Discontinuation of Cholinesterase Inhibitors Following Initiation of Memantine and Admission to Long-Term Care Among Older Adults

Abstract

IMPORTANCE Discontinuing cholinesterase inhibitors when initiating memantine in patients with dementia may be reasonable to reduce treatment burden, costs, and the risk of adverse drug events. OBJECTIVE To assess the association of cholinesterase inhibitor discontinuation on long-term care institutionalization among older adults with dementia who initiate memantine. DESIGN, SETTING, AND PARTICIPANTS This retrospective propensity score-matched cohort study used Medicare claims data from January 2014 to December 2019. Participants included fee-for-service Medicare beneficiaries with dementia. Data were analyzed from September 2021 to August 2024. EXPOSURES Discontinuation vs continuation of cholinesterase inhibitor. MAIN OUTCOMES AND MEASURES The primary outcome was 1-year long-term care institutionalization-free days. Secondary outcomes include all-cause death and adverse drug events over 1 year. We performed subgroup analyses based on age, sex, dementia type (Alzheimer disease vs other), frailty, and dementia severity (mild vs moderate or severe) based on claims-based algorithms. The primary outcome was analyzed using nonparametric restricted mean survival time analysis. RESULTS Among 16 292 beneficiaries who initiated memantine, 1820 (11.2%) discontinued cholinesterase inhibitors. In the propensity score-matched cohort of 3612 beneficiaries, the mean (SD) age was 80.7 (6.7) years, 2261 (62.6%) were female, and 1989 (55.0%) had a diagnosis of Alzheimer disease. Over 1 year, long-term care institutionalization occurred in 51 of 1806 beneficiaries (2.8%) who discontinued cholinesterase inhibitors (3.4 per 100 person-years) and 62 of 1806 beneficiaries (3.4%) who continued (4.1 per 100 person-years). There was no statistically significant difference in the 1-year mean institutionalization-free days between discontinuation and continuation groups (360.6 [95% CI, 359.3 to 362.0] days vs 359.1 [95% CI, 357.5 to 360.6] days; mean difference, 1.5 [95% CI, −0.5 to 3.6] days). The mean difference in the long-term care institutionalization-free days did not differ by age category, sex, dementia type, frailty, or dementia stage. Individuals who discontinued had a lower rate of fall-related injury (0.9 vs 2.0 per 100 person-years; hazard ratio [HR], 0.47 [95% CI, 0.25 to 0.88]). There was no difference between the discontinuation and continuation groups in all-cause death (10.4 vs 11.6 per 100 person-years; HR, 0.89 [95% CI, 0.72 to 1.10]). CONCLUSIONS AND RELEVANCE In this study, discontinuing cholinesterase inhibitors upon memantine initiation was not associated with an increased risk of long-term care institutionalization Key Points Question Is discontinuing cholinesterase inhibitors upon memantine initiation associated with an increased risk of long-term care institutionalization among community-dwelling older adults with dementia? Findings In this comparative effectiveness study of 3612 Medicare beneficiaries with dementia receiving cholinesterase inhibitors who initiated memantine, those who discontinued the cholinesterase inhibitor had similar 1-year mean long-term care institutionalization-free days and all-cause mortality, but had a lower risk of fall-related injury compared with those who continued the cholinesterase inhibitor. Meaning These findings suggest that discontinuing cholinesterase inhibitors when initiating memantine in older adults with dementia may be a reasonable approach to reduce treatment burden. but with a lower risk of fall-related injury among older adults with dementia. These findings offer valuable insights for clinicians aiming to reduce treatment burden in this population.