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. Key PointsQuestion: Does anticholinergic drug use influence the cognitive functioning of subjects with familial and genetic risk factors for Alzheimer's disease? Findings: Anticholinergic drug exposure was associated with declines in mental status, verbal learning and memory, psychomotor speed, and cognitive flexibility, especially among apolipoprotein ε4 carriers. Importance: Medical providers may want to consider the anticholinergic drug burden when prescribing definite anticholinergic drugs to patients with familial and genetic risk factors for Alzheimer's disease. Next Steps: Future research is needed to test a link between anticholinergic drug use and measured tau or amyloid activity in populations with increased risk for Alzheimer's disease.