Cholinesterase inhibitors in patients with diabetes mellitus and dementia: an open-cohort study of ~23 000 patients from the Swedish Dementia Registry

Abstract

ObjectiveCholinesterase 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 methodsWe 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.ResultsAfter 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.ConclusionsWe 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.

Initial in-hospital heart rate is associated with long-term survival in patients with acute ischemic stroke

“…However, whether beta-blockers, calcium-channel blockers, or I(f) channel inhibitor are associated with survival benefit in patients with coronary artery disease is still inconclusive [50][51][52]. In addition to the above agents, cholinesterase inhibitors can also slow the heart rate via increasing cholinergic effect and show some potential in improving the lifespan [53][54][55]; however, further studies are needed to investigate whether they can improve survival after AIS. We hope that using appropriate medications to reduce heart rate may play a role in improving the long-term survival after AIS in the future.…”

The Cholinergic Drug Galantamine Alleviates Oxidative Stress Alongside Anti-inflammatory and Cardio-Metabolic Effects in Subjects With the Metabolic Syndrome in a Randomized Trial

“…A recent meta-analysis-based study highlights that galantamine and other AChE inhibitor treatments are associated with lower risk of CV events including stroke, acute coronary syndrome, and cardiovascular mortality ( 66 ). In addition, a very recent study reported that AChE inhibitor treatments are associated with lower mortality in patients with diabetes mellitus with Alzheimer's disease or patients with mixed-pathology dementia, with a specific benefit provided by galantamine or another AChE inhibitor—donepezil ( 67 ). In light of all of these findings, it seems reasonable to suggest that further studies with galantamine treatments would be of specific interest for patients with Alzheimer's disease with MetS or diabetes ( 68 – 70 ).…”

The Impact of Disease Registries on Advancing Knowledge and Understanding of Dementia Globally

“…Using SveDem (Xu et al, 2021) found that cholinesterase inhibitors use was associated with higher memory over time (as measured by MMSE) and lower death compared to patients not using Cholinesterase inhibitors. Similarly, using SveDem (Secnik et al, 2020a), found that cholinesterase inhibitors use was associated with reduced mortality. One study found that cholinesterase inhibitors use reduces neurological and functional problems in pre-stroke dementia (Wakisaka et al, 2021).…”