Anticholinergic medications: A potentially modifiable risk factor for development of MCI

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 4 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+)(&[epsilon]4+) individuals showed greater than 2-fold increased risk (HR = 2.47, p < .001) for incident MCI relative to (aCH...