Degenerative diseases - Alzheimer's, Dementia Flashcards
What is dementia?
A description of a set of symptoms which show an acquired decline in memory and other cognitive functions in an alert person sufficiently severe to cause functional impairment and present for more than 6 months.
- An acquired loss in multiple domains of higher mental function
- A progressive decline
- Occurs in clear consciousness
What are the major causes of dementia?
- Alzheimer’s disease
- Vacular dementia
- Dementia with lewy bodies
- Fronto-temporal dementia
- Parkinson’s disease + dementia
- Reversible dementias
Name some rare causes of dementia
Vit B12 deficiency,
hypothyroidism, infective (HIV, syphillis, CJD), intracranial mass (subdural haematoma, hydrocephalus, tumour), Huntington’s disease, alcohol/drug use
Major causes of late onset demntia (>65)
Alzeimer’s (55%), vascular (20%), lewy body (20%), others (5%).
Major causes of early onset dementia
Alzeimer’s (33%), vascular (15%), fronto-temporal (15%), Others (35%) - huntington’s, infection (HIV), infalmmatory (MS), toxic (alcohol)
What is Alzheimer’s disease?
A chronic neurodegenerative disease that usually starts slowly and worsens over time. It involes the build up of amyloid plaques and neurofibrillary tangles within brain tissue.
It is a primary degenerative cerebral disease
Pathology of alzheimer’s
Tempero-parietal dementia
- Neruofibrillary tangles
- Senile plaques (amyloid B protein)
- Apoliprotein E4
- Cerebral atrophy
What is the pathogenesis of amyloid plaques in Alzheimer’s disease?
Abnormal breakdown of membrane Amyloid precursor proteins (involed in neuronal growth and repair), meaning that previously soluble breakdwon products are no longer soluble (Amyloid-beta). Clumps (plaques) of beta-amyloid form in between neurons, which disrupt conduction mechanisms. Plaques also illicit an inflammatory response, and cause amyloid angiopathy, which weakens vessel walls and increase risk of haemorrhage
What is the pathogenesis of neurofibullary tangles in Alzheimer’s disease?
The presence of amyloid plaques leads to the activation of kinase, which adds phophate groups to Tau proteins in the microtubules inside the neuronal cells. This causes a conformational change in Tau protein structure, which causes them to stop supporting microtubules, break away and form neurofibrillary tangles
What macroscopic changes occur due to neuronal cell death in alzheimer’s disease?
-
Atrophy
- Narrowing gyri
- Widening sulci
- Increased ventricular volume
What are the symptoms of alzheimer’s disease?
Progresses slowly over years
- Memory disturbance - short term memory first
- Global cognitive decline with intact personality
- Decline in launguage,
- Decline in executive function (planning)
- Disorientation - temporal = visuospatial skills
- Progresses to broad, often global cognitive dysfunction, behavioural change (eg agitation, aggression or apathy) and functional impairment (BPSD)
O/E May be increased tone
What is vascular dementia?
Dementia caused by problems in the supply of blood to the brain, typically a series of minor strokes, leading to worsening cognitive decline that occurs step by step
What are risk factors for vascular dementia?
- DM
- Hypertension
- Smoking
- Other vascular disease
How does vascular dementia present?
Problems occur in a stepwise fashion
- Frontal lobe, extrapyramidal, pseudobulber and emotional lability is common
- Urinary incontinence and falls without other explanation
- Executive dysfunction may predominate
- Gait abnormalities
What would you see in neuroimaging in someone with vascular dementia?
- Multiple large vessel infarcts
- White matter infarcts/periventricular white matter changes
What is dementia with lewy bodies?
A dementia syndrome that is characterized by the development of abnormal collections of (alpha-synuclein) protein within the cytoplasm of neurons (known as Lewy bodies)
How does dementia with lewy bodies present?
General
- Deficits of attention, frontal executive, visuospatial.
Of the following, Two = probable, One = possible:
- Fluctuations in cognitive function and alertness
- Prominent auditory and visual hallucinations - often with paranoia and delusions
- Parkinsonism
Commonly presents with falls due to visuospatial impairment
What drugs can worsen confusion in dementia with lewy bodies?
- Typical antipsychotics - haloperidol
- Levodopa
- Dopamine
How could you distinguish dementia with lewy bodies from delerium?
- Insidious onset
- No underlying illness found
- Complex hallucinations - not misrepresentation of stimuli
- Persistent delusions
- Antipsychotics worsen status
How would Parkinson’s disease with dementia present?
- Typical parkinsonian motor features
- Presentation variable - may resemble vascular, alzheimer’s or lewy body
- Often preceded by parkinson’s
What is frontotemporal dementia?
A group of disorders caused by progressive nerve cell loss in the brain’s frontal lobes or its temporal lobes. This invariably cause deterioration in behavior and personality, language disturbances, or alterations in muscle or motor functions.
There is frontal and temporal atrophy wihtout alzeimer’s histology.
What are the features of fronto-temporal dementia?
Early onset - insidious/slow
- Behavioural – personality change, often changes in eating habits (and eraly dysphasia)
- Speech disorder - altered output, stereotypy, echolalia, perseveration, mutism
- Neuropsychology - frontal dysexecutive syndrome. Memory, praxis and visuospatial function not severely impaired. Disinhibition.
- Lack of Insight - early on
Memory and visulo-spatial is relatively preserved
What are the core features of dementia syndrome?
A - activities of daily living
B - Behavioural and Psychiatric Symptoms of dementia
C - cognitive impairment
D - Decline
What are the cognitive features of dementia?
Memory
-
Dysmnesia (memory impairment), plus one of the following:
- Dysphasia - expressive/receptive
- Dyspraxia - inability to carry out motor tasks
- Dysgnosia - difficulty recognising objects
- Dysexecutive function
Functional
- ADL’s
What are the behavioural and psychiatric symptoms of dementia?
- Psychosis (hallucinations and delusions)
- Depression (and other mood disturbances) - in 30%
- Altered circadian rhythms
- Agitation/irritability
- Anxiety
- Agnosia
Personality change in 75%
What physical signs can be seen in dementia?
- Signs of vascular disease
-
Signs of late dementia
- Primitive reflexes
- Global hyperreflexia
When performing a mental state exam for someone with suspected dementia, what would you want to exclude as differential diagnoses?
- Delerium - Agitation, restlessness, poor attention, fluctuating consicousness
- Depression - low affect, poor motivation
What investigations would you do in someone with dementia to look for potetnially reversible causes?
- Bloods - FBC, U+E’s, B12, Folate, ESR, Calcium, LFT’s, TSH, CRP
- ECG
- CXR
- Consider EEG, Neuroimaging (vascular damage, haemorrhage or structural pathology?) or LP