BackgroundUse 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.MethodsThis 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.ResultsA 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.ConclusionsReducing 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.