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

Han, Jee-young, MD, MSc*,†; Besser, Lilah M., PhD, MSPH; Xiong, Chengjie, PhD*,†; Kukull, Walter A., PhD§; Morris, John C., MD*,†

Alzheimer Disease & Associated Disorders: April-June 2019 - Volume 33 - Issue 2 - p 87–94
doi: 10.1097/WAD.0000000000000291
Original Articles

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.

*Knight Alzheimer Disease Research Center

Washington University in St. Louis School of Medicine, St. Louis, MO

School of Urban and Regional Planning and Institute for Healthy Aging and Lifespan Studies, Florida Atlantic University, Boca Raton, FL

§National Alzheimer’s Coordinating Center, University of Washington, Seattle, WA

The NACC database is funded by NIA/NIH Grant U01 AG016976 (PI Walter Kukull, PhD). NACC data are contributed by the NIA-funded Alzheimer Disease Centers: P30 AG019610 (PI Eric Reiman, MD), P30 AG013846 (PI Neil Kowall, MD), P50 AG008702 (PI Scott Small, MD), P50 AG025688 (PI Allan Levey, MD, PhD), P50 AG047266 (PI Todd Golde, MD, PhD), P30 AG010133 (PI Andrew Saykin, PsyD), P50 AG005146 (PI Marilyn Albert, PhD), P50 AG005134 (PI Bradley Hyman, MD, PhD), P50 AG016574 (PI Ronald Petersen, MD, PhD), P50 AG005138 (PI Mary Sano, PhD), P30 AG008051 (PI Thomas Wisniewski, MD), P30 AG013854 (PI M. Marsel Mesulam, MD), P30 AG008017 (PI Jeffrey Kaye, MD), P30 AG010161 (PI David Bennett, MD), P50 AG047366 (PI Victor Henderson, MD, MS), P30 AG010129 (PI Charles DeCarli, MD), P50 AG016573 (PI Frank LaFerla, PhD), P50 AG005131 (PI James Brewer, MD, PhD), P50 AG023501 (PI Bruce Miller, MD), P30 AG035982 (PI Russell Swerdlow, MD), P30 AG028383 (PI Linda Van Eldik, PhD), P30 AG053760 (PI Henry Paulson, MD, PhD), P30 AG010124 (PI John Trojanowski, MD, PhD), P50 AG005133 (PI Oscar Lopez, MD), P50 AG005142 (PI Helena Chui, MD), P30 AG012300 (PI Roger Rosenberg, MD), P30 AG049638 (PI Suzanne Craft, PhD), P50 AG005136 (PI Thomas Grabowski, MD), P50 AG033514 (PI Sanjay Asthana, MD, FRCP), P50 AG005681 (PI John C. Morris, MD), P50 AG047270 (PI Stephen Strittmatter, MD, PhD).

J.C.M. reports receiving research support from grants P50AG005681, P01AG003991, P01AG026276, and UF01AG032438 from the NIH. W.A.K. reports receiving grant U01 AG016976 from the NIH. The remaining authors declare no conflicts of interest.

Reprints: John C. Morris, MD, Knight Alzheimer Disease Research Center, Washington University School of Medicine, 4488 Forest Park Avenue, Suite 130, St Louis, MO 63108 (e-mail:

Received June 5, 2018

Accepted December 1, 2018

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