of DementiaEmeritus Prof of Neurology and Former Professor of Neurology Head Institute of Neurology
PROF.A.V.SRINIVASAN, MD, DM, Ph.D,DSc(HON), F.A.A.N, F.I.A.N,
Differential diagnosis
Senescence – a second childhood !
Whatever the Mind can conceive and Believe, the mind can Achieve Napoleon Hill
MemoryMemory
Memory holds together past and Memory holds together past and present , gives continuity and dignity present , gives continuity and dignity to human life …. The companion…to human life …. The companion…the tutor , the poet, the library with the tutor , the poet, the library with which you travel . which you travel .
Every discovery contains an irrational element or 4 creative intuition Khrl Popper
DementiaDementia – as a concept – as a concept
Mental disorder – accompaniment of Mental disorder – accompaniment of senescence ?senescence ?
Alzheimer-1906- Amyloid plaques,Alzheimer-1906- Amyloid plaques,
neurofibrillary tanglesneurofibrillary tangles Dementia : concept / a symptom/ a Dementia : concept / a symptom/ a
sign ,not a disease - sign ,not a disease - decline in cognitive and intellectual decline in cognitive and intellectual functions compared to previous status functions compared to previous status
One is the most independent, unconventional and individualistic of all numbers
Case burden of Dementia
Incidence: Vas et al . 2001 – 0.2& in males 0.3 & in females Chandra et al - 4.7 per 1000 person years in age
65 or above
Reputation is made in a moment; character is built in a life time
Reversible dementiasReversible dementias
Common causes; Alcohol, Medication Common causes; Alcohol, Medication related Metabolic – Hypothyroidism / related Metabolic – Hypothyroidism / parathyr. B 12 def. CNS infections – parathyr. B 12 def. CNS infections – HIV , syphilis Surgical causes – NPH, HIV , syphilis Surgical causes – NPH, chronic SDH tumourchronic SDH tumour
Improves with treatment Improves with treatment
Experience can be defined as yesterday’s answer to today’s problems
Features suggesting reversibilityFeatures suggesting reversibility
Shorter duration of illnessShorter duration of illness Subcortical type of dementiaSubcortical type of dementia Moderately severe disturbanceModerately severe disturbance Younger age of onsetYounger age of onset Prominent gait disturbanceProminent gait disturbance Urinary dysfunctionUrinary dysfunction Focal neurological signsFocal neurological signs
“Anger Begins In Folly And Ends In Repentance”
Reversible dementias …
Lab – CBC , PS,ESR, blood glucose LFT , RFT, Thyroid function tests Serum electrolytes incl. Calcium Serum B 12, VDRL, HIV
Neuropsychological evaluation MRI ,CT CSF examination incl. VDRL EEG
Two is the most gentle of all numbers and represents, diplomacy and tact
Conditions akin to dementia
Depression - onset precisely dated , rapid progression , pervasive affective changes , unwilling to attempt cognitive testing
No risk factors for dementia Can be a co-morbid condition
“Social Isolation is in itself a pathogenicFactor for disease production”
Akin To Dementia …Akin To Dementia …
DeliriumDelirium– Acute onset Acute onset – Fluctuating courseFluctuating course– Autonomic disturbances Autonomic disturbances – Precipitating factors like infection, Precipitating factors like infection,
metabolic and drugsmetabolic and drugs
The Truth is Fear & Immorality are two of the greatest inhibitors of Performance to progress
Benign syndrome of MIBenign syndrome of MI
Emil Kraeplin – OBSEmil Kraeplin – OBS Consider when Consider when
symptoms not progresssymptoms not progress Normal ageing >> Border Normal ageing >> Border
zone << ADzone << AD related to systemic related to systemic
neurological diseases, neurological diseases, alcoholism, CCF, COPDalcoholism, CCF, COPD
Science is below the mind;
Spirituality is beyond the mind
AGE ASSOCIATED AGE ASSOCIATED COGNITIVE DECLINECOGNITIVE DECLINE
Decline of more than one SD in Decline of more than one SD in area of cognitive functioning in area of cognitive functioning in comparision with age matched comparision with age matched controlscontrols
When they tell you to grow up, they mean stop When they tell you to grow up, they mean stop growinggrowing
AssessmentAssessment
Neuropychological instruments are useful inNeuropychological instruments are useful in
diagnosing and classifying the type of diagnosing and classifying the type of dementia dementia
Judging the severity of dementiaJudging the severity of dementia following progressfollowing progress Assess efficacy of RxAssess efficacy of Rx
In any field, find the strangest thing and explore it
Assessment of dementia
• Criterias used for identification
• NINCDS-ADRDA ( AD)
• VaD diagnostic criteria
• FTD diag. criteria
• DSM IV
• Diagnosis of presence and extent assessed with MMSE , CDR
Of a burning and unremitting character - F.W.PAVY
Rx of dementia …Rx of dementia …
• Treat potentially reversible primary Treat potentially reversible primary and concomitant conditionsand concomitant conditions
• Multidisciplinary activity consists of Multidisciplinary activity consists of neurologist, psychiatrist neurologist, psychiatrist neurophysiologist and social workerneurophysiologist and social worker
• A concerned general practitioner A concerned general practitioner knowing the patient & familyknowing the patient & family
Three is the most playful of all numbers and also creative, inspirational and motivating
Dementia with lewy bodyDementia with lewy body
Prominent attention deficit, fluctuating Prominent attention deficit, fluctuating cognition, visualcognition, visual hallucins, parkinsonism hallucins, parkinsonism
Dopaminergic drugs useful Dopaminergic drugs useful Aypical antipsychotic drugs are used Aypical antipsychotic drugs are used
because marked sensitivity to neuroleptics because marked sensitivity to neuroleptics Rivastigmine improves cognition and Rivastigmine improves cognition and
some behavioural disturbances some behavioural disturbances
Nine is the most humanitarian of all numbers. It is effort and sacrifice without the need for reward.
Rx …Rx …____________________________________________________________________________________________
Non-Pharmacological measuresNon-Pharmacological measures Minimise sensory deprivationMinimise sensory deprivation Oral hygiene / NutritionOral hygiene / Nutrition Maintain daily routines, reminders, diaries Maintain daily routines, reminders, diaries Flooring/clothingFlooring/clothing Foot-wears, walking aidsFoot-wears, walking aids
NATURE, TIME AND PATIENCE are the 3 great physicians
Care giver supportsCare giver supports Acceptance , measures to counter physical, Acceptance , measures to counter physical,
psychological, financial burdenpsychological, financial burden No denial or guiltNo denial or guilt Forming groups Forming groups Education or providing recent treatment optionsEducation or providing recent treatment options Instituionalisation if necessaryInstituionalisation if necessary
Number four is the most practical of all numbers, with attention and a sharp eye for details
RxRx - a team work - a team work
TTogetherogetherEEveryoneveryoneAAchiveschivesMMoreore
It is a great misfortune not to possess sufficient wit to speak well nor sufficient judgment to keep silent
-La Broyers character
Is there an answer for Dementia
Discipline Weighs ounces Regret weighs Tons
General principles inGeneral principles in PharmacotherapyPharmacotherapy
One agent at a timeOne agent at a time Increase dose at 5-7 days intervalIncrease dose at 5-7 days interval Sedative side effects used to Sedative side effects used to
advantageadvantage Improving cognition not the only goalImproving cognition not the only goal Treat ass. behavioural disordersTreat ass. behavioural disorders High CNS side effects can occur in very High CNS side effects can occur in very
old patients old patientsFive is the most dynamic of all numbers. It is persuasive, versatile and adaptable
Pharmacological Treatment Pharmacological Treatment of Dementiaof Dementia
Cholinesterase inhibitors ( ChE-I)Cholinesterase inhibitors ( ChE-I) NMDA receptors antagonistsNMDA receptors antagonists Anti-oxidant drugsAnti-oxidant drugs Anti-psychotic drugsAnti-psychotic drugs
“Men of Genius Admired: Men of Wealth envied women of power feared but only women of character are trusted”
A- Friedman
ChE-IChE-I Inhibits acetyl cholinesterase Inhibits acetyl cholinesterase Increases Increases
synaptic residue time of Ach.synaptic residue time of Ach. Increased signal in post synaptic Increased signal in post synaptic
cholinergic neuroncholinergic neuron Enhances cognition, improves behaviour, Enhances cognition, improves behaviour,
improves global function improves global function
Knowledge without action is useless;Action without knowledge is foolish
ChE-IBritish psychiatrists group recommend in
probable AD in NINDS criteria, MMSE >10 (mild to moderate), duration > 6mths
Long term therapy found beneficialWhen the drug is withdrawn, worsening of
ADL, behaviour needs restarting the drugs
Number sixth is the most loving of all numbers and is harmonious with all other number
AChEI -DosagesAChEI -Dosages
• Donapezil :Start on 5 mg OD, if tolerated increase to 10 mg OD , max. dose – 10 mg a day
• Galantamine : Start on 4 mg BD and after 4 wks- 8mg BD may increase to max. dose 12 mg BD
• Rivastigmine :Start on 1.5 mg BD –after 2 wks 3mg BD may increase to max. dose 6 mg BD
Number seven is the most spiritual of all numbers. It is the seeker of truth.
NMDA Receptor NMDA Receptor AntagonistAntagonist
Glutamine – learning , memoryGlutamine – learning , memory AD- increased glutamate activity at AD- increased glutamate activity at
NMDA receptor NMDA receptor excitotoxic cell excitotoxic cell deathdeath
Memantine – non competitive voltage Memantine – non competitive voltage dependant NMDA receptor antagonist dependant NMDA receptor antagonist low to moderate affinity low to moderate affinity
Improves cognitive and global function Improves cognitive and global function We learn by thinking and the quality of the learning outcome is
determined by the quality of our thoughtsR.B. Schmeck
MEMANTINEMEMANTINE Started in the dose of 5mg per day in first week Started in the dose of 5mg per day in first week
and increased to 10mg per day and increased to 10mg per day Memantine can be combined with ChE-I Memantine can be combined with ChE-I
(Donapezil) for synergistic action (Donapezil) for synergistic action Antioxidant drugs like vitamin E Selegeline Antioxidant drugs like vitamin E Selegeline
found to delay the occurance of milestones in found to delay the occurance of milestones in the progression of dementia the progression of dementia
Eight is the most result-oriented of all numbers and represents a balanced world
Other drugsOther drugs Ginkgo biloba:Ginkgo biloba:
Mixed results in trials. The effect is smaller Mixed results in trials. The effect is smaller than AChEI sthan AChEI s
Oestrogens:Oestrogens:Not successful, risk of Venous thrombosisNot successful, risk of Venous thrombosis
NSAIDs:NSAIDs:Observations showed lower risk of AD with Observations showed lower risk of AD with NSAIDs but clinical trials disproved efficacy NSAIDs but clinical trials disproved efficacy
The True Art of Memory is The Art of Attention - S.Johnson
No time to lose No time to lose
Early diagnosis and Early diagnosis and intervention results in clinical intervention results in clinical and financial benefit by and financial benefit by alleviating the patient and alleviating the patient and care giver burden care giver burden
Take time to think; it is the source of powerTake time to read; it is the foundation of wisdomTake time to work; it is the price of success
Vascular dementiaVascular dementia
Very common cause in India due to Very common cause in India due to high prevalence of CVA/risk factors high prevalence of CVA/risk factors
Unlike other dementias, disease Unlike other dementias, disease modifying treatments (OHA, AHT, lipid modifying treatments (OHA, AHT, lipid lowering drug) can be beneficiallowering drug) can be beneficial
Prevention of stroke and its Prevention of stroke and its recurrence is usefulrecurrence is useful
“By Nature All Men/ Women are alike butby Education widely different” - Chinese
Two Diverging / Converging Two Diverging / Converging
Pataways associated with Pataways associated with VaDVaDRisk factor Risk factor CVD CVD Ischemic Ischemic Brain injury Brain injury MRI lesion MRI lesion
Clinical syndromeClinical syndromeHTNHTN
Arteriosclerosis Arteriosclerosis 1. occlusion 1. occlusion complete infarct complete infarct lacune lacune lacunnar state lacunnar state
Arteriosclerosis Arteriosclerosis 2. Hypoperfusion 2. Hypoperfusion incomplete infarct incomplete infarct WHSM WHSM Bingswanger syndrome Bingswanger syndrome
Experience can be defined as
yesterday’s answer to today’s problems
Short comingsShort comings1.1. Not interchangeable hence four fold rise in Not interchangeable hence four fold rise in
frequencyfrequency2.2. DSM IV R most liberalDSM IV R most liberal3.3. NINDS- AIREN criteria conservativeNINDS- AIREN criteria conservative4.4. Gold standard for VaD (pathological definition Gold standard for VaD (pathological definition
difficult)difficult)5.5. Most of the criteria failed to distinguish Most of the criteria failed to distinguish
between small and large vessel subtypesbetween small and large vessel subtypes
“Healthy Mind and Healthy expression of Emotion go hand in Hand”
Diagnosis and prognosis
Risk factors Modifiable Non-modifiable
Hypertension Age
Hyperglycemia Gender
Race
Heredity
Discipline Weighs ounces Regret weighs Tons
Diagnosis and prognosis contd….
Vascular phenotype : “CVD” Arteriosclerosis Amyloid angiopathy Other small vessel disease
“You have got to be before you can do
and do before you can have”
Diagnosis and prognosisDiagnosis and prognosis contd….contd….
Vascular Vascular distributiondistribution
Mechanism Mechanism of Brain of Brain injuryinjury
Pathological Pathological phenotype phenotype “Infarct”“Infarct”
Single arterySingle artery
Small arterioleSmall arterioleAcute ischemiaAcute ischemia Multiple lacunar Multiple lacunar
infarctsinfarcts
Single arterySingle artery Acute ischemiaAcute ischemia Single Single strategically strategically placed lacunar placed lacunar infarctinfarct
Border zoneBorder zone
Small arterioleSmall arterioleChronic Chronic
hypo perfusionhypo perfusionWhite matter White matter demyelination demyelination and axonal lossand axonal loss
Diagnosis and prognosisDiagnosis and prognosis contd….contd….
neuro imaging phenotypeneuro imaging phenotype
CT lucency (lacunes and leukoariosis)CT lucency (lacunes and leukoariosis)
MRI hyper intensity (lacunes and WMSH)MRI hyper intensity (lacunes and WMSH)
A true commitment is a heart felt promise to yourself from which you will not back
down -
D. Mcnally
Diagnosis and prognosisDiagnosis and prognosis contd…. contd….
Localisation / Localisation / neural networkneural network
Clinical phenotype or Clinical phenotype or syndromesyndrome
Cortico-basal ganglia Cortico-basal ganglia – thalamocortical – thalamocortical loopsloops
Lacunar stateLacunar state
Apathy, depression, abulia Apathy, depression, abulia Dysexecutive syndromeDysexecutive syndrome
Normal visual fieldsNormal visual fields
ParkinsonismParkinsonism
Cortico-basal ganglia Cortico-basal ganglia thalamocortical loopsthalamocortical loops
Strategic infarct dementiaStrategic infarct dementia
Dysexecutive syndromeDysexecutive syndrome
Frontal lobe syndromeFrontal lobe syndrome
Deep white matter Deep white matter connectionsconnections
Binswanger’s syndromeBinswanger’s syndrome
Slowly progressive depression, Slowly progressive depression, bradykinesia, dysexecutive bradykinesia, dysexecutive syndrome, gait apraxia, urinary syndrome, gait apraxia, urinary incontinenceincontinence
Diagnosis of Dementia after strokeDiagnosis of Dementia after stroke
Four sets of criteria are used Four sets of criteria are used SensSens SpecSpec
1.1. Hachinski ischemic score 89% 89%Hachinski ischemic score 89% 89% < 4 AD / 18, > 7 MID / 18< 4 AD / 18, > 7 MID / 18
2.2. DSM IV DSM IV 43% 95% 43% 95%
33. NINDS – AIREN. NINDS – AIREN 50% 98% 50% 98%
4.4. ADDTC criteria ADDTC criteria 50% 90% 50% 90%
Every discovery contains an irrational element or
4 creative intuition - Khrl Popper
AD Vs VaDAD Vs VaD
ADAD VaDVaD
Neuro transmitter defect Neuro transmitter defect Hemodynamic defectHemodynamic defect
Female predominance Female predominance Male predominanceMale predominance
Gradual onsetGradual onset Abrupt onsetAbrupt onset
Steady deterioration Steady deterioration Stepwise deterioration, Stepwise deterioration,
fluctuating coursefluctuating course
BP normal BP normal HypertensionHypertension
No history of stroke No history of stroke History of strokeHistory of stroke
Global decline in cognitive Global decline in cognitive function function
Focal neurological symptoms Focal neurological symptoms and signsand signs
Unlikely to respond to Unlikely to respond to treatment treatment
May respond to a drug which May respond to a drug which modifies microcirculation and modifies microcirculation and enhance cerebral tissue enhance cerebral tissue perfusionperfusion
A good teacher is a perpetual learner
VaD ChE-I especially Galantamine is
found effective in VaD +/- AD Pseudo bulbar palsy with emotional
incontinene responds to SSRI , TCA or levadopa
“Serious, sincere, systematic study surely secures supreme success”
Role of RIVASTIGMINE in VaDRole of RIVASTIGMINE in VaD
No.of patients : 12No.of patients : 12Age group Age group : 50 – 80 years : 50 – 80 yearsFemaleFemale : 4 : 4MaleMale : 8 : 8Most of them had diabetes and hypertension Most of them had diabetes and hypertension Not based on subtype of VaD Not based on subtype of VaD 30% showed remarkable improvement in cognitive,30% showed remarkable improvement in cognitive,curative and affective functions of the braincurative and affective functions of the brainFuture study neededFuture study needed
“ He who cannot forgive others destroys the bridge over which he himself must
pass” - Annoy
Strategies to preventStrategies to prevent – – STROKE – TO - DEMENTIASTROKE – TO - DEMENTIA
TEN-STEP APPROACHTEN-STEP APPROACH1.1. Treat hypertension optimallyTreat hypertension optimally2.2. Treat diabetesTreat diabetes3.3. Control hyperlipidaemia, uControl hyperlipidaemia, use dietary control for se dietary control for
diabetes, obesity and hyperlipidaemiadiabetes, obesity and hyperlipidaemia
4.4. Persuade patients to cease smoking and Persuade patients to cease smoking and decrease alcohol intakedecrease alcohol intake
5.5. Prescribe anticoagulants for atrial fibrillationPrescribe anticoagulants for atrial fibrillation6.6. Provide antiplatelet therapy for high risk Provide antiplatelet therapy for high risk
patientspatients
A open foe may prove a curse ; but
a pretended friend is worse
Strategies to prevent – Strategies to prevent – STROKE-TO-DEMENTIASTROKE-TO-DEMENTIA contd…contd…
7.7. Perform carotid endarterectomy for severe (>70%) carotid Perform carotid endarterectomy for severe (>70%) carotid stenosisstenosis
8. 8. Recommend lifestyle changes (e.g., weight loss, exercise, Recommend lifestyle changes (e.g., weight loss, exercise, reducereduce
stress, decrease salt intake)stress, decrease salt intake)
9.9. N-methyl-D-aspartate receptor antagonists, antioxidants) N-methyl-D-aspartate receptor antagonists, antioxidants)
10.10. Intervene early for stroke and transient ischemic attacks with Intervene early for stroke and transient ischemic attacks with
neuroprotective agents (e.g., propentofylline, calcium channelneuroprotective agents (e.g., propentofylline, calcium channel
antagosists, -? Rivastigmineantagosists, -? Rivastigmine
It is a great misfortune not to possess sufficient wit to speak well
nor sufficient judgment to keep silent - La Broyers character
FTLDFTLD Prominent aphasia and neuro-Prominent aphasia and neuro-
psychiatric complaints psychiatric complaints Familial, mutation in Ch. 17Familial, mutation in Ch. 17 SSRI decreases disinhibition, SSRI decreases disinhibition,
compulsioncompulsion Adrenergic agonists ,Idazoxan Adrenergic agonists ,Idazoxan
improves planning ,attention & improves planning ,attention & episodic memoryepisodic memory
“The Truth is fear and immorality are two of the greatest inhibitors of Performance to progress”
HIV associated DementiaHIV associated Dementia
Symptoms- Change in personality- mild to Symptoms- Change in personality- mild to psychotic psychotic
Loss of concentration, confusionLoss of concentration, confusion Cognitive impairementCognitive impairement Progressive subcortical dementiaProgressive subcortical dementia Signs –FND, seizures, meningeal signs, Signs –FND, seizures, meningeal signs,
increased ICP signsincreased ICP signs
“Healthy Mind and Healthy expression of Emotion go hand in Hand”
Care and Cure !
It is not your position that makes you happy or unhappy It is your disposition
Rx of
Neuropsychiatric Problems
An accurate diagnosis for both dementing illness and concomitant psychiatric symptoms
Treatment of psychiatric problems reduce the distress of patient as well as caregiver
As one is common to all numbers, it is often seen as the origin of all things
Rx of Psychiatric sympt.
Agitation – Mood stabilisers like CBZ, divalproax,
Trazadone for night time aggression Buspirone for anxiety related aggression Medroxyprogesterone for sex aggression
Anxiety - Oxazepam, Lorazepam, Buspirone
Two symbolizes partnership implying that accomplishments are best through coordination.
Rx … Apathy -
Methylphenidate, dextro-amphetamine Modafenil
Insomnia - Trazadone, Zolpidem
Delusion- atypical antipychotics Depression –
SSRI, Comb. RI eg. Venlafaxin,Mirtazepin
Hate screeches, fear squeals; conceits trumpetsbut love sings lullabies
Antipsychotic drugs
when behavioural changes are severe and urgent treatment is needed, a Psychotropic drug can be used prior to use of a ChE-I drug
Three can be seen in the divisions of a human in mind, body and spirit
Therapy--? Future
“Knowledge can be communicated but not Wisdom” - Hermann Hesse
Future Future therapiestherapies
Recently, intranasal insulin – improves Recently, intranasal insulin – improves cognitive function in AD who lack Apo E cognitive function in AD who lack Apo E
Gene therapy using nerve growth factor Gene therapy using nerve growth factor administered by implanting genetically administered by implanting genetically engineered autologous fibroblasts engineered autologous fibroblasts
“Motivation is the Spark that lights the Fire of Knowledge and
fuels the engine of Accomplishment
Future therapies
• Regenerating neurons show trophic response reduction in rate of cognitive decline by 50 % for about 2 years
• Beta secretase inhibitors are found to interrupt amyloid cascade
Learn to adapt, adjust and accommodate Learn to give, not to take and learn to serve not to rule
Future Therapies
• Drugs to counter Glycogen synthase kinase,which is involved in phosphorylation of tau,is under study
• Plaque busters inserts themselves in polymerizing amyloid and so slows accumulation of Neuritic plaques
In all of us, even in good men, there is a wild - beast nature which peers out in sleep
Dedicated to my family for making everything worthwhile
Thank youThank youMy sincere thanks to
Mr.K.THUDHIMUGAN for his meticulous computer work
My sincere thanks to Mr.K.THUDHIMUGAN for his meticulous
computer work
READ not to contradict or confute
Nor to Believe and Take for Granted
but TO WEIGH AND CONSIDER