Geriatric assessment with management for older patients with cancer receiving radiotherapy: a cluster-randomised controlled pilot study.

BACKGROUND: Geriatric assessment and management (GAM) improve outcomes in older patients with cancer treated with surgery or chemotherapy. It is unclear whether GAM may provide better function and quality of life (QoL), or be cost-effective, in a radiotherapy (RT) setting. METHODS: In this Norwegian cluster-randomised controlled pilot study, we assessed the impact of a GAM intervention involving specialist and primary health services. It was initiated in-hospital at the start of RT by assessing somatic and mental health, function, and social situation, followed by individually adapted management plans and systematic follow-up in the municipalities until 8 weeks after the end of RT, managed by municipal nurses as patients' care coordinators. Thirty-two municipal/city districts were 1:1 randomised to intervention or conventional care. Patients with cancer ≥ 65 years, referred for RT, were enrolled irrespective of cancer type, treatment intent, and frailty status, and followed the allocation of their residential district. The primary outcome was physical function measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (QLQ-C30). Secondary outcomes were overall quality of life (QoL), physical performance, use and costs of health services. Analyses followed the intention-to-treat principle. Study registration at ClinicalTrials.gov ID NCT03881137. RESULTS: We included 178 patients, 89 in each group with comparable age (mean 74.1), sex (female 38.2%), and Edmonton Frail Scale scores (mean 3.4 [scale 0-17], scores 0-3 [fit] in 57%). More intervention patients received curative RT (76.4 vs 61.8%), had higher irradiation doses (mean 54.1 vs 45.5 Gy), and longer lasting RT (mean 4.4 vs 3.6 weeks). The primary outcome was completed by 91% (intervention) vs 88% (control) of patients. No significant differences between groups on predefined outcomes were observed. GAM costs represented 3% of health service costs for the intervention group during the study period. CONCLUSIONS: In this heterogeneous cohort of older patients receiving RT, the majority was fit. We found no impact of the intervention on patient-centred outcomes or the cost of health services. Targeting a more homogeneous group of only pre-frail and frail patients is strongly recommended in future studies needed to clarify the role and organisation of GAM in RT settings.

Neopterin, kynurenine metabolites, and indexes related to vitamin B6 are associated with post-stroke cognitive impairment: The Nor-COAST study.

BACKGROUND AND AIMS: We have previously shown that systemic inflammation was associated with post-stroke cognitive impairment (PSCI). Because neopterin, kynurenine pathway (KP) metabolites, and B6 vitamers are linked to inflammation, in our study we investigated whether those biomarkers were associated with PSCI. MATERIAL AND METHODS: The Norwegian Cognitive Impairment After Stroke study is a prospective multicenter cohort study of patients with acute stroke recruited from May 2015 through March 2017. Plasma samples of 422 participants (59 % male) with ischemic stroke from the index hospital stay and 3 months post-stroke were available for analyses of neopterin, KP metabolites, and B6 vitamers using liquid chromatography-tandem mass spectrometry. Mixed linear regression analyses adjusted for age, sex, and creatinine, were used to assess whether there were associations between those biomarkers and cognitive outcomes, measured by the Montreal Cognitive Assessment scale (MoCA) at 3-, 18-, and 36-month follow-up. RESULTS: Participants had a mean (SD) age of 72 (12) years, with a mean (SD) National Institutes of HealthStroke Scale score of 2.7 (3.6) at Day 1. Higher baseline values of quinolinic acid, PAr (i.e., an inflammatory marker based on vitamin B6 metabolites), and HKr (i.e., a marker of functional vitamin B6 status based on selected KP metabolites) were associated with lower MoCA score at 3, 18, and 36 months post-stroke (p < 0.01). Higher baseline concentrations of neopterin and 3-hydroxykynurenine were associated with lower MoCA scores at 18 and 36 months, and higher concentrations of xanthurenic acid were associated with higher MoCA score at 36 months (p < 0.01). At 3 months post-stroke, higher concentrations of neopterin and lower values of pyridoxal 5́-phosphate were associated with lower MoCA scores at 18- and 36-month follow-up, while lower concentrations of picolinic acid were associated with a lower MoCA score at 36 months (p < 0.01). CONCLUSION: Biomarkers and metabolites of systemic inflammation, including biomarkers of cellular immune activation, indexes of vitamin B6 homeostasis, and several neuroactive metabolites of the KP pathway, were associated with PSCI. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02650531.

Diagnostic accuracy of the Clock Drawing Test in screening for early post-stroke neurocognitive disorder: the Nor-COAST study.

BACKGROUND: Post-stroke neurocognitive disorder, though common, is often overlooked by clinicians. Moreover, although the Montreal Cognitive Assessment (MoCA) has proven to be a valid screening test for neurocognitive disorder, even more time saving tests would be preferred. In our study, we aimed to determine the diagnostic accuracy of the Clock Drawing Test (CDT) for post-stroke neurocognitive disorder and the association between the CDT and MoCA. METHODS: This study is part of the Norwegian Cognitive Impairment After Stroke study, a multicentre prospective cohort study following patients admitted with acute stroke. At the three-month follow-up, patients were classified with normal cognition, mild neurocognitive disorder, or major neurocognitive disorder according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria. Any neurocognitive disorder compromised both mild- and major neurocognitive disorder. The CDT at the three-month assessment was given scores ranging from 0 to 5. Patients able to complete the CDT and whose cognitive status could be classified were included in analyses. The CDT diagnostic accuracy for post-stroke neurocognitive disorder was identified using receiver operating characteristic curves, sensitivity, specificity, positive predictive value, and negative predictive value. The association between the MoCA and CDT was analysed with Spearman's rho. RESULTS: Of 554 participants, 238 (43.0%) were women. Mean (SD) age was 71.5 (11.8) years, while mean (SD) National Institutes of Health Stroke Scale score was 2.6 (3.7). The area under the receiver operating characteristic curve of the CDT for major neurocognitive disorder and any neurocognitive disorder was 0.73 (95% CI, 0.68-0.79) and 0.68 (95% CI, 0.63-0.72), respectively. A CDT cutoff of < 5 yielded 68% sensitivity and 60% specificity for any neurocognitive disorder and 78% sensitivity and 53% specificity for major neurocognitive disorder. Spearman's correlation coefficient between scores on the MoCA and CDT was 0.50 (95% CI, 0.44-0.57, p < .001). CONCLUSIONS: The CDT is not accurate enough to diagnose post-stroke neurocognitive disorder but shows acceptable accuracy in identifying major neurocognitive disorder. Performance on the CDT was associated with performance on MoCA; however, the CDT is inferior to MoCA in identifying post-stroke neurocognitive disorder. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02650531). Retrospectively registered January 8, 2016.

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.

Delirium in acute stroke is associated with increased cognitive and psychiatric symptoms over time: The Nor-COAST study.

BACKGROUND: Delirium, an acute and fluctuating mental disturbance of attention, cognition, and consciousness, commonly occurs in acute stroke. Research on long-term outcomes of stroke patients experiencing delirium is limited, especially regarding cognitive and psychiatric symptoms. METHODS: As part of the Nor-COAST study, 373 patients were screened for delirium using the Confusion Assessment Method (CAM) in the acute phase of stroke. Patients were included in the mixed-model linear regression analyses if they had available data from the follow-ups at three, 18 or 36 months, totaling 334 (44.6 % women, mean (SD) age: 72.1 (12.5) years, 17 (5.1 %) diagnosed with delirium). Global cognition was measured using the Montreal Cognitive Assessment (MoCA). Psychiatric symptoms were measured using the Hospital Anxiety and Depression Scale (HADS) and the Neuropsychiatric Inventory-Questionnaire (NPI-Q). RESULTS: At three months, delirium was associated with a higher NPI-Q score (Mean (SD) 2.9 (3.6) vs 1.4 (2.2)). At 18 and 36 months, delirium was associated with a lower MoCA score (Mean (SD) 19.7 (6.6) vs 24.3 (5.0), and 20.6 (7.6) vs 24.6 (4.8)), higher HADS anxiety symptoms (5.0 (4.3) vs 3.3 (3.3), and 5.9 (4.1) vs 3.4 (3.6)), higher HADS depression symptoms (7.2 (4.7) vs 3.4 (3.3), and 6.6 (5.1) vs 3.7 (3.7)), and higher NPI-Q score (2.4 (4.4) vs 1.7 (2.3), 2.6 (4.5) vs 1.0 (1.9)). Delirium significantly predicted the psychiatric symptoms hallucinations and agitation. CONCLUSIONS: Patients with delirium in the acute phase of stroke may be particularly vulnerable to developing cognitive and psychiatric symptoms in the chronic phase.

Changes in sedentary behavior in the chronic phase following stroke.

BACKGROUND: Sedentary behavior increases risk for cardiovascular diseases. Little is known about sedentary behavior through the chronic phase after stroke. We aimed to describe how long and short bouts of sedentary behavior changed over the first three years after stroke and if cognition at baseline was an independent risk factor for sedentary behavior. METHODS: This is a sub-study of the Norwegian cognitive impairment after stroke (Nor-COAST) study, a multicenter study recruiting patients with acute stroke. Sedentary behavior was monitored with a thigh-worn sensor (ActivPal3®), at three-, 18- and 36-months post stroke. Stroke severity was assessed by National Institutes of Health Stroke Scale (NIHSS) and cognition by Montreal cognitive assessment (MoCA). Mixed model analysis with mean number of sedentary minutes accumulated daily as the dependent variable was repeated for all four zones (<30min, 30-60min, 60-90min, >90min) and for total sedentary time. RESULTS: The number of included participants was 528 (mean age 71.4, NIHSS on day 1, 2.7). The total amount of sedentary time accumulated between 08.00-22.00 increased significantly from about 9.8 hours at three months to 10.1 hours at 36 months post stroke (p=0.002). Patient characteristics associated with prolonged duration of the sedentary bouts and sedentary time were age, high BMI, comorbidities, and impaired physical function. No significant associations between MoCA score and sedentary time were found. CONCLUSION: The participants became increasingly sedentary and had fewer breaks in sedentary time from three to 36 months after stroke. Baseline cognition was not related to later sedentary behavior.

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.

The impact of cognitive function on physical activity, physical function and quality of life in older adults following a hip fracture.

OBJECTIVE: To determine the impact of cognitive function on physical activity (PA), physical function and health-related quality of life (HRQoL) in older adults within the first year after hip fracture (HF) surgery. METHODS: We included 397 home-dwelling individuals aged 70 years or older with the ability to walk 10 m before the fracture. Cognitive function was measured at 1 month and other outcomes were assessed at 1, 4 and 12 months postoperatively. Mini-Mental State Examination was used to assess cognitive function, accelerometer-based body-worn sensors to register PA, Short Physical Performance Battery to test physical function and EuroQol-5-dimension-3-level to estimate the HRQoL. Data were analysed by linear mixed-effects models with interactions and ordinal logistic regression models. RESULTS: Cognitive function, adjusted for the pre-fracture ability to perform activities of daily living, comorbidity, age and gender, had an impact on PA [b = 3.64, 95% confidence interval (CI): 2.20-5.23, P < 0.001] and physical function (b = 0.08, 95% CI: 0.04-0.11, P < 0.001; b = 0.12, 95% CI: 0.09-0.15, P < 0.001; and b = 0.14, 95% CI: 0.10-0.18, P < 0.001 at 1, 4 and 12 months, respectively). The cognitive function did not have a considerable impact on HRQoL. CONCLUSIONS: For older adults with HFs, cognitive function 1 month postoperatively had a significant impact on PA and physical function in the first postoperative year. For the HRQoL, little or no evidence of such an effect was found.

Estimation of recurrent atherosclerotic cardiovascular event risk in patients with established cardiovascular disease: the updated SMART2 algorithm.

AIMS: The 10-year risk of recurrent atherosclerotic cardiovascular disease (ASCVD) events in patients with established ASCVD can be estimated with the Secondary Manifestations of ARTerial disease (SMART) risk score, and may help refine clinical management. To broaden generalizability across regions, we updated the existing tool (SMART2 risk score) and recalibrated it with regional incidence rates and assessed its performance in external populations. METHODS AND RESULTS: Individuals with coronary artery disease, cerebrovascular disease, peripheral artery disease, or abdominal aortic aneurysms were included from the Utrecht Cardiovascular Cohort-SMART cohort [n = 8355; 1706 ASCVD events during a median follow-up of 8.2 years (interquartile range 4.2-12.5)] to derive a 10-year risk prediction model for recurrent ASCVD events (non-fatal myocardial infarction, non-fatal stroke, or cardiovascular mortality) using a Fine and Gray competing risk-adjusted model. The model was recalibrated to four regions across Europe, and to Asia (excluding Japan), Japan, Australia, North America, and Latin America using contemporary cohort data from each target region. External validation used data from seven cohorts [Clinical Practice Research Datalink, SWEDEHEART, the international REduction of Atherothrombosis for Continued Health (REACH) Registry, Estonian Biobank, Spanish Biomarkers in Acute Coronary Syndrome and Biomarkers in Acute Myocardial Infarction (BACS/BAMI), the Norwegian COgnitive Impairment After STroke, and Bialystok PLUS/Polaspire] and included 369 044 individuals with established ASCVD of whom 62 807 experienced an ASCVD event. C-statistics ranged from 0.605 [95% confidence interval (CI) 0.547-0.664] in BACS/BAMI to 0.772 (95% CI 0.659-0.886) in REACH Europe high-risk region. The clinical utility of the model was demonstrated across a range of clinically relevant treatment thresholds for intensified treatment options. CONCLUSION: The SMART2 risk score provides an updated, validated tool for the prediction of recurrent ASCVD events in patients with established ASCVD across European and non-European populations. The use of this tool could allow for a more personalized approach to secondary prevention based upon quantitative rather than qualitative estimates of residual risk.

Higher concentrations of kynurenic acid in CSF are associated with the slower clinical progression of Alzheimer's disease.

INTRODUCTION: The kynurenine pathway's (KP) malfunction is closely related to Alzheimer's disease (AD), for antagonistic kynurenic acid (KA) and agonistic quinolinic acid act on the N-methyl-D-aspartate receptor, a possible therapeutic target in treating AD. METHODS: In our longitudinal case-control study, KP metabolites in the cerebrospinal fluid were analyzed in 311 patients with AD and 105 cognitively unimpaired controls. RESULTS: Patients with AD exhibited higher concentrations of KA (ß = 0.18, P < 0.01) and picolinic acid (ß = 0.20, P < 0.01) than the controls. KA was positively associated with tau pathology (ß = 0.29, P < 0.01), and a higher concentration of KA was associated with the slower progression of dementia. DISCUSSION: The higher concentrations of neuroprotective metabolites KA and picolinic acid suggest that the activation of the KP's neuroprotective branch is an adaptive response in AD and may be a promising target for intervention and treatment. Highlights Patients with Alzheimer's disease (AD) exhibited higher concentrations of kynurenic acid and picolinic acid than controls. Higher concentrations of kynurenic acid were associated with slower progression of AD. Potential neurotoxic kynurenines were not increased among patients with AD. Activation of the kynurenine pathway's neuroprotective branch may be an adaptive response in AD.

Genome-wide association identifies the first risk loci for psychosis in Alzheimer disease.

Psychotic symptoms, defined as the occurrence of delusions or hallucinations, are frequent in Alzheimer disease (AD with psychosis, AD + P). AD + P affects ~50% of individuals with AD, identifies a subgroup with poor outcomes, and is associated with a greater degree of cognitive impairment and depressive symptoms, compared to subjects without psychosis (AD - P). Although the estimated heritability of AD + P is 61%, genetic sources of risk are unknown. We report a genome-wide meta-analysis of 12,317 AD subjects, 5445 AD + P. Results showed common genetic variation accounted for a significant portion of heritability. Two loci, one in ENPP6 (rs9994623, O.R. (95%CI) 1.16 (1.10, 1.22), p = 1.26 × 10-8) and one spanning the 3'-UTR of an alternatively spliced transcript of SUMF1 (rs201109606, O.R. 0.65 (0.56-0.76), p = 3.24 × 10-8), had genome-wide significant associations with AD + P. Gene-based analysis identified a significant association with APOE, due to the APOE risk haplotype ε4. AD + P demonstrated negative genetic correlations with cognitive and educational attainment and positive genetic correlation with depressive symptoms. We previously observed a negative genetic correlation with schizophrenia; instead, we now found a stronger negative correlation with the related phenotype of bipolar disorder. Analysis of polygenic risk scores supported this genetic correlation and documented a positive genetic correlation with risk variation for AD, beyond the effect of ε4. We also document a small set of SNPs likely to affect risk for AD + P and AD or schizophrenia. These findings provide the first unbiased identification of the association of psychosis in AD with common genetic variation and provide insights into its genetic architecture.

The relationship of acute delirium with cognitive and psychiatric symptoms after stroke: a longitudinal study.

OBJECTIVE: Delirium, a common complication after stroke, is often overlooked, and long-term consequences are poorly understood. This study aims to explore whether delirium in the acute phase of stroke predicts cognitive and psychiatric symptoms three, 18 and 36 months later. METHOD: As part of the Norwegian Cognitive Impairment After Stroke Study (Nor-COAST), 139 hospitalized stroke patients (49% women, mean (SD) age: 71.4 (13.4) years; mean (SD) National Institutes of Health Stroke Scale (NIHSS) 3.0 (4.0)) were screened for delirium with the Confusion Assessment Method (CAM). Global cognition was measured with the Montreal Cognitive Assessment (MoCA), while psychiatric symptoms were measured using the Hospital Anxiety and Depression Scale (HADS) and the Neuropsychiatric Inventory-Questionnaire (NPI-Q). Data was analyzed using mixed-model linear regression, adjusting for age, gender, education, NIHSS score at baseline and premorbid dementia. RESULTS: Thirteen patients met the criteria for delirium. Patients with delirium had lower MoCA scores compared to non-delirious patients, with the largest between-group difference found at 18 months (Mean (SE): 20.8 (1.4) versus (25.1 (0.4)). Delirium was associated with higher NPI-Q scores at 3 months (Mean (SE): 2.4 (0.6) versus 0.8 (0.1)), and higher HADS anxiety scores at 18 and 36 months, with the largest difference found at 36 months (Mean (SE): 6.2 (1.3) versus 2.2 (0.3)). CONCLUSIONS: Suffering a delirium in the acute phase of stroke predicted more cognitive and psychiatric symptoms at follow-up, compared to non-delirious patients. Preventing and treating delirium may be important for decreasing the burden of post-stroke disability.

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.

Is Frailty Index a better predictor than pre-stroke modified Rankin Scale for neurocognitive outcomes 3-months post-stroke?

BACKGROUND: The prognostic value of frailty measures for post-stroke neurocognitive disorder (NCD) remains to be evaluated. AIMS: The aim of this study was to compare the predictive value of pre-stroke FI with pre-stroke modified Rankin Scale (mRS) for post-stroke cognitive impairment. Further, we explored the added value of including FI in prediction models for cognitive prognosis post-stroke. METHODS: We generated a 36-item Frailty Index (FI), based on the Rockwood FI, to measure frailty based on pre-stroke medical conditions recorded in the Nor-COAST multicentre prospective study baseline assessments. Consecutive participants with a FI score and completed cognitive test battery at three months were included. We generated Odds Ratio (OR) with NCD as the dependent variable. The predictors of primary interest were pre-stroke frailty and mRS. We also measured the predictive values of mRS and FI by the area (AUC) under the receiver operating characteristic curve. RESULTS: 598 participants (43.0% women, mean/SD age = 71.6/11.9, mean/SD education = 12.5/3.8, mean/SD pre-stroke mRS = 0.8/1.0, mean/SD GDS pre-stroke = 1.4/0.8, mean/SD NIHSS day 1 3/4), had a FI mean/SD score = 0.14/0.10. The logistic regression analyses showed that FI (OR 3.09), as well as the mRS (OR 2.21), were strong predictors of major NCD. When FI and mRS were entered as predictors simultaneously, the OR for mRS decreased relatively more than that for FI. AUC for NCD post-stroke was higher for FI than for mRS, both for major NCD (0.762 vs 0.677) and for any NCD (0.681 vs 0.638). CONCLUSIONS: FI is a stronger predictor of post-stroke NCD than pre-stroke mRS and could be a part of the prediction models for cognitive prognosis post-stroke. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02650531 .

Test Accuracy of the Montreal Cognitive Assessment in Screening for Early Poststroke Neurocognitive Disorder: The Nor-COAST Study.

BACKGROUND AND PURPOSE: We determined the diagnostic accuracy of the Montreal Cognitive Assessment (MoCA) for poststroke neurocognitive disorder defined according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria in a prospective observational study. METHODS: Consecutive participants able to complete a cognitive test battery and MoCA 3 months poststroke were included. The reference standard of neurocognitive disorder was defined as a score of ≥1.5 SD below the normative mean in ≥1 cognitive domain on the cognitive test battery. RESULTS: Among 521 participants (43.6% women; mean age/SD, 71.5/12.0 years; mean education/SD, 12.4/3.8 years), the area under the receiver operating characteristic curve of MoCA for neurocognitive disorder was 0.80 (95% CI, 0.76-0.84). Using the standard MoCA cutoff <26, sensitivity was 0.71 (0.69-0.79) with specificity of 0.73 (0.66-0.76). MoCA cutoff of <27 gave higher sensitivity (0.82 [0.77-0.85]) at the expense of specificity (0.60 [0.53-0.66]). DISCUSSION: MoCA has reasonable accuracy for poststroke neurocognitive disorder diagnosed using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02650531.

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 ).

Clinically accessible neuroimaging predictors of post-stroke neurocognitive disorder: a prospective observational study.

BACKGROUND: Neurocognitive disorder (NCD) is common in stroke survivors. We aimed to identify clinically accessible imaging markers of stroke and chronic pathology that are associated with early post-stroke NCD. METHODS: We included 231 stroke survivors from the "Norwegian Cognitive Impairment after Stroke (Nor-COAST)" study who underwent a standardized cognitive assessment 3 months after the stroke. Any NCD (mild cognitive impairment and dementia) and major NCD (dementia) were diagnosed according to "Diagnostic and Statistical Manual of Mental Disorders (DSM-5)" criteria. Clinically accessible imaging findings were analyzed on study-specific brain MRIs in the early phase after stroke. Stroke lesion volumes were semi automatically quantified and strategic stroke locations were determined by an atlas based coregistration. White matter hyperintensities (WMH) and medial temporal lobe atrophy (MTA) were visually scored. Logistic regression was used to identify neuroimaging findings associated with major NCD and any NCD. RESULTS: Mean age was 71.8 years (SD 11.1), 101 (43.7%) were females, mean time from stroke to imaging was 8 (SD 16) days. At 3 months 63 (27.3%) had mild NCD and 65 (28.1%) had major NCD. Any NCD was significantly associated with WMH pathology (odds ratio (OR) = 2.73 [1.56 to 4.77], p = 0.001), MTA pathology (OR = 1.95 [1.12 to 3.41], p = 0.019), and left hemispheric stroke (OR = 1.8 [1.05 to 3.09], p = 0.032). Major NCD was significantly associated with WMH pathology (OR = 2.54 [1.33 to 4.84], p = 0.005) and stroke lesion volume (OR (per ml) =1.04 [1.01 to 1.06], p = 0.001). CONCLUSION: WMH pathology, MTA pathology and left hemispheric stroke were associated with the development of any NCD. Stroke lesion volume and WMH pathology were associated with the development of major NCD 3 months after stroke. These imaging findings may be used in the routine clinical setting to identify patients at risk for early post-stroke NCD. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02650531 , Registered 8 January 2016 - Retrospectively registered.

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.

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.

Gait, physical function, and physical activity in three groups of home-dwelling older adults with different severity of cognitive impairment - a cross-sectional study.

BACKGROUND: The research on associations between gait, physical function, physical activity (PA), and cognitive function is growing. Still, clinical assessments of cognitive function and motor function is often kept separate. In this study, we aimed to look at a broad range of measures of gait, physical function, and PA in three groups of home-dwelling older adults with no or questionable dementia, mild dementia, and moderate/severe dementia. METHODS: This cross-sectional study included 100 home-dwelling older adults, recruited from an outpatient geriatric memory clinic. Severity of dementia was categorised using the clinical dementia rating scale (CDR), with no or questionable dementia (CDR score 0 and 0.5), mild dementia (CDR score 1) and moderate/severe dementia (CDR score 2 and 3). We used thigh worn accelerometers to measure daily PA, the Short Physical Performance Battery (SPPB) to measure physical function, and an electronic gait mat to evaluate gait characteristics. Associations between severity of dementia and measures of PA, physical function, and gait characteristics were assessed by linear regression. RESULTS: Participants' (mean age 78.9 (SD 6.7) years, 57% women) average gait speed was 0.93 m/sec, and average upright time was 301 min/day. Statistically significant associations were found for the severity of dementia and gait speed (p=0.002), step time (p=0.001), physical function (SPPB, p=0.007), and PA (upright time, p=0.031), after adjusting for age. Overall, having no or questionable dementia was associated with faster gait speed (mean difference 0.163 (95% CI: 0.053 to 0.273)), shorter step time (-0.043 (-0.082 to -0.005)), better SPPB score (1.7 (0.5 to 2.8)), and longer upright time (78.9 (18.9 to 139.0)), compared to those with mild dementia. Furthermore, having no or questionable dementia was also associated with faster gait speed and better SPPB scores, as compared to those with moderate to severe dementia. No evidence of any differences was found between the participants with the mild dementia versus the moderate to severe dementia. CONCLUSIONS: After adjusting for age, we found that the no or questionable dementia group to be associated with better gait and physical function, and more PA, as compared with the two groups with mild or moderate/severe dementia. Evaluation of gait, physical function, and PA can add clinically important information of everyday functioning in memory clinics meeting geriatric patients, but investigations on how to use these results to guide interventions are still needed.