| 1. |
- Secnik, Juraj, et al.
(författare)
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Cholinesterase inhibitors in patients with diabetes mellitus and dementia : an open-cohort study of similar to 23 000 patients from the Swedish Dementia Registry
- 2020
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Ingår i: BMJ Open Diabetes Research & Care. - : BMJ. - 2052-4897. ; 8:1
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Tidskriftsartikel (refereegranskat)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.
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| 2. |
- Sečník, Juraj
(författare)
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Diabetes mellitus in patients with dementia : clinical care and pharmacological treatment
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Diabetes mellitus (DM) and dementia are frequent chronic disorders in the older population, however their relationship is complex - while DM is an established risk factor for dementia, cognitive symptoms in dementia may hinder the self-management essential in DM care. Importantly, the co-occurrence of DM and dementia is common in clinical practice, however the research examining patients suffering from both disorders is scarce. This thesis analyzes the bidirectional associations between DM and dementia in patients with both disorders in Sweden, with specific focus on pharmacological care. The thesis is based on the merged data from the Swedish Dementia Registry and the Swedish Prescribed Drug Register, Swedish National Patient Register, Swedish Cause of Death Register, Total Population Register and the Longitudinal Integrated Database for Health Insurance and Labour Market Studies. All included studies were observational, study 1 was cross-sectional and in studies 2-5 longitudinal open-cohort design was used. Study 1 compares the characteristics of patients with DM and dementia to patients without DM. We show that DM is prevalent in 16.5% of patients with dementia, and that DM is associated with diagnosis at younger age, vascular dementia and mixed-pathology dementia (MixDem), and less frequent use of cholinesterase inhibitors (ChEI) and memantine. In study 2 we analyze the association between ChEI and mortality in patients with DM and Alzheimer’s disease (AD) or MixDem. We show that the initiation of ChEI class, donepezil and galantamine is associated with lower all-cause mortality, and the direction and strength of the association is comparable to DM-free patients. Study 3 explores the changes in long-term utilization of antidiabetic medication in patients with type 2 DM or other/unspecified DM with and without dementia. We conclude that utilization as well as new dispensation of insulin is significantly higher among patients with dementia, while the newer antidiabetic drugs are less commonly prescribed. Study 4 compares the mortality risk associated with six major antidiabetic drugs in patients with type 2 DM or other/unspecified DM and with and without dementia diagnosis. Overall, the initiation of insulin in patients with type 2 DM or other/unspecified DM is associated with higher mortality, regardless of dementia status. Additionally, we observe lower mortality in patients with dementia who used sodium-glucose cotransporter-2 inhibitors (SGLT-2i). Lastly, study 5 examines whether the use of antidiabetic medications is associated with longitudinal changes in Mini-Mental State Examination (MMSE) scores in patients with AD or MixDem. Importantly, we conclude slower decline in MMSE scores among users of metformin and dipeptidyl-peptidase-4 inhibitors. In conclusion, the patients with DM and dementia constitute a unique cohort less likely to receive treatment with ChEI despite the observed lower mortality associated with ChEI in our and previous studies. Moreover, we describe higher utilization of insulin and lower use of newer antidiabetic medications in patients with dementia, reflecting the Swedish clinical approach. Furthermore, we suggest that antidiabetic medications may provide cognitive benefit in patients with AD or MixDem. Additional studies focusing on optimization of antidiabetic and dementia medication, glycemic control as well as cognitive changes are needed to disentangle the role of DM in patients with manifest dementia.
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| 3. |
- Zupanic, Eva, et al.
(författare)
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Secondary Stroke Prevention After Ischemic Stroke in Patients with Alzheimer's Disease and Other Dementia Disorders
- 2020
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Ingår i: Journal of Alzheimer's Disease. - Amsterdam : IOS Press. - 1387-2877 .- 1875-8908. ; 73:3, s. 1013-1021
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Recurrent ischemic stroke (IS) increases the risk of cognitive decline. To lower the risk of recurrent IS, secondary prevention is essential.OBJECTIVE: Our aim was to compare post-discharge secondary IS prevention and its maintenance up to 3 years after first IS in patients with and without Alzheimer's disease and other dementia disorders.METHODS: Prospective open-cohort study 2007-2014 from the Swedish national dementia registry (SveDem) and the Swedish national stroke registry (Riksstroke). Patients with dementia who experienced an IS (n = 1410; 332 [23.5%] with Alzheimer's disease) were compared with matched non-dementia IS patients (n = 7150). We analyzed antiplatelet, anticoagulant, blood pressure lowering, and statin treatment as planned medication initiation at discharge and actual dispensation of medications at first, second, and third year post-stroke.RESULTS: At discharge, planned initiation of medication was higher in patients with dementia compared to non-dementia patients for antiplatelets (OR with 95% CI for fully adjusted models 1.23 [1.02-1.48]) and lower for blood pressure lowering medication (BPLM; 0.57 [0.49-0.67]), statins (0.57 [0.50-0.66]), and anticoagulants (in patients with atrial fibrillation - AF; 0.41 [0.32-0.53]). When analysis for antiplatelets was stratified according to the presence of AF, ORs for receiving antiplatelets remained significant only in the presence of AF (in the presence of AF 1.56 [1.21-2.01], in patients without AF 0.99 [0.75-1.33]). Similar trends were observed in 1st, 2nd, and 3rd year post-stroke.CONCLUSIONS: Dementia was a predictor of lower statin and BPLM use. Patients with dementia and AF were more likely to be prescribed antiplatelets and less likely to receive anticoagulants.
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