Cumulative anticholinergic exposure and white matter hyperintensity burden in community-dwelling older adults

Anticholinergic exposure is associated with dementia risk; however, the mechanisms for this association remain unclear. The objective of this study was to examine the association between anticholinergic exposure and white matter hyperintensity (WMH) burden. This was a retrospective analysis of data from the Adult Changes in Thought (ACT) study, a prospective cohort study among adults aged ≥65 years on dementia risk factors. We used data collected through March 2020 for this analysis. The sample included ACT participants who were referred for and had a clinical magnetic resonance imaging (MRI) scan and ≥10 years of continuous healthcare enrollment prior to the scan. Our primary exposure was total standardized daily dose (TSDD) of anticholinergics. Outcomes included three semi-quantitative ratings of WMH volume. We used separate linear regression models for each outcome to estimate and compare covariate-adjusted mean values of WMH ratings in each exposure group. Of the 1043 individuals included in the analyses, 28% had no use, 33% had 1-90 TSDD, 15% had 91-365 TSDD, 7% had 366-1095 TSDD, and 17% had ≥1096 TSDD. The mean age was 81 years, most were female (58%) and White race (88%). Compared to those with no use, the ≥1096 TSDD group had a higher (worse) adjusted mean [95% confidence intervals] Fazekas (4.0 [3.8, 4.2] vs. 3.4 [3.2, 3.5]; p: