Authors: Alexandra J. Weigand, Mark W. Bondi, Kelsey R. Thomas, Noll L. Campbell, Douglas R. Galasko, David P. Salmon, Daniel Sewell, James B. Brewer, Howard H. Feldman, Lisa Delano-Wood
Summary: Objective: To determine the cognitive consequences of anticholinergic medications (aCH) in cognitively normal older adults as well as interactive effects of genetic and cerebrospinal fluid (CSF) Alzheimer’s disease (AD) risk factors.
Methods: 688 cognitively normal participants from the Alzheimer’s Disease Neuroimaging Initiative were evaluated (mean age = 73.5, 49.6% female). Cox regression examined risk of progression to mild cognitive impairment (MCI) over a 10-year period, and linear mixed effects models examined 3-year rates of decline in memory, executive function, and language as a function of aCH. Interactions with APOE ε4 genotype and CSF biomarker evidence of AD pathology were also assessed.
Results: aCH+ participants had increased risk of progression to MCI (HR = 1.42, p = .02), and there was a significant aCH x AD-risk interaction such that (aCH+)(ε4+) individuals showed greater than 2-fold increased risk (HR = 2.47, p < .001) for incident MCI relative to (aCH-)(ε4-), while (aCH+)(p-tau/Aß+) individuals demonstrated greater than 4-fold (HR = 4.25, p < .001) increased risk relative to (aCH-)(p-tau/Aß-). Linear mixed effects models revealed that aCH predicted a steeper slope of decline in memory (t = -2.31, p = .02) and language (t = -2.35, p = .02), with effects exacerbated in individuals with AD risk factors.
Conclusions: aCH increased risk of incident MCI and cognitive decline, and effects were significantly enhanced among individuals with genetic risk factors and CSF-based AD pathophysiological markers. Findings underscore the adverse impact of aCH medications on cognition and the need for deprescribing trials, particularly among individuals with elevated risk for AD.
Source: Neurology, 2020, 10.1212/WNL.0000000000010643