Dementia pdf - د. الهام الجماس

Fifth stage

Medicine

Lec-2

د.الهام

5/3/2017

Dementia

 Definition

 Diagnostic criteria

 Epidemiology

 Differential diagnosis typical features and treatment of certain dementia syndromes

Definition

 Dementia is a clinical syndrome characterised by a decline of intellectual

function in comparison with the patient’s previous level of cognition.

 Social and occupational activities and behaviour are also influenced.

 A decline in the activities of daily living (ADL) often accompanies first two.

Criteria

 DSM IV Criteria for the dementia:

 Development of multiple cognitive deficit including memory impairment and at

least one of the following:

 aphasia

 apraxia

 agnosia

 executive functioning disturbance

 The cognitive deficit must,

 be sufficiently severe to cause impairment in occupational and social

functioning.

 represent a decline from a previous higher level of functioning.

 Aphasia: is a language disorder that affects ability to comprehend or express spoken

or written language or both.

 The term apraxia is defined as inability to correctly perform learned skilled

movements with the arms etc.

 no weakness,

 no ataxia,

 no seizure,

 no involuntary movement

 Agnosia can be defined as inability to recognise familiar objects, faces, sounds or

words.

 perception, (normal)

 memory, (normal)

 language (normal)

 intellectual function(normal)

o DSM IV Criteria for the dementia:

 Diagnosis should not be made if the cognitive deficits occur exclusively

during the course of delirium.

 Dementia may be etiologically related to a general medical condition, to

the persisting effects of the substance abuse (including toxin exposure),
or to a combination of these factors.



Over 65, about 5-10 percent of population has some kind of cognitive decline.



This ratio reaches, 20-50 percent of all population in the age of 85.



Dementia is a health problem both for the developed and developing countries.

Epidemiology II

1980

2000

2025(est)

Developing world

Developed world

Classification of dementias – I

 Primary degenerative dementias

 Dementia pure: neurodegenerative disorders primarily involving cerebral

cortex

 Alzheimer’s disease

 Focal degenerations

 Dementia plus: neurodegenerative disorders involving additional brain areas

such as basal ganglia or other subcortical structures

 Dementia with Lewy bodies

 Parkinson’s disease

 FTD-Parkinsonism-17; FTD with motor neuron disease

 MSA

Alzheimer

disease

60%

Lewy body

disease

20%

Vascular

15%

Others

 Corticobasal degeneration

 PSP

 Huntington diseae

 Some forms of SCA

 Familial multiple system taupathy

 Progressive subcortical gliosis

Classification of dementias – II

 Secondary forms of dementia

 Disorders damaging the brain tissue directly

 Vascular-ischaemic causes

 Infections

 Demyelinating disorders

 Inborn metabolic disorders

 Traumatic brain injury

 Post-radiation dementia

 Some brain tumors

 Parasitic cysts or brain abscess

 Disorders changing intracranial contents and distorting brain structures

 Normal pressure or obstructive hydrocephalus

 Subdural or intraparenchymal haematoma

 Primary or metastatic brain tumors

 Systemic diseases or conditions affecting the brain

 Metabolic-nutritional

 Endocrine

 Toxic

 Systemic immune-mediated or inflammatory disorders

Dementia: Differential diagnosis
Pseudo-dementia of depression

Clinical Picture Pseudo-dementia

Dementia

Mode of onset

Rapid, with change in behaviour Insidious, months and years

Mood/behaviour

Stable or apathy, depressed Fluctuating, normal to apathy or

irritable

mood

Intellectual functions Complains more,

Objective deficits on tests, but

but neuropsychological testing, patients tend to minimize or rationalize

reveals good results.

errors.

Reason for Self-referral, anxious about AD Patients are brought by their family
consultation members who notice change

in the memory or behaviour.

Dementia: Differential diagnosis:
Dementia vs Delirium

Feature

Dementia

Delirium

Onset

Insidious

Sudden

Duration

Months to years

Hours to days

Course

Progressive

Fluctuating

Attention

Normal

Fluctuating arousal

and inattention

Speech

Normal

Slurred, incoherent

Language

Aphasic

Anomia, dysgraphia

Memory

Learning deficit (AD)

Encoding deficits

Cognition

Acalculia, concrete (AD)

Disorganized

Awareness

Impaired

Motor signs

None

Tremor, and asterixis

EEG

Mild-diffuse slowing

Moderate to severe

diffuse slowing

Dementia: Differential diagnosis:
Cortical vs Subcortical

Disease Groups Can Present as Pure Dementia I

 Space- Occupying Lesions

 Neoplasm

 Normal-pressure hydrocephalus

 Subdural hematoma

 Parasitic cyst, brain abscesses

Feature

Cortical dementia

Subcortical dementia

Onset

Insidious

Duration

Months to years

Course

Progressive

Progressive or constant

Attention

Normal

Normal (slow response time)

Speech

Normal

Hyphophonic, dysarthric, mute

Language

Aphasic

Normal or anomic

Memory

Learning deficit (AD)

Retrieval deficit

Cognition

Acalculia, concrete (AD) Slow

Awareness

Impaired

Usually preserved

Motor signs

None

Tremor, chorea, rigidity, dystonia

EEG

Mild-diffuse slowing

Normal-mild slowing

 Infectious Organisms

 HIV

 Syphilis

 Herpes simplex

 Lyme disease

 Whipple’s disease

 Nutritional-Metabolic-Toxic

 Wernicke-Korsakoff disease

 Chronic alcoholism

 B12 deficiency

 Pellegra

 Organic solvent exposure

 Heavy metal intoxication

 Hepatic encephalopathy

 Immune Inflammatory

 Paraneoplastic limbic encephalitis

 Systemic lupus

 Cerebritis associated with collagen-immune diseases

Disease Groups Can Present as Pure Dementia II

 Vascular Disease

 Multiple infarcts

 Binswanger’s disease

 Various arteritides

 CADASIL

 Storage Diseases

 Metachromatic Leukodystrophy

 Kuf’s disease

 Prion Diseases

 Creutzfeld-Jacob

 Fatal familial insomnia

 Primary (degenerative) Neuronal Diseases

 Alzheimer’s disease

 Focal atrophies (frontotemporal dementia, primary progressive aphasia)

 Pick’s disease

 Diffuse Lewy body disease

 Hereditary taupathies

Diseases that can present with sensory- motor deficits +
dementia

 Parkinson’s disease

 Progressive supranuclear palsy

 Cortico-basal ganglionic degeneration

 Huntington’s disease

 Wilson’s disease

 Hallervorden-Spatz disease

 Spinocerebellar ataxias

 Amyotrophic lateral sclerosis

 Multiple sclerosis

 Gerstmann-Sträussler-Scheinker disease

 Kuru

Treatable Dementias

Thyroid disease

B12 deficiency

Thiamine deficiency (Wernicke’s encephalopathy)

Pellegra

Alcohol

Hepatic encephalopathy

Normal- pressure hydrocephalus

Sub-dural haematoma

Benign brain tumors

Chronic meningitis

Abscess

Cyst

Alzheimer’s Disease (AD): Genetics, prevalence, risk
factors I

 In 5-10 % of AD patients disease shows an autosomal dominant trait.

 It’s onset is at 30s or 40s.

 APP (chromosome 21), presenilin1(chromosome 14) and presenilin2

(chromosome 1) mutations cause this type of inheritance.

 All of them result in excessive production of insoluble ß amyloid .

 In patients with Down syndrome the AD pathology occurs when they are

30-40 years old because of the over-production of ß amyloid due to the
existence of an extra chromosome 21.

Alzheimer’s Disease (AD): Genetics, prevalence, risk

factors II

 In 90-95 % of the patients AD does not show an autosomal dominant transmission.

 The disease onset is at about their 65s.

 But in this group, some of the patients come from the families where the prevalence

of AD is higher than general populations (nondominant familial AD).

 The rest of the patients comes from families, their prevalence of AD is similar to that

of the general population (sporadic AD).

Alzheimer’s Disease (AD): Genetics, prevalence, risk
factors III

 The most important risk factor for AD is age. Prevalence doubles for every 5 years

after the age of 65 (10%) and reaches 40% among those older than 85.

 Head injury, female gender and a positive family history are other known risk

factors.

 An additional risk factor has been linked to chromosome 19 that encodes

apolipoprotein E (ApoE).

 The e4 allele frequency is 20% in the general population and 40% in AD.

AD: Clinical Picture
(ABC’s of AD)

 AD is an amnestic dementia with an insidious onset and indolent course.

 It causes disturbances in daily living activities, behavioural symptoms and cognitive

decline.

 Diagnosis death about 15-20 years.

 Symptoms change as the pathology of the disease progresses.

Neuro-psychiatric Symptomatology in AD

AD: Initial Stage I

 Memory problems

 forgets names, repeat themselves, misplaces their belongings, makes lists

 may fluctuate in intensity, good for remote events and recent events with high

emotional impact.

 poor for ordinary recent events

 clues and multiple choices are useful.

AD: Initial Stage II

 Language and behavioural problems

 speech becomes less fluent and loses spontaneity.

 difficulty in word finding.

 Self awareness of impairment may elicit depression.

100

Percentage

 may keep working, especially when he/she is protected by understanding staff in

his/her office.

 may have some difficulties in choosing dress, complex financial tasks.

 may keep house, pay bill, drive car, participate social activities

AD: Intermediate Stage I

 Memory problems

 recognition difficulties (forgets remote events)

 forgets faces

 inability to use clues or lists

 spatial orientation disturbances (getting lost in unfamiliar environment)

 inability to store new data (even for minutes)

AD: Intermediate Stage II

 Language and behavioural problems

 word finding difficulty in ordinary conversations

 increased misunderstanding

 become indifferent to their symptoms, depression subsides.

 paranoid ideation (spousal infidelity, stolen personal object due to

misplacement)

 sun downing (worsening of cognitive and behavioural symptoms at the end of

the day)

 Independency in housekeeping, dressing, bathing, grooming, paying bills are

gradually lost

AD: Final Stage I

 Memory problems

 living in past

 inability to recognize family members

 family members recognized as if they are not themselves (they recognized as

their imitations)

 getting lost even in familiar surroundings

 inability recognize home and rooms

AD: Final Stage II

 Language and behavioural problems

 incoherent speech

 loss of speech

 wandering

 purposeless movements

 crying

 agitation

 difficulties in moving and feeding, bathing, continence towards the end of

stage

 myoclonus, rigidity, gait difficulties

 become bedridden and death due to infections or emboli.

Regional distribution of pathology

 Distribution of pathology in AD is not random, but starts in transentorhinal cortex

and ends in neocortex

Clinical and laboratory diagnosis

 No lab. test for definitive diagnosis in a living patient.

 Biopsy or autopsy is gold standard

 The NINCDS-ADRDA criteria have been purposed to probable AD (PRAD).

 Post mortem confirmation studies revealed a 90 % or higher concordance with

criteria in diagnosis of PRAD

NINCDS/ADRDA Criteria for Alzheimer's Disease I

 Criteria for clinical diagnosis of Probable AD include:



Dementia established by clinical exam and documented by, confirmed
by further neuropsychological tests.



Deficits in two or more areas of cognition.



Progressive worsening of memory and other cognitive functions.



No disturbance of consciousness.



Onset between the ages of 40 and 90.

 Absence of systemic diseases or other brain diseases that could explain the cognitive

changes.

NINCDS/ADRDA Criteria for Alzheimer's Disease II

 The diagnosis of Probable AD is supported by:



Progressive deterioration of specific cognitive functions such as
language, motor skills, and perception (aphasia, apraxia, agnosia,
respectively).



Impaired activities of daily living.



Positive family history, particularly if documented neuropathologically.

 Lab results: Normal lumbar puncture, EEG, and evidence of cerebral atrophy on CT or

MRI.

NINCDS/ADRDA Criteria for Alzheimer's Disease III

 Other clinical features consistent with diagnosis of Probable AD, after exclusion of

other causes of dementia:



Plateaus in clinical course.



Associated symptoms: depression, insomnia, incontinence, delusions,
illusions, hallucinations, catastrophic verbal, emotional, or physical
outbursts, sexual disorders, and weight loss.



Other neurological abnormalities in some patients, especially with more
advanced disease and including motor signs such as increased motor
tone, myoclonus, or gait disorder.



Seizures in advanced disease.

 CT normal for age.

NINCDS/ADRDA Criteria for Alzheimer's Disease IV

 Features that make the diagnosis of Probable AD unlikely or uncertain:

 Sudden apoplectic onset.

 Focal neurological findings such as hemiparesis, sensory loss, visual field

deficits, and incoordination early in the course of the illness.



Seizures

or gait disturbances at the onset or very early in the course of the

illness.

Laboratory tests

Routine

Optional

Blood glucose

CBC

Chest X-ray

Vitamin B

level

ECG

Thyroid function tests

EEG

AST, ALT

Drug levels

LDH

Urinalysis

BUN

HIV testing

Uric acid

Heavy metals in urine

Sedimentation rate

CSF analysis

Syphilis serology

PET/SPECT

CT, MRI

Treatment I

 Cognitive symptoms

 Centrally active cholinesterase inhibitors

 Donepezil (Aricept 5 mg) 1x1 at bedtime for 1 month then 1x2

 Rivastigmin ( Exelon 1,5; 3; 4,5 and 6 mg) 2x1 increase dose one step for

one week, max 2x6 mg

 Antioxidants

 Gingko biloba extracts

 Vitamin E

 Vitamin C

 Estrogens (as antioxidant and acetyl choline production enhancer)

 Anti inflammatory drugs

 COX-2 inhibitors

 Indomethasine

Treatment II

 Behavioural symptoms

 Psychotic features

 Typical neuroleptics (avoid in Lewy body dementia)

 Haloperidol

 Thioridazine

 Chlorpromazine

 Sulpiride

 Pimoside

 Atypical neuroleptics

 Clozapine(!) agranulocytosis

 Olanzapine

 Risperidone

 Quetiapine

 Depressive features

(Avoid antidepressants with prominent anticholinergic effect)

 SSRI’s

 Fluoxetine

 Sertraline

 Citalopram

Treatment III

 SNRI’s

 Venlafaxine

 Sleep disturbances

 Trasodone

 Anxiety

 benzodiazepines

 beta blockers

 Mood Stabilisers

 Valproate Na

 Gabapentine

 Carbamazepine

 Lithium

Regional distribution of atrophy in the common
dementias

 Alzheimer’s disease:

predominantly parietal and temporal

 Frontotemporal dementia: predominantly frontal and temporal

 Dementia with Lewy bodies

: as for AD, but with additional subcortical pathology

 Vascular dementia:

vascular distribution

Non-Alzheimer Dementias: Frontotemporal Dementia

 Early deterioration in social conduct, personality, initiative, insight and attention

 Rudeness, disinhibition and distractibility

 Speech--->Non fluent and reduced in quantity

 Visio-spatial abilities, EEG and memory are normal (at least in the beginning).

 Familial forms are linked to the chromosome 17

 May occurs with parkinsonian symptoms and ALS in the same patient

Non-Alzheimer Dementias:
Lewy Body Dementia

 Cortex and sub cortical areas(basal ganglia and locus coeruleus) contain Lewy bodies

that is made of alfa synuclein as in Parkinson’s disease.

 Mild parkinsonian symptoms begin with dementia is the hallmark.

 Symptoms may fluctuate during the day

 Visual hallucinations and increased susceptibility to the typical neuroleptics are the

other key features

Non-Alzheimer Dementias:
Vascular Dementia

 National Institute of Neurological Disorders and Stroke (NINDS) criteria:

 Cerebrovascular disease (CVD) as defined by the presence of focal signs on

neurologic examination such as: hemiparesis, facial weakness, Babinski sign,
sensory deficit, hemianopia, dysarthria consistent with stroke (with or without
history of stroke).

 Evidence of relevant CVD by brain imaging including multiple large-vessel

infarcts or a single strategically placed infarct (angular gyrus, thalamus, basal

forebrain), as well as multiple basal ganglia and white matter lacunes or
extensive periventricular white matter lesions, or combinations thereof. Other
criteria include.

 Any combination of onset of dementia within 3 months following a recognised

stroke.

 Abrupt deterioration in cognitive functions.

 Fluctuating or stepwise progression of cognitive deficits.

 Hypertension.