MEDI7301 Final: Dementia

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apricotchimpanzee245

23 Jun 2018

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Department

Medicine

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MEDI7301

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multiple

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Dementia

Introduction Dementia is a syndrome characterised by progressive, usually irreversible, global

cognitive deficits

First symptom is generally memory impairment ---> progression to other

deficits including abstract thinking, judgement, verbal fluency (aphasia), orientation,

comprehension and ability to complete complex tasks (apraxia)

In addition to cognitive changes, dementia patients experience behavioural

change and non-cognitive sx called neuropsychiatric sx

oPersonality change, loss of impulse control, impaired social and

occupational functioning, deterioration in personal care

oMood changes including shallow euphoria with associated poverty

of thought

oDelusions - persecutory, misidentification of friends and relatives,

mirror images or TV perceived as real

Alzheimer's (62%), vascular (15%), Lewy body (4%), fronto-temporal (2%)

Neurobiology Alzheimer's

dementia

Hallmark of disease is amyloid plaques and NFTs

Amyloid plaques - insoluble B-amyloid peptide

deposits as senile plaques or B-pleated sheets, that are found in the

hippocampus, amygdala and cerebral cortex; greater density with

advanced disease

Neurofibrillary tangles (NFTs) containing

phosphorylated tau protein - location in cortex, hippocampus and

substantial nigra

Up to 50% loss of neurons and synapses in cortex and

hippocampus

Genetics (40% +ve family hx for Alzheimer's, autosomal

dominant)

Chromosome 21 contains gene for amyloid precursor

protein (APP)

Chromosome 19 contains gene for apolipoprotein E4

Chromosome 14 contains gene for presenilin 1 (B-

amyloid peptide)

Chromosome 1 contains gene for presenilin 11 (B-

amyloid peptide)

Vascular dementia Thromboembolic or hypertensive infarction of small and

medium sized vessels

Cognitive deficits following a single stroke

Severe cognitive deficit following certain midbrain and

thalamic strokes

Fixed or recovered; partial or complete

Multi-infarct dementia

Multiple strokes leading to stepwise deterioration in

cognitive function

Between strokes, there are periods of relative stability

Progressive small vessel disease (Binswanger disease)

Multiple microvascular infarcts of perforating vessels

leads to progressive lacunae formation and white matter leukoariosis

on MRI

Subcortical dementia with a clinical course

characterised by gradual intellectual decline, generalised slowing and

motor problems (eg gait disturbance and dysarthria)

Lewy body

dementia

Lewy bodies

Eosinophilic intracytoplasmic neuronal inclusions of

abnormally phosphorylated neurofilament proteins aggregated with

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ubiquitin and A-synuclein, found in brain stem nuclei (esp basal

ganglia), paralimbic and neocortical structures

Associated neuronal loss

Lewy neurites

Distinctive pattern of ubiquitin and A-synuclein

immunoreactive neuritic degeneration located in substantia nigra,

hippocampal region, dorsal vagal nucleus, basal nucleus basilis of

Meynert and transtentorial cortex

Alzheimer-type changes

Senile plaques in similar density and distribution,

fewer neurofibrillary tangles, less tau pathology

Frontotemporal

dementia

Macroscopic

Bilateral atrophy of frontal and anterior temporal

regional pathology

Degeneration of the striatum

Microscopic (3 subtypes)

Common 'microvacuolar' type (60%) - loss of large

cortical nerve cells, spongiform degeneration (microvacuolation) of

the superficial neurophil, minimal gliosis and no swellings or

inclusions in remaining nerve cells

Pick type (25%) - loss of large cortical nerve cells,

widespread gliosis, minimal or no spongiform (microvacuolar)

change, swollen neurons and inclusions +ve for tau and ubiquitin,

limbic system and striatum more seriously damaged

MND associated (15%) - demonstrate microvacuolar

histological features like MND

Etiology Reversible causes

Infection Creutzfeldt-Jakob disease (prion disease),

neurosyphilis, HIV, TB, subacute sclerosing panencephalitis

Endocrine Hypothyroidism, hyper-PTH, Cushings, Addisons

Metabolic Uraemia, hepatic encephalopathy, hypoglycemia, Ca

imbalance, Mg imbalance, electrolyte imbalance

Vitamin

deficiency

B12, folate, pellagra, B1

Other Normal pressure hydrocephalus

Epilepsy

Irreversible causes

Introduction All generally have early onset dementia; treat

problem to reverse cognitive impairment

Parenchymal/

degenerative

Alzheimer's disease, vascular dementia, fronto-

temporal dementia, Parkinson's disease, Huntington's disease, Wilson's

disease, MS, motor neuron disease, Lewy body disease, progressive

supranuclear palsy, corticobasal degeneration

Intracranial Tumour, head trauma, subdural hematoma, CVA

Toxins Prolonged alcohol misuse (it may be reversible if

little grey matter loss), heavy metal poisoning

Natural history Alzheimer's dementia is characteristically a disease of older age (usually after 65yo)

oGenerally 8-10 year decline

oGradual and progressive decline without distinguishing features

Vascular dementia has a stepwise progression of cognitive decline

oGenerally start with lacunar infarcts (small)

Lewy body dementia is abrupt with a rapid decline

oMortality generally within 1-2 years

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Pseudo-

dementia

A phenotype approximated by a wide variety of underlying disorders, including

depression, schizophrenia, mania, dissociative disorders, psychoactive drugs etc

Major subclass is depressive pseudodementia/ depressive dementia/ major

depression with depressive dementia

Older people exhibit symptoms consistent with dementia, but is actually

caused by depression

Symptoms include loss of memory and vagueness, slowing of movement,

reduced or slowed speech

Important to discern since dementia is untreatable vs depression is

treatable with anti-depressant and/or ECT

Pseudo-dementia vs dementia

Pseudo-

dementia

Abrupt and short onset

Memory test - often answer 'I don't know' and will not

try to answer it, intact attention and concentration, appear upset and

distressed

MMSE - generally lose marks on orientation and

memory, language intact

Dementia Insidious onset

Memory test - give 'wrong answers' despite best

intentions to get right, poor attention and concentration, appear indifferent

or unconcerned

MMSE - generally lose marks with working memory

and executive function

DSM-5 criteria Major neurocognitive disorder

Evidence of significant cognitive decline from a previous level of

performance in one or more cognitive domains (complex attention, executive function,

learning and memory, language, perceptual-motor or social cognition) based on

oConcern from the individual, a knowledgeable informant or clinician

that there has been a significant decline in cognitive function

AND

A substantial impairment in cognitive performance, preferably documented

by standardized neuropsychological testing or, in its absence, another quantified

clinical assessment

Cognitive deficits interfere with independence in everyday activities (eg at a

minimum, requiring assistance with complex IADLs such as paying bills of managing

medications)

Cognitive deficits do not occur exclusively in the context of a delirium

Cognitive deficits are not better explained by another mental disorder (eg MDD,

schizophrenia)

Mild neurocognitive disorder

Evidence of modest cognitive decline from a previous level of performance

in one or more cognitive domains (complex attention, executive function, learning and

memory, language, perceptual-motor or social cognition) based on

oConcern from the individual, a knowledgeable informant or clinician

that there has been a mild decline in cognitive function

AND

A modest impairment in cognitive performance, preferably documented by

standardized neuropsychological testing or, in its absence, another quantified clinical

assessment

Cognitive deficits do not interfere with capacity for independence in everyday

activities (eg complex IADLs such as paying bills or managing medications are preserved,

but require greater effort, compensatory strategies or accommodation)

Cognitive deficits do not occur exclusively in the context of a delirium

Cognitive deficits are not better explained by another mental disorder (eg MDD,

schizophrenia)

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Document Summary

Dementia is a syndrome characterised by progressive, usually irreversible, global cognitive deficits. First symptom is generally memory impairment ---> progression to other deficits including abstract thinking, judgement, verbal fluency (aphasia), orientation, comprehension and ability to complete complex tasks (apraxia) In addition to cognitive changes, dementia patients experience behavioural change and non-cognitive sx called neuropsychiatric sx o. Personality change, loss of impulse control, impaired social and occupational functioning, deterioration in personal care o of thought o. Mood changes including shallow euphoria with associated poverty. Delusions - persecutory, misidentification of friends and relatives, mirror images or tv perceived as real. Alzheimer"s (62%), vascular (15%), lewy body (4%), fronto-temporal (2%) Hallmark of disease is amyloid plaques and nfts dementia. Amyloid plaques - insoluble b-amyloid peptide deposits as senile plaques or b-pleated sheets, that are found in the hippocampus, amygdala and cerebral cortex; greater density with advanced disease. Neurofibrillary tangles (nfts) containing phosphorylated tau protein - location in cortex, hippocampus and substantial nigra.

MEDI7301 Final: Dementia

Document Summary

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