Correspondence:
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Correspondence to: Shelly L. Gray, Pharm D, MS, University of Washington School of Pharmacy, Box 357630, Seattle, WA 98195, USA. Tel.: +1 206 616 5061; E-mail: [email protected].
Abstract: Background: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. Objective:To examine the relationship between anticholinergic exposure and dementia-related neuropathologic changes. Methods: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. Results: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. Conclusions: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.
