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Abstract
Objective To determine the cognitive consequences of anticholinergic medications (aCH) in cognitively normal older adults as well as interactive effects of genetic and CSF Alzheimer disease (AD) risk factors.
Methods A total of 688 cognitively normal participants from the Alzheimer's Disease Neuroimaging Initiative were evaluated (mean age 73.5 years, 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 (hazard ratio [HR] 1.47, p = 0.02), and there was a significant aCH × AD risk interaction such that aCH+/ε4+ individuals showed greater than 2-fold increased risk (HR 2.69, p < 0.001) for incident MCI relative to aCH−/ε4−), while aCH+/CSF+) individuals demonstrated greater than 4-fold (HR 4.89, p < 0.001) increased risk relative to aCH−/CSF−. Linear mixed effects models revealed that aCH predicted a steeper slope of decline in memory (t = −2.35, p = 0.02) and language (t = −2.35, p = 0.02), 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 pathophysiologic 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.
Glossary
- Aβ=
- β-amyloid;
- ACB=
- Anticholinergic Cognitive Burden;
- aCH=
- anticholinergic medications;
- AD=
- Alzheimer disease;
- ADNI=
- Alzheimer's Disease Neuroimaging Initiative;
- CI=
- confidence interval;
- D=
- daily dosage for a given drug;
- GDS=
- Geriatric Depression Scale;
- HR=
- hazard ratio;
- LLR=
- log-likelihood ratio;
- MED=
- minimally efficacious dosage;
- NBM=
- nucleus basalis of Meynert;
- p-tau=
- phosphorylated tau
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
A complete listing of ADNI investigators can be found in the coinvestigators list at links.lww.com/WNL/B195.
Data used in preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report.
- Received August 16, 2019.
- Accepted in final form May 18, 2020.
- © 2020 American Academy of Neurology
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