1. Frontiers in the
treatment of
Dementia
A.Gunasekaran,P.V.Krishnan
,M.Radha,A.Nithyanandam
PROF.A.V.SRINIVASAN

2. Senescence – a second
childhood !

3. 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 .

4. 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

5. Assessment
• Neuropychological instruments are useful
in
• diagnosing and classifying the type of
dementia
• Judging the severity of dementia
• following progress
• Assess efficacy of Rx

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 personyears
in age 65 or above

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

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

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

10. 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

11. 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

12. akin to dementia …
• Delirium
• Acute onset
• Fluctuating course
• Autonomic disturbances
• Precipitating factors like infection ,
metabolic disturbances, drugs

13. 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

14. Age associated cognitive decline
•
• Decline of more than one SD
in area of cognitive
functioning in comparision
with age matched controls

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

16. Mx of dementia …
• Treat potentially reversible
primary and concomitant
conditions
• Multidisciplinary activity
consists of neurologist,
psychiatrist neuropsychologist
and social worker
• A concerned general practioner
knowing the patient & family

17. Mx - a team work
• Together
• Everyone
• Achives
• More

18. Mx …
• Non-Pharmacological measures
• Minimise sensory deprivation
• Oral hygiene / Nutrition
• Maintain daily
routines,reminders,diaries
• Flooring/clothing
• Foot-wears, walking aids

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

20. Is there answer for
Alzhiemer’s disease?

21. 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

22. Phar macological
tr eatment of dementia
 Cholinesterase inhibitors ( ChE-I)
 NMDA receptors antagonists
 Anti-oxidant drugs
 Anti-psychotic drugs

23. 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

24. ChE-I
 British psychiatrists group recommend in
probable AD in NINDS criteria, MMSE
>10 (mild to moderate), duration > 6
mths
 Long term therapy found beneficial
 When the drug is withdrawn, worsening
of ADL ,behaviour needs restarting the
drugs

25. 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

26. 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

27. 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

28. 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

29. No time to lose
• Early diagnosis and intervention
results in clinical and finicial
benefit by alleviating the patient
and care giver burden

30. 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

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

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
Experience can be defined as
incomplete infarct WHSM 
Bingswanger answer to today’s problems
yesterday’s syndrome

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
“HealthyMind and Healthyexpression of
Emotion go hand in Hand”

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

35. Diagnosis and prognosis contd….
Vascular phenotype : “CVD”
 Arteriosclerosis
 Amyloid angiopathy
 Other small vessel disease
“Y have got to be before y can do
ou ou
and do before y can have”
ou

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 com itm is a heart felt prom to
m ent ise
yourself fromwhich y will not back down -
ou
D. Mcnally

38. Diagnosis and prognosis contd….
Localisation / Clinical phenotype or
neural network syndrome
Cortico-basal ganglia – Lacunar state
thalamocortical loops Apathy, depression, abulia
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
4 sets of criteria are used Sens
Spec
1. Hachinski ischemic score 89%
89%
< 4 AD / 18, > 7 MID / 18
2. DSM IV 43%
95%
Every discovery contains an irrational 50%
3. NINDS – AIREN element or
98% 4 creative intuition
4. ADDTC criteria 50% Popper
Khrl

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
function symptoms and signs
Unlikely to respond to May respond to a drug
treatment which modifies
microcirculation and
enhance cerebral tissue

41. VaD
• ChE-I espescially Galantamine is found
effective in VaD +/- AD
• Pseudobulbar palsy with emotional
incontinene responds to SSRI , TCA or
levadopa

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 destroy the bridge
s
over which he him m pass” - Annoy
self ust

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 foe may prove a curse ; but
A open
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
It antagosists, - ? Rivastigmine
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

46. Care and Cure !

47. Mx of neuropsychiatric
problems
 An acurate diagnosis for both
dementing illness and concomitant
psychiatric symptoms
 Treatment of psychiatric problems
reduce the distress of patient as well as
caregiver

48. Mx 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

49. Mx …
• Apathy -
Methylphenidate,dextro-amphetamine
Modafenil
• Insomnia -
Trazadone , Zolpidem
• Delusion- atypical antipychotics
• Depression -
SSRI, comb. RI eg. Venlafaxin,Mirtazepin

50. 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

51. Therapy -- ? Future

52. Future therapies
• Recently,intranasal insulin – improves
cognitive function in AD who lack Apo E
• Gene therapy using nerve growth factor
administered by implantinggenetically
engineered autologous fibroplasts

53. 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

54. 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

55. Thank
You !