DEMENTIA – AN OVERVIEWDr. A.V. Srinivasan, Dr. S. Yogaraj, Dr. G. Sarala

Dr. A.V. SrinivasanAddl. Prof. of Neurology

Institute of NeurologyChennai – 600 003

GLOSSARY OF TERMS 1) MCI2) Dementia3) Amnesia

a) Retrograde Amnesiab) Anterograde Amnesia

4) Amentia5) Senescence (Benign forgetfulness )

Mind is the great level of all things;

human thought is the process by which human ends are ultimately answered

- Daniel Webster

PHONE CALLS / HISTORY

• What is the patient’s predominant neurologic condition? In addition to memory loss, is there confusion, agitation, delirium or stupor?

• Is this new memory dysfunction or does the patient have known dementia?

• How old is the patient?

• Does the patient have acute medical problems?

In all of us, even in good men, there is a wild - beast nature which peers out in sleep

Elevator Thoughts / Walking ThoughtsV (vascular): Cerebral infarction, Multiple strokes

I (infectious): Syphilis, Chronic meningitis

T (traumatic): Subdural hematoma, head injury

A (autoimmune): CNS vasculitis, Multiple sclerosis

M (metabolic/toxic): Renal failure, Hepatic failure

I (idiopathic/inherited): TGA, Alzheimer’s disease

N (neoplastic): Brain tumour, Meningeal carcinomatosis

S (seizure, pSychiatric, structural): Complex partial seizure, postictal state

Thinking is the hardest work there is, which is probable reason why so few engage in it.

- Henry Ford

Selective Physical Examination

• HEENT

• Cardiopulmonary

• Abdomen

• Extremities

Success in life is a matter not so much of talent and opportunity

as of concentration and perseverance

- C.W. Wendte

Neurological Examination1) Mental status

a) Alertness

b) Aphasia

1) Fluency

2) Naming 3) Auditory comprehension of single and multi step commands 4) Repetition of unfamiliar phrases 5) Reading aloud 6) Writing 7) Listen for phonemic paraphasias

Habit is either the best of servants or worst of masters

- Nathaniel Emmons

Neurological Examinationc) Memory

d) Calculations

e) Hemineglect

f) Apraxia

g) Drawing

2) Motor

3) Coordination and gait

4) Frontal “release” signsIt is the disease of not listening, the malady of not marking,

that I am troubled withal

- Shakespeare

Classification of Dementia1) Aetiological classification2) According to localization of pathological

process3) Brain structures involved (cortical and

subcortical dementias)4) DSM & ICD multiaxial coding syste,

Of these, the etiological classification is the most commonly used one

Memory, the daughter of attention ,

is the teeming mother of knowledge

- Martin Tupper

Classification of Dementia

• Alzheimer’s disease (AD)

• Vascular Dementia (VaD)

• Lewy Body Dementia

• Pick’s Disease

• Reversible Dementia

We possess by nature the factors out of which personality can be made, and to organize them into effective personal life is every

man’s primary responsibility

- Harry Emerson Fosdick

Selected causes of potentially Reversible Dementia

Metabolic disorders Thyroid diseaseElectrolyte imbalanceRenal failureLiver failure

Adverse drug reactions Sedative hypnoticsBarbituratesAnticholinergicsMany others

Autoimmune disorders VasculitisLupus erythematosus

Time and Wo rds canno t be re calle d - Fulle r

Selected causes of potentially Reversible Dementia

Infections AIDS encephalopathySyphilisLyme encephalitis

Tumours PrimaryMetastatic

Poisoning Heavy metalsInsecticidesalcohol

Discipline Weighs ounces Regret weighs Tons

Selected causes of potentially Reversible Dementia

Nutritional Deficiencies Vitamin B6, B12ThiamineFolate

Psychiatric disorders Depression

Other Normal pressure hydrocephalusHead trauma

“Character gets you out of bed commitment moves you to action faith, hope and Discipline follow through to completion”

Frequency of causes of Dementia pooled from 32 studies

Cause Occurrence (%)

Alzheimer’s disease (AD) 57

Vascular Dementia 13

Depression 4.5

Alcohol 4.2

Normal pressure hydrocephalus 1.6

Metabolic 1.5

Medication 1.5

Neoplasm 1.5

Frequency of causes of Dementia pooled from 32 studies

Cause Occurrence (%)

Parkinson’s disease 1.2

Huntington’s disease 0.9

Mixed AD & VD 0.8

Infection 0.6

Subdural haematoma 0.4

Post-trauma 0.4

Others 7.1

Not demented 3.7

Management• Check the vital signs• Check the finger stick glucose level• Order the following laboratories tests stat:

Complete blood count (RBC)Chemistry panelErythrocyte sedimentation rate (ESR)Electrocardiogram (ECG)Chest X-RayUrinalysisToxicology screen and ethanol level (if indicated)

If the patient is too agitated to examine, follow the algorithm of delirium

Opinion is ultimately determined by the feelings

and not by the intellect

Selective History and Chart Review• What was the time course of onset of the patient’s

memory dysfuncion?• Has the patient started any new medication within the

time frame of the memory loss?• Is there any underlying medical illness?• Have there been other cognitive or behavioural

changes bedsides memory loss, such as difficulty making change in the grocery store, change in reading habits, or disorientation, particularly in the evening?

• Is there any history of head trauma?

The True Art of Memory is The Art of Attention - S.Johnson

Medications that may be associated with memory impairment

Corticosteroids Chlorpromazine

Isoniazid Anticonvulsants (overdose)

Benzodiazepines Interleukins

Barbiturates Methotrexate

Bromides Clioquinol (antifungal)

Success is a prize to be won. Action is the road to it.

Chance is what may lurk in the shadows at the road side.

- O. Henry

Management

Diagnostic Testing

1. Blood tests (Thyroid function tests, Venereal Disease Research Laboratory (VDRL) test, Vitamin B12 level, HIV testing (if indicated))

2. Imaging (CT, MRI, SPECT, PET, TGA)

3. Electroencephalogram (EEG)

4. Lumbar puncture

People of mediocre ability often achieve success because they don’t know enough to quit

- Bernard Baruch

TreatmentTreatment of Behavioral Dysfunction

1. Agitation, delusions or hallucinations/ illusions

2. Insomnia

3. Anxiety

4. Depression

At twenty the will rules

At thirty the intellect

At forty the Judgment

Disease specific Treatment of the Pathophysiologic Process

1. Alzheimer’s disease2. Parkinson’s disease, Lewy body disease

and progressive supranuclear palsy3. Normal pressure hydrocephalus4. Huntington’s disease5. AIDS dementia complex6. Transient global amnesia7. Wernicke-Korsakoff syndrome

Maintaining the right attitude is easier than

regaining the right mental attitude

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

Pathogenesis of dementia due to VaD

1. Lacunar hypothesis

2. Binswanger’s subtype of VaD

3. VaD with coexisting Alzheimer’s disease

Expert is one who think to his

chosen mode of ignorance

Clinical syndromes1. Lacunar state --- 85%2. Strategic infarct dementia(e.g. thalamic

dementia) --- unknown %3. Binswanger’s syndrome --- 10 – 15%

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

Features suggestive of vascular dementia

From the historyOnset associated with a strokeImprovement following acute eventAbrupt onset

From the examFindings typical of stroke e.g., hemiparesis, hemianopia

From imagingInfarct(s) above the tentorium

Every thing should be made as simple as possible; but not simpler

Patterns of blood supply to the cerebral hemispheres

Vascular distribution

Arterial supply Collateral supply

Cortex Corpus callosum

shorter Shorter

Sub cortical U fibers External / extreme capsules

Intermediate Intermediate

Inter digitating

Basal Ganglia Centrum semiovale / PVWM

Long

Long

Medical School can be a tool of torture or an Instrument of Inspiration”

Categories of vascular DementiaCategory Clinical presentation

Lacunar infarctions Progressive dementia, focal deficits, or apathetic, frontal-lobe-like syndrome, may have no stroke history

Single strategic infarctions Sudden onset aphasia, agnosia, anterograde amnesia, frontal lobe syndrome

Multiple infarctions Step-wise appearance of cognitive & motor deficits

Mixed AD – VaD Progressive dementia with remote or concurrent history of stroke

White matter infarctions (Binswanger’s disease)

Dementia, apathy, agitation, bilateral cortico-spinal/bulbar signs

Character gets you out of bed commitment moves you to action faith, hope and Discipline follow through to completion

DiagnosisVascular

distributionMechanism of Brain injury

Pathological phenotype “Infarct”

Single arterySmall arteriole

Acute ischemia Multiple lacunar infarcts

Single artery Acute ischemia Single strategically placed lacunar infarct

Border zoneSmall arteriole

Chronic hypo perfusion

White matter demyelination and axonal loss

It is the providence of the knowledge to speak and it is the privilege of the wisdom to listen - Hodly’s

Diagnostic criteria

1. Hachinski’s ischemic score

2. DSM IV criteria

3. ADDTC criteria

4. NINDS – AIREN criteria

5. Binswanger’s criteria

Give us the GRACE to acce pt with se re nity the thing s that canno t be chang e d the COURAGE to chang e the thing s that sho uld be chang e d and the WISDOM to kno w the diffe re nce

Short comings

1. Not interchangeable hence four fold rise in frequency

2. DSM IV R most liberal3. NINDS- AIREN criteria conservative4. 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”

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%

3. NINDS – AIREN 50% 98%

4. ADDTC criteria 50% 90%

Every discovery contains an irrational element or

4 creative intuition Khrl Popper

Clinical characteristics of Neuro behavioral syndrome of VaD

• Mental changes of dementia with single brain lesion

• Sub cortical infarcts

• Multi Infarct Dementia: -

• Sub cortical arteriosclerotic leukoencephalopathy

A great many people think they are thinking when they are merely re arranging their prejudices

W. James

AD Vs VaDAD 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 function Focal neurological symptoms and signs

Unlikely to respond to treatment May respond to a drug which modifies microcirculation and enhance cerebral tissue perfusion

The Truth is fear and immorality are two of the greatest inhibitors of Performance to progress

Prognosis

1. Risk factors

• Advanced age

• Education

• Lacunar subtype

• Lt. Hemisphere CVA

• Non white

Develops dementia following ischemic stroke

“ Fools Admire but of men of sense approve”- A. Pope

Prognosis contd….

2. In Lacunar stroke - Leukoariosis is

a poor prognosis

3. Recurrence of stroke

Hence

• Atrophy

• cognitive impairment

• WMSH are inter related in VaD

“ Social Isolation is in itself a pathogenicFactor for disease production”

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

Prevention and Treatment of vascular dementia

I. Brain at risk stage

The aged

Hypertensive

Smokers

Diabetics

Atrial fibrillators

Cardiac patients

Serious, sincere, systematic studies,

surely secure supreme success

II. Pre-dementia stage

Patients with TIA

Patients with stroke

Patients with subtle cognitive infarctions

Patients with silent cerebral infarctions

“Men of Genius Admired: Men of Wealth envied

women of power feared but only women of character are trusted”

A- Friedman

III. Dementia stage

Cardiac embolism

Atherosclerotic cerebrovascular disease

Hypertensive cerebrovascular disease

“Motivation is the Spark that lights

the Fire of Knowledge and

fuels the engine of Accomplishment”

Potential therapies of vascular dementia

1. Brain at risk stage

Smoking cessation

Exercise (prevention and management of diabetes)

Diet (control of diabetes, hyperlipidemias, obesity)

Antihypertensives (ACE inhibitors and ca++ channel- blockers maybe particularly suitable)

Lipid lowering agents

Anticoagulants (for atrial fibrillation)

Aspirin (for selected patients at high risk)

“Peace Rules the day where reason Rules the mind” Colling

2. Pre-dementia stage Carotid endarterectomy (symptomatic patients with

-carotid stenosis of 70-99%)AnticoagulantsAspirinTiclopidineAgents that interfere with amyloid deposition vesselsCa++ channel blockers (pre treatment to attenuate

-effect of infarcts)

“By Nature All Men/ Women are alike butby Education widely different”

- Chinese

3. Dementia stage

Antidepressents

Antihypertensives – 6 mm of Hg reduction in systolic or diastolic BP -reduces the risk of stroke by 40%

Cholinergics - Tacrine, Galantamine, rivastigmine, donepezil

NMDA antagonist – Memantine

Aspirin

Ticlopidine The Truth is fear and immorality are two of the greatest

inhibitors of Performance too progress

Prevention & Treatment

Anti dementia drug trials (not based on subtype of VaD)

Alkaloid derivatives

(hydergine or nicergoline)

Pentoxyfylline

Piracetam

Memantine

Donepezil

Gingko biloba

Modest benefit

“ He who cannot forgive others destroys the bridge over which he himself must pass” - Annoy

Role of RIVASTIGMINE in VaD

No.of patients : 15Age group : 50 – 80 yearsFemale : 6Male : 9Most of them had diabetes and hypertension Not based on subtype of VaD 30% showed remarkable improvement in cognitive, curative

and affective functions of the brainFuture study needed in pre dementia and dementia stages

Thought is the labour of the intellect

Reverie is its pleasure

Strategies to prevent – STROKE-TO-DEMENTIATEN-STEP APPROACH

1. Treat hypertension optimally2. Treat diabetes3. 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 fibrillation6. Provide antiplatelet therapy for high risk patients

A open foe may prove a curse ; but

a pretended friend is worse

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

READ not to contradict or confuteNor to Believe and Take for Granted but TO WEIGH AND CONSIDER

THANK YOU

“My Opinions are founded on knowledge but modified by experience”