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Exposure to Strong Anticholinergic Medications and Dementia-Related Neuropathology in a Community-Based Autopsy Cohort JOURNAL OF ALZHEIMERS DISEASE Gray, S. L., Anderson, M. L., Hanlon, J. T., Dublin, S., Walker, R. L., Hubbard, R. A., Yu, O., Montine, T. J., Crane, P. K., Sonnen, J. A., Keene, C., Larson, E. B. 2018; 65 (2): 607–16

Abstract

Anticholinergic medication exposure has been associated with increased risk for dementia. No study has examined the association between anticholinergic medication use and neuropathologic lesions in a community-based sample.To examine the relationship between anticholinergic exposure and dementia-related neuropathologic changes.Within a community-based autopsy cohort (N?=?420), we ascertained use of anticholinergic medications over a 10-year period from automated pharmacy data and calculated total standardized daily doses (TSDD). We used modified Poisson regression to calculate adjusted relative risks (RRs) and 95% confidence intervals (CIs) for the association between anticholinergic exposure and dementia-associated neuropathology. Inverse probability weighting was used to account for selection into the autopsy cohort.Heavy anticholinergic exposure (=1,096 TSDD) was not associated with greater neuropathologic changes of Alzheimer's disease; the adjusted RRs for heavy use of anticholinergics (=1,096 TSDD) compared to no use were 1.22 (95% CI 0.81-1.88) for neuritic plaque scores and 0.89 (0.47-1.66) for extent of neurofibrillary degeneration. Moderate (91-1,095 TSDD) and heavy use of anticholinergics was associated with a significantly lower cerebral microinfarct burden compared with no use with adjusted RRs of 0.44 (0.21-0.89) and 0.24 (0.09-0.62), respectively. Anticholinergic exposure was not associated with macroscopic infarcts or atherosclerosis.Use of anticholinergic medications is not associated with Alzheimer's disease-related neuropathologic changes but is associated with lower cerebral microinfarct burden. Further research into biological mechanisms underlying the anticholinergic-dementia link is warranteds.

View details for DOI 10.3233/JAD-171174

View details for Web of Science ID 000442247800019

View details for PubMedID 30056417