Pharmacotherapy for Neurocognitive Disorders Based on the Hypothesis of Endogenous Appearance of Anticholinergic Activity

Neurodegener Dis. 2015;15(3):157-61. doi: 10.1159/000381513. Epub 2015 Jun 30.

Abstract

We previously proposed the hypothesis of endogenous anticholinergic activity (AA) in Alzheimer's disease (AD). According to this hypothesis, the downregulation of acetylcholine seen in AD is associated with upregulation/hyperactivity of N-methyl-D-aspartate receptor (NMDAR). The hyperactivation of NMDAR then induces inflammation, which, in turn, causes AA to appear endogenously. Based on this hypothesis, we commented that cholinesterase inhibitors (ChEIs) are 'preventative' therapy for AD and NMDAR antagonists are the true 'treatment' for AD. We also noted that ChEIs, such as donepezil, could treat delirium. Moreover, we proposed measuring serum anticholinergic activity in patients, particularly AD patients, in out-of-hospital pharmacies to monitor the anticholinergic burden for targeted treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / metabolism
  • Cholinergic Antagonists / metabolism*
  • Cholinesterase Inhibitors / therapeutic use*
  • Cognition Disorders / drug therapy*
  • Cognition Disorders / metabolism*
  • Dementia
  • Humans
  • Receptors, N-Methyl-D-Aspartate / metabolism

Substances

  • Cholinergic Antagonists
  • Cholinesterase Inhibitors
  • Receptors, N-Methyl-D-Aspartate
  • Acetylcholine