Cholinesterase Inhibitors May Not Benefit Mild Cognitive Impairment and Mild Alzheimer Disease Dementia

Alzheimer Dis Assoc Disord. 2019 Apr-Jun;33(2):87-94. doi: 10.1097/WAD.0000000000000291.


Introduction: We investigated whether cholinesterase inhibitors (ChEIs) benefit cognitive outcomes in mild cognitive impairment due to Alzheimer disease (MCI-AD) and in mild AD dementia (ADdem).

Methods: Data from 2242 individuals, clinically diagnosed with MCI-AD [Clinical Dementia Rating (CDR), 0 or 0.5] or with mild ADdem (CDR, 0.5 or 1), were available from the National Alzheimer's Coordinating Center's (NACC) Uniform Data Set (UDS). General linear mixed models were used to examine the annual change in the CDR Sum of Boxes (CDR-SB) and in neuropsychological performance. We compared slopes before and after ChEI initiation among ChEI users, and also compared the change in scores of ChEI users versus nonusers.

Results: Thirty-four percent of 944 MCI-AD and 72% of 1298 ADdem participants were ChEI users. Cognitive decline was greater after ChEI initiation in MCI-AD and ADdem groups (eg, MCI-AD, CDR-SB: 0.03 points/y before initiation; 0.61 points/y after initiation, P<0.0001). Both MCI-AD and ADdem groups had faster decline after ChEI initiation than nonusers (eg, MCI-AD, CDR-SB: 0.61 points/y, ChEI users; 0.24 points/y, nonusers, P<0.0001).

Discussion: This study suggests that ChEI use may not improve the cognitive course in MCI-AD and mild ADdem.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Alzheimer Disease / diagnosis*
  • Alzheimer Disease / drug therapy*
  • Cholinesterase Inhibitors / therapeutic use*
  • Cognitive Dysfunction / diagnosis*
  • Cognitive Dysfunction / drug therapy*
  • Disease Progression
  • Female
  • Humans
  • Male
  • Mental Status and Dementia Tests / statistics & numerical data
  • Neuropsychological Tests / statistics & numerical data


  • Cholinesterase Inhibitors

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