Central Acetylcholinesterase Inhibitor

Aka: Central Acetylcholinesterase Inhibitor, Central Cholinesterase Inhibitor

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II. Medications

  1. Aricept (Donepezil)
  2. Rivastigmine (Exelon)
  3. Galantamine (Reminyl)

III. Mechanism

  1. Decreased cerebral Cholinergic Activity in Alzheimer Disease, Lewy Body Dementia, Vascular Dementia
  2. Cholinergic inhibitors reversibly bind Cholinesterase at Synapse between CNS Neurons
    1. Results in decreased Acetylcholine degradation, and hence increased Cholinergic Activity

IV. Efficacy

  1. Minimal clinical benefit, despite Statistically Significant improvement in cognitive function in trials
  2. Improve neuropsychiatric scores 7 points
    1. Seven point improvement equals ~1 year of decline
    2. Benefits may persist for 1-2 years
    3. Rogers (1998) Arch Intern Med 158:1021-31 [PubMed]
  3. Meta-analysis shows marginal benefit to risk ratio
    1. Where NNT is Number Needed to Treat
    2. NNT for global improvement: 10
    3. NNT for cognitive improvement: 12
    4. NNT for significant side effects to stop med: 16
    5. Lanctot (2003) CMAJ 169:557-64 [PubMed]

V. Adverse Effects

  1. No hepatotoxicity with newer agents (contrast with Tacrine, Cognex - the initial agent in class)
  2. Cardiovascular effects
    1. Atrioventricular Block
  3. Gastrointestinal effects
    1. Decreased appetite and Anorexia
    2. Diarrhea
    3. Nausea or Vomiting
    4. Weight loss
  4. Neurologic effects
    1. Dizziness
    2. Headache

VI. References

  1. Epperly (2017) Am Fam Physician 95(12): 771-8 [PubMed]

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