Title | Exposure to Strong Anticholinergic Medications and Dementia-Related Neuropathology in a Community-Based Autopsy Cohort. |
Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | Gray, SL, Anderson, ML, Hanlon, JT, Dublin, S, Walker, RL, Hubbard, RA, Yu, O, Montine, TJ, Crane, PK, Sonnen, JA, C Keene, D, Larson, EB |
Journal | J Alzheimers Dis |
Volume | 65 |
Issue | 2 |
Pagination | 607-616 |
Date Published | 2018 |
ISSN | 1875-8908 |
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 (Nā=ā420), 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 (ā„1,096 TSDD) was not associated with greater neuropathologic changes of Alzheimer's disease; the adjusted RRs for heavy use of anticholinergics (ā„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. |
DOI | 10.3233/JAD-171174 |
Alternate Journal | J. Alzheimers Dis. |
PubMed ID | 30056417 |
PubMed Central ID | PMC6154381 |
Grant List | P50 AG005136 / AG / NIA NIH HHS / United States P50 NS062684 / NS / NINDS NIH HHS / United States R03 AG042930 / AG / NIA NIH HHS / United States U01 AG006781 / AG / NIA NIH HHS / United States |