Anticholinergic exposure and its association with dementia/Alzheimer's disease and mortality in older adults

BACKGROUND: Use of anticholinergic (ACH) medications is associated with increased risk of cognitive decline in the elderly. However, little is known about this association from a health plan perspective. METHODS: This retrospective cohort study used the Humana Research Database to identify individuals with at least one ACH medication dispensed in 2015. Patients were followed until incidence of dementia/Alzheimer’s disease, death, disenrollment or end of December 2019. Multivariate Cox regression models were used to assess the association between ACH exposure and study outcomes, adjusting for demographics and clinical characteristics. RESULTS: A total of 12,209 individuals with no prior ACH use or dementia/Alzheimer’s disease diagnosis were included. As ACH polypharmacy increased (i.e., from no ACH exposure, to one, two, three, and four or more ACH medications), there was a stair-step increase in the incidence rate of dementia/Alzheimer’s disease (15, 30, 46, 56 and 77 per 1,000 person-years of follow-up) and in the incidence of mortality (19, 37, 80, 115 and 159 per 1,000 person-years of follow-up). After adjusting for confounders, ACH exposure to one, two, three and four or more ACH medications was associated with a 1.6 (95% CI 1.4–1.9), 2.1 (95% CI 1.7–2.8), 2.6 (95% CI 1.5–4.4), and 2.6 (95% CI 1.1–6.3) times, respectively, increased risk of a dementia/Alzheimer’s disease diagnosis compared to periods of no ACH exposure. ACH exposure to one, two, three and four or more medications was associated with a 1.4 (95% CI 1.2–1.6), 2.6 (95% CI 2.1–3.3), 3.8 (95% CI 2.6–5.4), and 3.4 (95% CI 1.8–6.4) times, respectively, increased risk of mortality compared to periods of no ACH exposure. CONCLUSIONS: Reducing ACH exposure may potentially minimize long-term adverse effects in older adults. Results suggest populations which may benefit from targeted interventions to reduce ACH polypharmacy.