Tempo, sesso, genere, storia e demenza Time, sex, gender ... · ©2012 MFMER | slide-27 Historical events Bertolt Brecht, 1940; Slavoj Zizek, 2010; Rocca 2017 ... (Bertolt Brecht,

©2017 MFMER | slide-1

Walter A. Rocca, MD, MPH

Mayo Clinic

Rochester, MN, USA

I have nothing to disclose

Tempo, sesso, genere, storia e demenza

Time, sex, gender, history,

and dementia


1. The decline of dementia: time ● Alzheimer’s disease (AD) vs. dementia

● History: USA, Canada, and UK

● Possible opposing trends for AD and other dementias

2. Possible explanations: sex, gender, history ● Sex and gender factors

● Positive individual and societal changes

● Changes in smoking, diet, and lifestyle

● Changes in education and socioeconomic factors

● Changes in intelligence quotient (IQ)

● Negative individual and societal changes

3. Conclusions: hope for prevention

Outline

Rocca et al., 2011; Jones and Green, 2013; Jones and Green, 2016; Rocca, 2017


1

The decline of

dementia

Πάντα ῥεῖ (panta rhei)

Everything flows

(Heraclitus, 535-475 BC)


Rocca et al., 1998; Rocca et al., 2011

2011: Time trends for dementia Olmsted Co., Minnesota

Incid

en

ce

ra

te p

er

10

0,0

00

pe

r ye

ar

Calendar year

90-94

85-89

80-84

0

1,000

2,000

3,000

4,000

5,000

6,000

7,000

1975 1977 1979 1981 1983 1985 1987 1989 1991 1993

+ Men Women

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwimj-Wbi7zMAhUsuIMKHWvPAOgQjRwIBw&url=http://www.mapsofworld.com/usa/&psig=AFQjCNG78xC_0Mani-l3bihmq4I6rWefLA&ust=1462302416546759


2015: Time trends for dementia Canada

Sposato et al., 2015

0

1

2

3

4

5

6

7

2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013

Incid

en

ce

pe

r 1

,00

0 p

op

ula

tio

n

Calendar year

Dementia (-7%)

Stroke (-32%)

Trend p = 0.009

Trend p < 0.001

+ Men Women


Satizabal et al., 2016

2016: Time trends for dementia Framingham, Massachusetts

Trend p = 0.08

Epoch 1 ~ 1980

0.25

0.5

1.0

2.0

0.96 0.89

0.64

1.0

0.53 0.52

0.70

1.0

5-y

ea

r h

aza

rds r

atio

, lo

ga

rith

mic

Trend p < 0.001

Epoch 2 ~ 1990

Epoch 3 ~ 2000

Epoch 4 ~ 2010

Men

Women

> Men Women

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwimj-Wbi7zMAhUsuIMKHWvPAOgQjRwIBw&url=http://www.mapsofworld.com/usa/&psig=AFQjCNG78xC_0Mani-l3bihmq4I6rWefLA&ust=1462302416546759


2016: Time trends for dementia United Kingdom - 3 areas

Matthews et al., 2016

1990-1993

2008-2011

Incid

ence r

ate

per

1,0

00 p

ers

on y

ears

80

70

60

50

40

30

20

10

0

Men Women

65-69 70-74 75-79 80-84 85+ 65-69 70-74 75-79 80-84 85+

80

70

60

50

40

30

20

10

0

Age, years Age, years

> Men Women

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwiezerSiLzMAhWMvIMKHVMJDFAQjRwIBw&url=http://www.mapsofworld.com/united-kingdom/&psig=AFQjCNGjV5DEFLvAJAtuB_OSLyBh9RO1Lw&ust=1462301746228944


0

1

2

3

4

5

6

7

2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013


Cerasuolo et al., 2017

Incid

en

ce

pe

r 1

,00

0 p

op

ula

tio

n

Calendar year

Dementia (-4%)

Dementia (-7%)

Stroke (-32%)

Stroke (-32%)

Men

Women




0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

Stroke (-22%)

Women

Men

Ages 20-49 Ages 50-64

Calendar year Calendar year

Incid

ence p

er

1,0

00 p

opula

tion

In

cid

ence p

er

1,0

00 p

opula

tion

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

20

02

20

03

20

04

20

05

20

06

20

07

20

08

20

09

20

10

20

11

20

12

20

13

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.52

00

2

20

03

20

04

20

05

20

06

20

07

20

08

20

09

20

10

20

11

20

12

20

13

Stroke (-5%)

Stroke (-24%)

Stroke (+8%)

Dementia (+19%) Dementia (+31%)

Dementia (+20%)

Dementia (+16%)




Ages 65-79 Ages 80+

Calendar year Calendar year

Incid

ence p

er

1,0

00 p

opula

tion

In

cid

ence p

er

1,0

00 p

opula

tion

0

2

4

6

8

10

12

14

16

18

0

2

4

6

8

10

12

14

16

18

20

02

20

03

20

04

20

05

20

06

20

07

20

08

20

09

20

10

20

11

20

12

20

13

0

15

30

45

60

75

90

0

15

30

45

60

75

902

00

2

20

03

20

04

20

05

20

06

20

07

20

08

20

09

20

10

20

11

20

12

20

13

Stroke (-37%)

Stroke (-37%)

Stroke (-37%)

Stroke (-39%)

Dementia (-0.2%)

Dementia (-18%)

Dementia (+1%)

Dementia (-13%)

Women

Men


Alzheimer’s

disease

Vascular

dementia

Vascular cerebral lesion burden

Neurodegenerative burden

Dementia vs. Alzheimer’s disease

Sposato et al., 2015; Viswanathan et al., 2009

Alzheimer pathology

Cortical Lewy bodies


● Dementia with late onset, limited familial

aggregation, and predominant neurovascular

lesions is decreasing over time

● Dementia with early onset, familial aggregation, and predominant neurodegenerative lesions is increasing over time

● Late onset dementia drives the overall trend

● Supporting evidence: ● Decline in the incidence of stroke

● Increase in the incidence of parkinsonism

● Increase in the incidence of amyotrophic lateral sclerosis (ALS)

Possible opposing trends

Rocca 2017; Rocca 2017, WCN poster


2

Possible explanations

Felix, qui potuit rerum cognoscere causas

Happy the person who was able to know

the causes of things (Virgil, 70-19 BC)



Scientific American MIND, May/June 2010

Men Women

Brain differences in men and women


● Chromosomes: XX vs. XY

● Gonads: ovaries vs. testicles

● Hormones: estrogen and progesterone vs. testosterone

● Reproduction: pregnancy, breast feeding, oral contraception

Sex = biology

Institute of Medicine, 2001; Institute of Medicine 2010; Rocca et al., 2014


● Subjective

– Masculinity vs. femininity

– Gender identity

● Societal and cultural (political)

– Access to education

– Access to jobs or sports

– Access to medical care

– Allowed to drive a car, vote for the president, or choose a partner

Gender = culture and society

Institute of Medicine, 2001; Institute of Medicine 2010; Rocca et al., 2014


Life course approach

Dementia Protective factors -

Risk factors +

Waterland et al., 2007


Protective factors -

Risk factors +

Waterland et al., 2007; Courtesy of Dr. Miller, 2013

Dimorphic life course approach

Dementia


● Decline in heart disease and stroke incidence and mortality for 4-5 decades

● Better control of hypertension (e.g., β-blockers)

● Better control of diabetes (e.g., metformin)

● Better control of serum lipids (e.g., statins)

● Introduction of agents to prevent clots (e.g., low dose aspirin)

Positive individual and societal changes



● Reduction in cigarette smoking – e.g., USA, from 1965 to 2009 (44 years). - Down from 52% to 24% in men

- Down 34% to 18% in women

● Improved food preservation (refrigeration) and availability of fresh food long-distance

● Improved recognition of the benefits of exercise and physical activity (e.g., walking, swimming, yoga)

● Better information about prevention

Changes in smoking, diet, and lifestyle



● Persons ≥65 years from 1990 to 2003 – USA - Up from 53% to 72% for high school diploma

- Up from 11% to 17% for college degree

● Education and brain development and function (brain reserve), or better health behaviors

● Persons ≥65 years, median household net worth up from $119,000 to $196,000 from 1989 to 2005 – USA (in constant 2005$)

● More wealth = better general living conditions (job, housing, heating + cooling, diet, medical care, etc.)

Changes in education and socioeconomic factors



● Mean IQ up 13.8 points in 46 years, 1932-1978 – USA

● Changes in environmental factors, education, and socioeconomic status

● Flynn effect. Remains partly unexplained

Changes in intelligence quotient (IQ)

Flynn, 1984; Rocca et al., 2011


● Improved survival after myocardial infarction and stroke

● Increased prevalence of subclinical vascular disease (silent strokes)

● Increased prevalence of hypertension and diabetes - e.g., US African Americans > 65 years, 1994-2002 - Up from 73% to 83% for hypertension (+ 10%)

- Up from 26% to 36% for diabetes (+ 10%)

● Increased prevalence of obesity

● Increase in multimorbidity and polypharmacy

Negative individual and societal changes



The epidemic of obesity: 1992-2009

CDC, 2010

Overweight

BMI ≥ 25


● The men and women who became demented in the past 20-30 years lived through more than half a century of history

● Positive events: electricity, telephone, radio, television, computers, internet, refrigeration and food transportation, airplanes …

● Negative events: epidemics, natural disasters, climate changes, urbanization, pollution, wars, violence, traumas, famine, persecution, incarceration, migration, stress …

● History affects men and women differently

History


● 1914-1918: World War 1; Russian Revolution

● 1916-1920: Spanish flu pandemic

● 1929-1937: The Great Depression

● 1940-45: Word War 2, concentration camps, atomic explosions, restriction of food, stress

● 1945-1989: Cold War, Korea War, Vietnam War

● 1960s: Student protests and terrorism in Europe

● 1989: End of the Eastern block and cold war

● Gulf War 1; September 11, 2001; Gulf War 2, and destabilization of the Middle East

● 2010-2011: The Arab spring

Historical events

Rocca 2017


Historical events

Bertolt Brecht, 1940; Slavoj Zizek, 2010; Rocca 2017

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwiDjqrumL7MAhXEvYMKHXciAzgQjRwIBw&url=http://exodus.exblog.jp/3940648&psig=AFQjCNHdD6odhfCqyMKmiYHtcch7p3oXMA&ust=1462374818512458

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwjZwua3mb7MAhUnvYMKHV7YAzQQjRwIBw&url=http://themillenniumreport.com/2014/09/dimitri-khalezov-discusses-nuclear-911-twin-tower-controlled-demolition-explained/&psig=AFQjCNFSFreAT9-wWShd8HDwtYV9orbL9w&ust=1462374972655165


3

Conclusions:

hope for prevention

Truly I live in dark times! (Bertolt Brecht, 1940)

Living in the end times (Slavoj Zizek, 2010)


● The burden of disease is malleable, may change

● Humans can modify the burden of diseases

● Diseases appear and disappear in history over epochs (e.g., syphilis, tuberculosis, Zika, pellagra, peptic ulcer)

● The trends may vary by sex and gender, race/ethnicity, and across countries

● Trends of chronic disease reflect complex interactions; they are very delicate (ephemeral and contingent)

● Cautious optimism and pragmatic narratives

● Possible opposing trend for AD and other dementias

History and diseases



Prevention of dementia

• Modify risk factors in the entire population – May need to be very early in life

– Environmental protection (air, water, food)

– Better education, physical activity, cognitive stimulation

• Focus prevention on people at high risk – Prediction score or formula

– Genetic risk score (family history, APOE genotype)

• Early diagnosis and secondary prevention – Biomarkers, early manifestations, imaging, CSF

– Neuroprotective drug or other intervention

• Treatment after onset of AD or dementia


Conclusions

“History offers reasons for hope”

however,

“Rocca and colleagues have warned that increases in obesity, diabetes, and hypertension could

undermine the gains achieved through improved education, wealth, and control of vascular risk

factors.

Even if a dementia decline has begun, it might not last: the outcome depends on the balance of

diverging trends.”

Jones and Green, 2016


Thank you

“The river flowed from century to century,

and human affairs play themselves out on its banks.

Play themselves out to be forgotten the next day, while the river flows on.” (Milan Kundera, 1984)

Documents

Tempo, sesso, genere, storia e demenza Time, sex, gender ... · ©2012 MFMER | slide-27 Historical events Bertolt Brecht, 1940; Slavoj Zizek, 2010; Rocca 2017 ... (Bertolt Brecht,