OVERVIEW OF DEMENTIA

DR. ALIM AKHTAR BHUIYAN

MBBS, DTM & H (U.K.), M.D. (U.S.A), POSTPOST- DOCTORAL FELLOWSHIP IN EPILEPSY (U.S.A) US BOARD CERTIFIED IN NEUROLOGY

CONSULTANT NEUROGOLIST, APOLLO HOSPITALS, DHAKA

DementiaDementia-What it means?
Key points:  Impairment of multiple domains of cognitive functions:  Memory impairment - Must----- a. New material learning b. Forget previous learning With at least one of the following cognitive disturbance: i. Aphasia-language disturbance ii. Apraxia- impaired ability to carry out motor activities despite intact motor function iii. Agnosia- failure to recognize/ identify familiar object despite intact sensory function iv. 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 Dementia
Global 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 Dementia

Scenario of Dementia
Developed countries
USA 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 dementias

Alzheimers disease Frontotemporal Dementia & Picks disease Dementia with Lewy bodies

A.

B.

Dementia (Alzheimers disease )

Pathology (Gross) : Every part of cerebral cortex is involved with relative sparing of occipital pole Marked atrophy, widened sulci Shrinkage of gyri Thinning of cortical ribbon Ventricular dilatation especially temporal horn, atrophy of amygdala & hippocampus

AD: a progressive CNS disorder with a characteristic pathology

Brain atrophy

Senile plaques

Neurofibrillary tangles

Katzman, 1986; Cummings and Khachaturian, 1996

Pathology of Vascular Dementia

Approach to Dementia
Key points
Determine presence of Dementia -Decision is solely & essentially clinical Determine primary degenerative/other potential treatable causes of dementia Co-morbid medical illness. Treatment of an intervening illness may reverse a worsening of dementia

Approach to Dementia
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 Dementia - History

Evaluation 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 - History

2. Time course & progression
EN NPH MID AD CZD

Weeks
    

Months

Years

Encephalitis MID-Stroke for stroke CZD NPH AD

Approach to Dementia - History

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 driving Danger
- to patient/others

Approach to Dementia - History

5. Etiologically directed history
 Vascular disease-Risk factors  Infections/toxic/metabolic/trauma  Psychiatric-depression, insomnia,agitation

6. Family history
 Dementia  Other diseases: Thyroid, Infections.

Clinical differentiation of Major Dementias

Disease AD Initial symptom
Memory loss

Mental status

Neuropsychiatry

Neurology
Initially normal

Imaging
Entorhinal & hippocampal atrophy Cortical or subcortical infarctions etc.

Episodic Initially memory loss normal

Vascular (VaD)

Often sudden, variable initial symptoms, focal lesions Apathy, reduced judgment,/insi ght/speech/ language, hyperorality

Frontal/exec Apathy, -utive delusions, cognitive anxiety slowing, can spare memory Frontal/ Apathy, executive, euphoria, language,spa depression re drawing

Usually motor slowing, spasticity, can be normal

FTD

Vertical gaze palsy,axial rigidity, dystonia

Frontal & or temporal lobe atrophy

Investigations in Dementia (contd.)

A. Routine:
1. Thyroid function test: eg. Hypothyroidism 2. Serum Vit. B12 Assay- Pernicious Anaemia 3. 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 disease 4. Electrolytes: Eg. Increased K+ in CRF, Addisons Disease

Investigations in Dementia (contd.)

B. Optional Focused Tests:
1. Chest Skiagram: Cardiomegaly- Stroke, Hypothyroidism, Anaemia, Alcoholism, Etc.  Ca- Bronchus  Pulmonary Tuberculosis  Vasculitis- SLE, Wegeners Granulomatosis  Sarcoidosis 2. CSF Study:  CNS INFECTIONS. Eg. HIV, Neurosyphilis  Decreased A42- 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 :

y maintenance of personal hygiene y safety y nutrition y 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 treatment
Non-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 - TCA, - MAOls, - Paroxetine - Benzhexol - Benztropine

Antidepressant : Anticholinergics :

- 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 treatment
Pharmacological (contd)
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 benzodiazepins- preferably short acting. -

Anxiolytics: in non aggressive agitation and insomnia;

Treatment of complications and comorbidities

Like Dementia other diseases rise with advancing age

Hypertension Diabetes mellitus IHD Heart failure Arthritis Infections

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 Rivastigmine Donepizil Galantamine Tacrine Mode of action AChE inhibitor ,, ,, ,, Global + + + + Efficiency in Cognitive Functional + + + + + + + ?

Tolerability ++ 1 ++1 ++1

++ : 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 its effectiveness in wide range of dementias relatively less S/E profile available in our country

*But its use may be limited for its relatively higher cost

NEW CLASS OF DRUGS USED FOR THE SYMPTOMATIC TREATMENT OF DEMENTIAS NMDA Receptor Antagonist : MEMANTINE
receptor antagonist

An uncompetitive moderate affinity N-methyl-D-aspartate 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 Also helpful in mild to moderate vascular dementia;

psychomotor functioning, benefit in activities of daily living, reduction of care dependence & excellent tolerability in AD

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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