Dataset Information

The cognitive effects of anticholinergic drugs on apolipoprotein ε4 carriers and noncarriers in the Wisconsin Registry for Alzheimer's Prevention study.

ABSTRACT:

Objectives

The purpose of the study was to test the hypothesis that anticholinergic drug exposure is associated with cognitive decline in the Wisconsin Registry for Alzheimer's Prevention (WRAP) study. Secondary aims were to assess if the effects of anticholinergic drugs on different domains of cognitive functioning varied for the entire sample and by apolipoprotein ε4 status.

Methods

The WRAP study includes a sample of 1,573 subjects who self-reported medication use and were administered several cognitive tests four times over a decade. Partial correlations assessed relationships between reported days of definite anticholinergic drug exposure with changes in cognitive performance. Linear mixed models were conducted testing main effects for anticholinergic drug use and interaction effects between anticholinergic drug use, apolipoprotein ε4 status, and time on neuropsychological assessment performance.

Results

Partial correlations indicated that days of anticholinergic drug exposure was associated with a decline in mental status for the entire sample (r = -.043, p = .011), and immediate verbal memory (r = -.066, p = .043), delayed verbal memory (r = -.077, p = .018), psychomotor speed (r = -.066, p = .043), and cognitive flexibility (r = -.067, p = .040) of apolipoprotein ε4 carriers only. The linear mixed-model results suggested that anticholinergic drug users had a greater decline than nonusers in delayed memory, psychomotor speed, and cognitive flexibility. Apolipoprotein ε4 carrier, anticholinergic drug users performed worse in delayed memory than nonusers and noncarrier, anticholinergic drug users.

Conclusions

Anticholinergic drug use may have deleterious effects on the cognitive functioning of subjects in populations at risk for dementia, especially among apolipoprotein ε4 carriers. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

SUBMITTER: Collin BG

PROVIDER: S-EPMC8366520 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:Studies have suggested associations between self-reported engagement in health behaviors and reduced risk of cognitive decline. Most studies explore these relationships using one health behavior, often cross-sectionally or with dementia as the outcome. In this study, we explored whether several individual self-reported health behaviors were associated with cognitive decline when considered simultaneously, using data from the Wisconsin Registry for Alzheimer's Prevention (WRAP), an Alzheimer's disease risk-enriched cohort who were non-demented and in late midlife at baseline. METHOD:We analyzed longitudinal cognitive data from 828 participants in WRAP, with a mean age at baseline cognitive assessment of 57 (range = 36-78, sd = 6.8) and an average of 6.3 years (standard deviation = 1.9, range = 2-10) of follow-up. The primary outcome was a multi-domain cognitive composite, and secondary outcomes were immediate/delayed memory and executive function composites. Predictors of interest were self-reported measures of physical activity, cognitive activity, adherence to a Mediterranean-style diet (MIND), and interactions with each other and age. We conducted linear mixed effects analyses within an Information-theoretic (IT) model averaging (MA) approach on a set of models including covariates and combinations of these 2- and 3-way interactions. The IT approach was selected due to the large number of interactions of interest and to avoid pitfalls of traditional model selection approaches. RESULTS:Model-averaged results identified no significant self-reported health behavior*age interactions in relationship to the primary composite outcome. In secondary outcomes, higher MIND diet scores associated with slower decline in executive function. Men showed faster decline than women on delayed memory, independent of health behaviors. There were no other significant interactions among any other health behaviors and cognitive trajectories. CONCLUSIONS:When multiple covariates and health behaviors were considered simultaneously, there were limited weak associations with cognitive decline in this age range. These results may be explained alone or in combination by three alternative explanations: 1) the range of cognitive decline is in middle age is too small to observe relationships with health behaviors, 2) the putative associations of these health behaviors on cognition may not be robust in this age range, or 3) the self-reported measures of the health behaviors may not be optimal for predicting cognitive decline. More study may be needed that incorporates sensitive measures of health behaviors, AD biomarker profiles, and/or other disease comorbidities.