WELCOME

DEMENTIA

PRESENTED BY DR. AHMED TANJIMUL ISLAMGHORAR DIM, SOMCH

DSM – IV Criteria for Dementia Memory Impairment plus

• APHASIA (Deterioration of Language function)

• APRAXIA (inability to Execute Motor function)

• AGNOSIA (inability to Recognise or Naming of Object)

Disturbance in executive functioning

with• Impairment in occupational or social functioning

70% of dementia is Alzheimer’s

10-15% is Vascular dementia

10-15% Lewy Body dementias

5-10% Others

Overall Situation:

Alzheimer’s disease

70 %

Vacular Dementia

15-20%

Lewy Body Dementia

10-15 %

Others 5 %

Classification :

Types :

Dementia Classification:Primary (degenerative) dementiaSecondary dementia

Dementia Types:Cortical dementiaSubcortical dementia

PsudodementiaA group of disease due to functional disease rather than organic dementia• Depression• Hysterical Dementia• Psychogenic amnesia

Causes of Dementia

Primary Degenerative Dementia:•Alzheimer’s Disease

•Frontotemporal dementia

•Dementia with Lewy Body

Secondary Dementia:VITAMIN Deficiency

ENDOCRINE Chronic Infections

Thiamine B1

Hypothyroidism Neurosyphilis

B3 Adrenal deficiency

HIV

B12 Cushing Syndrome

Prions

Hypoparathyroidism

TOXIC Head Trauma:

Neoplastic

DIALYSIS DEMENTIA

Chronic Subdural Heatoma

Primary Brain Tumor

Drug Poisoning

Post Encephalatis

Secondary Brain Tumor

Heavy Poisoing

Normal Pressure Hydrocephalitis

Paraeoplastic

CORTICAL SUBCORTICAL MIXED

Alzheimer’s Parkinson’s Vascular Dementia

Frontotemporal Dementia

Huntington’s disease

Lewy body dementia

CJD Normal pressure hydrocaphalus

Neurosyphilis

SUBCORTICAL

CORTICAL

Memory impairment

moderate Severe

Mathemetical skills

Preserved Impaired

Mood depressed Normal

Motor speed Slowed Normal

Movements abnormal

Common Rare

mutism Absent Present

(REVERSIBLE DEMENTIA

IRREVERSIBLE DEMENTIA

D= Drugs, Delirium Alzhemer

E= Endocrine disorders

Lewy Body dementia

M= Metabolic Frontotemporal Dementia (Picks disease)

E= Emotional Parkinsons disease

N= Nutritional Huntington’s disease

T = Toxic, Tumor, Trauma

Cruze feltd jakob disease

A= Alcohol

IS IT DEPRESSION OR DEMENTIA??

VS

Depression Dementia:

Little effort on tasks

Struggles to complete tasks

Don’t know answers

Attempts answers, but incorrect

Absence of Dyspraxia,

Have Dyspraxias, Agnosias,

No language problem

Language problem

IS IT DELIRIUM or DEMENTIA ??

Is it Dementia??

Is it Depressio

n or

Dementia

Is it Delirium

or Dementia

Is it Alzheimer’

s??

Is There any

Reversable

Cause??

If not Alzheimer’s What is it??

ALZHEIMER’S DISEASE :

video

Alzeimer’s Disease

Loss of cholinergic

neurons

Senile plaques & neurofibrillary

tangels

Glutamate transmission dysfunctiion

30% symptoms

70% Symptoms

Alzheimer’s Staging:

Alzheimer’s

Pathology (Gross) :

Every part of cerebral cortex is involved with relative sparing of occipital pole

Marked Atrophy.

Widened Sulci

Shrinkage of Gyri

Ventricular Dilatation

AD: a progressive CNS disorder)

BrainAtrophy

**Senile Plaque

**Neurofibrillary Tangles

Pathology (HALLMARK)

Pathology of AD (Microscopic)

Pathology of AD (Microscopic)

Pathology of AD (Microscopic)

video2

Cholinergic deficit– progressive loss of

cholinergic neurones

– progressive decrease in available ACh

– impairment in ADL, behaviour and cognition

Hippocampus

Cortex

N. basalis Meynert

Pathophysiology of AD (Biochemical)

ALZHEIMER’S VASCULAR

Onset Incidious Sudden

Risk factors Family history CVD risks

Mental status Recent Memory

Psychomotor slowing

Neuro exam No Focal neuro deficit

Behavioral Delusion, Poor insight

Apathy, Depression

MRI Diffuse /Temporal atrophy

Stroke

ALZHEIMER’S

VASCULAR LBD FTD

Short term Memory Loss

Personality change

Parkinsonism

Prominent Behavior change

Dysphasia Dyspraxia

Labile Mood

Fluctuating Alertness

Expressive Dysphasia

Wandering Preserved Insight

Visual Hallucination

Early loss of insight

DEMENTIA:Common diagnostic strategies:

Clinical : History (from patient, family) Bedside Examination (e.g.

MMSE) Physical Examination

Neuropsychological Assessment. Imaging. Lab Screening for other causes.

History : Nature of the

problem Memory? Behavioral Emotional

Who perceives the problem? Patient? Family?

Tempo of the illness Gradual Fast

Stepwise

Family history

Other medical problems Neurological

(e.g. movement disorder)

Systemic (e.g. thyroid disease, vascular disease)

Examination of Higher Functions

BEDSIDE TESTS :

•MMSE

•CLOCK DRAWING

•ADAS cog (Alzeimer’d disease assesment scale cognitive)•Detailed Psychometry

COGNITIVE FUNCTION

BEHAVIOUR & PSYCHOLOGICAL FEATURES

ACTIVITY OF DAILY LIVING

DEPRESSION

MMSE Neuropsychiatric inventory

Bristol Scale Cornel Scale

Clock Drawing Test

Behave AD AD functional Assesment scale

Geriatric Depression Scale

Seven Minute Screen

Cohen Mansfield Aggression Inventory

Disability Assesment Dementia

Mental Test Score

Mini Mental State Examiation :

Staging of Disease by MMSENormal 27-30Mild 25-26Mild- Moderate 10-24Moderate- Severe 6-9Very Severe <6

Clock Drawing “Draw a clock and set the hands to

ten minutes to two” Marked out of ten e.g.

Perfect 10

Noticable palcement errors of the hand

8

Numbers & clock face not conected

3

uninterruptable 1

Imaging : Structural imaging (CT or MRI )

Exclusion of structural abnormalities Volumetric studies

Functional imaging PET SPECT

In A, MRI shows cortical atrophy

and ventricular enlargement.

In B, PET scan shows reduced glucose metabolism in the parietal lobes bilaterally (blue green) as compared with more normal metabolism in other cortical areas (yellow)

Probable Alzheimer’s Disease

BASELINE TESTS:

Baseline investigations for Dementia:CBC, ESR S. Electrolytes

Calcium, Phosphate Syphilis

Chest X ray HIV

CT, MRI Thyroid Function test

B12, Folate Liver function tests

EEG, ECG Renal Function Tests

Diagnosis Flow Chart:

HistoryMemory = Activity in

Daily Living

Cognitive Screening

Test

MMSE + CLOCK Drawing

Exclede Reversable causes by Baseline

Tests

Neuroimaging

MANAGEMENT OF DEMENTIA

Management :Dementia

Reduce Cognitive Symptoms

Reduce Behaviour Symptoms

Slow disease progression

Delay the Onset of Disease

Behavioral Strategy

Scheduled toileting, prompted voiding for incontinence.

Graded assistance, & positive reinforcement to increase functional independence

Music, esp. during meals, bathing Walking , Light Exercise

Management of Dementia

Supportive treatment Non-pharmacological Pharmacological

Treatment of complications & co-morbidities

Symptomatic Treatment of AD

. The mainstay of symptomatic treatment of AD, so far, is the cholinergic treatment strategies and most widely used, till now, are the Cholinesterase (ChE) inhibitors.

. These agents •Reduce the metabolism of acetylcholine

•Prolonging its action at cholinergic synapses.

Cholinesterase inhibitors: two classes exist for the treatment of Dementia

Class Inhibit

Dual ChE inhibitors

– Rivastigmine Both AChE

– Tacrine and BuChE

Single ChE inhibitors

– Donepezil AChE

– Galantamine

Weinstock, 1999

MEMANTINE NMDA receptor

antagonist Severe AD

Also useful in Vascular Dementia

Improves cognitive function

Improves the daily activity of life.

DELAY OF PROGRESSION:

Duration

Memantine alone 2-3 yearsMemantine + Ch E inhibitors

5-6 years

Ch E Inhibitors alone 1.5 years

Proposed or unregulated drugs which require further studies

Selegeline

Vit-E

Oestrogen

Prednisolone

NSAIDs

Ginkgo biloba

Statins

IVIg

Glycogen syntehtase kinase 3 (GSK 3)

β-secretase inhibitors

γ-secretase inhibitors

α-secretase enhancers

Immunotherapy

ALZEIMER’S VASCULAR FRONTOTEMPORAL

LEWY BODY

DONEPEZIL ChE Inhibitors

No ChE inhibitors

ChE inhibitors

RIVASTIGMIE

HMG CoA SSRI SSRI

GALANTAMINE

Stroke Prevent

Antipsychotics

Memantine

MEMANTINE Memantine Memantine Levadopa

SSRI Antipsychotic

Rivastigmine Cautions

Renal impairment Hepatic impairment Sick sinus syndrome Conduction abnormalities. H/O Asthma or COPD Pregnancy .

Transdermal Patch Technology: Reservoir versus Matrix

Nitti VW, et al Urology. 2006;67:657–64

Drug contained in adhesive layer along with polymer

Smaller and thinner than reservoir patches

Reservoir

Matrix

Drug contained in separate layer, with a rate-controlling membrane

Matrix DiffusionControlled Patch

Release Liner

Drug + Polymer + Adhesive

Backing

Rate-ControlledReservoir/Membrane Patch

Dermal Layer

Backing

DrugReservoir

Release Liner Adhesive Layer

Exelon Transdermal 9.5 mg/24 h Patch

Where to Apply Exelon Patch

Apply to: Upper and lower back

Upper arm Chest

The skin should be clean, dry and hairless before the patch is applied

Normal daily activities, such as bathing, are permitted

Exelon Transdermal Patch: Smooth Continuous Delivery Through the Skin

Exelon 6 mg BID capsule

Exelon 9.5 mg/24 h patch

Pla

sma

conc

entr

atio

n (n

g/m

L)

Exelon 9.5 mg/24 h patch delivered comparable average concentrations (AUC) to those provided by an oral dose of 6 mg BID (12 mg/day)*

* Model-predicted analysis based on actual patient data corrected for body weight.

0

5

10

15

20

25

0 6 12 18 24

Time (hours)

Starting transdermal ChEI therapy

Rivastigmine 4.6 mg/24 h

patch

Rivastigmine 9.5 mg/24 h

patch

Starting dose Target dose

4 weeks

One-step dose increase

When to Refer to SPECIALIST:

•Early Onset

•Presentation Atypical

•Severe Parkinsonism

•Focal Finding

•Behaviors seeming to be Untreatable

Thank You