1. Differential diagnosis
of Dementia
PROF.A.V.SRINIVASAN, MD, DM, Ph.D,DSc(HON), F.A.A.N, F.I.A.
Emeritus Prof of Neurology and
Former Professor of Neurology
Head Institute of Neurology

3. Senescence – a second
childhood !
Whatever the Mind can conceive and Believe,
the mind can Achieve
Napoleon Hill

4. Memory
 Memory holds together past and present ,
gives continuity and dignity to human life
…. The companion…the tutor , the poet,
the library with which you travel .
Every discovery contains an irrational element or 4 creative intuition
Khrl Popper

5. Dementia – as a concept
 Mental disorder – accompaniment of
senescence ?
 Alzheimer-1906- Amyloid plaques,
neurofibrillary tangles
 Dementia : concept / a symptom/ a
sign ,not a disease - decline in cognitive
and intellectual functions compared to
previous status
One is the most independent, unconventional and individualistic of all numbers

6. 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

7. Reversible dementias
 Common causes; Alcohol, Medication
related Metabolic – Hypothyroidism /
parathyr. B 12 def. CNS infections – HIV ,
syphilis Surgical causes – NPH, chronic
SDH tumour
 Improves with treatment
Experience can be defined as
yesterday’s answer to today’s problems

8. Features suggesting reversibility
 Shorter duration of illness
 Subcortical type of dementia
 Moderately severe disturbance
 Younger age of onset
 Prominent gait disturbance
 Urinary dysfunction
 Focal neurological signs
“Anger Begins In Folly And Ends In Repentance”

9. 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

10. 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 pathogenic
Factor for disease production”

11. Akin To Dementia …
 Delirium
– Acute onset
– Fluctuating course
– Autonomic disturbances
– Precipitating factors like infection, metabolic
and drugs
The Truth is Fear & Immorality are two of the greatest
inhibitors of Performance to progress

12. Benign syndrome of MI
 Emil Kraeplin – OBS
 Consider when
symptoms not progress
 Normal ageing >> Border
zone << AD
 related to systemic
neurological diseases,
alcoholism, CCF, COPD
Science is below the mind;

13. AGE ASSOCIATED
COGNITIVE DECLINE
 Decline of more than one SD in
area of cognitive functioning in
comparision with age matched
controls
When they tell you to grow up, they mean stop growing

14. Assessment
Neuropychological instruments are useful in
 diagnosing and classifying the type of
dementia
 Judging the severity of dementia
 following progress
 Assess efficacy of Rx
In any field, find the strangest thing and explore it

15. 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

16. Rx of dementia …
• Treat potentially reversible primary and
concomitant conditions
• Multidisciplinary activity consists of
neurologist, psychiatrist neurophysiologist
and social worker
• A concerned general practitioner knowing
the patient & family
Three is the most playful of all numbers and also
creative, inspirational and motivating

17. Dementia with lewy body
 Prominent attention deficit, fluctuating
cognition, visual hallucins, parkinsonism
 Dopaminergic drugs useful
 Aypical antipsychotic drugs are used
because marked sensitivity to neuroleptics
 Rivastigmine improves cognition and
some behavioural disturbances
Nine is the most humanitarian of all numbers. It is
effort and sacrifice without the need for reward.

18. Rx … ______________________________________________
 Non-Pharmacological measures
 Minimise sensory deprivation
 Oral hygiene / Nutrition
 Maintain daily routines, reminders, diaries
 Flooring/clothing
 Foot-wears, walking aids
NATURE, TIME AND PATIENCE
are the 3 great physicians

19. Care giver supports
 Acceptance , measures to counter physical,
psychological, financial burden
 No denial or guilt
 Forming groups
 Education or providing recent treatment options
 Instituionalisation if necessary
Number four is the most practical of all numbers,
with attention and a sharp eye for details

20. Rx - a team work
Together
Everyone
Achives
More
It is a great misfortune not to possess sufficient wit to speak well
nor sufficient judgment to keep silent
-La Broyers character

21. Is there an answer for
Dementia
Discipline Weighs ounces Regret weighs Tons

22. General principles in
Pharmacotherapy
 One agent at a time
 Increase dose at 5-7 days interval
 Sedative side effects used to advantage
 Improving cognition not the only goal
 Treat ass. behavioural disorders
 High CNS side effects can occur in very
old patients
Five is the most dynamic of all numbers. It is persuasive,
versatile and adaptable

23. Pharmacological
Treatment of Dementia
 Cholinesterase inhibitors ( ChE-I)
 NMDA receptors antagonists
 Anti-oxidant drugs
 Anti-psychotic drugs
“Men of Genius Admired:
Men of Wealth envied
women of power feared but only
women of character are trusted”
A- Friedman

24. ChE-I
 Inhibits acetyl cholinesterase  Increases
synaptic residue time of Ach.
 Increased signal in post synaptic
cholinergic neuron
 Enhances cognition, improves behaviour,
improves global function
Knowledge without action is useless;
Action without knowledge is foolish

25. ChE-I
British psychiatrists group recommend in
probable AD in NINDS criteria, MMSE >10
(mild to moderate), duration > 6mths
Long term therapy found beneficial
When 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

26. AChEI -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.

27. NMDA Receptor Antagonist
 Glutamine – learning , memory
 AD- increased glutamate activity at NMDA
receptor  excitotoxic cell death
 Memantine – non competitive voltage
dependant NMDA receptor antagonist
low to moderate affinity
 Improves cognitive and global function
We learn by thinking and the quality of the learning outcome is
determined by the quality of our thoughts
R.B. Schmeck

28. MEMANTINE
 Started in the dose of 5mg per day in first
week and increased to 10mg per day
 Memantine can be combined with ChE-I
(Donapezil) for synergistic action
 Antioxidant drugs like vitamin E Selegeline
found to delay the occurance of milestones
in the progression of dementia
Eight is the most result-oriented of all numbers and represents a balanced world

29. Other drugs
 Ginkgo biloba:
Mixed results in trials. The effect is smaller
than AChEI s
 Oestrogens:
Not successful, risk of Venous thrombosis
 NSAIDs:
Observations showed lower risk of AD with
NSAIDs but clinical trials disproved efficacy
The True Art of Memory is The Art of Attention
- S.Johnson

30. No time to lose
 Early diagnosis and
intervention results in clinical
and financial benefit by
alleviating the patient and
care giver burden
Take time to think; it is the source of power
Take time to read; it is the foundation of wisdom
Take time to work; it is the price of success

31. Vascular dementia
 Very common cause in India due to high
prevalence of CVA/risk factors
 Unlike other dementias, disease modifying
treatments (OHA, AHT, lipid lowering drug)
can be beneficial
 Prevention of stroke and its recurrence is
useful
“By Nature All Men/ Women are alike but
by Education widely different”
- Chinese

32. Two Diverging / Converging
Pataways associated with VaD
Risk factor CVD Ischemic Brain injury MRI
lesion Clinical syndrome
HTN
Arteriosclerosis 1. occlusion complete infarct
lacune  lacunnar state
Arteriosclerosis 2. Hypoperfusion incomplete
infarct WHSM  Bingswanger syndrome
Experience can be defined as
yesterday’s answer to today’s problems

33. Short comings
1. Not interchangeable hence four fold rise in
frequency
2. DSM IV R most liberal
3. NINDS- AIREN criteria conservative
4. Gold standard for VaD (pathological definition
difficult)
5. Most of the criteria failed to distinguish
between small and large vessel subtypes
“Healthy Mind and Healthy expression of
Emotion go hand in Hand”

34. Diagnosis and prognosis
Risk factors
Modifiable Non-modifiable
Hypertension Age
Hyperglycemia Gender
Race
Heredity
Discipline Weighs ounces
Regret weighs Tons

35. 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”

36. Diagnosis and prognosis contd….
Vascular Mechanism of Pathological
distribution Brain injury phenotype
“Infarct”
Single artery Acute ischemia Multiple lacunar
Small arteriole infarcts
Single artery Acute ischemia Single strategically
placed lacunar
infarct
Border zone Chronic White matter
Small arteriole hypo perfusion demyelination and
axonal loss

37. Diagnosis and prognosis contd….
neuro imaging phenotype
 CT lucency (lacunes and leukoariosis)
 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

38. Diagnosis and prognosis contd….
Localisation / Clinical phenotype or
neural network syndrome
Cortico-basal ganglia Lacunar state
– thalamocortical Apathy, depression, abulia
loops Dysexecutive syndrome
Normal visual fields
Parkinsonism
Cortico-basal ganglia Strategic infarct dementia
thalamocortical loops Dysexecutive syndrome
Frontal lobe syndrome
Deep white matter Binswanger’s syndrome
connections Slowly progressive depression,
bradykinesia, dysexecutive
syndrome, gait apraxia, urinary
incontinence

39. Diagnosis of Dementia after stroke
Four sets of criteria are used Sens Spec
1. Hachinski ischemic score 89% 89%
< 4 AD / 18, > 7 MID / 18
2. DSM IV 43% 95%
3. NINDS – AIREN 50% 98%
4. ADDTC criteria 50% 90%
Every discovery contains an irrational element or
4 creative intuition - Khrl Popper

40. AD Vs VaD
AD VaD
Neuro transmitter defect Hemodynamic defect
Female predominance Male predominance
Gradual onset Abrupt onset
Steady deterioration Stepwise deterioration,
fluctuating course
BP normal Hypertension
No history of stroke History of stroke
Global decline in cognitive Focal neurological symptoms
function and signs
Unlikely to respond to May respond to a drug which
treatment modifies microcirculation and
enhance cerebral tissue
perfusion
A good teacher is a perpetual learner

41. 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”

42. Role of RIVASTIGMINE in VaD
No.of patients : 12
Age group : 50 – 80 years
Female : 4
Male : 8
Most of them had diabetes and hypertension
Not based on subtype of VaD
30% showed remarkable improvement in cognitive,
curative and affective functions of the brain
Future study needed
“ He who cannot forgive others destroys the bridge over
which he himself must pass” - Annoy

43. Strategies to prevent –
STROKE – TO - DEMENTIA
TEN-STEP APPROACH
1. Treat hypertension optimally
2. Treat diabetes
3. Control hyperlipidaemia, use dietary control
for diabetes, obesity and hyperlipidaemia
4. Persuade patients to cease smoking and
decrease alcohol intake
5. Prescribe anticoagulants for atrial fibrillation
6. Provide antiplatelet therapy for high risk
patients
A open foe may prove a curse ; but
a pretended friend is worse

44. Strategies to prevent –
STROKE-TO-DEMENTIA contd…
7. Perform carotid endarterectomy for severe (>70%) carotid
stenosis
8. Recommend lifestyle changes (e.g., weight loss, exercise,
reduce
stress, decrease salt intake)
9. N-methyl-D-aspartate receptor antagonists, antioxidants)
10. Intervene early for stroke and transient ischemic attacks with
neuroprotective agents (e.g., propentofylline, calcium channel
antagosists, -? Rivastigmine
It is a great misfortune not to possess sufficient wit to speak well
nor sufficient judgment to keep silent - La Broyers character

45. FTLD
 Prominent aphasia and neuro-psychiatric
complaints
 Familial, mutation in Ch. 17
 SSRI decreases disinhibition, compulsion
 Adrenergic agonists ,Idazoxan improves
planning ,attention & episodic memory
“The Truth is fear and immorality are two of the
greatest inhibitors of Performance to progress”

46. HIV associated Dementia
 Symptoms- Change in personality- mild to
psychotic
 Loss of concentration, confusion
 Cognitive impairement
 Progressive subcortical dementia
 Signs –FND, seizures, meningeal signs,
increased ICP signs
“Healthy Mind and Healthy expression of Emotion go hand in Hand”

47. Care and Cure !
It is not your position that makes you happy or unhappy
It is your disposition

48. 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

49. 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.

50. Rx …
 Apathy -
Methylphenidate, dextro-amphetamine
Modafenil
 Insomnia -
Trazadone, Zolpidem
 Delusion- atypical antipychotics
 Depression –
SSRI, Comb. RI eg. Venlafaxin,Mirtazepin
Hate screeches, fear squeals; conceits trumpets
but love sings lullabies

51. 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

52. Therapy--? Future
“Knowledge can be communicated but not Wisdom” - Hermann Hesse

53. Future therapies
 Recently, intranasal insulin – improves
cognitive function in AD who lack Apo E
 Gene therapy using nerve growth factor
administered by implanting genetically
engineered autologous fibroblasts
“Motivation is the Spark that lights
the Fire of Knowledge and
fuels the engine of Accomplishment

54. 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

55. 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

57. Dedicated to my family for
making everything worthwhile

58. READ not to contradict or confute
Nor to Believe and Take for Granted
but TO WEIGH AND CONSIDER
Thank you
My sincere thanks to
Mr.K.THUDHIMUGAN for his meticulous
computer work