Alzheimer's

• Alzheimer's dementia:

  • Most common cause of dementia in the UK - accounting for about half of all dementia diagnoses
  • Slightly more common in females
  • Tends to progress steadily over time
• Aetiology:

  • Amyloid plaques (clumps of beta-amyloid) and neurofibrillary tangles (bundles of filaments with neurones, mostly made from tau protein
  • Accumulation of these leads to a reduction in information transmission (affects Ach), and eventually to the death of brain cells
• Clinical features:

  • Usually develops after the age of 65
  • Memory impairment - short term memory
  • Visuospatial impairment - such as getting lost when driving
  • Language impairment - difficulty finding the right words
  • Late features include disorientation and behavioural changes
• Drug treatment:

  • Usually only offered in mild/early disease
  • Acetylcholinesterase inhibitors - donepezil, rivastigmine or galantamine
  • Memantine - blocks NMDA receptors
• NICE guidelines recommend using the MMSE to monitor the progression of Alzheimer's disease and to help determine when acetylcholinesterase inhibitors should be started to discontinued

  • should not be used for a diagnosis of dementia
• Amyloid plaques and neurofibrillary tangles result in a reduction in acetylcholine production

  So Acetylcholinesterase inhibitors are first line treatment - inhibit the break down of acetylcholine

  • Donepezil
  • Rivastigmine
  • Galantamine
• Risk factors:

  • Greatest risk factor is increasing age
  • Apolipoprotein E (APOE) gene - people who inherit a copy of APOE have an increased risk of developing Alzheimer's
  • Down's syndrome - have an extra copy of chromosome 21, which contains the gene that produces amyloid precursor protein = development of plaques
  • Family history - first degree relative
• Cognitive testing in specialty memory clinic:

  • Mini-mental state exam (MMSE): helpful in assessing severity and when to start medication
  • Montreal cognitive assessment (MoCA): similar to MMSE but considered more sensitive for detecting mild cognitive impairment
  • Addenbrooke's cognitive examination (ACE): more detailed test
  • The above tests would not be used in primary care due to the length of time they take to complete
• Cognitive tests in primary care/ED:

  • AMTS: very basic, can miss early dementia - most commonly used in the acute setting
  • 6-CIT: takes 2-3 minutes, includes takes that challenge attention and executive dysfunction so can detect early dementia - especially Alzheimer's and frontotemporal types
• Imaging:

  • gold standard = MRI, also good at excluding reversible causes such as hydrocephalus
• Contraindications to acetylcholinesterase inhibitors:

  • Bradycardia
  • Heart block