The 2022 update of the Canadian Stroke Best Practice Recommendations (CSBPR) for Acute Stroke Management, 7^th edition, is a comprehensive summary of current evidence-based recommendations, appropriate for use by an interdisciplinary team of healthcare providers and system planners caring for persons with an acute stroke or transient ischemic attack. These recommendations are a timely opportunity to reassess current processes to ensure efficient access to acute stroke diagnostics, treatments, and management strategies, proven to reduce mortality and morbidity. The topics covered include prehospital care, emergency department care, intravenous thrombolysis and endovascular thrombectomy (EVT), prevention and management of inhospital complications, vascular risk factor reduction, early rehabilitation, and end-of-life care. These recommendations pertain primarily to an acute ischemic vascular event. Notable changes in the 7^th edition include recommendations pertaining the use of tenecteplase, thrombolysis as a bridging therapy prior to mechanical thrombectomy, dual antiplatelet therapy for stroke prevention,¹ the management of symptomatic intracerebral hemorrhage following thrombolysis, acute stroke imaging, care of patients undergoing EVT, medical assistance in dying, and virtual stroke care. An explicit effort was made to address sex and gender differences wherever possible. The theme of the 7^th edition of the CSBPR is building connections to optimize individual outcomes, recognizing that many people who present with acute stroke often also have multiple comorbid conditions, are medically more complex, and require a coordinated interdisciplinary approach for optimal recovery. Additional materials to support timely implementation and quality monitoring of these recommendations are available at www.strokebestpractices.ca.

Frailty is common in stroke and has important disease- and treatment-modifying effects. The need to develop clinical practice and research for the impact of frailty on stroke is likely to increase in the coming decades as the global population ages, resulting in a higher burden of frailty that is likely to be borne disproportionately by lower- and middle-income countries. The global nature of frailty in stroke necessitates global action. This World Stroke Organization Scientific Statement synthesizes the current evidence relating to the prevalence and effects of frailty across the stroke pathway. Furthermore, it includes expert consensus on priority areas from a global panel: standardization of frailty assessments for research, explicit measurements of frailty (in addition to disability) in large clinical trials, dedicated studies investigating the treatment-modifying effects of frailty in acute stroke and secondary prevention, research investigating the impact of frailty on the different aspects of recovery and rehabilitation after stroke, and understanding the mechanisms underpinning the relationship between frailty and stroke for potential therapeutic exploitation. This scientific statement has been reviewed and approved by the World Stroke Organization Executive.

Importance: Age is a leading predictor of poor outcomes after brain injuries like stroke. The extent to which age is associated with preexisting burdens of brain changes, visible on neuroimaging but rarely considered in acute decision-making or trials, is unknown.Objectives: To explore the mediation of age on functional outcome by neuroimaging markers of frailty (hereinafter neuroimaging frailty) in patients with acute ischemic stroke receiving endovascular thrombectomy (EVT).Design, Setting, and Participants: This cohort study was a post hoc analysis of the Safety and Efficacy of Nerinetide (NA-1) in Subjects Undergoing Endovascular Thrombectomy for Stroke (ESCAPE-NA1) randomized clinical trial, which investigated intravenous (IV) nerinetide in patients who underwent EVT within a 12-hour treatment window. Patients from 48 acute care hospitals in 8 countries (Canada, US, Germany, Korea, Australia, Ireland, UK, and Sweden) were enrolled between March 1, 2017, and August 12, 2019. Markers of brain frailty (brain atrophy [subcortical or cortical], white matter disease [periventricular or deep], and the number of lacunes and chronic infarctions) were retrospectively assessed while reviewers were blinded to other imaging (eg, computed tomography angiography, computed tomography perfusion) or outcome variables. All analyses were done between December 1, 2022, and January 31, 2023.Exposures: All patients received EVT and were randomized to IV nerinetide (2.6 mg/kg of body weight) and alteplase (if indicated) treatment vs best medical management.Main Outcome and Measures: The primary outcome was the proportion of the total effect of age on 90-day outcome, mediated by neuroimaging frailty. A combined mediation was also examined by clinical features associated with frailty and neuroimaging markers (total frailty). Structural equation modeling was used to create latent variables as potential mediators, adjusting for baseline, early ischemic changes; stroke severity; onset-to-puncture time; nerinetide treatment; and alteplase treatment.Results: Among a total of 1105 patients enrolled in the study, 1102 (median age, 71 years [IQR, 61-80 years]; 554 [50.3%] male) had interpretable imaging at baseline. Of these participants, 549 (49.8%) were treated with IV nerinetide. The indirect effect of age on 90-day outcome, mediated by neuroimaging frailty, was associated with 85.1% of the total effect (β coefficient, 0.04 per year [95% CI, 0.02-0.06 per year]; P < .001). When including both frailty constructs, the indirect pathway was associated with essentially 100% of the total effect (β coefficient, 0.07 per year [95% CI, 0.03-0.10 per year]; P = .001).Conclusions and Relevance: In this cohort study, a secondary analysis of the ESCAPE-NA1 trial, most of the association between age and 90-day outcome was mediated by neuroimaging frailty, underscoring the importance of features like brain atrophy and small vessel disease, as opposed to chronological age alone, in predicting poststroke outcomes. Future trials could include such frailty features to stratify randomization or improve adjustment in outcome analyses.

Lecanemab and donanemab are monoclonal antibody therapies that remove amyloid-beta from the brain. They are the first therapies that alter a fundamental mechanism, amyloid-beta deposition, in Alzheimer disease (AD). To inform Canadian decisions on approval and use of these drugs, the Canadian Consortium on Neurodegeneration in Aging commissioned Work Groups to review evidence on the efficacy and safety of these new therapies, as well as their projected impacts on Canadian dementia systems of care. We included persons with lived experience with Alzheimer disease in the discussion about the benefits and harms. Our review of the trial publications found high quality evidence of statistically significant group differences, but also recognized that there are mixed views on the clinical relevance of the observed differences and the value of therapy for individual patients. The drugs are intended for persons with early AD, at a stage of mild cognitive impairment or mild dementia. If patients are treated, then confirmation of AD by positron emission tomography or cerebrospinal fluid analysis and monitoring for risk of amyloid-related imaging abnormalities was recommended, as done in the clinical trials, although it would strain Canadian resource capacity. More data are needed to determine the size of the potentially eligible treatment population in Canada.

Survivors of stroke are at high risk of dementia, but it is unclear whether this elevated risk is due to other confounding factors. We sought to determine the magnitude and time course of dementia risk after stroke with robust comparison with matched nonstroke populations in an entire province. We conducted a population-wide analysis of over 15 million people in Ontario, Canada, between 2002 and 2022. Using linked administrative databases, we identified adults hospitalized for ischemic stroke, intracerebral hemorrhage, or acute myocardial infarction (AMI). We performed 1:1 matching of people with stroke to all residents of Ontario (reference population) without stroke and separately to those with AMI, on age, sex, rural residence, neighborhood deprivation, and vascular comorbidities. We calculated the incident rate per 100 person-years and hazard ratios (HRs) for all-cause dementia between 90 days after stroke and 1 year, 5 years, 10 years, and total follow-up and evaluated time-varying HRs. In sensitivity analyses, we adjusted for new stroke in follow-up and the cumulative number of health care encounters. Of 175,980 stroke survivors, 174,817 (99.3%) were successfully matched to people in the reference population and 151,673 (90%) were matched to those with AMI. Over a mean follow-up of 5.6 years (SD 4.71, maximum 20 years), a total of 32,621 (18.7%) were diagnosed with dementia after stroke compared with 21,929 (12.5%) in the Ontario reference population. The rate of dementia per 100 person-years over total follow-up time was higher after acute stroke compared with the reference population (3.34 vs 1.89) and the AMI cohort (3.19 vs 1.75). The HR of dementia was higher in those with stroke compared with the reference population (1.76, 95% CI 1.73-1.79) and the AMI cohort (1.82, 1.79-1.85). HRs varied across time, with over 2.5-fold increase in dementia risk within 1 year, decreasing to 1.5-fold at 5 years and 1.3-fold at 20 years after stroke. Estimates were similar in sensitivity analyses. Recurrent stroke was associated with 3-fold increased dementia risk. In this population-wide study, almost one-fifth of stroke survivors were diagnosed with dementia, with an 80% higher risk of dementia after robust matching to those without stroke. Targeted dementia prevention efforts in acute and chronic survivors of stroke are needed.

Background: Although age-standardized stroke occurrence has been decreasing, the absolute number of stroke events globally, and in Canada, is increasing. Stroke surveillance is necessary for health services planning, informing research design, and public health messaging. We used administrative data to estimate the number of stroke events resulting in hospital or emergency department presentation across Canada in the 2017–18 fiscal year.Methods: Hospitalization data were obtained from the Canadian Institute for Health Information (CIHI) Discharge Abstract Database and the Ministry of Health and Social Services in Quebec. Emergency department data were obtained from the CIHI National Ambulatory Care Reporting System (Alberta and Ontario). Stroke events were identified using ICD-10 coding. Data were linked into episodes of care to account for readmissions and interfacility transfers. Projections for emergency department visits for provinces/territories outside of Alberta and Ontario were generated based upon age and sex-standardized estimates from Alberta and Ontario.Results: In the 2017–18 fiscal year, there were 108,707 stroke events resulting in hospital or emergency department presentation across the country. This was made up of 54,357 events resulting in hospital admission and 54,350 events resulting in only emergency department presentation. The events resulting in only emergency department presentation consisted of 25,941 events observed in Alberta and Ontario and a projection of 28,409 events across the rest of the country.Conclusions: We estimate a stroke event resulting in hospital or emergency department presentation occurs every 5 minutes in Canada.