Neurology: Dementia Flashcards
1
Q
What is Dementia?
A
Clinical syndrome with multiple causes defined by:
- Acquired loss of higher mental function affecting two or more cognitive domains including episode memory, language function, frontal executive function, visuospatial function, apraxia
- Being of sufficient severity to affect ADLs
- Chronic condition (>6 months)
Dementia robs patients of their independence and serious burden on carers and a major socioeconomic challenge for society as a whole
2
Q
What are key parts of taking a dementia history?
A
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Memory:
- Is the patient repetitive, e.g. with questions?
- Is there a temporal gradient of amnesia – preservation of more distant memories with amnesia for recent events?
- Is there difficulty learning to use new devices, e.g. computer, mobile phone?
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Functional ability:
- Has work performance or ability to cook and do domestic tasks declined?
- Has responsibility for finances and administration shifted to the spouse?
- Does the patient get easily muddled?
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Personality and frontal lobe function:
- Has personality altered?
- More aggressive/apathetic/lacking initiative
- Disinhibition
- Change in food preference or religiosity
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Language:
- Difficulty with word finding or remembering names
-
Visuospatial ability:
- Does the patient get lost in familiar places?
- Difficulty dressing, e.g. putting jacket on the wrong way round
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Psychiatric features:
- Features of depression
- Tempo of progression
- Family history of dementia
- Alcohol and drug use
- Medication
- Any other neurological problems, e.g. parkinsonism, gait disorder, strokes
3
Q
What are examinations for Dementia?
A
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Bedside Cognitive Assessment
- Mini-mental state examination
- commonly used to assess cognitive function but has its limitations such as relative insensitivity to milder cognitive impairment and to frontal lobe dysfunction
- ACE is a tool used to address deficiencies of MMSE
- Clock drawing for visuospatial function
- Naming and reading tasks for language function
- Verbal fluency
- Frontal assessment battery: Conceptual similarity to abstract thinking and stop-go tasks
- Check for primitive reflexes such as grasp, palmo-mental and pout reflexes and preservation or utilization behaviour with frontal lobe involvement
- Mini-mental state examination
-
Test
- Limb praxis – copying hand gestures and miming tasks
- Oro-buccal praxis – show me how you would blow out candle
4
Q
What are investigations for Dementia?
A
- Blood Tests: Full blood count, Erythrocyte sedimentation rate, Vitamin B12, Urea and electrolytes, Glucose, Liver Biochemistry, Serum Calcium, Thyroid Stimulating Hormone, T3, T4, HIV Serology, Syphilis Serology
- Imaging: CT or MRI brain scan to exclude structural tumours or hydrocephalus. Radionuclide scan can also directly visualize the amyloid depositions
- Other (selected patients only): Cerebrospinal fluid, Genetic Studies, Electroencephalography, Brain Biopsy
- Detailed neuropsychiatric assessment: appropriate in most this quantification of relative involvement of different cognitive domains
- Younger patients (<65 years): more intensive investigation may be necessary such as EEG, Genetic tests, Voltage-gated potassium channel antibodies, anti-neuronal antibodies, HIV serology and metabolic tests
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CSF examination:
- Alzheimer’s disease – raised tau and reduced Aβ42
- Creutzfeldt-Jakob disease – Protein 14-3-3 increased
5
Q
What are the risk factors for Alzheimer’s Disease?
A
Genetics
- 1st degree relative with Alzheimer’s disease confers doubled lifetime risk of AD. Rare autosomal dominant monogenic ear-onset forms of familial AD with high penetrance caused by mutations in specific genes taken together for 1% of AD.
- Other genes are E4 allele, Amyloid precursor protein, Presenilin 1 and 2
Environmental
- Age
- Head trauma
- Vascular risk factors increase
6
Q
What are clinical features of Alzheimer’s Disease?
A
- Memory Impairment: episodic memory is affected. Progressive loss of ability to learn, retain and process new information. Relative preservation of distant memory and amnesia for more recent events.
- Language: Usually become impaired as disease advances. Difficulty with word finding characteristic.
- Apraxia: ability to carry out skilled motor activities is impaired
- Agnosia: failure to recognise object such as clothing and place or people
- Frontal executive function: organising, planning and sequencing is impaired
- Parietal presentation: visuospatial difficulties and difficulty with orientation in space and navigation may occur typically in later stages of disease
- Posterior Cortical Atrophy: least common presentation of AD. Memory initially well preserved
- Personality: basic personality and social behaviour remain intact until late AD
- Anosognosia: lack of insight by patient into their difficulties is common
- Tempo: onset insidious and progression gradual but inexorable over decade or longer with eventual deVere deficits in multiple cognitive domains
- Late non-cognitive features: myoclonus may develop followed by seizures. Sleep-wake cycle reversal and incontinence may place strain on carers. Motor function usually strikingly preserved so patient capable of wandering and getting lost
7
Q
What is the molecular pathology and aetiology of Alzheimer’s Disease?
A
- Deposition of β-amyloid (Aβ) in amyloid plaques in the cortex. Amyloid may also be laid down in cerebral blood vessels lead to amyloid angiopathy
- Structural and conformation changes in Tau protein which are binding blocks of neurofibrillary tangle. The protein aggregates damages synapses and ultimately lead to neuronal death
8
Q
What are investigations for Alzheimer’s Disease?
A
- MRI – characteristic atrophy of mesial temporal lobe structures including hippocampi, progressing eventually to generalized cerebral atrophy
- CSF tau and β-amyloid measurement is helpful in cases of diagnostic difficulty but not yet widely available
9
Q
What are early features of dementia with lewy bodies and parkinson’s diseases dementia?
A
- Visual hallucinations: often take form of people or animals or sense of presence
- Fluctuating cognition with variation in attention and alertness
- Sleep disorders
- Dysautonomia
- Parkinsonism
- Memory loss may be absent in early stages. Delusion and transient loss of consciousness occur.
- Lewy bodies, inclusion containing aggregates of protein α-synuclein first described in Parkinson’s disease, are found in the cortex.
10
Q
What are differences between dementia with lewy bodies and Parkinson’s disease dementia?
A
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In dementia with Lewy bodies
- cognitive features dominate
- parkinsonism may evolve later and is typically mild.
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In Parkinson’s disease dementia
- cognitive problems are late feature occurring at least 1 year after onset and usually after age of 75.
Both conditions respond to cholinesterase inhibitors. Patient with DLB may be very sensitive to neuroleptic drugs with dramatic worsening
11
Q
What is Vascular Dementia?
A
- Multiple infarct dementia, cerebral small-vessel disease and post stroke dementia. Most vascular dementias are of mixed cause
- Vascular dementia distinguished from AD by its clinical features and imaging
12
Q
What is the history of Vascular Dementia?
A
- Dementia can be progressive and similar to AD. Sometimes history of TIAs or dementia follow succession of cerebrovascular events and has stepwise course
- Apraxic gait disorder, pyramidal signs and urinary incontinence are common additional features
13
Q
What is the investigation for Vascular Dementia?
A
- Widespread small-vessel disease seen on MRI and may produce variety of cognitive deficits reflecting site of ischemic damage
14
Q
What is Frontotemporal dementia (Pick’s Disease)?
A
- Describe group of neurodegenerative disorders characterised by asymmetric frontal lobe and temporal lobe atrophy on MRI and at post-mortem
- There is no cure or specific treatment presently
15
Q
What is the pathology of Frontotemporal dementia (Pick’s Disease)?
A
- 25% cases are familial associated with mutations in tau and progranulin gene and C9ORF72 gene.
- Consists of deposition of abnormally aggerated proteins: phosphorylated tau, transactive response DNA-binding protein 43 or fused in sarcoma. 10% of patients have overlap syndrome with motor neurone disease or parkinsonian disorders such as progressive supranuclear palsy.
