Dementia Flashcards
Dementia is a clinical syndrome with multiple causes. It is a progressive, debilitating disease, serious burden on carers and major socio-economic challenge for society.
How is dementia defined clinically?
- Acquired loss of higher mental function affecting 2 or more cognitive domains including:
=> episodic memory (acquisition of new information) - usually involved
=> language function
=> frontal executive function
=> visuospatial function
=> apraxia
- Sufficient severity to cause social or occupational impairment
- Chronic and stable (distinguishes it from delirium which is acute and fluctuating)
How common is dementia?
Dementia is becoming more common due to an ageing population.
> 65yrs = 6% prevalence
> 85yrs = 20% prevalence
What does the clinical assessment of dementia entail?
- A thorough history
- Collateral history from spouse or relative is essential
=> patients may downplay or deny symptoms (anosognia)
=> or constantly look to the relative for answers (head turning sign) - Bedside cognitive assessment - the mini-mental state exam
What exams are carried out during the bedside cognitive assessment exam?
- Mini-mental state examination (MMSE)
=> Limitations: insensitive to milder cognitive impairment and to frontal lobe dysfunction
=> Addenbrooke’s cognitive examination (ACE) addresses this limitation whilst being a bedside test - Assess episodic memory: ask for an account of recent news
- Individual cognitive domain tests:
=> Visuospatial function (parietal brain) - clock drawing
=> Frontal assessment battery - naming & reading tasks for language function, verbal fluency, conceptual similarity to test abstract thinking and stop-go tasks
=> Primitive reflexes (frontal lobe) - grasp, palmo-mental and pout reflexes, perseveration or utilisation behaviour
- Limb praxis: copying hand gestures e.g. ‘Show me how you brush your teeth’
- Oro-buccal praxis: e.g. ‘Show me how you blow out a candle’
6. Complete the neurological exam by looking for any evidence of: => papillooedema => parkisonism => myoclonus => gait disorders
What are the investigations for dementia?
- Blood test: FBC, ESR, vitamin B12, U&E, thyroid function, LFT, glucose, serum calcium
- MRI:
=> 1st choice in cognitive disorders
=> Identifies regional brain atrophy - distinguishes between different types of degenerative dementia
=> e.g. hippocampal atrophy in Alzheimer’s or temporal and frontal lobe atrophy in frontotemporal dementia - CT :
=> excludes structural lesions i.e. tumours or hydrocephalus
=> less anatomical resolution - Detailed neuropsychometric assessment
=> quantifies the involvement of different cognitive domains and may assess progression over time - Younger patients (<65yrs) :
=> more intensive tests i.e. EEG, genetic tests (Huntington’s; familial AD) - CSF examination:
=> measuring CSF protein markers
=> e.g. AD, CSF tay is raised and Abeta42 is reduced - New imaging modalities:
=> radionuclide scans
=> radioactive ligands bind to amyloid and allow direct visualisation of amyloid deposition in the brain
=> earlier and more accurate diagnosis potential
What is mild cognitive impairment ?
Intermediate state between normal cognition and dementia
Mild cognitive impairement can be pre-dementia
=> 10-15% develop overt AD per year
Causes of Dementia:
1. Degenerative: => Alzheimer's disease => Dementia with Lewy bodies => Frontotemporal dementia => Huntington's disease => Parkinson's disease => Prion disease e.g. Creutzfeldt-Jakob, prions
- Vascular:
=> Vascular dementia
=> Cerebral vasculitis (rare) - Vitamin deficiency: B12 and thiamine
- Trauma: severe or repeated brain injury
- Toxic:
=> Alcohol
=> Solvent misuse
=> Heavy metals
Causes of Dementia:
- Metabolic: Uraemia ; Liver failure
- Intracranial lesions:
=> Subdural haematoma
=> Tumours
=> Hydrocephalus
8. Infections: => HIV => Neurosyphillis => Whipple's disease => Tuberculosis
- Endocrine:
=> Hypothyroidism
=> Hypoparathyroidism - Psychiatric: depression causing pseudo-dementia
Alzheimer’s disease (AD) can only be diagnosed definitively by histopathology but sufficient clinical features are enough to diagnose it.
What are the clinical features of Alzheimer’s disease?
- Memory impairment
=> Episodic day to day memory affected
=> Loss of ability to learn, retain and process new information
=> Loss of working memory i.e. temporal gradient with relative preservation of distant memory and amnesia of recent events (short term memory loss) - Language impaired i.e. difficulty finding words
- Apraxia: impaired motor skills
- Agnosia: failure to recognise objects i.e. clothes, places, people
- Frontal executive function impaired i.e. organising, planning and sequencing
- Parietal impairment
=> visuospatial difficulties i.e. orientation in space
=> difficulty navigating - Basic personality and social behaviour intact until late AD unlike frontotemporal dementia
- Anosognosia: lack of insight into their problems
- Tempo:
=> insidious onset - not noticed by family members initially
=> gradual progression
=> eventual severe deficits - Late non-cognitive features
=> myoclonus followed by seizures
=> sleep wake cycle reversal
=> incontinence
=> motor function preserved so patient at risk of wandering and getting lost
=> impaired swallowing in severe case = aspiration pneumonia
What investigations are carried out in AD?
MRI
=> atrophy of temporal lobe inc. hippocampi
=> eventually progressing to generalised cerebral atrophy
Characteristic MRI and psychometric testing is sufficient to diagnose AD in presence of a clinical picture (progressive amnestic cognitive disorder in an older person)
CSF tau and beta-amyloid measurement may be helpful in diagnostic difficulty
The cause of AD is still unknown but molecular pathology is understood.
What is the underlying molecular pathology in AD?
- Deposition of beta-amyloid plaques in the cortex
=> amyloid precursor proteins (APP) processed by secretase enzymes to form pathogenic Abeta monomers
=> Abeta monomers polymerise to make amyloid plaques
=> beta-amyloid deposition pre-date clinical symptoms by ~25 years
- Hyperphosphorylation of tau proteins forming paired helical filaments => binding blocks of neurofibrillary tangles
=> tau proteins aggregate and damage synapses leading to neuronal death
- Basal forebrain cholinergic deficit
=> explains response to anti-cholinergic inhibitor drugs
What is the genetics underlying AD?
=> 2x risk if first degree relative with AD
=> Early onset familial AD = rare autosomal disorder
=> 2-3x increased risk with E4 allele of the apolipoprotein E gene
=> 6-8x increased risk with 2 copies of E4 alelle
=> Point mutations in amyloid precursor protein can cause AD + 3 copies of APP gene on chromosome 21 in Down’s syndrome = high incidence of AD
=> Presenilin 1 & 2: mutations affect gamma-secretase function. PS1 mutations = 50% monogenic AD
What are the environmental risk factors for AD?
Age - AD incidence increases exponentially with age
Head trauma
Vascular risk factors
What is dementia with lewy bodies (DLB)?
DLB characterised by early feature of:
=> visual hallucinations i.e. of people or animals or the sense of presence
=> fluctuating cognition i.e. attention, alertness
=> sleep disorder i.e. REM sleep behaviours disorder
=> dysautonomia
=> parkinsomism
=> delusions & transient loss of consciousness
=> Lewy bodies and aggregates of alpha-synuclein (found in Parkinson’s disease) found in cortex
How does dementia with lewy body differ to Parkinson’s disease dementia?
In DLB cognitive features dominate, mild parkisonism may develop later
V.S.
In Parkinson’s disease dementia, cognitive features are a late feature (>75yrs)
What is vascular dementia?
Common cause of dementia due to different mechanisms:
=> multi-infarct dementia
=> cerebral small vessel disease
=> post-stroke dementia
*most vascular dementia have a mixed cause
=> Hx of TIA’s
Additional features:
=> apraxic gait disorder
=> pyramidal signa
=> urinary incontinence
Widespread small vessel disease = typical MRI finding
