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Background: The United States lacks a timely and accurate nationwide surveillance system for acute ischemic stroke (AIS). We use the Get With The Guidelines-Stroke registry to apply poststratification survey weights to generate national assessment of AIS epidemiology, hospital care quality, and in-hospital outcomes. Methods: Clinical data from the Get With The Guidelines-Stroke registry were weighted using a Bayesian interpolation method anchored to observations from the national inpatient sample. To generate a US stroke forecast for 2019, we linearized time trend estimates from the national inpatient sample to project anticipated AIS hospital volume, distribution, and race/ethnicity characteristics for the year 2019. Primary measures of AIS epidemiology and clinical care included patient and hospital characteristics, stroke severity, vital and laboratory measures, treatment interventions, performance measures, disposition, and clinical outcomes at discharge. Results: We estimate 552 476 patients with AIS were admitted in 2019 to US hospitals. Median age was 71 (interquartile range, 60–81), 48.8% female. Atrial fibrillation was diagnosed in 22.6%, 30.2% had prior stroke/transient ischemic attack, and 36.4% had diabetes. At baseline, 46.4% of patients with AIS were taking antiplatelet agents, 19.2% anticoagulants, and 46.3% cholesterol-reducers. Mortality was 4.4%, and only 52.3% were able to ambulate independently at discharge. Performance nationally on AIS achievement measures were generally higher than 95% for all measures but the use of thrombolytics within 3 hours of early stroke presentations (81.9%). Additional quality measures had lower rates of receipt: dysphagia screening (84.9%), early thrombolytics by 4.5 hours (79.7%), and statin therapy (80.6%). Conclusions: We provide timely, reliable, and actionable US national AIS surveillance using Bayesian interpolation poststratification weights. These data may facilitate more targeted quality improvement efforts, resource allocation, and national policies to improve AIS care and outcomes.

Introduction: Cognitive and functional impairment after stroke are common, but the relation between cognitive and functional decline after stroke is not well studied. Methods: We used the comprehensive cohort in the Canadian Longitudinal Study on Aging to identify those with prior stroke, and we calculated reliable cognitive change scores from baseline to follow-up for the memory and executive domains. Functional decline was defined as an increase in the number of dependent daily activities. Using formal mediation analysis, we tested the presence and degree of mediation of the association between stroke and functional decline by cognitive decline. Results: There were 22,648 individuals with memory change scores (325 with stroke) and 17,613 individuals with executive change scores (241 with stroke). History of stroke was significantly associated with memory decline (−0.26 standard deviations, 95% CI −0.33 to −0.19), executive decline (−0.22, 95% CI −0.36 to −0.09), and new functional impairment (adjusted odds ratio 2.31, 95% CI 1.80–2.97) over a median of 3-year follow-up. Cognitive decline was a significant mediator of functional decline. Memory decline mediated only 5% of the relationship, whereas executive and overall cognitive decline mediated 13% and 22%, respectively. Conclusion: Cognitive decline is a mediator of the association between prior stroke and functional decline; consequently, strategies to delay, attenuate, or prevent cognitive decline after stroke may be important to preserving long-term functional status.

Background: to investigate the frequency and distribution of new ischemic brain lesions detected by diffusion-weighted imaging on brain magnetic resonance imaging after aortic arch surgery. Methods: This preplanned secondary analysis of the randomized, controlled ACE (Aortic Surgery Cerebral Protection Evaluation) CardioLink-3 trial compared the safety and efficacy of innominate versus axillary artery cannulation during elective proximal aortic arch surgery. Participants underwent pre and postoperative magnetic resonance imaging. New ischemic lesions were defined as lesions visible on postoperative, but not preoperative diffusion weighted imaging. Results: Of the 111 trial participants, 102 had complete magnetic resonance imaging data. A total of 391 new ischemic lesions were observed on diffusion-weighted imaging in 71 (70%) patients. The average number of lesions in patients with ischemic lesion were 5.5±4.9 with comparable numbers in the right (2.9±2.0) and left (3.0±2.3) hemispheres ( P =0.49). Half the new lesions were in the middle cerebral artery territory; 63% of the cohort had ischemic lesions in the anterior circulation, 49% in the posterior circulation, 42% in both, and 20% in watershed areas. A probability mask of all diffusion-weighted imaging lesions revealed that the cerebellum was commonly involved. More severe white matter hyperintensity on preoperative magnetic resonance imaging (odds ratio, 1.80 [95% CI, 1.10–2.95]; P =0.02) and lower nadir nasopharyngeal temperature during surgery (odds ratio per 1°C decrease, 1.15 [95% CI, 1.00–1.32]; P =0.05) were associated with the presentation of new ischemic lesion; older age (risk ratio per 1-year increase, 1.02 [95% CI, 1.00–1.04]; P =0.03) and lower nadir temperature (risk ratio per 1°C decrease, 1.06 [95% CI, 1.00–1.14]; P =0.06) were associated with greater number of lesions. Conclusions: In patients who underwent elective proximal aortic arch surgery, new ischemic brain lesions were common, and predominantly involved the middle cerebral artery territory or cerebellum. Underlying small vessel disease, lower temperature nadir during surgery, and advanced age were risk factors for perioperative ischemic lesions. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02554032.

The 2022 update of theCanadian Stroke Best Practice Recommendations (CSBPR) for Acute Stroke Management, 7thedition, 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 acuteischemicvascular event. Notable changes in the 7thedition include recommendations pertaining the use of tenecteplase, thrombolysis as a bridging therapy prior to mechanical thrombectomy, dual antiplatelet therapy for stroke prevention,1the 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 7thedition 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 atwww.strokebestpractices.ca.

Background: Cerebral small vessel disease (cSVD) is a major cause of stroke and dementia. Previous studies on the prevalence of cSVD are mostly based on single geographically defined cohorts in high-income countries. Studies investigating the prevalence of cSVD in low- and middle-income countries (LMICs) are expanding but have not been systematically assessed. Aim: This study aims to systematically review the prevalence of cSVD in LMICs. Results: Articles were searched from the Ovid MEDLINE and EMBASE databases from 1 January 2000 to 31 March 2022, without language restrictions. Title/abstract screening, full-text review, and data extraction were performed by two to seven independent reviewers. The prevalence of cSVD and study sample size were extracted by pre-defined world regions and health status. The Risk of Bias for Non-randomized Studies tool was used. The protocol was registered on PROSPERO (CRD42022311133). A meta-analysis of proportion was performed to assess the prevalence of different magnetic resonance imaging markers of cSVD, and a meta-regression was performed to investigate associations between cSVD prevalence and type of study, age, and male: female ratio. Of 2743 studies identified, 42 studies spanning 12 global regions were included in the systematic review. Most of the identified studies were from China (n = 23). The median prevalence of moderate-to-severe white matter hyperintensities (WMHs) was 20.5%, 40.5%, and 58.4% in the community, stroke, and dementia groups, respectively. The median prevalence of lacunes was 0.8% and 33.5% in the community and stroke groups. The median prevalence of cerebral microbleeds (CMBs) was 10.7% and 22.4% in the community and stroke groups. The median prevalence of moderate-to-severe perivascular spaces was 25.0% in the community. Meta-regression analyses showed that the weighted median age (51.4 ± 0.0 years old; range: 36.3–80.2) was a significant predictor of the prevalence of moderate-to-severe WMH and lacunes, while the type of study was a significant predictor of the prevalence of CMB. The heterogeneity of studies was high (>95%). Male participants were overrepresented. Conclusions: This systematic review and meta-analysis provide data on cSVD prevalence in LMICs and demonstrated the high prevalence of the condition. cSVD research in LMICs is being published at an increasing rate, especially between 2010 and 2022. More data are particularly needed from Sub-Saharan Africa and Central Europe, Eastern Europe, and Central Asia.

Contains fulltext : 290906.pdf (Publisher’s version ) (Open Access) OBJECTIVE: Determining the underlying causes of intracerebral hemorrhage (ICH) is of major importance, because risk factors, prognosis, and management differ by ICH subtype. We developed a new causal CLASsification system for ICH Subtypes, termed CLAS-ICH, based on recent advances in neuroimaging. METHODS: CLAS-ICH defines 5 ICH subtypes: arteriolosclerosis, cerebral amyloid angiopathy, mixed small vessel disease (SVD), other rare forms of SVD (genetic SVD and others), and secondary causes (macrovascular causes, tumor, and other rare causes). Every patient is scored in each category according to the level of diagnostic evidence: (1) well-defined ICH subtype; (2) possible underlying disease; and (0) no evidence of the disease. We evaluated CLAS-ICH in a derivation cohort of 113 patients with ICH from Massachusetts General Hospital, Boston, USA, and in a derivation cohort of 203 patients from Inselspital, Bern, Switzerland. RESULTS: In the derivation cohort, a well-defined ICH subtype could be identified in 74 (65.5%) patients, including 24 (21.2%) with arteriolosclerosis, 23 (20.4%) with cerebral amyloid angiopathy, 18 (15.9%) with mixed SVD, and 9 (8.0%) with a secondary cause. One or more possible causes were identified in 42 (37.2%) patients. Interobserver agreement was excellent for each category (kappa value ranging from 0.86 to 1.00). Despite substantial differences in imaging modalities, we obtained similar results in the validation cohort. INTERPRETATION: CLAS-ICH is a simple and reliable classification system for ICH subtyping, that captures overlap between causes and the level of diagnostic evidence. CLAS-ICH may guide clinicians to identify ICH causes, and improve ICH classification in multicenter studies. ANN NEUROL 2023;93:16-28. 01 januari 2023

INTRODUCTIONIt remains unclear to which extent vascular burden promotes neurodegeneration and cognitive dysfunction in a cohort spanning low-to-severe small vessel disease (SVD) and amyloid-beta pathology.METHODSIn 120 subjects, we investigated 1) whether vascular burden, quantified as total or lobar white matter hyperintensity (WMH) volumes, is associated with different cognitive domains; and 2) whether the total WMH effect on cognition is mediated by amyloid (18F-AV45-PET), glucose metabolism (18F-FDG-PET), and/or cortical atrophy.RESULTSIncreased total WMH volume was associated with poorer performance in all cognitive domains tested, with the strongest effects observed for semantic fluency. These relationships were mediated mainly through cortical atrophy, particularly in the temporal lobe, and to a lesser extent through amyloid and metabolism. WMH volumes differentially impacted cognition depending on lobar location and amyloid status.DISCUSSIONOur study suggests mainly an amyloid-independent pathway in which vascular burden affects cognitive impairment through temporal lobe atrophy.

Background: Asundexian (Bayer AG, Leverkusen, Germany), an oral small molecule factor XIa (FXIa) inhibitor, might prevent thrombosis without increasing bleeding. Asundexian's effect for secondary prevention of recurrent stroke is unknown. Methods: In this randomised, double-blind, placebo-controlled, phase 2b dose-finding trial (PACIFIC-Stroke), patients with acute (within 48 h) non-cardioembolic ischaemic stroke were recruited from 196 hospitals in 23 countries. Patients were eligible if they were aged 45 years or older, to be treated with antiplatelet therapy, and able to have a baseline MRI (either before or within 72 h of randomisation). Eligible participants were randomly assigned (1:1:1:1), using an interactive web-based response system and stratified according to anticipated antiplatelet therapy (single vs dual), to once daily oral asundexian (BAY 2433334) 10 mg, 20 mg, or 50 mg, or placebo in addition to usual antiplatelet therapy, and were followed up during treatment for 26–52 weeks. Brain MRIs were obtained at study entry and at 26 weeks or as soon as possible after treatment discontinuation. The primary efficacy outcome was the dose–response effect on the composite of incident MRI-detected covert brain infarcts and recurrent symptomatic ischaemic stroke at or before 26 weeks after randomisation. The primary safety outcome was major or clinically relevant non-major bleeding as defined by International Society on Thrombosis and Haemostasis criteria. The efficacy outcome was assessed in all participants assigned to treatment, and the safety outcome was assessed in all participants who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT04304508, and is now complete. Findings: Between June 15, 2020, and July 22, 2021, 1880 patients were screened and 1808 participants were randomly assigned to asundexian 10 mg (n=455), 20 mg (n=450), or 50 mg (n=447), or placebo (n=456). Mean age was 67 years (SD 10) and 615 (34%) participants were women, 1193 (66%) were men, 1505 (83%) were White, and 268 (15%) were Asian. The mean time from index stroke to randomisation was 36 h (SD 10) and median baseline National Institutes of Health Stroke Scale score was 2·0 (IQR 1·0–4·0). 783 (43%) participants received dual antiplatelet treatment for a mean duration of 70·1 days (SD 113·4) after randomisation. At 26 weeks, the primary efficacy outcome was observed in 87 (19%) of 456 participants in the placebo group versus 86 (19%) of 455 in the asundexian 10 mg group (crude incidence ratio 0·99 [90% CI 0·79–1·24]), 99 (22%) of 450 in the asundexian 20 mg group (1·15 [0·93–1·43]), and 90 (20%) of 447 in the asundexian 50 mg group (1·06 [0·85–1·32]; t statistic –0·68; p=0·80). The primary safety outcome was observed in 11 (2%) of 452 participants in the placebo group versus 19 (4%) of 445 in the asundexian 10 mg group, 14 (3%) of 446 in the asundexian 20 mg group, and 19 (4%) of 443 in the asundexian 50 mg group (all asundexian doses pooled vs placebo hazard ratio 1·57 [90% CI 0·91–2·71]). Interpretation: In this phase 2b trial, FXIa inhibition with asundexian did not reduce the composite of covert brain infarction or ischaemic stroke and did not increase the composite of major or clinically relevant non-major bleeding compared with placebo in patients with acute, non-cardioembolic ischaemic stroke. Funding: Bayer AG.

IMPORTANCE: The effectiveness and safety of intravenous alteplase given before or concurrently with endovascular thrombectomy (EVT) is uncertain. Randomized clinical trials suggest there is little difference in outcomes but with only modest precision and insufficient power to analyze uncommon outcomes including symptomatic intracranial hemorrhage (sICH). OBJECTIVE: To determine whether 8 prespecified outcomes are different in patients with acute ischemic stroke treated in routine clinical practice with EVT with alteplase compared with patients treated with EVT alone without alteplase. It was hypothesized that alteplase would be associated with higher risk of sICH. DESIGN, SETTING, AND PARTICIPANTS: This was an observational cohort study conducted from February 1, 2019, to June 30, 2020, that included adult patients with acute ischemic stroke treated with EVT within 6 hours of time last known well, after excluding patients without information on discharge destination and patients with in-hospital stroke. Participants were recruited from Get With The Guidelines–Stroke, a large nationwide registry of patients with acute ischemic stroke from 555 hospitals in the US. EXPOSURES: Intravenous alteplase or no alteplase. MAIN OUTCOMES AND MEASURES: Prespecified outcomes were discharge destination, independent ambulation at discharge, modified Rankin score at discharge, discharge mortality, cerebral reperfusion according to modified Thrombolysis in Cerebral Infarction grade, and sICH. RESULTS: There were 15 832 patients treated with EVT (median [IQR] age, 72.0 [61.0-82.0] years; 7932 women [50.1%]); 10 548 (66.7%) received alteplase and 5284 (33.4%) did not. Patients treated with alteplase were younger, arrived via Emergency Medical Services sooner, were less likely to have certain comorbidities, including atrial fibrillation, hypertension, and diabetes, but had similar National Institutes of Health Stroke Severity (NIHSS) scores. Compared with patients who did not receive alteplase treatment, patients treated with alteplase were less likely to die (11.1% [1173 of 10 548 patients] vs 13.9% [734 of 5284 patients]; adjusted odds ratio [aOR] 0.83; 95% CI, 0.77-0.89; P

The seventh edition of the Canadian Stroke Best Practice Recommendations for Rehabilitation and Recovery following Stroke includes a new section devoted to the provision of virtual stroke rehabilitation. This consensus statement uses Grading of Recommendations, Assessment, Development and Evaluations methodology and Appraisal of Guidelines for ResearchEvaluation II principles. A literature search was conducted using PubMed, Embase, and Cochrane databases. An expert writing group reviewed all evidence and developed recommendations, as well as consensus-based clinical considerations where evidence was insufficient for a recommendation. All recommendations underwent internal and external review. These recommendations apply to hospital, ambulatory care, and community-based settings where virtual stroke rehabilitation is provided. This guidance is relevant to health professionals, people living with stroke, healthcare administrators, and funders. Recommendations address issues of access, eligibility, consent and privacy, technology and planning, training and competency (for healthcare providers, patients and their families), assessment, service delivery, and evaluation. Virtual stroke rehabilitation has been shown to safely and effectively increase access to rehabilitation therapies and care providers, and uptake of these recommendations should be a priority in rehabilitation settings. They are key drivers of access to high-quality evidence-based stroke care regardless of geographical location and personal circumstances in Canada.

BACKGROUND: Existing data and clinical trials could not determine whether faster intravenous thrombolytic therapy (IVT) translates into better long-term functional outcomes after acute ischemic stroke among those treated with endovascular thrombectomy (EVT). Patient-level national data can provide the required large population to study the associations between earlier IVT, versus later, with longitudinal functional outcomes and mortality in patients receiving IVT+EVT combined treatment. METHODS: This cohort study included older US patients (age ≥65 years) who received IVT within 4.5 hours or EVT within 7 hours after acute ischemic stroke using the linked 2015 to 2018 Get With The Guidelines–Stroke and Medicare database (38 913 treated with IVT only and 3946 with IVT+EVT). Primary outcome was home time, a patient-prioritized functional outcome. Secondary outcomes included all-cause mortality in 1 year. Multivariate logistic regression and Cox proportional hazards models were used to evaluate the associations between door-to-needle (DTN) times and outcomes. RESULTS: Among patients treated with IVT+EVT, after adjusting for patient and hospital factors, including onset-to-EVT times, each 15-minute increase in DTN times for IVT was associated with significantly higher odds of zero home time in a year (never discharged to home) (adjusted odds ratio, 1.12 [95% CI, 1.06–1.19]), less home time among those discharged to home (adjusted odds ratio, 0.93 per 1% of 365 days [95% CI, 0.89–0.98]), and higher all-cause mortality (adjusted hazard ratio, 1.07 [95% CI, 1.02–1.11]). These associations were also statistically significant among patients treated with IVT but at a modest degree (adjusted odds ratio, 1.04 for zero home time, 0.96 per 1% home time for those discharged to home, and adjusted hazard ratio 1.03 for mortality). In the secondary analysis where the IVT+EVT group was compared with 3704 patients treated with EVT only, shorter DTN times (≤60, 45, and 30 minutes) achieved incrementally more home time in a year, and more modified Rankin Scale 0 to 2 at discharge (22.3%, 23.4%, and 25.0%, respectively) versus EVT only (16.4%, P 60 minutes. CONCLUSIONS: Among older patients with stroke treated with either IVT only or IVT+EVT, shorter DTN times are associated with better long-term functional outcomes and lower mortality. These findings support further efforts to accelerate thrombolytic administration in all eligible patients, including EVT candidates.

BackgroundPrevious reports have suggested that patients with cerebral amyloid angiopathy (CAA) may harbor smaller white matter, basal ganglia, and cerebellar volumes compared to age-matched healthy controls (HC) or patients with Alzheimer’s disease (AD). We investigated whether CAA is associated with subcortical atrophy.MethodsThe study was based on the multi-site Functional Assessment of Vascular Reactivity cohort and included 78 probable CAA (diagnosed according to the Boston criteria v2.0), 33 AD, and 70 HC. Cerebral and cerebellar volumes were extracted from brain 3D T1-weighted MRI using FreeSurfer (v6.0). Subcortical volumes, including total white matter, thalamus, basal ganglia, and cerebellum were reported as proportion (%) of estimated total intracranial volume. White matter integrity was quantified by the peak width of skeletonized mean diffusivity.ResultsParticipants in the CAA group were older (74.0 ± 7.0, female 44%) than the AD (69.7 ± 7.5, female 42%) and HC (68.8 ± 7.8, female 69%) groups. CAA participants had the highest white matter hyperintensity volume and worse white matter integrity of the three groups. After adjusting for age, sex, and study site, CAA participants had smaller putamen volumes (mean differences, −0.024% of intracranial volume; 95% confidence intervals, −0.041% to −0.006%; p = 0.005) than the HCs but not AD participants (−0.003%; −0.024 to 0.018%; p = 0.94). Other subcortical volumes including subcortical white matter, thalamus, caudate, globus pallidus, cerebellar cortex or cerebellar white matter were comparable between all three groups.ConclusionIn contrast to prior studies, we did not find substantial atrophy of subcortical volumes in CAA compared to AD or HCs, except for the putamen. Differences between studies may reflect heterogeneity in CAA presenting syndromes or severity.

IntroductionCerebral amyloid angiopathy (CAA) is a small vessel disease that causes covert and symptomatic brain hemorrhaging. We hypothesized that persons with CAA would have increased brain iron content detectable by quantitative susceptibility mapping (QSM) on magnetic resonance imaging (MRI), and that higher iron content would be associated with worse cognition.MethodsParticipants with CAA (n = 21), mild Alzheimer’s disease with dementia (AD-dementia; n = 14), and normal controls (NC; n = 83) underwent 3T MRI. Post-processing QSM techniques were applied to obtain susceptibility values for regions of the frontal and occipital lobe, thalamus, caudate, putamen, pallidum, and hippocampus. Linear regression was used to examine differences between groups, and associations with global cognition, controlling for multiple comparisons using the false discovery rate method.ResultsNo differences were found between regions of interest in CAA compared to NC. In AD, the calcarine sulcus had greater iron than NC (β = 0.99 [95% CI: 0.44, 1.53], q < 0.01). However, calcarine sulcus iron content was not associated with global cognition, measured by the Montreal Cognitive Assessment (p > 0.05 for all participants, NC, CAA, and AD).DiscussionAfter correcting for multiple comparisons, brain iron content, measured via QSM, was not elevated in CAA compared to NC in this exploratory study.

INTRODUCTIONThis study compares three operational definitions of mild behavioral impairment (MBI) in the context of MBI prevalence estimates and dementia risk modeling.METHODSParticipants were dementia-free older adults (n=13701) from the National Alzheimer’s Coordinating Center. Operational definitions of MBI were generated based on neuropsychiatric symptoms at one (OV), two-consecutive (TCV), or >2/3 (TTV) of dementia-free study visits. Definitions were compared in prevalence and in Cox regressions using MBI to predict incident dementia.RESULTSOV MBI was the most prevalent (54.4%), followed by TCV (32.3%) and TTV (26.7%) MBI. However, OV MBI had the lowest rate of incident dementia (HR=2.54, 95%CI: 2.33–2.78) and generated poorer model metrics than TCV MBI (HR=4.06, 95%CI: 3.74–4.40) and TTV MBI (HR=5.77, 95%CI: 5.32–6.26).DISCUSSIONCase ascertainment with longer timeframe MBI operational definitions may more accurately define groups at risk of dementia in datasets lacking tools designed to detect MBI.HIGHLIGHTSMild behavioral impairment (MBI) can identify older adults at risk of dementia.Neuropsychiatric symptom (NPS) assessment tools can be proxy measures for MBI.Hazard for dementia was highest for MBI defined by NPS presence at >2/3 of visits.

BackgroundParkinson’s disease (PD) and dementia with Lewy bodies (DLB) are part of a spectrum of Lewy body disorders, who exhibit a range of cognitive and gait impairments. Cognitive-motor interactions can be examined by performing a cognitive task while walking and quantified by a dual task cost (DTC). White matter hyperintensities (WMH) on magnetic resonance imaging have also been associated with both gait and cognition. Our goal was to examine the relationship between DTC and WMH in the Lewy body spectrum, hypothesizing DTC would be associated with increased WMH volume.MethodsSeventy-eight participants with PD, PD with mild cognitive impairment (PD-MCI), PD with dementia or DLB (PDD/DLB), and 20 cognitively unimpaired participants were examined in a multi-site study. Gait was measured on an electronic walkway during usual gait, counting backward, animal fluency, and subtracting sevens. WMH were quantified from magnetic resonance imaging using an automated pipeline and visual rating. A median split based on DTC was performed. Models included age as well as measures of global cognition and cardiovascular risk.ResultsCompared to cognitively unimpaired participants, usual gait speed was lower and DTC was higher in PD-MCI and PDD/DLB. Low DTC participants had higher usual gait speed. WMH burden was greater in high counting DTC participants. Frontal WMH burden remained significant after adjusting for age, cardiovascular risk and global cognition.ConclusionIncreased DTC was associated with higher frontal WMH burden in Lewy body disorders after adjusting for age, cardiovascular risk, and global cognition. Higher DTC was associated with age.

This cohort study examines patterns in prescriptions of dual antiplatelet therapy after publication of important trials and release of updated guidelines.

BackgroundGait impairment contributes to falls and frailty. Some studies suggest that cerebral small vessel disease (CSVD) is associated with gait impairment in the general population. We systematically reviewed and meta-analysed the literature on associations of CSVD with gait impairment and falls.MethodsThe protocol was published in PROSPERO (CRD42021246009). Searches of Medline, Cochrane and Embase databases were conducted on 30 March 2022. Cross-sectional and longitudinal studies of community-dwelling adults were included, reporting relationships between diagnosis or neuroimaging markers of CSVD and outcomes related to gait or falls. Partial correlation coefficients were calculated and pooled using a random-effects model for meta-analysis.ResultsThe search retrieved 73 studies (53 cross-sectional; 20 longitudinal). Most studies reported an association between CSVD and gait impairments or falls risk: 7/7 studies on CSVD score or diagnosis, 53/67 studies on white matter hyperintensities (WMHs), 11/21 studies on lacunar infarcts, 6/15 studies on cerebral microbleeds and 1/5 studies on perivascular spaces. Meta-analysis of 13 studies found that higher WMH volume was mildly correlated with lower gait speed, in all studies (r = −0.23, 95% confidence interval: −0.33 to −0.14, P ConclusionsFindings suggest that CSVD severity is associated with gait impairment, history of falls and risk of future falls. Prevention of CSVD should be part of a comprehensive public health strategy to improve mobility and reduce risk of falls in later life.

Background:The Passive Surveillance Stroke Severity (PaSSV) Indicator was derived to estimate stroke severity from variables in administrative datasets but has not been externally validated.Methods:We used linked administrative datasets to identify patients with first hospitalization for acute stroke between 2007-2018 in Alberta, Canada. We used the PaSSV indicator to estimate stroke severity. We used Cox proportional hazard models and evaluated the change in hazard ratios and model discrimination for 30-day and 1-year case fatality with and without PaSSV. Similar comparisons were made for 90-day home time thresholds using logistic regression. We also linked with a clinical registry to obtain National Institutes of Health Stroke Scale (NIHSS) and compared estimates from models without stroke severity, with PaSSV, and with NIHSS.Results:There were 28,672 patients with acute stroke in the full sample. In comparison to no stroke severity, addition of PaSSV to the 30-day case fatality models resulted in improvement in model discrimination (C-statistic 0.72 [95%CI 0.71–0.73] to 0.80 [0.79–0.80]). After adjustment for PaSSV, admission to a comprehensive stroke center was associated with lower 30-day case fatality (adjusted hazard ratio changed from 1.03 [0.96–1.10] to 0.72 [0.67–0.77]). In the registry sample (N = 1328), model discrimination for 30-day case fatality improved with the inclusion of stroke severity. Results were similar for 1-year case fatality and home time outcomes.Conclusion:Addition of PaSSV improved model discrimination for case fatality and home time outcomes. The validity of PASSV in two Canadian provinces suggests that it is a useful tool for baseline risk adjustment in acute stroke.

Objective To compare the utility of the Mild Behavioral Impairment-Checklist (MBI-C) and Neuropsychiatric Inventory Questionnaire (NPI-Q) to capture NPS in subjective cognitive decline (SCD), mild cognitive impairment (MCI), and dementia. Methods In this cross-sectional memory clinic study, linear regression models compared MBI-C (n = 474) and NPI-Q (n = 1040) scores in relation to Montreal Cognitive Assessment (MoCA) score. Results MBI prevalence was 37% in subjective cognitive decline, 54% in mild cognitive impairment, and 62% in dementia. Worse diagnostic status was associated with higher MBI-C and NPI-Q score ( P < .001), lower MoCA ( P < .001), and greater age ( P < .001). Higher MBI-C (β −.09; 95% CI −.13, −.05) and NPI-Q (β −.17; 95% CI −.23, −.10) scores were associated with lower MoCA scores, with psychosis most strongly associated (β −1.11; 95% CI −1.56, −.65 vs β −1.14; 95% CI −1.55, −.73). Conclusions The MBI-C captures global and domain-specific NPS across cognitive stages. Both the MBI-C and NPI-Q have utility in characterizing NPS.

Background: The benefits of tPA (tissue-type plasminogen activator) in acute ischemic stroke are time-dependent. However, delivery of thrombolytic therapy rapidly after hospital arrival was initially occurring infrequently in hospitals in the United States, discrepant with national guidelines. Methods: We evaluated door-to-needle (DTN) times and clinical outcomes among patients with acute ischemic stroke receiving tPA before and after initiation of 2 successive nationwide quality improvement initiatives: Target: Stroke Phase I (2010–2013) and Target: Stroke Phase II (2014–2018) from 913 Get With The Guidelines-Stroke hospitals in the United States between April 2003 and September 2018. Results: Among 154 221 patients receiving tPA within 3 hours of stroke symptom onset (median age 72 years, 50.1% female), median DTN times decreased from 78 minutes (interquartile range, 60–98) preintervention, to 66 minutes (51–87) during Phase I, and 50 minutes (37–66) during Phase II ( P P P Conclusions: A nationwide quality improvement program for acute ischemic stroke was associated with substantial improvement in the timeliness of thrombolytic therapy start, increased thrombolytic treatment, and improved clinical outcomes.

Background and ObjectivesMild cognitive impairment (MCI) is an at-risk state for dementia; however, not all individuals with MCI transition to dementia, and some revert to normal cognition (NC). Here, we investigate whether mild behavioral impairment (MBI), the late-life onset of persistent neuropsychiatric symptoms (NPS), improves the prognostic specificity of MCI.MethodsParticipants with MCI from the National Alzheimer's Coordinating Center Uniform Data Set were included. NPS were operationalized with the Neuropsychiatric Inventory Questionnaire to identify participants without NPS and those with MBI (persistent, late-onset NPS). Individuals with late-onset NPS not meeting the MBI persistence criterion (NPS_NOT_MBI) were retained for secondary analyses. Progression to dementia, stable MCI, and reversion to NC after 3 years of follow-up were defined per National Institute on Aging–Alzheimer’s Association and Petersen criteria.ResultsThe primary sample consisted of 739 participants (NPS− n = 409 and MBI+ n = 330; 75.16 ± 8.6 years old, 40.5% female). After 3 years, 238 participants (33.6%) progressed to dementia, and 90 (12.2%) reverted to NC. Compared to participants without NPS, participants with MBI were significantly more likely to progress to dementia (adjusted odds ratio [AOR] 2.13, 95% CI 1.52–2.99), with an annual progression rate of 14.7% (vs 8.3% for participants with MCI without NPS). Compared to participants without NPS, participants with MBI were less likely to revert to NC (AOR 0.48, 95% CI 0.28–0.83, 2.5% vs 5.3% annual reversion rate). The NPS_NOT_MBI group (n = 331, 76.5 ± 8.6 years old, 45.9% female) were more likely to progress to dementia (AOR 2.18, 95% CI 1.56–3.03, 14.3% annual progression rate) but not less likely to revert to NC than those without NPS. Accordingly, both NPS_NOT_MBI and MBI+ participants had lower Mini-Mental State Examination scores than NPS− participants after 3 years.DiscussionLate-onset NPS improve the specificity of MCI as an at-risk state for progression to dementia. However, only persistent late-onset NPS are associated with a lower likelihood of reversion to NC, with transient NPS (i.e., NPS_NOT_MBI) not differing from the NPS− group. Clinical prognostication can be improved by incorporating late-onset NPS, especially those that persist (i.e., MBI), into risk assessments. Clinical trials may benefit from enrichment with these higher-risk participants with MCI.

Pandemics may promote hospital avoidance, and added precautions may exacerbate treatment delays for medical emergencies such as stroke. We sought to evaluate ischemic stroke presentations, management and outcomes during the first year of the COVID-19 pandemic.We conducted a population-based study, using linked administrative and stroke registry data from Alberta to identify all patients presenting with stroke before the pandemic (Jan. 1, 2016 to Feb. 27, 2020) and in 5 periods over the first pandemic year (Feb. 28, 2020 to Mar. 31, 2021), reflecting changes in case numbers and restrictions. We evaluated changes in hospital admissions, emergency department presentations, thrombolysis, endovascular therapy, workflow times and outcomes.The study included 19 531 patients in the prepandemic period and 4900 patients across the 5 pandemic periods. Presentations for ischemic stroke dropped in the first pandemic wave (weekly adjusted incidence rate ratio [IRR] 0.54, 95% confidence interval [CI] 0.50 to 0.59). Population-level incidence of thrombolysis (adjusted IRR 0.50, 95% CI 0.41 to 0.62) and endovascular therapy (adjusted IRR 0.63, 95% CI 0.47 to 0.84) also decreased during the first wave, but proportions of patients presenting with stroke who received acute therapies did not decline. Rates of patients presenting with stroke did not return to prepandemic levels, even during a lull in COVID-19 cases between the first 2 waves of the pandemic, and fell further in subsequent waves. In-hospital delays in thrombolysis or endovascular therapy occurred in several pandemic periods. The likelihood of in-hospital death increased in Wave 2 (adjusted odds ratio [OR] 1.48, 95% CI 1.25 to 1.74) and Wave 3 (adjusted OR 1.46, 95% CI 1.07 to 2.00). Out-of-hospital deaths, as a proportion of stroke-related deaths, rose during 4 of 5 pandemic periods.The first year of the COVID-19 pandemic saw persistently reduced rates of patients presenting with ischemic stroke, recurrent treatment delays and higher risk of in-hospital death in later waves. These findings support public health messaging that encourages care-seeking for medical emergencies during pandemic periods, and stroke systems should re-evaluate protocols to mitigate inefficiencies.

Background: Basilar artery occlusion (BAO) is a devastating condition without definitive evidence to guide treatment. Whereas the association between faster treatment times with endovascular therapy (EVT) and better outcomes in anterior circulation is well established, whether this relationship exists for patients with BAO is not well delineated. Methods: We used individual-level patient data from the Get With The Guidelines–Stroke nationwide US registry prospectively collected from January 2015 to December 2019. We identified individuals with BAO treated with EVT within 24 hours of symptom onset. The primary outcomes examined were in-hospital mortality, discharge home, ambulatory at discharge, independent at discharge (modified Rankin Scale score 0 to 2), substantial reperfusion (modified Thrombolysis in Cerebral Infarction score 2b or 3), and symptomatic intracranial hemorrhage. Using logistic regression models, we evaluated the association between time from symptom onset to treatment with EVT and outcomes. Results: Among 3015 patients with BAO treated with EVT, the mean age was 65.9 years, 38.8% were women, and the median National Institutes of Health Stroke Scale score at presentation was 17 (interquartile range, 8–26). Median onset to EVT time was 406 minutes (interquartile range, 252–688). From 2015 to 2019, there was an overall increase in the median onset to EVT times (380–411 minutes; P =0.016) but no significant change in the proportion of patients treated within 6 hours of symptom onset (48.4%–44.0%; P =0.17). After risk adjustment for patient and hospital-level factors, there were significantly lower odds of in-hospital mortality (adjusted odds ratio [aOR], 0.55 [95% CI, 0.45–0.68]) and symptomatic intracranial hemorrhage (aOR, 0.52 [95% CI, 0.32–0.84]) and significantly higher odds of ambulation at discharge (aOR, 1.72 [95% CI, 1.37–2.16]), discharge home (aOR, 2.19 [95% CI, 1.73–2.77]), and independence at discharge (aOR, 2.21 [95% CI, 1.66–2.95]) when onset to EVT time was ≤6 hours compared with >6 hours. The fastest decay in good outcomes per hour occurred within 6 hours of symptom onset. Conclusions: Among patients receiving EVT for BAO, faster treatment from symptom onset was associated with improved outcomes. These findings support efforts to achieve rapid treatment with EVT for patients with BAO.

Background and ObjectivesPrior regional or single-center studies have noted that 4% to 7% of eligible patients with acute ischemic stroke (AIS) decline IV tissue plasminogen activator (tPA). We sought to determine the prevalence of tPA declination in a nationwide registry of patients with AIS and to investigate differences in declination by race/ethnicity.MethodsWe used the Get With The Guidelines–Stroke registry to identify patients with AIS eligible for tPA and admitted to participating hospitals between January 1, 2016, and March 28, 2019. We compared patient demographics and admitting hospital characteristics between tPA-eligible patients who received and those who declined tPA. Using multivariable logistic regression, we determined patient and hospital factors associated with tPA declination.ResultsAmong 177,115 tPA-eligible patients with AIS at 1,976 sites, 6,545 patients (3.7%) had tPA declination as the sole documented reason for not receiving tPA. Patients declining treatment were slightly older, were more likely to be female, arrived more often at off-hours and earlier after symptom onset, and were more likely to present to Primary Stroke Centers. Compared with non-Hispanic White, non-Hispanic Black race/ethnicity was independently associated with increased (adjusted odds ratio [aOR] 1.21, 95% CI 1.11–1.31), Asian race/ethnicity with decreased (aOR 0.72, 95% CI 0.58–0.88), and Hispanic ethnicity (any race) with similar odds of tPA declination (OR 0.98, 95% CI 0.86–1.13) in multivariable analysis.DiscussionAlthough the overall prevalence of tPA declination is low, eligible non-Hispanic Black patients are more likely and Asian patients less likely to decline tPA than non-Hispanic White patients. Reducing rates of tPA declinations among non-Hispanic Black patients may be an opportunity to address disparities in stroke care.

Background: The incidence of stroke in developed countries is increasing selectively in young individuals, but whether this is secondary to traditional vascular risk factors is unknown. Methods: We used the Canadian Community Health Survey from 2000 to 2016 to create a large population-representative cohort of individuals over the age of 30 and free from prior stroke. All analyses were stratified by age decile. We linked with administrative databases to determine emergency department visits or hospitalizations for acute stroke until December 2017. We calculated time trends in risk factor prevalence (hypertension, diabetes, obesity, and smoking) using meta-regression. We used Cox proportional hazard models to evaluate the association between vascular risk factors and stroke risk, adjusted for demographic, co-morbid, and social variables. We used competing risk regression to account for deaths and calculated population-attributable fractions. In a sensitivity analysis, we excluded those with prior heart disease or cancer. Results: We included 492,400 people in the analysis with 8865 stroke events over a median follow-up time of 8.3 years. Prevalence of hypertension, diabetes, and obesity increased over time while smoking decreased. Associations of diabetes, hypertension, and obesity with stroke risk were progressively stronger at younger age (adjusted hazard ratio for diabetes was 4.47, 95% confidence interval (CI) = 1.95–10.28 at age 30–39, vs 1.21, 95% CI = 0.93–1.57 at age 80+), although the obesity association was attenuated with adjustment. Smoking was associated with higher risk of stroke without a gradient across age deciles, although had the greatest population-attributable fraction at younger age. The hazard ratio for stroke with multiple concurrent risk factors was much higher at younger age (adjusted hazard ratio for 3–4 risk factors was 8.60, 95% CI = 2.97–24.9 at age 30–39 vs 1.61, 95% CI = 0.88–2.97 at age 80+) and results were consistent when accounting for the competing risk of death and excluding those with prior heart disease or cancer. Conclusions: Diabetes and hypertension were associated with progressively elevated relative risk of stroke in younger individuals and prevalence was increasing over time. The association of obesity with stroke was not significant after adjustment for other factors. Smoking had the greatest prevalence and population-attributable fraction for stroke at younger age. Our findings assist in understanding the relationship between vascular risk factors and stroke across the life span and planning public health measures to lower stroke incidence in the young.

Background and Purpose: The spectrum of brain infarction in patients with embolic stroke of undetermined source (ESUS) has not been well characterized. Our objective was to define the frequency and pattern of brain infarcts detected by magnetic resonance imaging (MRI) among patients with recent ESUS participating in a clinical trial. Methods: In the NAVIGATE ESUS trial (New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial Versus ASA to Prevent Embolism in Embolic Stroke of Undetermined Source), an MRI substudy was carried out at 87 sites in 15 countries. Participants underwent an MRI using a specified protocol near randomization. Images were interpreted centrally by those unaware of clinical characteristics. Results: Among the 918 substudy cohort participants, the mean age was 67 years and 60% were men with a median (interquartile range) of 64 (26–115) days between the qualifying ischemic stroke and MRI. On MRI, 855 (93%) had recent or chronic brain infarcts that were multiple in 646 (70%) and involved multiple arterial territories in 62% (401/646). Multiple brain infarcts were present in 68% (510/755) of those without a history of stroke or transient ischemic attack before the qualifying ESUS. Prior stroke/transient ischemic attack ( P 0 ( P P =0.01) were associated with multiple infarcts. Topographically, large and/or cortical infarcts were present in 89% (757/855) of patients with infarcts, while in 11% (98/855) infarcts were exclusively small and subcortical. Among those with multiple large and/or cortical infarcts, 57% (251/437) had one or more involving a different vascular territory from the qualifying ESUS. Conclusions: Most patients with ESUS, including those without prior clinical stroke or transient ischemic attack, had multiple large and/or cortical brain infarcts detected by MRI, reflecting a substantial burden of clinical stroke and covert brain infarction. Infarcts most frequently involved multiple vascular territories. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02313909.

STUDY OBJECTIVES: Although cognitive impairment in obstructive sleep apnea (OSA) is primarily attributed to intermittent hypoxemia and sleep fragmentation, hypercapnia may also play a role in patients whose OSA is complicated by hypoventilation. This study investigated the impact of hypercapnia on cognitive function in severe sleep-disordered breathing (OSA accompanied by hypoventilation). METHODS: Patients with severe OSA (apnea-hypopnea index >30 events/h; n = 246) underwent evaluation for accompanying hypoventilation with polysomnography that included continuous transcutaneous carbon dioxide (TcCO(2)) monitoring and awake arterial blood gas analysis. Patients were categorized as having no hypoventilation (n = 84), isolated sleep hypoventilation (n = 40), or awake hypoventilation (n = 122). Global cognitive function was evaluated using the Montreal Cognitive Assessment (MoCA), memory with the Rey Auditory Verbal Learning Test (RAVLT), and processing speed with the Wechsler Adult Intelligence Scale, Fourth Edition (WAIS-IV), Digit Symbol Coding subtest (DSC). RESULTS: Apnea-hypopnea index was similar across groups (P = .15), but the sleep and awake hypoventilation groups had greater nocturnal hypoxemia compared with the no-hypoventilation group (P < .01). Within all groups, mean MoCA scores were < 26, which is the validated threshold to indicate mild cognitive impairment; RAVLT scores were lower than age-matched norms only in the awake-hypoventilation group (P ≤ .01); and DSC scores were lower than age-matched norms within all groups (P < .01). In multivariable regression analyses, higher arterial partial pressure of carbon dioxide (PaCO(2)) and TcCO(2) during wakefulness were associated with lower MoCA and DSC scores (P ≤ .03), independent of confounders including overlap syndrome (OSA + chronic obstructive pulmonary disease). CONCLUSIONS: Awake hypoventilation is associated with greater deficits in cognitive function in patients with severe sleep-disordered breathing. CITATION: Beaudin AE, Raneri JK, Ayas NT, Skomro RP, Smith EE, Hanly PJ; on behalf of Canadian Sleep and Circadian Network. Contribution of hypercapnia to cognitive impairment in severe sleep-disordered breathing. J Clin Sleep Med. 2022;18(1):245–254.

Background The relationship between duration of transient neurological events and presence of diffusion‐weighted lesions by symptom type is unclear. Methods and Results This was a substudy of SpecTRA (Spectrometry for Transient Ischemic Attack Rapid Assessment), a multicenter prospective cohort of patients with minor ischemic cerebrovascular events or stroke mimics at academic emergency departments in Canada. For this study we included patients with resolved symptoms and determined the presence of diffusion‐weighted imaging (DWI) lesion on magnetic resonance imaging within 7 days. Using logistic regression, we evaluated the association between symptom duration and DWI lesion, assessing for interaction with symptom type (focal only versus nonfocal/mixed), and adjusting for age, sex, education, comorbidities, and systolic blood pressure. Of 658 patients included, a DWI lesion was present in 232 (35.1%). There was a significant interaction between symptom duration and symptom type. For those with focal‐only symptoms, there was a continuous increase in DWI probability up to 24 hours in duration (ranging from ≈40% to 80% probability). In stratified analyses, the increase in probability of DWI lesion with increased duration of focal symptoms was seen in women but not men. For those with nonfocal or mixed symptoms, predicted probability of DWI lesion was ≈35% and was greater in men, but did not increase with longer duration. Conclusions Increased duration of neurological deficits is associated with greater probability of DWI lesion in those with focal symptoms only. For individuals with nonfocal or mixed symptoms, about one‐third had DWI lesions, but the probability did not increase with duration. These results may be important to improve risk stratification of transient neurological events.