Acetylcholinesterase inhibitors and risk of stroke and death in people with dementia

Tan, Edwin C.K.; Johnell, Kristina; García-Ptacek, Sara; Haaksma, Miriam L.; Fastbom, Johan; Bell, John; Eriksdotter, Maria

doi:10.1016/j.jalz.2018.02.011

Cited by 40 publications

(44 citation statements)

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“…Donepezil was the most commonly prescribed ChEI, which probably reflects that it was the first approved ChEI and is better tolerated compared with galantamine and rivastigmine’s oral form 11. In addition, we found that donepezil was the only ChEI consistently associated with reduction in cardiovascular mortality, corroborating previous data on cardiovascular and cerebrovascular outcomes from Nordström, Tan and others 7 8 35. Hwang and colleagues also found anti-inflammatory effects in donepezil treatment, however only in high doses 39…”

Section: Discussionsupporting

confidence: 89%

“…ChEI provide a modest, but significant effect on cognition; however, few studies have considered their long-term use 5 6. Moreover, several studies have found improved survival and positive changes in the relative risks for cardiovascular events in ChEI-treated patients with dementia 7–9. On the other hand, the increased incidence of hypotension, falls and gastrointestinal side-effects may counterbalance their protective effect 10.…”

Section: Introductionmentioning

confidence: 99%

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

Sečník

Schwertner

Alvarsson

et al. 2020

BMJ Open Diab Res Care

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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.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

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

Sečník

Schwertner

Alvarsson

et al. 2020

BMJ Open Diab Res Care

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“…[30] Acetylcholinesterase inhibitors have been shown to be associated with a reduced risk of stroke and mortality in people with Alzheimer's disease and dementia. [31,32] The use of anticholinergic medications may thus oppose these protective effects. Although partipants in our study were less likely to be using an acetylcholinesterase inhibitor if they had a higher ACB score, 40% of those with an ACB score of ≥2 were still concurrently prescribed an acetylcholinesterase inhibitor.…”

Section: Discussionmentioning

confidence: 99%

Anticholinergic Burden and Risk of Stroke and Death in People with Different Types of Dementia

Tan

Eriksdotter

García-Ptacek

et al. 2018

JAD

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“…Acetylcholinesterase enzyme is responsible to breakdown acetylcholine, a neurotransmitter. The inhibition of this enzyme can hamper the transmission of the nerve impulse; causing neurotoxicity and in result to impact on the dynamics of ecosystems (Tan et al, 2018). Studies have showed the AChE inhibition in different organisms' exposure to glyphosate such as polychaeta (Tarouro et al, 2018); fish (Gholami-Seyedkolaei et al, 2013); and mussels (Sandrini et al, 2013).…”

Section: Resultsmentioning

confidence: 99%

Biochemical and genotoxicity assessment of a polluted urban river using the native fish Astyanax altiparanae Garutti & Britski (Teleostei, Characidae)

Calado¹,

Andrade²,

Garrido³

et al. 2020

Ecotoxicol. Environ. Contam.

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Agriculture residues and domestic effluents are contaminants that reach aquatic ecosystems leading to toxic effects to environment and human health. These contaminants impacting mainly developing countries, due to precarious treatment of effluents and lack of legislation in the use of pesticides. Perequê River (South of Brazil) is impacted by pesticides (mainly glyphosate) and domestic effluents. The aims of this study were to analyze the concentration of glyphosate in water and sediments of Perequê River; and to evaluate the sublethal effects of the river contamination in Astyanax altiparanae using biomarkers. A sampling of water, sediment and fish were carried out in Perequê River (November/2016). The samples were collected in two sites, site 1 (S1) that is located on agriculture area and water catchment point; and site 2 (S2) located on the area with a domestic effluents influence. Water and sediment samples were used to glyphosate quantification. Fish were collected and tissues (brain, muscle, liver) were used to biochemical and genetic biomarkers. Glyphosate were quantified in S1, which is impacted by agriculture. Alterations in the liver biomarkers were not observed between the sites. However, the decrease in the AChE activity was observed in the S2, showing that the mixture of contaminants (urban and agriculture contaminants) can lead to anticholinesterasic effects. The sublethal effects observed can be a threat of environmental and human health.

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Acetylcholinesterase inhibitors and risk of stroke and death in people with dementia

Cited by 40 publications

References 25 publications

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

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

Anticholinergic Burden and Risk of Stroke and Death in People with Different Types of Dementia

Biochemical and genotoxicity assessment of a polluted urban river using the native fish Astyanax altiparanae Garutti & Britski (Teleostei, Characidae)

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