Alzheimer’s Disease

Question 1

What is the most common cause of dementia?

Answer 1

Alzheimer’s disease is the most common cause of dementia.

Question 2

Types of dementia

Answer 2

Alzheimer’s disease (AD): 50-75%
Vascular dementia (VD): 20%
Dementia with Lewy body (DLB): 15-20%
Frontotemporal dementia (FTD): 2%
Rare causes: Parkinson’s disease dementia (PDD), Huntington’s disease (HD), Prion disease, others.

Question 3

Aetiology of dementia - overview

Answer 3

Age: older age is a major risk for AD
Genetics*: most cases of AD are sporadic. Small number of inherited causes exist (<5%, autosomal dominant inheritance). Inherited causes suggested by early-onset disease. Mutations in the amyloid precursor protein (APP) and presenilin genes (PSEN1, PSEN2) have been identified.
Cardiovascular disease: smoking and diabetes increase risk. Exercise decreases risk.
Depression
Low educational attainment
Low social engagement and support
Others: head trauma, learning difficulties.

Question 4

The neurodegeneration in AD is hypothesised secondary to altered … and … protein metabolism.

Answer 4

The neurodegeneration in AD is hypothesised secondary to altered amyloid and tau protein metabolism.

Question 5

The two key pathological changes in AD are … plaques and … tangles:

Answer 5

Senile plaques (SP): deposits of beta-amyloid (aggregation of protein with a beta-sheet secondary structure). Dense, insoluble. Occur outside of neurons (i.e. extracellular).

Neurofibrillary tangles (NFT): aggregations of hyperphosphorylated tau proteins. Typically occur in areas of the brain involved in memory. Promote neuronal cell death. Form inside neurons (i.e. intracellular)

Question 6

What are the clinical features of dementia? Specifically, Alzheimer’s?

Answer 6

Cognitive impairment: poor memory, disorientation, language problems
Behavioural and psychological symptoms of dementia (BPSD): agitation, depression, sleep cycle disturbance, motor disturbance
Disease-specific features: AD is characterised by early impairment of memory. This manifests as short-term memory loss and difficulty learning new information
Activities of daily living: an increasing reliance on others for assistance, problems with high-level functioning (e.g. work, finance), problems with basic personal care

Question 7

In dementia patients - A formal mental status examination should be completed using a recognised …

Answer 7

Cognitive assessment tool - domains assessed:
Attention and concentration
Recent and remote memory
Language
Praxis: planned motor movement (e.g. perform a task)
Executive function
Visuospatial function

Question 8

Before diagnosing dementia, it is essential to exclude all alternative causes
What is done first?

Answer 8

Referral to a memory clinic - patients here undergo a formal history and examination (including medication review), full complement of baseline investigations inc bloods and neuro imaging to exclude an underlying cause, and a formal cognitive assessment.
During these, the specific type of dementia may become apparent

Question 9

Alzheimer’s disease may become apparent at memory clinic based on the following…

Answer 9

lack of other neurological symptoms, absence of major cardiovascular risk factors and predominant impairment in memory, thinking and behaviour

Question 10

Diagnostic criteria for dementia - 3 key components include

Answer 10

Functional ability
Cognitive domains (>2 domains)
Differentials excluded

Question 11

Define mild cognitive impairment

Answer 11

This describes cognitive deficits in one or more of the major cognitive domains, but the deficit is insufficient to interfere with independence in daily activities.

Mild cognitive impairment is an increasingly important term because it helps identify patients at risk of progression to dementia. Patients should have regular follow-up and be advised to undertake healthy brain activities (e.g. exercise, socialising).

Question 12

The main differentials to exclude in a patient with features of dementia are the three ‘D’s’:

Answer 12

Depression (and other psychiatric disorders): psychosis can be a feature of dementia.
Drugs: consider drugs with anti-cholinergic effects (e.g. anti-histamines, anti-psychotics, anti-epileptics)
Delirium: acute confusional state. May be prolonged recovery following episode.

Question 13

Bloods to order in suspected dementia patient (8)

Answer 13

Full blood count
Erythrocyte sedimentation rate (ESR)
Urea and electrolytes
Bone profile
HbA1c
Liver function tests
Thyroid function tests
Serum B12 and folate levels

Question 14

Overview of management of dementia

Answer 14

Assess capacity + advanced care planning
Physical and mental health
Driving - DVLA
Pharmacological management
Non-pharmacological
Managing BPSD
Care plans
End of life care

Question 15

Mild to moderate AD - what pharmacological therapy is indicated?

Answer 15

Acetylcholinesterase inhibitors (e.g. donepezil, revastigmine)

Question 16

Moderate to severe AD - what pharmacological therapy is indicated?

Answer 16

N-methyl-D-aspartic acid receptor antagonist (e.g. memantine). May be used in combination with acetylcholinesterase inhibitors.

Question 17

… has modest effects in patients with moderate-to-severe AD in terms of reducing functional decline.

Answer 17

Memantine has modest effects in patients with moderate-to-severe AD in terms of reducing functional decline.

Question 18

… inhibitors are associated with small improvements in cognition, neuropsychiatric symptoms, and ADLs in patients with mild-to-moderate AD. However, there is conflicting evidence on there impact on long-term outcomes (e.g. need for care home, effect on critical ADLs).

Answer 18

Acetylcholinesterase inhibitors are associated with small improvements in cognition, neuropsychiatric symptoms, and ADLs in patients with mild-to-moderate AD. However, there is conflicting evidence on there impact on long-term outcomes (e.g. need for care home, effect on critical ADLs).

Question 19

Alzheimer’s medication options? (3)

Answer 19

Donepezil, rivastigmine, memantine