Article Text
Abstract
Objective Cholinesterase inhibitors (ChEIs) and memantine are the only approved pharmacological treatments for Alzheimer’s disease (AD). Recent literature suggests reductions in cardiovascular burden and risk of stroke in ChEI users. However, the clinical effectiveness of these drugs in patients with diabetes mellitus (DM) and dementia has not been evaluated.
Research design and methods We conducted a registry-based open-cohort study of 22 660 patients diagnosed with AD and mixed-pathology dementia registered in the Swedish Dementia Registry until December 2015. Information on drug use, comorbidity and mortality was extracted using the linkage with the National Patient Registry, the Prescribed Drug Registry and the Cause of Death Registry. In total, 3176 (14%) patients with DM and 19 484 patients without DM were identified. Propensity-score matching, Cox-regression and competing-risk regression models were applied to produce HRs with 95% CIs for differences in all-cause, cardiovascular and diabetes-related mortality rates in ChEI users and non-users.
Results After matching the ChEI use in patients with DM was associated with 24% all-cause mortality reduction (HR 0.76 (95% CI 0.67 to 0.86)), compared with 20% reduction (0.80 (0.75 to 0.84)) in non-DM users. Donepezil and galantamine use were associated with a reduced mortality in both patients with DM (0.84 (0.74 to 0.96); 0.80 (0.66 to 0.97)) and patients without DM (0.85 (0.80 to 0.90); 0.93 (0.86 to 0.99)). Donepezil was further associated with reduction in cardiovascular mortality, however only in patients without DM (0.84 (0.75 to 0.94)). Rivastigmine lowered mortality only in the whole-cohort analysis and in patients without DM (0.82 (0.75 to 0.89)). Moreover, ChEI use was associated with 48% reduction in diabetes-related mortality (HR 0.52 (0.32 to 0.87)) in the whole-cohort analysis. Last, low and high doses were associated with similar benefit.
Conclusions We found reductions in mortality in patients with DM and AD or mixed-pathology dementia treated with ChEIs, specifically donepezil and galantamine were associated with largest benefit. Future studies should evaluate whether ChEIs help maintain self-management of diabetes in patients with dementia.
- alzheimer's disease
- dementia
- mortality
- cardiovascular mortality
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Footnotes
DR and ME contributed equally.
Contributors ES analyzed the data and codesigned the study. MA contributed to the introduction and discussion. NH suggested the statistical methods and contributed to discussion. JF extracted the data from the Drug Registry. BW interpreted the data and contributed to the discussion. SG-P kindly provided all raw registry data. DR and ME supervised and codesigned the study. JS designed the study, analyzed the data and wrote the manuscript. All authors have reviewed the manuscript’s content and approved of its final version.
Funding This study has been supported by the Swedish Brain Power, Swedish Research Council (grant numbers 2012-2291, 2016-02317, 2018-02843), Alzheimerfonden, CIMED, Stockholm County Council (ALF project), the Swedish Associations of Local Authorities and Regions, the Swedish Order of Saint John/Johanniterorden, Swedish Society for Medical Research, FORTE (the Swedish Council for Health, Working Life and Welfare, dnr: 2017-01646), the Swedish Stroke Association, Margaretha af Ugglas Foundation and the Stiftelsen för Gamla Tjänarinnor.
Competing interests None declared.
Patient consent for publication Not required.
Ethics approval Regional ethical committee in Stockholm, Sweden (2015/1313-32).
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement No data are available. The entities responsible for the original data and the Swedish law do not allow for sharing of the data from the Swedish national or quality-of-care registers.