Journals Club - Treating Alzheimer's disease

Dr Louise Newson, a GP in the West Midlands

Curriculum statement 9 Care of older adults

Key trials

  • One study demonstrated that donepezil preserves cognition and global function compared with placebo in patients with severe Alzheimer's disease (Neurology 2007; 69: 459-69).
  • The long-term effects and the optimal duration of treatment as patients continue to progress to more severe stages are still unknown (Expert Opin Pharmacother 2008; 9: 2,575-82).
  • The addition of memantine to a cholinesterase inhibitor has not been shown to offer any additional benefit for patients with mild-to-moderate Alzheimer's disease (Curr Alzheimer Res 2008; 5: 83-9).
  • Patients taking antipsychotic drugs and sedatives have a significantly higher risk of deterioration compared with those not taking them (J Neurol Neurosurg Psychiatry 2007; 78: 233-9).
  • One randomised controlled trial has shown that gingko biloba had no effect on the rate of progression to dementia in elderly participants with mild cognitive impairment (JAMA 2008; 300: 2,253-62).

Evidence base

  • A Cochrane review found that the three cholinesterase inhibitors are efficacious for mild-to-moderate Alzheimer's disease. Despite the slight variations in the mode of action of the three drugs there is no evidence of any differences between them with respect to efficacy (Cochrane Database Syst Rev 2006, Issue 1. Art. No.: CD005593).
  • The three cholinesterase inhibitors, donepezil, galantamine and rivastigmine are recommended by NICE as options in the management of patients with Alzheimer's disease of moderate severity only (Mini Mental State Exam (MMSE) score of between 10 and 20 points) and should be prescribed by a specialist.
  • However, the European Federation of Neurological Societies recommendations are that for patients with Alzheimer's disease, treatment with donepezil, galantamine or rivastigmine should be considered at the time of diagnosis (Eur J Neurology 2007, 14: e1-e26).
  • NICE does not recommend memantine for moderately severe to severe Alzheimer's disease, except as part of well-designed clinical studies.
  • Although SIGN recommends the use of the cholinesterase inhibitors, it does not recommend the use of memantine (SIGN. Management of patients with dementia. A national clinical guideline. 2006).
  • Clinical Knowledge Summaries on drug treatments for Alzheimer's disease are based on the current NICE guidance.


  • There are currently three cholinesterase inhibitors licensed in the UK for Alzheimer's disease. They may benefit about 50 per cent of patients. Once stopped, the decline in the patient's cognitive function may accelerate.
  • There has been ongoing discussion between NICE and dementia interest groups regarding the use of these medications.
  • The amended NICE guidelines have stated that clinicians should not rely solely on the MMSE test where it would be inappropriate to do so. This includes patients with learning or other disabilities (for example, sensory impairments) or linguistic or other communication difficulties.
  • The Mental Capacity Act came fully into force on 1 October 2007. It aims to protect people who cannot make decisions for themselves due to a learning disability or a mental health condition, for example Alzheimer's disease. It provides clear guidelines for carers and professionals about who can take decisions and when.

Key Points

  • Cholinesterase inhibitors are beneficial for patients with Alzheimer's disease.
  • NICE has amended its original guidance on the use of these drugs.
  • Memantine should only be prescribed for patients in clinical studies.
  • Antipsychotic drugs need to be prescribed with caution in patients with Alzheimer's disease.

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