OVERVIEW OVERVIEW OF OF

DEMENTIADEMENTIA

DR. ALIM AKHTAR BHUIYANDR. ALIM AKHTAR BHUIYANMBBS, DTM & H (U.K.), M.D. (U.S.A),MBBS, DTM & H (U.K.), M.D. (U.S.A),

POST- DOCTORAL FELLOWSHIP IN EPILEPSY (U.S.A)POST- DOCTORAL FELLOWSHIP IN EPILEPSY (U.S.A)US BOARD CERTIFIED IN NEUROLOGYUS BOARD CERTIFIED IN NEUROLOGY

CONSULTANT NEUROGOLIST,CONSULTANT NEUROGOLIST,APOLLO HOSPITALS, DHAKAAPOLLO HOSPITALS, DHAKA

Dementia-What it Dementia-What it means?means?

Dementia-What it Dementia-What it means?means?

Key points: Impairment of multiple domains of cognitive functions: Memory impairment - Must----- a. New material learning

b. Forget previous learningWith at least one of the following cognitive disturbance:

i. Aphasia-language disturbanceii. Apraxia- impaired ability to carry out motor activities despite

intact motor functioniii. Agnosia- failure to recognize/ identify familiar object despite

intact sensory functioniv. Disturbence in executive functions

Significant impairment of social & occupational functioning- decline from previous level

Gradual onset, continuing cognitive decline with alert & normal arousal.(DSM IV)

Scenario of DementiaScenario of DementiaScenario of DementiaScenario of DementiaGlobal Situation 10% of all above 70 yrs. has memory

impairment

Of them 50% have AD

Annual rate of progression to Dementia is 15% Doubling the incidence of Dementia above 65 yrs for every five yrs.

50% above the age of 85 yrs have dementia.

Lancet 361: 2003

Scenario of DementiaScenario of DementiaScenario of DementiaScenario of Dementia

Scenario of DementiaScenario of DementiaDeveloped countriesUSA

Incidence – 4.8% , moderate to severe memory impairment

Dementia – 187/100000/year

AD – 123/100000/year

3-4 million patients

Race – White – 85%

– Black – 09%

– Others – 06% Victor & Ropper 2002

Primary degenerative Primary degenerative dementiasdementias

Alzheimer’s diseaseFrontotemporal Dementia & Pick’s disease

Dementia with Lewy bodies

A.

B.

Dementia Dementia (Alzheimer’s (Alzheimer’s disease )disease )

Pathology (Gross) :Every part of cerebral cortex is

involved with relative sparing of occipital pole

Marked atrophy, widened sulciShrinkage of gyriThinning of cortical ribbonVentricular dilatation especially

temporal horn, atrophy of amygdala & hippocampus

AD: a progressive CNS AD: a progressive CNS disorderdisorder

with a characteristic with a characteristic pathologypathology

Brainatrophy

Senileplaques

Neurofibrillary tangles

Katzman, 1986; Cummings and Khachaturian, 1996

Pathology of Vascular Pathology of Vascular DementiaDementia

Approach to DementiaApproach to Dementia

Determine presence of Dementia-Decision is solely & essentially

clinicalDetermine primary degenerative/other

potential treatable causes of dementiaCo-morbid medical illness. Treatment of an

intervening illness may reverse a worsening of dementia

Key pointsKey points

• Obtain a meticulous history (temporal profile)

• Rate of intellectual decline• Impairment of social function• General health & relevant disorders-

stroke, head injury• Nutritional status• Drug history• Family history of dementia• Occupational exposures - toxins

Approach to DementiaApproach to Dementia

• Age-Younger: Secondary cases-Older: AD/other primary dementia

• History- Meticulous history-Patient-Independent informate-Spouse

1. Patient difficulties•Difficulties patient having•Family member notice

Approach to Dementia - Approach to Dementia - HistoryHistory

EvaluationEvaluation

EN MID CZD NPH AD

Approach to Dementia - Approach to Dementia - HistoryHistory

2. Time course & progression

Weeks Months Years

Encephalitis MID-Stroke for stroke CZD NPH AD

3. Function of the patient At work At home Performance of basic activities of daily life

4. Issue of safety Driving

- accident, traffic violation, lost in drivingDanger

- to patient/others

Approach to Dementia - Approach to Dementia - HistoryHistory

5. Etiologically directed historyVascular disease-Risk factors Infections/toxic/metabolic/traumaPsychiatric-depression, insomnia,agitation

6. Family historyDementiaOther diseases: Thyroid, Infections.

Approach to Dementia - Approach to Dementia - HistoryHistory

Clinical differentiation of Major Dementias

Disease Initial symptom

Mental status

Neuropsy-chiatry

Neurology Imaging

AD Memory loss Episodic memory loss

Initially normal

Initially normal

Entorhinal & hippocam-pal atrophy

Vascular

(VaD)

Often sudden, variable initial symptoms, focal lesions

Frontal/exec-utive cognitive slowing, can spare memory

Apathy, delusions, anxiety

Usually motor slowing, spasticity, can be normal

Cortical or subcortical infarctions etc.

FTD Apathy, reduced judgment,/insight/speech/ language, hyperorality

Frontal/ executive, language,spare drawing

Apathy, euphoria, depression

Vertical gaze palsy,axial rigidity, dystonia

Frontal & or temporal lobe atrophy

Investigations in Dementia (contd.) A. Routine:

1. Thyroid function test: eg. Hypothyroidism2. Serum Vit. B12 Assay- Pernicious Anaemia3. Complete blood count (may give a clue):

Vitamin deficiency states Organ failure Endocrinopathies neoplastic conditions Toxic causes. eg, Basophilic Stippling of RBC

in lead poisoning Vacuolated lymphocytes in Niemann-Pick

disease4. Electrolytes:Eg. Increased K+ in CRF, Addison’s Disease

Investigations in Dementia (contd.) B. Optional Focused Tests:

1. Chest Skiagram:- Cardiomegaly- Stroke, Hypothyroidism, Anaemia,

Alcoholism, Etc. Ca- Bronchus Pulmonary Tuberculosis Vasculitis- SLE, Wegener’s Granulomatosis Sarcoidosis

2. CSF Study: CNS INFECTIONS. Eg. HIV, Neurosyphilis Decreased Aß42- Amyloid & increased tau protein in AD-

Not diagnostic

General principles of management

Aim of management : to achieve optimal daily function relieve distress provide practical help for patients & care givers

Attention must be paid to the : maintenance of personal hygiene safety nutrition take care of incontinence of bowel & bladder;

minor physical upset such as dehydration, constipation, bronchitis, urinary infection

Management of Dementia• Supportive treatment

– Non-pharmacological– Pharmacological

• Treatment of complications &

co-morbidities

• Symptomatic treatment

Supportive treatmentNon-pharmacological

• Advice, support and a sensible explanation are important for the caregiver

• Reduce excessive stimulation

• Divide tasks into small, simple steps; allow ample time

• Eliminate caffeine and alcohol

• Take their concern seriously

Drugs to avoid in Dementia

Antipsychotics : - Chlorpromazine - Clozapine - Olanzapine - Promazine - Thioridazine

Antidepressant : - TCA, - MAOls, - ParoxetineAnticholinergics : - Benzhexol

- Benztropine- Hyoscine

- Orphenadrine- Procyclidine

Note: Anticholinergic drugs may reduce the effects of anticholinesterase in all domains of efficacy: memory, activity, behaviour all may be worsened.

Supportive treatmentPharmacological (cont’d)

Commonly used drugs are-• Antidepressants: in general tricyclics and other

anticolinergic treatments are best avoided, if possible. SSRIs are better tolerated

• Neuroleptics: modest efficacy in improving behaviour, in-suspicious, hallucination -

sleeplessness and agitated behaviour

• Anxiolytics: in non aggressive agitation and insomnia; benzodiazepins- preferably short acting.

Treatment of complications and comorbidities

• Hypertension

• Diabetes mellitus

• IHD

• Heart failure

• Arthritis

• Infections

Like Dementia other diseases rise with advancing age

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.

Specific Treatment

Summary of AChE Inhibitors in Dementia

Drug Mode of action Efficiency in

Global Cognitive Functional Tolerability

Rivastigmine AChE inhibitor + + + ++ 1

Donepizil ,, + + + ++1

Galantamine ,, + + + ++1

Tacrine ,, + + ?

++ : good

? : evidence absent/equivocal

+ : moderate

1 : Tolerability depends on dose & speed of

- : Poor titration

For neurodegenerative dementias:

• No curative treatment is available till now

• Specific symptomatic treatment by ChE inhibitors remains the mainstay of treatment

• Amongst the ChE inhibitors, Rivastigmine is the most preferred one because of it’s-

• effectiveness in wide range of dementias• relatively less S/E profile• available in our country

*But it’s use may be limited for it’s relatively higher cost

NEW CLASS OF DRUGS USED FOR THE SYMPTOMATIC TREATMENT OF DEMENTIAS

NMDA Receptor Antagonist : MEMANTINE

•An uncompetitive moderate affinity N-methyl-D-aspartate receptor antagonist

•Recently approved in Europe and the USA for the treatment of moderate to severe AD. Also available in Mexico and in several South American countries

• Clinical data on memantine show benefit in cognitive and psychomotor functioning, benefit in activities of daily living, reduction of care dependence & excellent tolerability in AD

•Also helpful in mild to moderate vascular dementia; improves cognition consistently across different cognitive scales, with at least no deterioration in global functioning and behaviour

•Devoid of concerning side effects at daily dose of 20mg

CONCLUSION

Management of dementia should be multidirectional

It is important to identify the type and stage of dementia

Supportive care and treatment of comorbidity are important and common for all types

Treatable cause needs to be sought and sorted accordingly

Neurodegenerative dementias need symptomatic treatment with ChE inhivitors

Rivastigmine is possibly the best choice of ChE inhibitor so far and covers wider range for mild to moderate cases; donepezile is a suitable and cheeper alternative

Memantine is being tried for moderate to severe cases

Other treatment options are on the way

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