Le demenze sono molto variabili nei loro fenotipi
female patients with DLB having a higher frequency of VH symptoms
Chiu et al Int J Geriatr Psychiatry 2017
Women show an advantage in verbal memory despite evidence of moderate hippocampalatrophy This advantage may represent a sex-specific form of cognitive reserve delaying verbal memory decline until more advanced disease stages
lrsquoanalisi dei gruppi evidenziache queste donne hanno piugrave di 15 anni di
scolaritagrave
Cognitive reserve
IN SINTESIhellip
bull Le donne sono maggiormente a rischio per demenza e specie per malattia di Alzheimer tutto sembra concorrere a farle ammalare di piugrave dei maschi
bull Lrsquo assetto genetico e ormonale il modo di connettere informazioni a livello cerebrale le tante malattie in piugrave il piugrave basso livello di scolaritagrave e la minore attivitagrave laquosocialeraquo rispetto ai maschihelliphellip
Take home messages
bull Le differenze di genere osservate nelle demenze ( per tipo sintomied espressione fenotipica) originano dale profonde differenzecerebrali (genetiche ormonali e di connessioni) che esistono tra I due sessi
bull La consapevolezza e la ricerca in questa direzione potrebberoportare in futuro ad avere trattamenti genere - specifici non solo per gli aspetti cognitivi ma ancora di piugrave per quelli comportamentali
Il ogni caso il futuro egrave disegnatohellip studiare di piugrave avere una maggiore vita sociale fare attivitagrave fisica combattere le malattiehelliphellip
Anno 1791 giorno 29 Dicembre helliphelliphelliphellip Magnifica Eleonora Miceli helliphelliphelliphelliphelliphelliphellipanni sei sopra cento helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellipin giusto ragionamento ed intelligenza dei sensihelliphelliphelliphelliphelliphellip
Serrastretta Parish Archives
She does not recognize anybody she does not understand anything she does not answer any questions and she is emotionally flat She stays in bed all day moving her eyes around without any kind of thoughts driving her mind or triggering any movements of her limbs She mumbles incomprehensible words She seems astonished and scaredrsquorsquo
She died of marasmus at the age of 40 yearsin 1905helliphellip
Le demenze sono molto variabili nei loro fenotipi
female patients with DLB having a higher frequency of VH symptoms
Chiu et al Int J Geriatr Psychiatry 2017
Women show an advantage in verbal memory despite evidence of moderate hippocampalatrophy This advantage may represent a sex-specific form of cognitive reserve delaying verbal memory decline until more advanced disease stages
lrsquoanalisi dei gruppi evidenziache queste donne hanno piugrave di 15 anni di
scolaritagrave
Cognitive reserve
IN SINTESIhellip
bull Le donne sono maggiormente a rischio per demenza e specie per malattia di Alzheimer tutto sembra concorrere a farle ammalare di piugrave dei maschi
bull Lrsquo assetto genetico e ormonale il modo di connettere informazioni a livello cerebrale le tante malattie in piugrave il piugrave basso livello di scolaritagrave e la minore attivitagrave laquosocialeraquo rispetto ai maschihelliphellip
Take home messages
bull Le differenze di genere osservate nelle demenze ( per tipo sintomied espressione fenotipica) originano dale profonde differenzecerebrali (genetiche ormonali e di connessioni) che esistono tra I due sessi
bull La consapevolezza e la ricerca in questa direzione potrebberoportare in futuro ad avere trattamenti genere - specifici non solo per gli aspetti cognitivi ma ancora di piugrave per quelli comportamentali
Il ogni caso il futuro egrave disegnatohellip studiare di piugrave avere una maggiore vita sociale fare attivitagrave fisica combattere le malattiehelliphellip
Anno 1791 giorno 29 Dicembre helliphelliphelliphellip Magnifica Eleonora Miceli helliphelliphelliphelliphelliphelliphellipanni sei sopra cento helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellipin giusto ragionamento ed intelligenza dei sensihelliphelliphelliphelliphelliphellip
Serrastretta Parish Archives
She does not recognize anybody she does not understand anything she does not answer any questions and she is emotionally flat She stays in bed all day moving her eyes around without any kind of thoughts driving her mind or triggering any movements of her limbs She mumbles incomprehensible words She seems astonished and scaredrsquorsquo
She died of marasmus at the age of 40 yearsin 1905helliphellip
female patients with DLB having a higher frequency of VH symptoms
Chiu et al Int J Geriatr Psychiatry 2017
Women show an advantage in verbal memory despite evidence of moderate hippocampalatrophy This advantage may represent a sex-specific form of cognitive reserve delaying verbal memory decline until more advanced disease stages
lrsquoanalisi dei gruppi evidenziache queste donne hanno piugrave di 15 anni di
scolaritagrave
Cognitive reserve
IN SINTESIhellip
bull Le donne sono maggiormente a rischio per demenza e specie per malattia di Alzheimer tutto sembra concorrere a farle ammalare di piugrave dei maschi
bull Lrsquo assetto genetico e ormonale il modo di connettere informazioni a livello cerebrale le tante malattie in piugrave il piugrave basso livello di scolaritagrave e la minore attivitagrave laquosocialeraquo rispetto ai maschihelliphellip
Take home messages
bull Le differenze di genere osservate nelle demenze ( per tipo sintomied espressione fenotipica) originano dale profonde differenzecerebrali (genetiche ormonali e di connessioni) che esistono tra I due sessi
bull La consapevolezza e la ricerca in questa direzione potrebberoportare in futuro ad avere trattamenti genere - specifici non solo per gli aspetti cognitivi ma ancora di piugrave per quelli comportamentali
Il ogni caso il futuro egrave disegnatohellip studiare di piugrave avere una maggiore vita sociale fare attivitagrave fisica combattere le malattiehelliphellip
Anno 1791 giorno 29 Dicembre helliphelliphelliphellip Magnifica Eleonora Miceli helliphelliphelliphelliphelliphelliphellipanni sei sopra cento helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellipin giusto ragionamento ed intelligenza dei sensihelliphelliphelliphelliphelliphellip
Serrastretta Parish Archives
She does not recognize anybody she does not understand anything she does not answer any questions and she is emotionally flat She stays in bed all day moving her eyes around without any kind of thoughts driving her mind or triggering any movements of her limbs She mumbles incomprehensible words She seems astonished and scaredrsquorsquo
She died of marasmus at the age of 40 yearsin 1905helliphellip
Women show an advantage in verbal memory despite evidence of moderate hippocampalatrophy This advantage may represent a sex-specific form of cognitive reserve delaying verbal memory decline until more advanced disease stages
lrsquoanalisi dei gruppi evidenziache queste donne hanno piugrave di 15 anni di
scolaritagrave
Cognitive reserve
IN SINTESIhellip
bull Le donne sono maggiormente a rischio per demenza e specie per malattia di Alzheimer tutto sembra concorrere a farle ammalare di piugrave dei maschi
bull Lrsquo assetto genetico e ormonale il modo di connettere informazioni a livello cerebrale le tante malattie in piugrave il piugrave basso livello di scolaritagrave e la minore attivitagrave laquosocialeraquo rispetto ai maschihelliphellip
Take home messages
bull Le differenze di genere osservate nelle demenze ( per tipo sintomied espressione fenotipica) originano dale profonde differenzecerebrali (genetiche ormonali e di connessioni) che esistono tra I due sessi
bull La consapevolezza e la ricerca in questa direzione potrebberoportare in futuro ad avere trattamenti genere - specifici non solo per gli aspetti cognitivi ma ancora di piugrave per quelli comportamentali
Il ogni caso il futuro egrave disegnatohellip studiare di piugrave avere una maggiore vita sociale fare attivitagrave fisica combattere le malattiehelliphellip
Anno 1791 giorno 29 Dicembre helliphelliphelliphellip Magnifica Eleonora Miceli helliphelliphelliphelliphelliphelliphellipanni sei sopra cento helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellipin giusto ragionamento ed intelligenza dei sensihelliphelliphelliphelliphelliphellip
Serrastretta Parish Archives
She does not recognize anybody she does not understand anything she does not answer any questions and she is emotionally flat She stays in bed all day moving her eyes around without any kind of thoughts driving her mind or triggering any movements of her limbs She mumbles incomprehensible words She seems astonished and scaredrsquorsquo
She died of marasmus at the age of 40 yearsin 1905helliphellip
IN SINTESIhellip
bull Le donne sono maggiormente a rischio per demenza e specie per malattia di Alzheimer tutto sembra concorrere a farle ammalare di piugrave dei maschi
bull Lrsquo assetto genetico e ormonale il modo di connettere informazioni a livello cerebrale le tante malattie in piugrave il piugrave basso livello di scolaritagrave e la minore attivitagrave laquosocialeraquo rispetto ai maschihelliphellip
Take home messages
bull Le differenze di genere osservate nelle demenze ( per tipo sintomied espressione fenotipica) originano dale profonde differenzecerebrali (genetiche ormonali e di connessioni) che esistono tra I due sessi
bull La consapevolezza e la ricerca in questa direzione potrebberoportare in futuro ad avere trattamenti genere - specifici non solo per gli aspetti cognitivi ma ancora di piugrave per quelli comportamentali
Il ogni caso il futuro egrave disegnatohellip studiare di piugrave avere una maggiore vita sociale fare attivitagrave fisica combattere le malattiehelliphellip
Anno 1791 giorno 29 Dicembre helliphelliphelliphellip Magnifica Eleonora Miceli helliphelliphelliphelliphelliphelliphellipanni sei sopra cento helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellipin giusto ragionamento ed intelligenza dei sensihelliphelliphelliphelliphelliphellip
Serrastretta Parish Archives
She does not recognize anybody she does not understand anything she does not answer any questions and she is emotionally flat She stays in bed all day moving her eyes around without any kind of thoughts driving her mind or triggering any movements of her limbs She mumbles incomprehensible words She seems astonished and scaredrsquorsquo
She died of marasmus at the age of 40 yearsin 1905helliphellip
Take home messages
bull Le differenze di genere osservate nelle demenze ( per tipo sintomied espressione fenotipica) originano dale profonde differenzecerebrali (genetiche ormonali e di connessioni) che esistono tra I due sessi
bull La consapevolezza e la ricerca in questa direzione potrebberoportare in futuro ad avere trattamenti genere - specifici non solo per gli aspetti cognitivi ma ancora di piugrave per quelli comportamentali
Il ogni caso il futuro egrave disegnatohellip studiare di piugrave avere una maggiore vita sociale fare attivitagrave fisica combattere le malattiehelliphellip
Anno 1791 giorno 29 Dicembre helliphelliphelliphellip Magnifica Eleonora Miceli helliphelliphelliphelliphelliphelliphellipanni sei sopra cento helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellipin giusto ragionamento ed intelligenza dei sensihelliphelliphelliphelliphelliphellip
Serrastretta Parish Archives
She does not recognize anybody she does not understand anything she does not answer any questions and she is emotionally flat She stays in bed all day moving her eyes around without any kind of thoughts driving her mind or triggering any movements of her limbs She mumbles incomprehensible words She seems astonished and scaredrsquorsquo
She died of marasmus at the age of 40 yearsin 1905helliphellip
Il ogni caso il futuro egrave disegnatohellip studiare di piugrave avere una maggiore vita sociale fare attivitagrave fisica combattere le malattiehelliphellip
Anno 1791 giorno 29 Dicembre helliphelliphelliphellip Magnifica Eleonora Miceli helliphelliphelliphelliphelliphelliphellipanni sei sopra cento helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellipin giusto ragionamento ed intelligenza dei sensihelliphelliphelliphelliphelliphellip
Serrastretta Parish Archives
She does not recognize anybody she does not understand anything she does not answer any questions and she is emotionally flat She stays in bed all day moving her eyes around without any kind of thoughts driving her mind or triggering any movements of her limbs She mumbles incomprehensible words She seems astonished and scaredrsquorsquo
She died of marasmus at the age of 40 yearsin 1905helliphellip
Anno 1791 giorno 29 Dicembre helliphelliphelliphellip Magnifica Eleonora Miceli helliphelliphelliphelliphelliphelliphellipanni sei sopra cento helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellipin giusto ragionamento ed intelligenza dei sensihelliphelliphelliphelliphelliphellip
Serrastretta Parish Archives
She does not recognize anybody she does not understand anything she does not answer any questions and she is emotionally flat She stays in bed all day moving her eyes around without any kind of thoughts driving her mind or triggering any movements of her limbs She mumbles incomprehensible words She seems astonished and scaredrsquorsquo
She died of marasmus at the age of 40 yearsin 1905helliphellip
She does not recognize anybody she does not understand anything she does not answer any questions and she is emotionally flat She stays in bed all day moving her eyes around without any kind of thoughts driving her mind or triggering any movements of her limbs She mumbles incomprehensible words She seems astonished and scaredrsquorsquo
She died of marasmus at the age of 40 yearsin 1905helliphellip