We conducted a retrospective, propensity-score matched-cohort study using prospectively collected data from the National Alzheimer’s Coordinating Center (NACC). The NACC started collecting their uniform data set through Alzheimer's Disease Research Centers in the United States in 2005 and all participants provided written consent at the time of enrollment.
We identified all participants enrolled between September 1, 2005 and January 1, 2020. We excluded patients who did not have a follow-up visit within 4-years of the initial visit, those whose medication list was not available for all visits, people that were using alpha-adrenergic antagonists at the time of enrollment, patients with a cognitive condition other than mild cognitive impairment or dementia, and those with an unknown APOE e4 carrier status.
Our primary exposure was the new use of a prostate specific alpha-adrenergic antagonist (tamsulosin, alfuzosin, or silodosin) at any one of the follow-up visits. Patients who started alpha-adrenergic antagonist medication were matched 1:1 to people not using this class of medication based on cognitive status at the initial visit, total number of NACC visits, and propensity for exposure. The propensity score was created using 38 covariates including age, sex, years of education, marital status, living situation, degree of independence, vision impairment, and hearing impairment.
Our primary outcome was cognitive decline measured with the CDR Dementia Staging Instrument (CDR, 0=no dementia, 4=severe cognitive impairment) and the mini-mental state examination (MMSE, which measures orientation, attention, memory, language and visual-spatial skills and is scored from 0-30, with lower scores associated with cognitive impairment). We considered a ≥1 point increase on the CDR, or a ≥3 point decrease on the MMSE to be a significant change. Secondary outcomes include the Boston naming test, Wechsler Adult Intelligence Scale-revised (WAIS-R), and the trail making test part B.
We calculated the score difference for each outcome measure between the visit after initial exposure (or the matched visit number for the unexposed) and the immediately preceding visit. Changes in outcome measure scores were compared between groups using t-tests. A conditional logistic regression model was used to evaluate if alpha-adrenergic antagonist medication exposure predicted a clinically important cognitive decline after adjusting for APOE e4 carrier status. Statistical analysis was carried out using SAS EG 8.3, and a two-sided p<0.05 was considered significant.