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Background: Metformin has been suggested to reduce dementia risk; however, most epidemiologic studies have been limited by immortal time bias or confounding due to disease severity., Objectives: To investigate the association of metformin initiation with incident dementia using strategies that mitigate these important sources of bias., Methods: Residents of Ontario, Canada ≥66 years newly diagnosed with diabetes from January 1, 2008 to December 31, 2017 entered this retrospective population-based cohort. To consider the indication for metformin monotherapy initiation, people with hemoglobin A1c of 6.5%-8.0% and estimated glomerular filtration rate ≥45 mL/min/1.73 m 2 were selected. Using the landmark method to address immortal time bias, exposure was grouped into "metformin monotherapy initiation within 180 days after new diabetes diagnosis" or "no glucose-lowering medications within 180 days." To address disease latency, 1-year lag time was applied to the end of the 180-day landmark period. Incident dementia was defined using a validated algorithm for Alzheimer's disease and related dementias. Adjusted hazard ratios (aHR) and confidence intervals (CIs) were estimated from propensity-score weighted Cox proportional hazard models., Results: Over mean follow-up of 6.77 years from cohort entry, metformin initiation within 180 days after new diabetes diagnosis (N = 12,331; 978 events; 65,762 person-years) showed no association with dementia risk (aHR [95% CI] = 1.05 [0.96-1.15]), compared to delayed or no glucose-lowering medication initiation (N = 22,369; 1768 events; 117,415 person-years)., Conclusion: Early metformin initiation was not associated with incident dementia in older adults newly diagnosed with diabetes. The utility of metformin to prevent dementia was not supported., (© 2023 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

Background: The use of intravenous thrombolysis is associated with improved clinical outcomes. Whether thrombolysis is associated with reduced incidence of poststroke dementia remains uncertain. We sought to estimate if the use of thrombolysis following first-ever ischemic stroke was associated with a reduced rate of incident dementia using a pragmatic observational design., Methods: We included first-ever ischemic stroke patients from the Ontario Stroke Registry who had not previously been diagnosed with dementia. The primary outcome was incident dementia ascertained by a validated diagnostic algorithm. We employed inverse probability of treatment-weighted Cox proportional hazard models to estimate the cause-specific hazard ratio for the association of thrombolysis and incident dementia at 1 and 5 years following stroke., Results: From July 2003 to March 2013, 7072 patients with ischemic stroke were included, 3276 (46.3%) were female and mean age was 71.0 (SD, 12.8) years. Overall, 38.2% of the cohort (n=2705) received thrombolysis, 77.2% (n=2087) of which was administered within 3 hours of stroke onset. In the first year following stroke, thrombolysis administration was associated with a 24% relative reduction in the rate of developing dementia (cause-specific hazard ratio, 0.76 [95% CI, 0.58-0.97]). This association remained significant at 5 years (cause-specific hazard ratio, 0.79 [95% CI, 0.66-0.91]) and at the end of follow-up (median 6.3 years; cause-specific hazard ratio, 0.79 [95% CI, 0.68-0.89])., Conclusions: Thrombolysis administration following first-ever ischemic stroke was independently associated with a reduced rate of dementia. Incident dementia should be considered as a relevant outcome when evaluating risk/benefit of thrombolysis in ischemic stroke patients.

Background: We assessed secular trends in the burden of ischaemic heart disease (IHD), stroke, and dementia in the Organization for Economic Co-operation and Development (OECD) countries., Methods: Using the Global Burden of Disease (GBD) Study 2017, we compared sex-specific and age-standardized rates of disability-adjusted life years (DALY); mortality, incidence, and prevalence of IHD and stroke; and dementia per 100,000 people, in the world, OECD countries, and Canada., Results: From 1990 to 2017, the crude incidence number of IHD, stroke, and dementia increased 52%, 76%, and 113%, respectively. Likewise, the prevalence of IHD (75%), stroke (95%), and dementia (119%) increased worldwide. In addition during the study period, the crude global number of deaths of IHD increased 52%, stroke by 41%, and dementia by 146% (9, 6, and 3 million deaths in 2017, respectively). Despite an increase in the crude number of these diseases, the global age-standardized incidence rate of IHD, stroke, and dementia decreased by -27%, - 11%, and - 5%, respectively. Moreover, there was a decline in their age-standardized DALY rates (- 1.17%, - 1.32%, and - 0.23% per year, respectively) and death rates (- 1.29%, - 1.46%, and - 0.17% per year, respectively), with sharper downward trends in Canada and OECD countries. Almost all trends flattened during the last decade., Conclusions: From 1990 to 2017, the age-standardized burden of IHD, stroke, and dementia decreased, more prominently in OECD countries than the world. However, their rising crude numbers mainly due to population growth and ageing require urgent identification of reversible risk and protective factors., (© 2021. Fondazione Società Italiana di Neurologia.)

Background and Purpose: Many patients with ischemic stroke present with multiple comorbidities that threaten survival and recovery. This study sought to determine the risks of adverse long-term stroke outcomes associated with multimorbid diabetes mellitus and depression., Methods: Retrospective analysis of prospectively collected data on consecutive patients without premorbid dementia admitted from the community for a first-ever acute ischemic stroke to comprehensive stroke centers across Ontario, Canada (2003-2013). Premorbid histories of diabetes mellitus and depression were ascertained within 5 years before stroke admission. Adjusted hazard ratios (aHR [95% CI]) of admission to long-term care, incident dementia, readmission for stroke or transient ischemic attack and all-cause mortality, over time among those discharged back into the community poststroke., Results: Among 23 579 stroke admissions, n=20 201 were discharged back into the community. Diabetes mellitus and depression were associated with synergistic hazards of admission to long-term care (X 2 =5.4; P =0.02) over a median follow-up of 5.6 years. This interaction was observed among women specifically; depression multimorbidity showed particularly high hazards of admission to long-term care (aHR Depression =1.57 [1.24-1.98]) and incident dementia (aHR Depression =1.85 [1.40-2.44]) among women with diabetes mellitus. In the whole cohort, diabetes mellitus and depression were associated individually with long-term care admission (aHR Diabetes =1.20 [1.12-1.29]; aHR Depression =1.19 [1.04-1.37]), incident dementia (aHR Diabetes =1.14 [1.06-1.23]; aHR Depression =1.27 [1.08-1.49]), stroke/transient ischemic attack readmission (aHR Diabetes =1.18 [1.10-1.26]; aHR Depression =1.24 [1.07-1.42]), and all-cause mortality (aHR Diabetes =1.29 [1.23-1.36]; aHR Depression =1.16 [1.05-1.29])., Conclusions: The risks of dementia and needing long-term care in the years after surviving a stroke were particularly elevated among women when premorbid diabetes mellitus and depression occurred together. Long-term stroke recovery strategies might target high-risk patients with mood and metabolic multimorbidity.

Among those aged 80 years and older in Ontario, Canada, stroke and dementia incidence declined concomitantly from 2002-03 to 2013-14. This study aimed to report the concurrent temporal trends of stroke and dementia prevalence in Ontario among the same age demographic. The prevalence of both stroke and dementia increased from 2003-04 to 2012-13 in both sexes and the magnitude in which prevalence of dementia increased over time exceeded that of stroke. The substantial increase in the prevalence of dementia may be because of increased recognition and diagnoses of dementia and increased survival of stroke patients who are at higher risk of developing dementia.

Introduction: We discovered a concomitant decline in stroke and dementia incidence rates at a whole population level in Ontario, Canada. This study explores these trends within demographic subgroups., Methods: We analyzed administrative data sources using validated algorithms to calculate stroke and dementia incidence rates from 2002 to 2013., Results: For more than 12 years, stroke incidence remained unchanged among those aged 20 to 49 years and decreased for those aged 50 to 64, 65 to 79, and 80+ years by 22.7%, 36.9%, and 37.9%, respectively. Dementia incidence increased by 17.3% and 23.5% in those aged 20 to 49 and 50 to 64 years, respectively, remained unchanged in those aged 65 to 79 years, and decreased by 15.4% in those aged 80+ years., Discussion: The concomitant decline in stroke and dementia incidence rates may depict how successful stroke prevention has targeted shared risk factors of both conditions, especially at advanced ages where such risk factors are highly prevalent. We lend support for the development of an integrated system of stroke and dementia prevention., (Copyright © 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.)

With an aging population, patients are increasingly likely to present with stroke and pre-existing dementia, which may lead to greater death and disability. The aim of this work was to assess the risk of all-cause mortality and poor functional outcomes after ischemic stroke in patients with and without pre-existing dementia. We conducted a multicenter cohort study of all patients presenting to 12 tertiary care institutions participating in the Registry of the Canadian Stroke Network (RCSN) with a first ischemic stroke between 2003 and 2008. Individuals with pre-existing dementia were matched using propensity-score methods with patients without dementia during their index hospitalization based on the following characteristics: age (within 3 years), sex, stroke severity, stroke subtype (lacunar vs. non-lacunar), level of consciousness, vascular risk factors, dysphagia, glucose and creatinine on admission, Charlson index, residence prior to hospitalization (home vs. other), pre-admission dependency, hospital arrival via ambulance, admission to stroke unit, thrombolysis, and palliative care. A propensity score for all-cause mortality and clinical outcomes was developed. Registry of the Canadian Stroke Network (RCSN) and Registered Persons Database (RPDB). The primary outcome was all-cause mortality at 30 days. Secondary outcomes included mortality at discharge and at 1 year, disability at discharge (modified Rankin scale ≥ 3), medical complications (pneumonia), and discharge disposition. A subgroup analysis assessing the risk of intracerebral hemorrhage among those receiving thrombolysis was also conducted. We matched 877 patients with an acute ischemic stroke and pre-existing dementia to 877 stroke patients without dementia. Patients were well matched. The mean age was 82 years and 58 % were women. Mortality at discharge, 30 days, and 1 year after stroke was similar in patients with and without dementia [for mortality at discharge RR 0.88 [95 % confidence interval (CI) 0.74-1.05]; mortality at 30-days: RR 0.88 (95 % CI 0.75-1.03) and mortality at 1 year: RR 1.01 (95 % CI 0.92-1.11). Patients with pre-existing dementia had similar disability at discharge and home disposition. In the subgroup of patients who received thrombolysis, there were no differences between those with and without dementia in the risk of intracerebral hemorrhage (RR 1.27; 95 % CI 0.69-2.35) and no differences in mortality or disability at discharge. Pre-existing dementia is not independently associated with mortality, disability, or institutionalization after ischemic stroke. Pre-existing dementia may not necessarily preclude access to thrombolytic therapy and specialized stroke care.

Background: Sulfonylureas are oral glucose‐lowering medications positioned as a second‐line therapy for type 2 diabetes. Evidence relating them to cognitive decline has been mixed. The objective was to determine whether sulfonylurea use was associated with a differential risk of dementia compared with dipeptidyl peptidase‐4 (DPP4) inhibitor use. Methods: Using administrative data from residents in Ontario, Canada, adults aged ≥66 years who were new users of a sulfonylurea or a DPP4 inhibitor from June 14, 2011, to March 31, 2021 entered this population‐based retrospective cohort study. Dementia was ascertained using a validated algorithm for Alzheimer's disease and related dementias. Propensity‐score weighted Cox proportional hazards models were used to obtain adjusted hazard ratios (aHR) and confidence intervals (CI) for time to incident dementia. The observation window started at 1 year after cohort entry to mitigate protopathic bias due to delayed diagnosis. The primary analysis used an intention‐to‐treat exposure definition. A separate propensity‐score weighted analysis was conducted to explore within‐class differences in dementia risk among sulfonylurea new users selected from the primary cohort. Results: Among 107,806 DPP4 inhibitor new users and 37,030 sulfonylurea new users, sulfonylureas compared with DPP4 inhibitors were associated with a higher risk of dementia (18.4/1000 person‐years; aHR [95% CI] = 1.09 [1.04–1.15]) over a mean follow‐up of 4.82 years from cohort entry. Glyburide compared to gliclazide exhibited a higher dementia risk (aHR [95% CI] = 1.17 [1.03–1.32]). Conclusion: New use of a sulfonylurea especially glyburide was associated with a higher dementia risk compared with new use of a DPP4 inhibitor in older adults with diabetes. See related Editorial by Lee et al. in this issue. [ABSTRACT FROM AUTHOR]

Introduction: Studies suggest associations between proton pump inhibitors (PPIs) and dementia risk; however, many neither considered histamine-2 receptor antagonists (H2RAs) nor baseline cognitive status. Methods: Participants (National Alzheimer's Coordinating Center Database; 2005-2021) using a PPI or H2RA were compared. Covariate-adjusted Cox regression was used to estimate hazard ratios (HR) for progression from normal cognition to mild cognitive impairment (MCI), and from MCI to dementia over 5 years. In a propensity-score-matched subsample of mild-moderate Alzheimer's disease (AD), mixed-effects negative binomial regression was used to estimate decline in delayed recall memory. Results: Compared to PPI, H2RAuse was associated with earlier progression fromMCI to dementia (HR = 1.40 [1.09-1.81]; n = 1701), and with faster memory decline in AD over time (rate ratio=0.76 [0.64-0.92]; n=628), but not with progression from normal cognition toMCI (HR = 0.94 [0.71-1.24]; n = 2784). Discussion: Compared to PPIs, H2RAs were associated with cognitive decline, specifically among people with pre-existing cognitive impairment. [ABSTRACT FROM AUTHOR]

Introduction We discovered a concomitant decline in stroke and dementia incidence rates at a whole population level in Ontario, Canada. This study explores these trends within demographic subgroups. Methods We analyzed administrative data sources using validated algorithms to calculate stroke and dementia incidence rates from 2002 to 2013. Results For more than 12 years, stroke incidence remained unchanged among those aged 20 to 49 years and decreased for those aged 50 to 64, 65 to 79, and 80+ years by 22.7%, 36.9%, and 37.9%, respectively. Dementia incidence increased by 17.3% and 23.5% in those aged 20 to 49 and 50 to 64 years, respectively, remained unchanged in those aged 65 to 79 years, and decreased by 15.4% in those aged 80+ years. Discussion The concomitant decline in stroke and dementia incidence rates may depict how successful stroke prevention has targeted shared risk factors of both conditions, especially at advanced ages where such risk factors are highly prevalent. We lend support for the development of an integrated system of stroke and dementia prevention. [ABSTRACT FROM AUTHOR]