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Long-term Effects of Cholinesterase Inhibitors on Cognitive Decline and Mortality
Open accessAbstract
OBJECTIVE: To investigate whether cholinesterase inhibitors (ChEIs) are associated with slower cognitive decline in Alzheimer dementia and decreased risk of severe dementia or death. METHODS: Patients with Alzheimer dementia from the Swedish Dementia Registry starting on ChEIs within 3 months of the dementia diagnosis were included and compared to nontreated patients with Alzheimer dementia. In a propensity score-matched cohort, the association between ChEI use and cognitive trajectories assessed by Mini-Mental State Examination (MMSE) scores was examined with a mixed model, and severe dementia (MMSE score <10) or death as an outcome was assessed with Cox proportional hazards models. RESULTS: The matched cohort included 11,652 ChEI users and 5,826 nonusers. During an average of 5 years of follow-up, 255 cases developed severe dementia, and 6,055 (35%) died. ChEI use was associated with higher MMSE score at each visit (0.13 MMSE points per year; 95% confidence interval [CI] 0.06-0.20). ChEI users had a 27% lower risk of death (0.73, 95% CI 0.69-0.77) compared with nonusers. Galantamine was associated with lower risk of death (0.71, 95% CI 0.65-0.76) and lower risk of severe dementia (0.69, 95% CI 0.47-1.00) and had the strongest effect on cognitive decline of all the ChEIs (0.18 MMSE points per year, 95% CI 0.07-0.28). CONCLUSIONS: ChEIs are associated with cognitive benefits that are modest but persist over time and with reduced mortality risk, which could be explained partly by their cognitive effects. Galantamine was the only ChEI demonstrating a significant reduction in the risk of developing severe dementia. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with Alzheimer dementia ChEIs decrease long-term cognitive decline and risk of death and that galantamine decreases the risk of severe dementia.
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“These include a study demonstrating that 11,652 Swedish propensity-matched patients with AD who took ChEIs, compared to 5,826 who did not, performed slightly and persistently better during mean 5-years follow-up (MMSE 0.13; 0.06 -0.20 points per year better), with a doseresponse effect.(494)”
From Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission (2024) · cites this paper as [494]
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“When multiple dispensations were used, their DDD were added [36].”
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Metadata
- Authors
- Xu, H., Garcia-Ptacek, S., Jönsson, L., Wimo, A., Nordström, P., & Eriksdotter, M.
- Affiliations
- Karolinska University Hospital (SE)
- From the Division of Clinical Geriatrics (H.X., S.G.-P., M.E.), Division of Neurogeriatrics (L.J., A.W.), Department of Neurobiology, Care Sciences and Society, and Department of Medical Epidemiology and Biostatistics (H.X.), Karolinska Institutet; Department of Internal Medicine (S.G.-P.), Neurology Section, Södersjukhuset, Stockholm, Sweden; H. Lundbeck A/S (L.J.), Copenhagen, Denmark; Department of Community Medicine and Rehabilitation (P.N.), Geriatric Medicine, Umeå University; and Theme Aging ...
- Corresponding author
- Xu, Hong
- Venue
- Neurology
- Published
- 2021-04-27
- Volume
- 96
- Issue
- 17
- Pages
- e2220-e2230
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- PMC
- PMC8166426
- OpenAlex
- W3138811377
- Cited by
- 182
- References
- 9
- Citations by year
- 2026: 23 · 2025: 32 · 2024: 26 · 2023: 35 · 2022: 49 · 2021: 16
- FWCI
- 22.60
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Neurology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DiVA at Umeå University (Umeå University) (submittedVersion, other-oa)
- Funders
- Svenska Sällskapet för Medicinsk Forskning
- Karolinska Institutet
- Stockholms Läns Landsting
- Umeå Universitet
- Forskningsrådet om Hälsa, Arbetsliv och Välfärd
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Pharmacology (medical) › Cholinesterase and Neurodegenerative Diseases
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Keywords
- cholinesterase inhibitors, Alzheimer's disease, cognitive decline, mortality, galantamine, advanced dementia, Mini-Mental State Examination, long-term treatment outcomes
- MeSH terms
- Mental Status and Dementia Tests, Aged, Aged, 80 and over, Alzheimer Disease, Cholinesterase Inhibitors, Female, Humans, Male, Time, Cohort Studies, Proportional Hazards Models, Cognitive Dysfunction
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