Abstract
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.
Glossary
- ChEI=
- cholinesterase inhibitor;
- CI=
- confidence interval;
- DDD=
- defined daily dose;
- DOMINO-AD=
- Donepezil and Memantine in Moderate to Severe Alzheimer's Disease;
- HR=
- hazard ratio;
- ICD-10=
- International Classification of Diseases, 10 revision;
- MMSE=
- Mini-Mental State Examination;
- RCT=
- randomized clinical trial;
- SveDem=
- Swedish Dementia Registry
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
↵* These authors contributed equally to this work.
The Article Processing Charge was funded by FORTE.
See page e2247
Class of Evidence: NPub.org/coe
Podcast: NPub.org/fqxxkt
- Received April 8, 2020.
- Accepted in final form January 4, 2021.
- Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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