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Background: Elevated blood pressure (BP) variability is predictive of increased risk for stroke, cerebrovascular disease, and other vascular brain injuries, independent of traditionally studied average BP levels. However, no studies to date have evaluated whether BP variability is related to diminished cerebrovascular reactivity, which may represent an early marker of cerebrovascular dysfunction presaging vascular brain injury., Methods: The present study investigated BP variability and cerebrovascular reactivity in a sample of 41 community-dwelling older adults (mean age 69.6 [SD 8.7] years) without a history of dementia or stroke. Short-term BP variability was determined from BP measurements collected continuously during a 5-minute resting period followed by cerebrovascular reactivity during 5-minute hypocapnia and hypercapnia challenge induced by visually guided breathing conditions. Cerebrovascular reactivity was quantified as percent change in cerebral perfusion by pseudo-continuous arterial spin labeling (pCASL)-MRI per unit change in end-tidal CO2., Results: Elevated systolic BP variability was related to lower whole brain cerebrovascular reactivity during hypocapnia (ß = -0.43 [95% CI -0.73, -0.12]; P = 0.008; adjusted R2 =.11) and hypercapnia (ß = -0.42 [95% CI -0.77, -0.06]; P = 0.02; adjusted R2 = 0.19)., Conclusions: Findings add to prior work linking BP variability and cerebrovascular disease burden and suggest BP variability may also be related to prodromal markers of cerebrovascular dysfunction and disease, with potential therapeutic implications., (© The Author(s) 2022. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Neurovascular imaging for patients with high-risk transient ischemic attack (TIA) or minor stroke in the emergency department (ED) with computed tomography angiography (CTA) of the head and neck is the guideline-recommended standard of care, but it is underutilized in routine practice. We conducted a quality initiative to improve adherence to guidelines., Methods: Between January 2017 and March 2019, we implemented a decision support tool integrated into the electronic ordering system to guide ED physicians to order a CTA on patients with high-risk TIA or minor stroke defined as ongoing neurological deficits in the ED or resolved motor or speech deficits in the preceding 48 h. Data were collected retrospectively pre-intervention and prospectively post-intervention. We used an interrupted time-series analysis for the before-after comparison of the use of CTA among patients who met criteria (main process measure) and those who did not meet criteria (balancing measure)., Results: Among 861 patients with TIA or minor stroke, the proportion of patients with high-risk events imaged with a CTA in the ED increased from 12.0% pre-intervention to 77.0% post-intervention and this shift was sustained over 11 months. CTA use in those without high-risk events increased to a lesser extent (15.3% versus 42.9%). The interrupted time-series analysis showed a step change immediately post-intervention where the increase in CTA use in patients with high-risk events was 51.7% higher than its use in those without high-risk events (p < 0.001). Compared to pre-intervention, the median ED length of stay increased by 2 h and neurology consultation in the ED was more frequent (5.8% versus 19.5%) post-intervention., Conclusion: We provide a detailed framework that improved adherence to acute imaging guidelines for patients with TIA or minor stroke and anticipate that our approach could improve acute imaging for such patients in most EDs., (© 2021. The Author(s), under exclusive licence to Canadian Association of Emergency Physicians (CAEP)/ Association Canadienne de Médecine d'Urgence (ACMU).)

Background: Improvements in management of transient ischemic attack (TIA) have decreased stroke and mortality post-TIA. Studies examining trends over time on a provincial level are limited. We analyzed whether efforts to improve management have decreased the rate of stroke and mortality after TIA from 2003 to 2015 across an entire province., Methods: Using administrative data from the Canadian Institute for Health Information's (CIHI) databases from 2003 to 2015, we identified a cohort of patients with a diagnosis of TIA upon discharge from the emergency department (ED). We examined stroke rates at Day 1, 2, 7, 30, 90, 180, and 365 post-TIA and 1-year mortality rates and compared trends over time between 2003 and 2015., Results: From 2003 to 2015 in Ontario, there were 61,710 patients with an ED diagnosis of TIA. Linear regressions of stroke after the index TIA showed a significant decline between 2003 and 2015, decreasing by 25% at Day 180 and 32% at 1 year (p < 0.01). The 1-year stroke rate decreased from 6.0% in 2003 to 3.4% in 2015. Early (within 48 h) stroke after TIA continued to represent approximately half of the 1-year event rates. The 1-year mortality rate after ED discharge following a TIA decreased from 1.3% in 2003 to 0.3% in 2015 (p < 0.001)., Interpretation: At a province-wide level, 1-year rates of stroke and mortality after TIA have declined significantly between 2003 and 2015, suggesting that efforts to improve management may have contributed toward the decline in long-term risk of stroke and mortality. Continued efforts are needed to further reduce the immediate risk of stroke following a TIA.

Background: Delayed presentation to the emergency department influences acute stroke care and can result in worse outcomes. Despite public health messaging, many young adults consider stroke as a disease of older people. We determined the differences in ambulance utilization and delays to hospital presentation between women and men as well as younger (18-44 years) versus older (≥45 years) patients with stroke., Methods: We conducted a population-based retrospective study using national administrative health data from the Canadian Institute of Health Information databases and examined data between 2003 and 2016 to compare ambulance utilization and time to hospital presentation across sex and age., Results: Young adults account for 3.9% of 463,310 stroke/transient ischemic attack/hemorrhage admissions. They have a higher proportion of hemorrhage (37% vs. 15%) and fewer ischemic events (50% vs. 68%) compared with older patients. Younger patients are less likely to arrive by ambulance (62% vs. 66%, p < 0.001), with younger women least likely to use ambulance services (61%) and older women most likely (68%). Median stroke onset to hospital arrival times were 7 h for older patients and younger men, but 9 h in younger women. There has been no improvement among young women in ambulance utilization since 2003, whereas ambulance use increased in all other groups., Conclusions: Younger adults, especially younger women, are less likely to use ambulance services, take longer to get to hospital, and have not improved in utilization of emergency services for stroke over 13 years. Targeted public health messaging is required to ensure younger adults seek emergency stroke care.

Background and Purpose- Depression and anxiety are common after stroke/transient ischemic attack (TIA). These conditions are associated with poor functional outcome and worse quality of life. However, few studies have explored predictors of poststroke risk of generalized anxiety, especially in patients without comorbid depressive symptoms. We aimed to explore predictors of high risk of generalized anxiety after stroke/TIA. Methods- Consecutive stroke and TIA referrals to the Sunnybrook Stroke Prevention Clinic over a 2-year period (April 2012-April 2014) who spoke English, were not severely aphasic, and who consented to complete neuropsychological testing were included in this analysis. Generalized anxiety and depressive symptoms were assessed using the Generalized Anxiety Disorder 7-item scale and Center for Epidemiological Studies Depression Scale, respectively. Results- Two hundred and fifty-eight patients completed the Generalized Anxiety Disorder 7-item scale, of whom 56 (22%) were at high risk for generalized anxiety (scores ≥10). Younger age (odds ratio=0.96; 95% CI, 0.93-0.99; P=0.004) and greater depressive symptoms (odds ratio=1.20; 95% CI, 1.14-1.26; P≤0.001) were significant predictors of being at high risk for generalized anxiety after stroke/TIA. Younger patients (≤50 years) were significantly more likely to be at high risk for both depression and generalized anxiety than older patients (30% versus 12%, χ 2 [1, N=258]=10.98, P=0.001). Our model explained 56% of the variance in risk of generalized anxiety after stroke. In patients without severe depressive symptoms (n=193, 75%), age and severity of depressive symptoms remained the only factors associated with risk of generalized anxiety. Conclusions- Anxiety is common after stroke/TIA and is highly correlated with poststroke depressive symptoms and age, even among those without severe depressive symptoms. Given the greater frequency of both generalized anxiety and depressive symptoms in young survivors, routine screening for depression and further evaluation of anxiety after stroke/TIA is warranted.

Depression and cognitive complaints are common after stroke; these issues have been studied in older populations, but not in the young. Two hundred and seventy four eligible stroke and TIA patients consented to participate and complete the Center for Epidemiologic Studies Depression Scale, and National Institute of Neurological Disorders and Stroke - Canadian Stroke Network 30-min neuropsychological battery; 57 (21%) were ≤ 50 years of age. Younger patients reported greater symptoms of depression and less executive dysfunction than older patients. This study highlights age differences in post-stroke depression symptoms and cognitive impairment, and emphasizes the need for screening across ages., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Independence and reintegration into community roles are important patient-centered outcomes after stroke. Depression and cognitive impairment are common post-stroke conditions that may impair long-term function even years after a stroke. However, screening for these post-stroke comorbidities remains infrequent in stroke prevention clinics and the utility of this screening for predicting long-term higher-level function has not been evaluated., Aims: To evaluate the ability of a validated brief Depression, Obstructive sleep apnea, and Cognitive impairment screen (DOC screen) to predict long-term (2-3 years after stroke) community participation and independence in instrumental activities of daily living post stroke., Methods: One hundred twenty-four patients (mean age, 66.3 [standard deviation = 15.7], 52.4% male) completed baseline depression and cognitive impairment screening at first stroke clinic visit, and telephone interviews 2 to 3 years post stroke to assess community independence (Frenchay Activities Index [FAI]) and participation (Reintegration to Normal Living Index [RNLI]). A subset of these patients also consented to complete detailed neuropsychological testing at baseline. Univariate and multivariate linear (FAI) and logistic (RNLI) regression analyses were used to determine the individual relationship between baseline data (predictors) and follow-up scores., Results: Older age (β = -0.17, P = .001), greater stroke severity (β = 1.84, P = .015), more depressive (β = -2.41, P = .023), and cognitive (β = -2.15, P = .046) symptoms independently predicted poor instrumental activity ( R 2 = .27; P < .001). Measures of executive dysfunction were the strongest correlates of poor instrumental activity. Higher depression risk was the only significant predictor of participation on the RNLI in regression modeling (odds ratio = 0.46, P = .028)., Conclusions: Baseline DOC screening in stroke prevention clinics shows that symptoms of depression and cognitive impairment are independent predictors of impaired higher-level functioning and community reintegration 2 to 3 years after stroke. Novel rehabilitation and psychological interventions targeting people with these conditions are needed to improve long-term patient-centered outcomes.

Background The incidence of stroke in young adults is increasing. While many young survivors are able to achieve a good physical recovery, subtle dysfunction in other domains, such as cognition, often persists, and could affect return to work. However, reported estimates of return to work and factors affecting vocational outcome post-stroke vary greatly. Aims The aims of this systematic review were to determine the frequency of return to work at different time points after stroke and identify predictors of return to work. Summary of review Two electronic databases (Medline and Embase) were systematically searched for articles according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A total of 6473 records were screened, 68 were assessed for eligibility, and 29 met all inclusion criteria (working-age adults with stroke, return to work evaluated as an outcome, follow-up duration reported, and publication within the past 20 years). Return to work increased with time, with median frequency increasing from 41% between 0 and 6 months, 53% at 1 year, 56% at 1.5 years to 66% between 2 and 4 years post-stroke. Greater independence in activities of daily living, fewer neurological deficits, and better cognitive ability were the most common predictors of return to work. Conclusion This review highlights the need to examine return to work in relation to time from stroke and assess cognition in working age and young stroke survivors. The full range of factors affecting return to work has not yet been explored and further evaluations of return to work interventions are warranted.

Objectives: To assess the efficacy of repetitive transcranial magnetic stimulation for post-stroke non-fluent aphasia through a review of current literature., Methods: Three electronic databases (Medline, Embase & Scopus) were searched for articles. Relevant studies were further evaluated and studies that met inclusion criteria were reviewed., Results: The literature search yielded 4713 studies. Thirty-five articles were further evaluated to be included. Thirteen met all inclusion criteria and were chosen for review. The studies provide moderate to strong evidence that rTMS may be an effective treatment for non-fluent stroke aphasia., Conclusion: There are some strong studies evaluating the efficacy of rTMS in non-fluent stroke patients but further research is required to fully establish the usefulness of this treatment. Future directions and limitations are presented.

Background and Purpose: Functional outcome after stroke is often only evaluated using the modified Rankin Scale, which primarily assesses activities of daily living. Stroke patients may experience difficulties with social reintegration and mental functions, feel isolated, and experience poor quality of life, even after physical recovery is complete. Functional assessments based solely on activity limitations may not be able to capture the full range of problems experienced by stroke survivors., Methods: Telephone interviews were conducted 2 to 3 years poststroke to assess outcome on multiple levels of functioning as stated in the WHO International Classification of Functioning: body function (Montreal Cognitive Assessment and Patient Health Questionnaire-2), activity (modified Rankin Scale), and participation (Reintegration to Normal Living Index)., Results: Ninety-six (68%) patients had a favorable functional outcome (modified Rankin Scale <2). Of these, 79, 91, and 93 patients completed the Montreal Cognitive Assessment, Reintegration to Normal Living Index, and Patient Health Questionnaire-2, respectively. Forty-three (54%) patients were cognitively impaired, 47 (52%) had restrictions in reintegration, and 30 (32%) endorsed symptoms of depression. There was no difference in Montreal Cognitive Assessment or Patient Health Questionnaire-2 scores between those who had activity limitations and those who had not., Conclusions: More than half of stroke patients with excellent functional recovery measured by the modified Rankin Scale continue to have cognitive impairment and participation restrictions, and one third of patients continue to have depression 2 to 3 years later. Current definitions of good functional outcome used in the majority of stroke acute trials focus on activity limitations, but greater attention to multiple levels of recovery is required., (© 2017 American Heart Association, Inc.)

Blood pressure variability is an emerging risk factor for stroke, cognitive impairment, and dementia, possibly through links with cerebral hypoperfusion. Recent evidence suggests visit-to-visit (e.g., over months, years) blood pressure variability is related to cerebral perfusion decline in brain regions vulnerable to Alzheimer's disease. However, less is known about relationships between short-term (e.g., < 24 hours) blood pressure variability and regional cerebral perfusion, and whether these relationships may differ by age. We investigated short-term blood pressure variability and concurrent regional cerebral microvascular perfusion in a sample of community-dwelling older adults without history of dementia or stroke and healthy younger adults. Blood pressure was collected continuously during perfusion MRI. Cerebral blood flow was determined for several brain regions implicated in cerebrovascular dysfunction in Alzheimer's disease. Elevated systolic blood pressure variability was related to lower levels of concurrent cerebral perfusion in medial temporal regions: hippocampus (β = -.60 [95% CI -.90, -.30]; p < .001), parahippocampal gyrus (β = -.57 [95% CI -.89, -.25]; p = .001), entorhinal cortex (β = -.42 [95% CI -.73, -.12]; p = .009), and perirhinal cortex (β = -.37 [95% CI -.72, -.03]; p = .04), and not in other regions, and in older adults only. Findings suggest a possible age-related selective vulnerability of the medial temporal lobes to hypoperfusion in the context of short-term blood pressure fluctuations, independent of average blood pressure, white matter hyperintensities, and gray matter volume, which may underpin the increased risk for dementia associated with elevated BPV.

Dilation of perivascular spaces (PVS) in the brain may indicate poor fluid drainage due to the accumulation of perivascular cell debris, waste, and proteins, including amyloid-beta (Aβ). No prior study has assessed whether plasma Aβ levels are related to PVS in older adults without dementia. Independently living older adults (N = 56, mean age = 68.2 years; Standard deviation (SD) = 6.5; 30.4% male) free of dementia or clinical stroke were recruited from the community and underwent brain MRI and venipuncture. PVS were qualitatively scored and dichotomized to low PVS burden (scores 0–1,) or high PVS burden (score>1). Plasma was assayed using a Quanterix Simoa Kit to quantify Aβ42 and Aβ40 levels. A significant difference was observed in plasma Aβ42/Aβ40 ratio between low and high PVS burden, controlling for age (F[1, 53] = 5.59, p = 0.022, η2 = 0.10), with lower Aβ42/Aβ40 ratio in the high PVS burden group. Dilation of PVS is associated with a lower plasma Aβ42/Aβ40 ratio, which may indicate higher cortical amyloid deposition. Future longitudinal studies examining PVS changes, and the pathogenesis of AD are warranted. [ABSTRACT FROM AUTHOR]

Background: Cerebral small vessel disease (SVD) is associated with increased risk of stroke and dementia. Progressive damage to the cerebral microvasculature may also trigger angiogenic processes to promote vessel repair. Elevated levels of circulating endothelial progenitor cells (EPCs) and pro-angiogenic signaling proteins are observed in response to vascular injury. We aimed to examine circulating levels of EPCs and proangiogenic proteins in older adults with evidence of SVD. Methods: Older adults (ages 55–90) free of dementia or stroke underwent venipuncture and brain magnetic resonance imaging (MRI). Flow cytometry quantified circulating EPCs as the number of cells in the lymphocyte gate positively expressing EPC surface markers (CD34+CD133+CD309+). Plasma was assayed for proangiogenic factors (VEGF-A, VEGF-C, VEGF-D, Tie-2, and Flt-1). Total SVD burden score was determined based on MRI markers, including white matter hyperintensities, cerebral microbleeds and lacunes. Results: Sixty-four older adults were included. Linear regression revealed that older adults with higher circulating EPC levels exhibited greater total SVD burden [β = 1.0 × 105, 95% CI (0.2, 1.9), p = 0.019], after accounting for age and sex. Similarly, a positive relationship between circulating VEGF-D and total SVD score was observed, controlling for age and sex [β = 0.001, 95% CI (0.000, 0.001), p = 0.048]. Conclusion: These findings suggest that elevated levels of circulating EPCs and VEGF-D correspond with greater cerebral SVD burden in older adults. Additional studies are warranted to determine whether activation of systemic angiogenic growth factors and EPCs represents an early attempt to rescue the vascular endothelium and repair damage in SVD. [ABSTRACT FROM AUTHOR]