Dementia and Neurocognitive Disorders · Oct 20, 2026

Association of Cholinesterase Inhibitor-Memantine Combination Therapy With Long-Term Community Management and Mortality in Patients With Dementia: A Nationwide Retrospective Cohort Study

By Kwon HS, Shin JO, Park GU et al.

BACKGROUND AND PURPOSE: Long-term real-world outcomes of acetylcholinesterase inhibitor (AChEI)-memantine combination therapy remain uncertain. We evaluated treatment patterns and associations of combination therapy with 5-year community management and mortality in patients with dementia. METHODS: Using customized Korean National Health Insurance Service data, we identified patients newly diagnosed with dementia from 2003 to 2018. The main analysis included patients who had not received memantine during the first year after diagnosis but initiated it thereafter. Five-year community management and all-cause mortality were compared between memantine monotherapy and AChEI-memantine combination therapy and examined according to combination-therapy duration. RESULTS: Among 942,068 patients, 552,945 (58.7%) received anti-dementia medication; treatment use increased from 25.5% in 2003 to 73.1% in 2018. Among later memantine initiators, 89,747 received combination therapy and 29,426 received monotherapy. Combination therapy was associated with higher 5-year community management (46.7% vs. 32.5%; absolute difference, 14.2 percentage points; p<0.001) and lower 5-year mortality (24.5% vs. 30.9%; absolute difference, -6.4 percentage points; p<0.001). With longer combination-therapy duration, community management increased from 34.4% to 60.2%, whereas mortality decreased from 35.2% to 11.1% (both p for trend <0.001). CONCLUSIONS: AChEI-memantine combination therapy was associated with more favorable 5-year outcomes than memantine monotherapy among later memantine initiators. These observational findings require confirmation with analyses addressing clinical severity, treatment selection, and time-related bias.

doi.org/10.12779/dnd.2026.25.4.253Open accessPubMed 43011219Populations