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

BMC Geriatr. 2023 Jun 30;23(1):401. doi: 10.1186/s12877-023-04095-7.

Abstract

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.

Keywords: Alzheimer’s disease; Anticholinergic; Beers criteria; Dementia; Mortality.

MeSH terms

  • Aged
  • Alzheimer Disease* / diagnosis
  • Alzheimer Disease* / drug therapy
  • Cholinergic Antagonists / adverse effects
  • Cognitive Dysfunction*
  • Databases, Factual
  • Humans
  • Retrospective Studies

Substances

  • Cholinergic Antagonists