Association of Cholinesterase Inhibitor-Memantine Combination Therapy With Long-Term Community Management and Mortality in Patients With Dementia: A Nationwide Retrospective Cohort Study.
5 affiliations
- 1Department of Neurology, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea.
- 2Department of Statistics, GN Co., Seoul, Korea.
- 3Department of Neurology, Ewha Womans University Mokdong Hospital, Ewha Womans University College of Medicine, Seoul, Korea.
- 4Department of Neurology, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicine, Cheonan, Korea.
- 5Department of Neurology, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea.
Abstract
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.
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BibTeX
@article{kwon2026association,
title = {{Association of Cholinesterase Inhibitor-Memantine Combination Therapy With Long-Term Community Management and Mortality in Patients With Dementia: A Nationwide Retrospective Cohort Study.}},
author = {Hyuk Sung Kwon and Jung-Ook Shin and Geun U Park and Geon Ha Kim and YoungSoon Yang and Chan-Nyoung Lee and Hojin Choi},
journal = {Dementia and neurocognitive disorders},
year = {2026},
month = oct,
doi = {10.12779/dnd.2026.25.4.253},
url = {https://europepmc.org/article/MED/43011219},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Association of Cholinesterase Inhibitor-Memantine Combination Therapy With Long-Term Community Management and Mortality in Patients With Dementia: A Nationwide Retrospective Cohort Study.
AU - Hyuk Sung Kwon
AU - Jung-Ook Shin
AU - Geun U Park
AU - Geon Ha Kim
AU - YoungSoon Yang
AU - Chan-Nyoung Lee
AU - Hojin Choi
PY - 2026
DA - 2026/10/20
JO - Dementia and neurocognitive disorders
DO - 10.12779/dnd.2026.25.4.253
UR - https://europepmc.org/article/MED/43011219
AB - 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.
SN - 1738-1495
SN - 2384-0757
ER -