Introduction
Alzheimer's disease (AD) is a progressive degenerative disease of the brain accounting for the majority of dementia seen in the UK.
Epidemiology
- Incidence: 300.00 cases per 100,000 person-years
- Peak incidence: 70+ years
- Sex ratio: 1:1
| Condition | Relative incidence |
|---|---|
| Alzheimer's disease | 1 |
| Frontotemporal lobar degeneration | 0.01 |
| <1 | 1-5 | 6+ | 16+ | 30+ | 40+ | 50+ | 60+ | 70+ | 80+ |
Pathophysiology
Genetics
Pathological changes
Neurofibrillary tangles
- most cases are sporadic
- 5% of cases are inherited as an autosomal dominant trait
- mutations in the amyloid precursor protein (chromosome 21), presenilin 1 (chromosome 14) and presenilin 2 (chromosome 1) genes are thought to cause the inherited form
- apoprotein E allele E4 - encodes a cholesterol transport protein
- risk factors include Down's syndrome
Pathological changes
- macroscopic: widespread cerebral atrophy, particularly involving the cortex and hippocampus
- microscopic: cortical plaques due to deposition of type A-Beta-amyloid protein and intraneuronal neurofibrillary tangles caused by abnormal aggregation of the tau protein. Hyperphosphorylation of the tau protein has been linked to AD
- biochemical: there is a deficit of acetylcholine from damage to an ascending forebrain projection
Neurofibrillary tangles
- paired helical filaments are partly made from a protein called tau
- tau is a protein that interacts with tubulin to stabilize microtubules and promote tubulin assembly into microtubules
- in AD are tau proteins are excessively phosphorylated, impairing the function
Clinical features
Symptoms
- Dementia (100%)
Management
Non-pharmacological management
Pharmacological management
Managing non-cognitive symptoms
Donepezil
- NICE recommend offering 'a range of activities to promote wellbeing that are tailored to the person's preference'
- NICE recommend offering group cognitive stimulation therapy for patients with mild and moderate dementia
- other options to consider include group reminiscence therapy and cognitive rehabilitation
Pharmacological management
- NICE updated it's dementia guidelines in 2018
- the three acetylcholinesterase inhibitors (donepezil, galantamine and rivastigmine) as options for managing mild to moderate Alzheimer's disease
- memantine (an NMDA receptor antagonist) is in simple terms the 'second-line' treatment for Alzheimer's, NICE recommend it is used in the following situation reserved for patients with
- → moderate Alzheimer's who are intolerant of, or have a contraindication to, acetylcholinesterase inhibitors
- → as an add-on drug to acetylcholinesterase inhibitors for patients with moderate or severe Alzheimer's
- → monotherapy in severe Alzheimer's
Managing non-cognitive symptoms
- NICE does not recommend antidepressants for mild to moderate depression in patients with dementia
- antipsychotics should only be used for patients at risk of harming themselves or others, or when the agitation, hallucinations or delusions are causing them severe distress
Donepezil
- is relatively contraindicated in patients with bradycardia
- adverse effects include insomnia