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 disease1
Frontotemporal lobar degeneration0.01
<1 1-5 6+ 16+ 30+ 40+ 50+ 60+ 70+ 80+

Pathophysiology

Genetics
  • 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

Management

Non-pharmacological management
  • 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