A Machine Learning Approach to Predict Post-stroke Fatigue. The Nor-COAST study.

OBJECTIVE: This study aimed to predict fatigue 18 months post-stroke by utilizing comprehensive data from the acute and sub-acute phases after stroke in a machine-learning set-up. DESIGN: A prospective multicenter cohort-study with 18-month follow-up. SETTING: Outpatient clinics at 3 university hospitals and 2 local hospitals. PARTICIPANTS: 474 participants with the diagnosis of acute stroke (mean ± SD age; 70.5 (11.3), 59% male; N=474). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The primary outcome, fatigue at 18 months, was assessed using the Fatigue Severity Scale (FSS-7). FSS-7≥5 was defined as fatigue. In total, 45 prediction variables were collected, at initial hospital-stay and 3-month post-stroke. RESULTS: The best performing model, random forest, predicted 69% of all subjects with fatigue correctly with a sensitivity of 0.69 (95% CI: 0.50, 0.86), a specificity of 0.74 (95% CI: 0.66, 0.83), and an Area under the Receiver Operator Characteristic curve of 0.79 (95% CI: 0.69, 0.87) in new unseen data. The proportion of subjects predicted to suffer from fatigue, who truly suffered from fatigue at 18-months was estimated to 0.41 (95% CI: 0.26, 0.57). The proportion of subjects predicted to be free from fatigue who truly did not have fatigue at 18-months was estimated to 0.90 (95% CI: 0.83, 0.96). CONCLUSIONS: Our findings indicate that the model has satisfactory ability to predict fatigue in the chronic phase post-stroke and may be applicable in clinical settings.

Reduced physical activity level was associated with poorer quality of life during the early phase of the COVID-19 pandemic: a sub-study of the last-long trial.

OBJECTIVES: To assess how physical activity levels changed in a stroke cohort during the COVID-19 (SARS-CoV-2) pandemic, and how these changes were associated with quality of life (QoL). METHODS: Between March and July 2021, 150 patients with stroke already included in the Life after Stroke (LAST-long) trial in Norway were invited to participate in this cross-sectional survey. Participants were asked to complete a questionnaire assessing changes in physical activity and self-reported health following the pandemic. Univariate and multivariate logistic regression analyses were used to explore the association between physical activity, loneliness, mental health, social activity and QoL. RESULTS: In all, 118 (79%) participants completed the questionnaire. A total of 80 (68%) reported less physical activity, 46 (39%) felt lonelier, and 43 (37%) reported worse mental health, while 50 (42%) reported reduced QoL compared with before the lockdown. In the univariate analyses less physical activity, feeling lonelier and changes in mental health were associated with reduced QoL. In the multivariate analysis only less physical activity odds ratio (OR) = 4.04 (95% confidence interval (95% CI) 1.44-11.34, p = 0.008) was significantly associated with reduced QoL. CONCLUSION: More than two-thirds of patients with stroke reported reduced physical activity during the COVID-19 pandemic, and less physical activity was strongly associated with reduced QoL.

Accelerometer-measured physical activity at 3 months as a predictor of symptoms of depression and anxiety 1 year after stroke: a multicentre prospective cohort study in central Norway.

OBJECTIVES: To study sedentary behaviour and physical activity at 3 months as predictors for symptoms of depression and anxiety at 1-year post-stroke. DESIGN: A prospective cohort study. PATIENTS: Patients with first-ever ischaemic stroke. METHODS: Mood was assessed 3- and 12-months post-stroke using the Hospital Anxiety and Depression Scale. Sedentary behaviour and physical activity were measured using accelerometry 3 months post-stroke. RESULTS: A total of 292 participants (116 (39.7%) females; mean age 71.7 (standard deviation 11.3) years) were included. At 12 months, 16.7% experienced depression and 19.5% anxiety, respectively. Adjusting for age and sex, regression analysis showed that comorbidity burden (ß 0.26; 95% confidence interval (95% CI) 0.02, 0.51; p = 0.038), stroke severity (ß 0.22; 95% CI 0.10, 0.35; p = 0.001), functional disability (ß 0.89, 95% CI 0.49, 1.30; p = 0.000), and global cognition (ß-0.15; 95% CI -0.25, -0.05; p = 0.004) predicted depression. Multi-adjusted analysis showed sedentary behaviour and physical activity did not significantly predict depression or anxiety (p > 0.05). CONCLUSION: Sedentary behaviour and physical activity did not significantly predict mood after stroke. Comorbidity burden, stroke severity, functional disability, and global cognition were identified as possible predictors of depression. More research is needed to determine the impact of physical activity on depression and anxiety symptoms.

Physical Activity Behavior and Its Association With Global Cognitive Function Three Months After Stroke: The Nor-COAST Study†.

OBJECTIVE: The purposes of this study were to determine the association between physical activity (PA) behavior and global cognitive function 3 months after stroke and to explore the role of physical capacity as a mediating factor. METHODS: Participants with stroke were successively recruited at 5 different hospitals in Norway. PA was measured using accelerometers, with a follow-up period of 7 consecutive days, and global cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). The general pattern of PA and the percentage of participants adhering to World Health Organization PA recommendations (at least 150 minutes of moderate-intensity aerobic PA per week) were investigated using descriptive statistics. Multiple regression and mediator analyses were used to examine the relationship between PA behavior and MoCA scores; physical capacity, measured with the Short Physical Performance Battery, served as the mediating variable. RESULTS: A total of 193 women (42.6%) and 260 men (57.4%) with a median age of 73.7 years (25th and 75th percentiles = 65.8 and 80.4, respectively) and a median MoCA score of 25 points (25th and 75th percentiles = 22 and 27, respectively) were included. Mean total time spent walking at moderate intensity was 251.7 (SD = 164.6) min/wk (mean bout length = 20.9 [SD = 7.3] seconds), which indicated 69.3% adherence to World Health Organization guidelines. With each point decrease in the MoCA score, there was an expected 8.6% increase in the odds of nonadherence to PA recommendations. Physical capacity was identified as an important mediating factor, explaining the strength of the association between cognition and PA behavior. CONCLUSIONS: In contrast to previous research, in the present study, most participants adhered to the updated global PA guidelines. However, people who had survived stroke and had reduced cognitive function were at higher risk of inactivity, an association mediated by physical capacity. IMPACT: A better understanding of the association between cognition and PA behavior after stroke might help for developing more targeted early-onset interventions.

Multimodal individualised intervention to prevent functional decline after stroke: protocol of a randomised controlled trial on long-term follow-up after stroke (LAST-long).

INTRODUCTION: Multimodal interventions have emerged as new approaches to provide more targeted intervention to reduce functional decline after stroke. Still, the evidence is contradictory. The main objective of the Life After Stroke (LAST)-long trial is to investigate if monthly meetings with a stroke coordinator who offers a multimodal approach to long-term follow-up can prevent functional decline after stroke. METHODS AND ANALYSIS: LAST-long is a pragmatic single-blinded, parallel-group randomised controlled trial recruiting participants living in six different municipalities, admitted to four hospitals in Norway. The patients are screened for inclusion and recruited into the trial 3 months after stroke. A total of 300 patients fulfilling the inclusion criteria will be randomised to an intervention group receiving monthly follow-up by a community-based stroke coordinator who identifies the participants' individual risk profile and sets up an action plan based on individual goals, or to a control group receiving standard care. All participants undergo blinded assessments at 6-month, 12-month and 18-month follow-up. Modified Rankin Scale at 18 months is primary outcome. Secondary outcomes are results of blood tests, blood pressure, adherence to secondary prophylaxis, measures of activities of daily living, cognitive function, physical function, physical activity, patient reported outcome measures, caregiver's burden, the use and costs of health services, safety measures and measures of adherence to the intervention. Mixed models will be used to evaluate differences between the intervention and control group for all endpoints across the four time points, with treatment group, time as categorical covariates and their interaction as fixed effects, and patient as random effect. ETHICS AND DISSEMINATION: This trial was approved by the Regional Committee of Medical and Health Research Ethics, REC no. 2018/1809. The main results will be published in international peer-reviewed open access scientific journals and to policy-makers and end users in relevant channels. TRIAL REGISTRATION NUMBER: ClincalTrials.gov Identifier: NCT03859063, registered on 1 March 2019.

Plasma Inflammatory Biomarkers Are Associated With Poststroke Cognitive Impairment: The Nor-COAST Study.

BACKGROUND: Inflammation is proposed to be involved in the pathogenesis of poststroke cognitive impairment. The aim of this study was to investigate associations between concentrations of systemic inflammatory biomarkers after ischemic stroke and poststroke cognitive impairment. METHODS: The Nor-COAST study (Norwegian Cognitive Impairment After Stroke) is a prospective observational multicenter cohort study, including patients hospitalized with acute stroke between 2015 and 2017. Inflammatory biomarkers, including the TCC (terminal C5b-9 complement complex) and 20 cytokines, were analyzed in plasma, collected at baseline, 3-, and 18 months poststroke, using ELISA and a multiplex assay. Global cognitive outcome was assessed with the Montreal Cognitive Assessment (MoCA) scale. We investigated the associations between plasma inflammatory biomarkers at baseline and MoCA score at 3-, 18-, and 36-month follow-ups; the associations between inflammatory biomarkers at 3 months and MoCA score at 18- and 36-month follow-ups; and the association between these biomarkers at 18 months and MoCA score at 36-month follow-up. We used mixed linear regression adjusted for age and sex. RESULTS: We included 455 survivors of ischemic stroke. Higher concentrations of 7 baseline biomarkers were significantly associated with lower MoCA score at 36 months; TCC, IL (interleukin)-6, and MIP (macrophage inflammatory protein)-1α were associated with MoCA at 3, 18, and 36 months (P<0.01). No biomarker at 3 months was significantly associated with MoCA score at either 18 or 36 months, whereas higher concentrations of 3 biomarkers at 18 months were associated with lower MoCA score at 36 months (P<0.01). TCC at baseline and IL-6 and MIP-1α measured both at baseline and 18 months were particularly strongly associated with MoCA (P<0.01). CONCLUSIONS: Higher concentrations of plasma inflammatory biomarkers were associated with lower MoCA scores up to 36 months poststroke. This was most pronounced for inflammatory biomarkers measured in the acute phase following stroke. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02650531.

Does implementation of a standardized pathway of stroke care affect functional outcome after stroke?

BACKGROUND: A stroke care pathway (SCP) was introduced in Norway in 2018. The goal of the pathway was to avoid delay in treatment and diagnostics of acute stroke and to secure treatment according to national guidelines. In this study, we aimed to evaluate how the implementation of the SCP affects outcome after stroke. METHODS: We performed a register-based study using data from the Norwegian Stroke Register that covers 87% of acute stroke patients in Norway. Patients included 1 year before and 1 year after the introduction of the care pathway were compared (2017 vs 2019). Change in functional outcome, the proportion of independent patients 90 days post-stroke, discharge destination, proportions admitted to stroke units and 90 days mortality were compared. Functional outcome was measured using modified Rankin Scale (mRS) and functional independence was defined as mRS 0-2. RESULTS: In total, 11,009 patients with 90 days follow-up data were analyzed. Comparing the cohorts from 2017 and 2019, there was no change in demographics or stroke characteristics. No statistically significant differences in mRS, admission to thrombolysis time, or 90 days mortality were found. However, the proportion of patients discharged directly home and treated in a stroke unit increased from 2017 to 2019. CONCLUSION: The implementation of a standardized pathway of stroke care in Norway did not lead to improvement in functional outcome or a reduction in 90 days mortality. However, the proportion of patients discharged directly home increased, and more patients were treated in stroke units in 2019 compared with 2017.

Neuroimaging markers of dual impairment in cognition and physical performance following stroke: The Nor-COAST study.

Background: Cognitive decline and decline in physical performance are common after stroke. Concurrent impairments in the two domains are reported to give increased risk of dementia and functional decline. The concept of dual impairment of physical performance and cognition after stroke is poorly investigated. Clinically accessible imaging markers of stroke and pre-existing brain pathology might help identify patients at risk. Objective: The primary aim of this study was to investigate to which extent pre-stroke cerebral pathology was associated with dual impairment in cognition and physical performance at time of stroke. Secondary aims were to examine whether white matter hyperintensities, medial temporal lobe atrophy, and stroke lesion volume and location were associated with dual impairment. Methods: Participants from the Norwegian Cognitive Impairment After Stroke (Nor-COAST) study with available MRI data at baseline were included in this cross-sectional study. Logistic regression analyses were conducted, with impairment status (no impairment, impaired cognition, impaired physical performance, and dual impairment) as the dependent variable and MRI markers as covariates. Pre-existing brain pathologies were classified into neurodegenerative, cerebrovascular, or mixed pathology. In addition, white matter hyperintensities and medial temporal lobe atrophy were included as independent covariates. Stroke volume and location were also ascertained from study-specific MRI scans. Results: Participants' (n = 348) mean (SD) age was 72.3 (11.3) years; 148 (42.5%) were women. Participants with dual impairment (n = 99) were significantly older, had experienced a more severe stroke, and had a higher comorbidity burden and poorer pre-stroke function. Stroke lesion volume (odds ratio 1.03, 95%, confidence interval 1.00 to 1.05, p = 0.035), but not stroke location or pre-existing brain pathology, was associated with dual impairment, after adjusting for age and sex. Conclusion: In this large cohort of stroke survivors having suffered mainly mild to moderate stroke, stroke lesion volume-but not pre-existing brain pathology-was associated with dual impairment early after stroke, confirming the role of stroke severity in functional decline.

Resilience and Its Association With Activities of Daily Living 3 Months After Stroke.

Independence in basic activities of daily living (ADL) is an important outcome after stroke. Identifying factors associated with independence can contribute to improve post-stroke rehabilitation. Resilience, which is the ability of coping with a serious event, might be such a factor. Still, the impact of resilience and its role in rehabilitation after stroke is poorly investigated. Hence, the purpose of this study was to assess whether resilience assessed early after stroke can be associated with independence in basic ADL 3 months later. Hospitalized patients with a diagnosed acute stroke and a modified Rankin Scale score ≤ 4 were included. Bivariate and multivariate linear regression were applied to assess whether resilience as measured by the Brief Resilience Scale within the first 2 weeks after stroke was associated with basic ADL measured by Barthel Index at 3-month follow-up. Age, sex, fatigue, stroke severity at admission and pre-stroke disability were added as covariates. Sixty-four participants (35 (54.7%) male), aged 75.9 (SD 8.6) years were included 4.3 (SD 2.8) days after stroke. There was no significant change in resilience from baseline 3.1 (SD 0.3) to 3 months later 3.2 (SD 0.5). Resilience was not associated with basic ADL in neither the bivariate (b = 2.01, 95% CI -5.21, 9.23, p = 0.580) nor in the multivariate regression models (b = 0.50, 95% CI -4.87, 6.88, p = 0.853). Our results showed that resilience remained stable during follow-up. Early measurement of resilience was not associated with independence in basic activities of daily living 3 months after stroke. These results, indicate that resilience is a personal trait not associated with the outcome of physical adversity. However, future research should investigate whether resilience is related to the outcomes of psychosocial adversity after a stroke.

Reasons and predictors of non-thrombolysis in patients with acute ischemic stroke admitted within 4.5 h.

OBJECTIVES: Thrombolytic treatment in acute ischemic stroke (AIS) reduces stroke-related disability. Nearly 40% of all patients with AIS (<4.5 h) receive thrombolysis, but there is a large variation in the use between hospitals. Little is known about reasons and predictors for not giving thrombolytic treatment. Therefore, we aimed to investigate reasons for non-thrombolysis in patients admitted within 4.5 h. METHODS: All patients with AIS (<4.5 h) admitted to Akershus University Hospital, Norway, between January 2015 and December 2017 were examined. Patient characteristics and reasons for not giving thrombolysis were registered. Descriptive statistics and logistic regression analyses were performed. RESULTS: Of 535 patients admitted with AIS (<4.5 h), 250 (47%) did not receive thrombolysis and of these only 26% had an absolute contraindication to treatment. Among the 74% with relative contraindications, the most common reasons given were mild and improving symptoms. Previous stroke (OR 3.32, 95%CI 1.99-5.52), arriving between 3 h and 4.5 h after onset (OR 7.76, 95%CI 3.73-16.11) or having mild symptoms (OR 2.33, 95%CI 1.56-3.49) were all significant predictors of not receiving thrombolytic treatment in the multivariable logistic regression model. CONCLUSION: A large proportion of patients with AIS do not receive thrombolysis. This study highlights up-to-date findings that arriving late in the time window, mild symptoms, and previous stroke are strong predictors of non-treatment. It is uncertain whether there is an underuse of thrombolysis in AIS. Increasing the utility of thrombolysis in the 4.5 h time window must be weighed against possible harms.

Perceived Caregiver Strain, 3- and 18-Month Poststroke, in a Cohort of Caregivers from the Life after Stroke Trial (LAST).

Aim: To gain more knowledge of caregiver strain in the Life After Stroke Trial (LAST) population. Methods: This is a substudy of the LAST study, including all caregivers' reports of perceived Caregiver Strain Index (CSI) at inclusion and 18-month follow-up irrespective of group allocation. The checklist "STROBE Statement-Checklist of items that should be included in reports of cohort studies" was used. Caregivers to adults (age ≥18 years), here defined as the person living with, a patient with a first-ever or recurrent stroke, community dwelling, with modified Rankin Scale (mRS) <5 and no serious comorbidities, was invited to fill out the Caregiver Strain Index at three months (10-16 weeks) poststroke. Domains indicating differences of change in perceived strain in the total sample were analyzed in a linear regression analysis. Results: Caregiver strain (n = 147) varying from 5% to 27% was reported by the caregivers at baseline and between 2% to18% at 18-month follow-up. The items indicating the highest level of strain at baseline and 18 months were as follows: "Care giving is confining," "There have been changes in personal plans," "There have been emotional adjustments," and "I feel completely overwhelmed." The samples were divided into age groups 0-79 years and 80-100 years, indicating a higher strain on the caregiver for persons 80-100 years at 18 months. Conclusion: Caregiver strain was relatively low both at baseline and at 18-month follow-up. Main caregiver strains were reported in terms of a sense of confinement, a tendency of emotional strain, and the altering of plans at both time points. Depression was one of the main explanatory factors for the perceived caregiver strain. The perception of caregiver strain was higher in age groups 80-100 years than age groups 0-79 years.

Physical Performance and Cognition as Predictors of Instrumental Activities of Daily Living After Stroke: A Prospective Multicenter Cohort Study.

OBJECTIVE: To investigate whether cognition and physical performance, both separately and combined, 3 months post stroke predict change in instrumental activities of daily living (IADL) up to 18 months and whether different paths of IADL could be identified by different scenarios, defined by combinations of high and low scores on physical performance and cognition. DESIGN: The study is part of the Norwegian Cognitive Impairment After Stroke study, a prospective multicenter cohort study including patients with acute stroke. SETTING: Stroke outpatient clinics at 3 university hospitals and 2 local hospitals. PARTICIPANTS: Adult survivors of stroke (N=544) were followed up at 3 and 18 months after stroke. Participants' mean ± SD age was 72.6±11.8 years, and 235 (43.2 %) were female. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The primary outcome was IADL as measured by Nottingham Extended Activities of Daily Living. At 3 months, Short Physical Performance Battery (SPPB) and Montreal Cognitive Assessment (MoCA) were used to assess physical performance and cognition, respectively. RESULTS: Mixed-effects linear regression analyses showed that the regression coefficient (95% CI) for the interaction with time was significant for MoCA, 0.238 (CI, 0.030-0.445; P=.025) but not for SPPB. The model combining SPPB and MoCA was significantly better than separate models (likelihood ratio P<.001). Overall, there was no improvement in IADL over time. A combination of SPPB and MoCA score in the upper quartile at 3 months was associated with improved IADL of 1.396 (CI, 0.252-2.540; P=.017) over time. CONCLUSIONS: Combining measures of cognition and physical performance gave the best prediction of change in IADL. Function at 3 months seems to be predictive for long-term IADL status, which highlights the importance of targeted rehabilitation in the early and subacute phases after stroke.

Associations between changes in gait parameters, balance, and walking capacity during the first 3 months after stroke: a prospective observational study.

BACKGROUND: Independent ambulation is a common rehabilitation goal after stroke, requiring adequate balance and efficiency of gait. Spatiotemporal gait parameters are expected to improve in the first 3 months and their association with balance and efficiency of gait may provide useful insights into the recovery of safe and independent mobility. OBJECTIVE: Examine the associations between changes in spatiotemporal gait parameters, balance, and walking capacity during the first 3 months after stroke. METHODS: This prospective observational study included participants diagnosed with stroke. Within the first 2 weeks after stroke onset and again 3 months (±2 weeks) later, gait was assessed using a GAITRite mat at self-selected gait speed, balance using the Berg Balance Scale (BBS), and walking capacity using the 6-minute walk test (6 MWT). Changes in gait parameters, balance, and walking capacity were assessed using paired sample t-tests, and linear regression analyses were used to assess associations between changes in spatiotemporal gait parameters, BBS, and 6MWT. RESULTS: Seventy-nine participants (mean (SD) age 75.4 (8.5) years; 44 men) were included. Gait parameters, balance, and walking capacity all improved during follow-up. The bivariate regression analyses showed associations between improvements in all gait parameters, except walk ratio, with improvement in balance, and in all gait parameters with improvement in walking capacity. Only gait speed was associated with balance (13.8 points, 95% CI 0.5, 27.8, p = .0042) and walking capacity (256 m, 95% CI 173,340, p < .001) in the multivariate analyses. CONCLUSION: Improved spatiotemporal gait parameters were associated with improved balance and walking capacity within the first 3 months after stroke.

Neopterin and kynurenic acid as predictors of stroke recurrence and mortality: a multicentre prospective cohort study on biomarkers of inflammation measured three months after ischemic stroke.

BACKGROUND: Chronic low-grade inflammation is associated with both ischemic stroke and sedentary behaviour. The aim of this study was to investigate the predictive abilities of biomarkers of inflammation and immune modulation associated with sedentary behaviour for ischemic stroke recurrence and mortality in a stroke population. METHODS: Patients admitted to hospital for acute stroke were recruited to the prospective multicentre cohort study, the Norwegian Cognitive Impairment After Stroke (Nor-COAST) study, from May 2015 until March 2017. Patients with ischemic stroke, blood samples available from the three-month follow-up, and no stroke recurrence before the three-month follow-up were included. Serum was analysed for C-reactive protein (CRP) with high-sensitive technique, and plasma for interleukin-6 (IL-6), neopterin, pyridoxic acid ratio index (PAr-index: 4-pyridoxic acid: [pyrioxal+pyridoxal-5'-phosphate]) and kynurenic acid (KA). Ischemic stroke recurrence and death were identified by the Norwegian Stroke Registry and the Cause of Death Registry until 31 December 2018. RESULTS: The study included 354 patients, 57% male, mean age 73 (SD 11) years, mean observation time 2.5 (SD 0.6) years, and median National Institute of Health Stroke Scale of 0 (IQR 1) at three months. CRP was associated with mortality (HR 1.40, CI 1.01, 1.96, p = 0.046), and neopterin was associated with the combined endpoint (recurrent ischemic stroke or death) (HR 1.52, CI 1.06, 2.20, p = 0.023), adjusted for age, sex, prior cerebrovascular disease, modified Rankin Scale, and creatinine. When adding neopterin and KA to the same model, KA was negatively associated (HR 0.57, CI 0.33, 0.97, p = 0.038), and neopterin was positively associated (HR 1.61, CI 1.02, 2.54, p = 0.040) with mortality. Patients with cardioembolic stroke at baseline had higher levels of inflammation at three months. CONCLUSION: Neopterin might be a valuable prognostic biomarker in stroke patients. The use of KA as a measure of anti-inflammatory capacity should be investigated further. TRIAL REGISTRATION: The study was registered at Clinicaltrials.gov ( NCT02650531 ). First posted on 08/01/2016.

Can functional walk tests add value to the prediction of cardiorespiratory fitness after stroke? A prospective cohort study.

BACKGROUND: Cardiorespiratory fitness is often impaired following stroke, and peak oxygen consumption (VO2peak) is an important prognostic value of all-cause mortality. The primary objective was to investigate whether functional walk tests assessed in the subacute phase after stroke added value in predicting VO2peak in chronic stroke, in addition to age, sex and functional dependency. Secondary objectives were to investigate associations between daily physical activity and functional walk tests, and with VO2peak in chronic stroke. METHODS: This prospective cohort study included eligible participants originally included in the randomized controlled trial Life After Stroke. Functional walk tests, i.e., six-minute walk test (6MWT) and maximal gait speed, were assessed at inclusion and 18 months later. VO2peak [ml/kg/min] was assessed by a cardiopulmonary exercise test on a treadmill 20 months after inclusion. Daily physical activity was measured by a uniaxial accelerometer (activPAL) at 18-month follow-up. RESULTS: Ninety-two community-dwelling individuals, with a mean (SD) age of 69.2 (10.6) years and 33 (35.9%) women, were included 3 months after stroke onset. Eighty-three (90.2%) participants had a modified Rankin Scale (mRS) score of 1 or 2, indicating functional independence. An overall assessment of four prediction models indicated the combination of age, sex, mRS and 6MWT as predictors to be the best fitted model in predicting VO2peak (adjusted R2 = 0.612). Secondary results showed statistically significant, but not clinically significant, associations between daily physical activity and functional walk tests, and with VO2peak. CONCLUSIONS: 6MWT add significant value to the prediction of mean VO2peak in the chronic phase in mild strokes, in combination with age, sex and functional dependency. This prediction model may facilitate clinical decisions and rehabilitation strategies for mildly affected stroke survivors in risk of low levels of VO2peak. Future studies should validate the model in various stages after stroke and in patients moderately and severely affected.

Investigating novel biomarkers of immune activation and modulation in the context of sedentary behaviour: a multicentre prospective ischemic stroke cohort study.

BACKGROUND: Sedentary behaviour is associated with disease, but the molecular mechanisms are not understood. Valid biomarkers with predictive and explanatory properties are required. Therefore, we have investigated traditional and novel biomarkers of inflammation and immune modulation and their association to objectively measured sedentary behaviour in an ischemic stroke population. METHODS: Patients admitted to hospital with acute ischemic stroke were included in the multicentre Norwegian Cognitive Impairment After Stroke (Nor-COAST) study (n = 815). For this sub-study (n = 257), sedentary behaviour was registered 3 months after stroke using position transition data from the body-worn sensor, ActivPal®. Blood samples were analysed for high sensitive C-reactive protein (hsCRP), the cytokines interleukin-6 (IL-6) and 10 (IL-10), neopterin, tryptophan (Trp), kynurenine (kyn), kynurenic acid (KA), and three B6 vitamers, pyridoxal 5'-phosphate (PLP), pyridoxal (PL), and pyridoxic acid (PA). The kynurenine/tryptophan ratio (KTR) and the pyridoxic acid ratio index (PAr = PA: PL + PLP) were calculated. RESULTS: Of the 815 patients included in the main study, 700 attended the three-month follow-up, and 257 fulfilled the inclusion criteria for this study. Sedentary time was significantly associated with levels of hsCRP, IL-6, neopterin, PAr-index, and KA adjusted for age, sex, waist circumference, and creatinine. In a fully adjusted model including all the significant biomarkers except hsCRP (because of missing values), sedentary time was independently positively associated with the PAr-index and negatively with KA. We did not find an association between sedentary behaviour, IL-10, and KTR. CONCLUSIONS: The PAr-index is known to capture several modes of inflammation and has previously shown predictive abilities for future stroke. This novel result indicates that the PAr-index could be a useful biomarker in future studies on sedentary behaviour and disease progression. KA is an important modulator of inflammation, and this finding opens new and exciting pathways to understand the hazards of sedentary behaviour. TRIAL REGISTRATION: The study was registered at Clinicaltrials.gov ( NCT02650531 ). First posted 08/01/2016.

Pre-stroke cognitive impairment is associated with vascular imaging pathology: a prospective observational study.

BACKGROUND: Chronic brain pathology and pre-stroke cognitive impairment (PCI) is predictive of post-stroke dementia. The aim of the current study was to measure pre-stroke neurodegenerative and vascular disease burden found on brain MRI and to assess the association between pre-stroke imaging pathology and PCI, whilst also looking for potential sex differences. METHODS: This prospective brain MRI cohort is part of the multicentre Norwegian cognitive impairment after stroke (Nor-COAST) study. Patients hospitalized with acute ischemic or hemorrhagic stroke were included from five participating stroke units. Visual rating scales were used to categorize baseline MRIs (N = 410) as vascular, neurodegenerative, mixed, or normal, based on the presence of pathological imaging findings. Pre-stroke cognition was assessed by interviews of patients or caregivers using the Global Deterioration Scale (GDS). Stroke severity was assessed with the National Institute of Health Stroke Scale (NIHSS). Univariate and multiple logistic regression analyses were performed to investigate the association between imaging markers, PCI, and sex. RESULTS: Patients' (N = 410) mean (SD) age was 73.6 (±11) years; 182 (44%) participants were female, the mean (SD) NIHSS at admittance was 4.1 (±5). In 68% of the participants, at least one pathological imaging marker was found. Medial temporal lobe atrophy (MTA) was present in 30% of patients, white matter hyperintensities (WMH) in 38% of patients and lacunes in 35% of patients. PCI was found in 30% of the patients. PCI was associated with cerebrovascular pathology (OR 2.5; CI = 1.4 to 4.5, p = 0.001) and mixed pathology (OR 3.4; CI = 1.9 to 6.1, p = 0.001) but was not associated with neurodegeneration (OR 1.0; CI = 0.5 to 2.2; p = 0.973). Pathological MRI markers, including MTA and lacunes, were more prevalent among men, as was a history of clinical stroke prior to the index stroke. The OR of PCI for women was not significantly increased (OR 1.2; CI = 0.8 to 1.9; p = 0.3). CONCLUSIONS: Pre-stroke chronic brain pathology is common in stroke patients, with a higher prevalence in men. Vascular pathology and mixed pathology are associated with PCI. There were no significant sex differences for the risk of PCI. TRIAL REGISTRATION: NCT02650531 , date of registration: 08.01.2016.

Effects of High-Intensity Interval Training After Stroke (The HIIT Stroke Study) on Physical and Cognitive Function: A Multicenter Randomized Controlled Trial.

OBJECTIVE: To assess the effects of high-intensity interval training (HIIT) on physical, mental, and cognitive functioning after stroke. DESIGN: The HIIT Stroke Study was a single-blind, multicenter, parallel-group randomized controlled trial. SETTING: Specialized rehabilitation units at 3 Norwegian hospitals. PARTICIPANTS: Adult stroke survivors (N=70) 3 months to 5 years after a first-ever stroke. Mean age was 57.6±9.2 years and 58.7±9.2 years in the intervention and control groups, respectively. INTERVENTIONS: Participants were randomized to standard care in combination with 4×4 minutes of treadmill HIIT at 85%-95% of peak heart rate or standard care only. OUTCOMES: Outcomes were measured using physical, mental, and cognitive tests and the FIM and Stroke Impact Scale. Linear mixed models were used to analyze differences between groups at posttest and 12-month follow-up. RESULTS: The intervention group showed a significant treatment effect (95% confidence interval [CI]) from baseline to posttest on a 6-minute walk test of 28.3 (CI, 2.80-53.77) meters (P=.030); Berg Balance Scale 1.27 (CI, 0.17-2.28) points (P=.025); and Trail Making Test Part B (TMT-B; -24.16 [CI, -46.35 to -1.98] s, P=.033). The intervention group showed significantly greater improvement on TMT-B at the 12-month follow-up (25.44 [CI, -49.01 to -1.87] s, P=.035). The control group showed significantly greater improvement in total Functional Independence Measure score with a treatment effect of -2.37 (CI, -4.30 to -0.44) points (P=.016) at 12-month follow-up. No significant differences were identified between groups on other outcomes at any time point. CONCLUSIONS: HIIT combined with standard care improved walking distance, balance, and executive function immediately after the intervention compared with standard care only. However, only TMT-B remained significant at the 12-month follow-up.

An Exploration of Sedentary Behavior Patterns in Community-Dwelling People With Stroke: A Cluster-Based Analysis.

BACKGROUND AND PURPOSE: Long periods of daily sedentary time, particularly accumulated in long uninterrupted bouts, are a risk factor for cardiovascular disease. People with stroke are at high risk of recurrent events and prolonged sedentary time may increase this risk. We aimed to explore how people with stroke distribute their periods of sedentary behavior, which factors influence this distribution, and whether sedentary behavior clusters can be distinguished? METHODS: This was a secondary analysis of original accelerometry data from adults with stroke living in the community. We conducted data-driven clustering analyses to identify unique accumulation patterns of sedentary time across participants, followed by multinomial logistical regression to determine the association between the clusters, and the total amount of sedentary time, age, gender, body mass index (BMI), walking speed, and wake time. RESULTS: Participants in the highest quartile of total sedentary time accumulated a significantly higher proportion of their sedentary time in prolonged bouts (P < 0.001). Six unique accumulation patterns were identified, all of which were characterized by high sedentary time. Total sedentary time, age, gender, BMI, and walking speed were significantly associated with the probability of a person being in a specific accumulation pattern cluster, P < 0.001 - P = 0.002. DISCUSSION AND CONCLUSIONS: Although unique accumulation patterns were identified, there is not just one accumulation pattern for high sedentary time. This suggests that interventions to reduce sedentary time must be individually tailored.Video Abstract available for more insight from the authors (see the Video Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A343).

Association between in-hospital frailty and health-related quality of life after stroke: the Nor-COAST study.

BACKGROUND: Stroke survivors are known to have poorer health-related quality of life (HRQoL) than the general population, but less is known about characteristics associated with HRQoL decreasing through time following a stroke. This study aims to examine how in-hospital frailty is related to HRQoL from 3 to 18 months post stroke. METHOD: Six hundred twenty-five participants hospitalised with stroke were included and followed up at 3 and/or 18 months post stroke. Stroke severity was assessed the day after admission with the National Institutes of Health Stroke Scale (NIHSS). A modified Fried phenotype was used to assess in-hospital frailty; measures of exhaustion, physical activity, and weight loss were based on pre-stroke status, while gait speed and grip strength were measured during hospital stay. HRQoL at 3- and 18-months follow-up were assessed using the five-level version of the EuroQol five-dimensional descriptive system (EQ-5D-5L) and the EuroQol visual analogue scale (EQ-5D VAS). We conducted linear mixed effect regression analyses unadjusted and adjusted for sex, age, and stroke severity to investigate the association between in-hospital frailty and post-stroke HRQoL. RESULTS: Mean (SD) age was 71.7 years (11.6); mean NIHSS score was 2.8 (4.0), and 263 (42.1%) were female. Frailty prevalence was 10.4%, while 58.6% were pre-frail. The robust group had EQ-5D-5L index and EQ-5D VAS scores at 3 and 18 months comparable to the general population. Also at 3 and 18 months, the pre-frail and frail groups had significantly lower EQ-5D-5L indices than the robust group (p <  0.001), and the frail group showed a larger decrease from 3 to 18 months in the EQ-5D-5L index score compared to the robust group (- 0.056; 95% CI - 0.104 to - 0.009; p = 0.021). There were no significant differences in change in EQ-5D VAS scores between the groups. CONCLUSION: This study on participants mainly diagnosed with mild strokes suggests that robust stroke patients have fairly good and stable post-stroke HRQoL, while post-stroke HRQoL is impaired and continues to deteriorate among patients with in-hospital frailty. This emphasises the importance of a greater focus on frailty in stroke units. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT02650531 ).