Clinical Practice Guidelines for Dementia: Recommendations for Cholinesterase Inhibitors and Memantine

Yeshin Kim¹, Dong Woo Kang², Geon Ha Kim³, Ko Woon Kim⁴, Hee-Jin Kim⁵, Seunghee Na⁶, Kee Hyung Park⁷, Young Ho Park⁸, Gihwan Byeon², Jeewon Suh⁹, Joon Hyun Shin¹⁰, YongSoo Shim¹¹, YoungSoon Yang¹², Yoo Hyun Um¹³, Seong-Il Oh¹⁴, Sheng-Min Wang¹⁵, Bora Yoon¹⁶, Sun Min Lee¹⁷, Juyoun Lee¹⁸, Jin San Lee¹⁴, Jae-Sung Lim¹⁹, Young Hee Jung²⁰, Juhee Chin²¹, Hyemin Jang²², Miyoung Choi²³, Yun Jeong Hong²⁴, Hak Young Rhee²⁵, Jae-Won Jang¹; Korean Dementia Association

Affiliations

¹ Department of Neurology, Kangwon National University Hospital, Kangwon National University College of Medicine, Chuncheon, Korea.
² Department of Psychiatry, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
³ Department of Neurology, Ewha Womans University Mokdong Hospital, Ewha Womans University College of Medicine, Seoul, Korea.
⁴ Department of Neurology, Jeonbuk National University Medical School and Hospital, Jeonju, Korea.
⁵ Department of Neurology, Hanyang University Hospital, College of Medicine, Hanyang University, Seoul, Korea.
⁶ Department of Neurology, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Incheon, Korea.
⁷ Department of Neurology, College of Medicine, Gachon University Gil Medical Center, Incheon, Korea.
⁸ Department of Neurology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.
⁹ Department of Neurology, National Medical Center, Seoul, Korea.
¹⁰ Dr Shin's Neurology Clinic, Wonju, Korea.
¹¹ Department of Neurology, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon, Korea.
¹² Department of Neurology, Soonchunhyang University Cheonan Hospital, Soonchunhyang University School of Medicine, Cheonan, Korea.
¹³ Department of Psychiatry, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
¹⁴ Department of Neurology, Kyung Hee University Hospital, Kyung Hee University College of Medicine, Seoul, Korea.
¹⁵ Department of Psychiatry, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
¹⁶ Department of Neurology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
¹⁷ Department of Neurology, Ajou University Hospital, Ajou University School of Medicine, Suwon, Korea.
¹⁸ Department of Neurology, Chungnam National University Hospital, Chungnam National University School of Medicine, Daejeon, Korea.
¹⁹ Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
²⁰ Department of Neurology, Hallym Sacred Heart Hospital, College of Medicine, Hallym University, Anyang, Korea.
²¹ Department of Psychology, Doheon Academy Hallym University, Chuncheon, Korea.
²² Department of Neurology, Seoul National University Hospital, Seoul, Korea.
²³ Division of Healthcare Technology Assessment Research, National Evidence-based Healthcare Collaborating Agency, Seoul, Korea.
²⁴ Department of Neurology, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu, Korea.
²⁵ Department of Neurology, Kyung Hee University Hospital at Gangdong, Kyung Hee University College of Medicine, Seoul, Korea.

PMID: 39944527
PMCID: PMC11813556
DOI: 10.12779/dnd.2025.24.1.1

Clinical Practice Guidelines for Dementia: Recommendations for Cholinesterase Inhibitors and Memantine

Yeshin Kim et al. Dement Neurocogn Disord. 2025 Jan.

. 2025 Jan;24(1):1-23.

doi: 10.12779/dnd.2025.24.1.1. Epub 2025 Jan 20.

Authors

Affiliations

¹ Department of Neurology, Kangwon National University Hospital, Kangwon National University College of Medicine, Chuncheon, Korea.
² Department of Psychiatry, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
³ Department of Neurology, Ewha Womans University Mokdong Hospital, Ewha Womans University College of Medicine, Seoul, Korea.
⁴ Department of Neurology, Jeonbuk National University Medical School and Hospital, Jeonju, Korea.
⁵ Department of Neurology, Hanyang University Hospital, College of Medicine, Hanyang University, Seoul, Korea.
⁶ Department of Neurology, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Incheon, Korea.
⁷ Department of Neurology, College of Medicine, Gachon University Gil Medical Center, Incheon, Korea.
⁸ Department of Neurology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.
⁹ Department of Neurology, National Medical Center, Seoul, Korea.
¹⁰ Dr Shin's Neurology Clinic, Wonju, Korea.
¹¹ Department of Neurology, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon, Korea.
¹² Department of Neurology, Soonchunhyang University Cheonan Hospital, Soonchunhyang University School of Medicine, Cheonan, Korea.
¹³ Department of Psychiatry, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
¹⁴ Department of Neurology, Kyung Hee University Hospital, Kyung Hee University College of Medicine, Seoul, Korea.
¹⁵ Department of Psychiatry, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
¹⁶ Department of Neurology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
¹⁷ Department of Neurology, Ajou University Hospital, Ajou University School of Medicine, Suwon, Korea.
¹⁸ Department of Neurology, Chungnam National University Hospital, Chungnam National University School of Medicine, Daejeon, Korea.
¹⁹ Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
²⁰ Department of Neurology, Hallym Sacred Heart Hospital, College of Medicine, Hallym University, Anyang, Korea.
²¹ Department of Psychology, Doheon Academy Hallym University, Chuncheon, Korea.
²² Department of Neurology, Seoul National University Hospital, Seoul, Korea.
²³ Division of Healthcare Technology Assessment Research, National Evidence-based Healthcare Collaborating Agency, Seoul, Korea.
²⁴ Department of Neurology, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu, Korea.
²⁵ Department of Neurology, Kyung Hee University Hospital at Gangdong, Kyung Hee University College of Medicine, Seoul, Korea.

PMID: 39944527
PMCID: PMC11813556
DOI: 10.12779/dnd.2025.24.1.1

Abstract

Background and purpose: This clinical practice guideline provides evidence-based recommendations for treatment of dementia, focusing on cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists for Alzheimer's disease (AD) and other types of dementia.

Methods: Using the Population, Intervention, Comparison, Outcomes (PICO) framework, we developed key clinical questions and conducted systematic literature reviews. A multidisciplinary panel of experts, organized by the Korean Dementia Association, evaluated randomized controlled trials and observational studies. Recommendations were graded for evidence quality and strength using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology.

Results: Three main recommendations are presented: (1) For AD, cholinesterase inhibitors (donepezil, rivastigmine, galantamine) are strongly recommended for improving cognition and daily function based on moderate evidence; (2) Cholinesterase inhibitors are conditionally recommended for vascular dementia and Parkinson's disease dementia, with a strong recommendation for Lewy body dementia; (3) For moderate to severe AD, NMDA receptor antagonist (memantine) is strongly recommended, demonstrating significant cognitive and functional improvements. Both drug classes showed favorable safety profiles with manageable side effects.

Conclusions: This guideline offers standardized, evidence-based pharmacologic recommendations for dementia management, with specific guidance on cholinesterase inhibitors and NMDA receptor antagonists. It aims to support clinical decision-making and improve patient outcomes in dementia care. Further updates will address emerging treatments, including amyloid-targeting therapies, to reflect advances in dementia management.

Keywords: Alzheimer Disease; Cholinesterase Inhibitors; Dementia; Memantine; Practice Guidelines.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest: The Steering and Working Committee members of the Clinical Practice Guideline Implementation Committee were checked for any consultancy or employment relationships with commercially related organizations, commercial equity holdings, research grants, honoraria, ownership of intellectual property rights related to the content of the guideline, or similar relationships involving their family or family-affiliated companies during the development or approval process of the guideline. All participating members confirmed that there were no conflicts of interest that could influence the development or approval process of this guideline.

Figures

**Fig. 1. Comparison of the effects of cholinesterase inhibitors and placebo on changes in MMSE.**
MMSE: Mini-Mental State Examination, SD: standard deviation, IV: interval variable, CI: confidence interval, AChEi: acetylcholinesterase inhibitor.

**Fig. 2. Comparison of the effects of cholinesterase inhibitors and placebo on changes in ADAS-Cog.**
ADAS-Cog: Alzheimer’s Disease Assessment Scale–Cognitive Subscale, SD: standard deviation, IV: interval variable, CI: confidence interval, AChEi: acetylcholinesterase inhibitor.

**Fig. 3. Comparison of the Effects of Cholinesterase Inhibitors and Placebo on Changes in ADCS-ADL.**
ADCS-ADL: Alzheimer’s Disease Cooperative Study–Activities of Daily Living, SD: standard deviation, IV: interval variable, CI: confidence interval, AChEi: acetylcholinesterase inhibitor.

**Fig. 4. Comparison of the Effects of Cholinesterase Inhibitors and Placebo on Changes in CIBIC-Plus/CGI-C.**
CIBIC-Plus/CGI-C: Clinician’s Interview-Based Impression of Change Plus Caregiver Input/Clinical Global Impression of Change, SD: standard deviation, IV: interval variable, CI: confidence interval, AChEi: acetylcholinesterase inhibitor.

**Fig. 5. Comparison of the risk of all adverse effects between cholinesterase inhibitors and placebo.**
M-H: Mantel-Haenszel, CI: confidence interval, AChEi: acetylcholinesterase inhibitor.

**Fig. 6. Comparison of the risk of moderate to severe adverse effects between cholinesterase inhibitors and placebo.**
M-H: Mantel-Haenszel, CI: confidence interval, AChEi: acetylcholinesterase inhibitor.

**Fig. 7. Comparison of the effects of NMDA receptor antagonists and placebo on changes in MMSE.**
NMDA: N-methyl-D-aspartate, MMSE: Mini-Mental State Examination, SE: standard error, IV: interval variable, CI: confidence interval.

**Fig. 8. Comparison of the effects of NMDA receptor antagonists and placebo on changes in ADCS-ADL.**
NMDA: N-methyl-D-aspartate, ADCS-ADL: Alzheimer’s Disease Cooperative Study–Activities of Daily Living, SD: standard deviation, IV: interval variable, CI: confidence interval.

**Fig. 9. Comparison of the effects of NMDA receptor antagonists and placebo on changes in SIB.**
NMDA: N-methyl-D-aspartate, SIB: Severe Impairment Battery, SD: standard deviation, IV: interval variable, CI: confidence interval.

**Fig. 10. Comparison of the effects of NMDA receptor antagonists and placebo on changes in CIBIC-Plus/CGI-C.**
NMDA: N-methyl-D-aspartate, CIBIC-Plus/CGI-C: Clinician’s Interview-Based Impression of Change Plus Caregiver Input/Clinical Global Impression of Change, SD: standard deviation, IV: interval variable, CI: confidence interval.

See this image and copyright information in PMC

References

1. Arvanitakis Z, Shah RC, Bennett DA. Diagnosis and management of dementia: review. JAMA. 2019;322:1589–1599. - PMC - PubMed
1. Pereira JB, Janelidze S, Ossenkoppele R, Kvartsberg H, Brinkmalm A, Mattsson-Carlgren N, et al. Untangling the association of amyloid-β and tau with synaptic and axonal loss in Alzheimer’s disease. Brain. 2021;144:310–324. - PMC - PubMed
1. Jack CR, Jr, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, et al. NIA-AA Research Framework: toward a biological definition of Alzheimer’s disease. Alzheimers Dement. 2018;14:535–562. - PMC - PubMed
1. Alzheimer A. Über eine eigenartige erkrankung der hirnrinde. All Z Psychiatr. 1907;64:146–148.
1. Overshott R, Burns A. Treatment of dementia. J Neurol Neurosurg Psychiatry. 2005;76(Suppl 5):v53–v59. - PMC - PubMed

LinkOut - more resources

Full Text Sources
- Korean Dementia Association
- PubMed Central

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Clinical Practice Guidelines for Dementia: Recommendations for Cholinesterase Inhibitors and Memantine

Affiliations

Clinical Practice Guidelines for Dementia: Recommendations for Cholinesterase Inhibitors and Memantine

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

LinkOut - more resources

Full Text Sources