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  • 1
    Online Resource
    Online Resource
    Subacute cognitive impairment after first-ever transient ischemic attack or ischemic stroke in young adults: The ODYSSEY study
    SAGE Publications ; 2023
    In:  European Stroke Journal Vol. 8, No. 1 ( 2023-03), p. 283-293
    Details
    In: European Stroke Journal, SAGE Publications, Vol. 8, No. 1 ( 2023-03), p. 283-293
    Abstract: We aimed to investigate the prevalence of cognitive impairment in the subacute phase after transient ischemic attack (TIA) and ischemic stroke (IS), factors associated with a vascular cognitive disorder, and the prevalence of subjective cognitive complaints and their relation with objective cognitive performance. Patients and methods: In this multicenter prospective cohort study, we recruited patients with first-ever TIA and IS, aged 18–49 years, between 2013 and 2021 for cognitive assessment up to 6 months after index event. We calculated composite Z-scores for seven cognitive domains. We defined cognitive impairment as a composite Z-score  〈  −1.5. We defined major vascular cognitive disorder as a Z-score  〈  −2.0 in one or more cognitive domains. Results: Fifty three TIA and 545 IS patients completed cognitive assessment with mean time to assessment of 89.7 (SD 40.7) days. The median NIHSS at admission was 3 (interquartile range, 1–5). Cognitive impairment was common in five domains (up to 37%), with similar proportion in TIA and IS patients. Patients with major vascular cognitive disorder had a lower education level, higher NIHSS scores and more frequent lesions in the left frontotemporal lobe than without vascular cognitive disorder ( p  〈  0.05 FDR-corrected). Subjective memory and executive cognitive complaints were present in about two-thirds of the patients, but were weakly associated with objective cognitive performance (β: −0.32 and −0.21, respectively). Discussion and conclusion: In the subacute phase after TIA or stroke in young adults, cognitive impairment and subjective cognitive complaints are prevalent, but they are weakly associated with each other.
    Type of Medium: Online Resource
    ISSN: 2396-9873 , 2396-9881
    URL: Article
    DOI: 10.1177/23969873221132032
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2023
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  • 2
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    Prevalence, risk factors, and long-term outcomes of cerebral ischemia in hospitalized COVID-19 patients – study rationale and protocol of the CORONIS study: A multicentre prospective cohort study
    SAGE Publications ; 2022
    In:  European Stroke Journal Vol. 7, No. 2 ( 2022-06), p. 180-187
    Details
    In: European Stroke Journal, SAGE Publications, Vol. 7, No. 2 ( 2022-06), p. 180-187
    Abstract: COVID-19 is often complicated by thrombo-embolic events including ischemic stroke. The underlying mechanisms of COVID-19-associated ischemic stroke, the incidence and risk factors of silent cerebral ischemia, and the long-term functional outcome in these patients are currently unknown. Patients and methods: CORONavirus and Ischemic Stroke (CORONIS) is a multicentre prospective cohort study investigating the prevalence, risk factors and long-term incidence of (silent) cerebral ischemia, and the long-term functional outcome among patients with COVID-19. We aim to include 200 adult patients hospitalized with COVID-19 without symptomatic ischemic stroke to investigate the prevalence of silent cerebral ischemia compared with 60 (matched) controls with MRI. In addition, we will identify potential risk factors and/or causes of cerebral ischemia in COVID-19 patients with ( n = 70) or without symptomatic stroke ( n = 200) by means of blood sampling, cardiac workup and brain MRI. We will measure functional outcome and cognitive function after 3 and 12 months with standardized questionnaires in all patients with COVID-19. Finally, the long-term incidence of (new) silent cerebral ischemia in patients with COVID-19 will be assessed with follow up MRI ( n = 120). Summary: The CORONIS study is designed to add further insight into the prevalence, long-term incidence and risk factors of cerebral ischemia, and the long-term functional outcome in hospitalized adult patients with COVID-19.
    Type of Medium: Online Resource
    ISSN: 2396-9873 , 2396-9881
    URL: Article
    DOI: 10.1177/23969873221092538
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2022
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  • 3
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    Online Resource
    Brain atrophy in cerebral small vessel diseases: Extent, consequences, technical limitations and perspectives: The HARNESS initiative
    SAGE Publications ; 2020
    In:  Journal of Cerebral Blood Flow & Metabolism Vol. 40, No. 2 ( 2020-02), p. 231-245
    Details
    In: Journal of Cerebral Blood Flow & Metabolism, SAGE Publications, Vol. 40, No. 2 ( 2020-02), p. 231-245
    Abstract: Brain atrophy is increasingly evaluated in cerebral small vessel diseases. We aim at systematically reviewing the available data regarding its extent, correlates and cognitive consequences. Given that in this context, brain atrophy measures might be biased, the first part of the review focuses on technical aspects. Thereafter, data from the literature are analyzed in light of these potential limitations, to better understand the relationships between brain atrophy and other MRI markers of cerebral small vessel diseases. In the last part, we review the links between brain atrophy and cognitive alterations in patients with cerebral small vessel diseases.
    Type of Medium: Online Resource
    ISSN: 0271-678X , 1559-7016
    URL: Article
    DOI: 10.1177/0271678X19888967
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2020
    detail.hit.zdb_id: 2039456-1
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  • 4
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    The Hyperintense study: Assessing the effects of induced blood pressure increase and decrease on MRI markers of cerebral small vessel disease: Study rationale and protocol
    SAGE Publications ; 2022
    In:  European Stroke Journal Vol. 7, No. 3 ( 2022-09), p. 331-338
    Details
    In: European Stroke Journal, SAGE Publications, Vol. 7, No. 3 ( 2022-09), p. 331-338
    Abstract: Neuroimaging markers of cerebral small vessel disease (SVD) are common in older individuals, but the pathophysiological mechanisms causing these lesions remain poorly understood. Although hypertension is a major risk factor for SVD, the direct causal effects of increased blood pressure are unknown. The Hyperintense study is designed to examine cerebrovascular and structural abnormalities, possibly preceding SVD, in young adults with hypertension. These patients undergo a diagnostic work-up that requires patients to temporarily discontinue their antihypertensive agents, often leading to an increase in blood pressure followed by a decrease once effective medication is restarted. This allows examination of the effects of blood pressure increase and decrease on the cerebral small vessels. Methods: Hyperintense is a prospective observational cohort study in 50 hypertensive adults (18–55 years) who will temporarily discontinue antihypertensive medication for diagnostic purposes. MRI and clinical data is collected at four timepoints: before medication withdrawal (baseline), once antihypertensives are largely or completely withdrawn ( T = 1), when patients have restarted medication ( T = 2) and reached target blood pressure and 1 year later ( T = 3). The 3T MRI protocol includes conventional structural sequences and advanced techniques to assess various aspects of microvascular integrity, including blood-brain barrier function using Dynamic Contrast Enhanced MRI, white matter integrity, and microperfusion. Clinical assessments include motor and cognitive examinations and blood sampling. Discussion: The Hyperintense study will improve the understanding of the pathophysiological mechanisms following hypertension that may cause SVD. This knowledge can ultimately help to identify new targets for treatment of SVD, aimed at prevention or limiting disease progression.
    Type of Medium: Online Resource
    ISSN: 2396-9873 , 2396-9881
    URL: Article
    DOI: 10.1177/23969873221100331
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2022
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  • 5
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    Online Resource
    Association of cerebral small vessel disease burden with brain structure and cognitive and vascular risk trajectories in mid-to-late life
    SAGE Publications ; 2022
    In:  Journal of Cerebral Blood Flow & Metabolism Vol. 42, No. 4 ( 2022-04), p. 600-612
    Details
    In: Journal of Cerebral Blood Flow & Metabolism, SAGE Publications, Vol. 42, No. 4 ( 2022-04), p. 600-612
    Abstract: We characterize the associations of total cerebral small vessel disease (SVD) burden with brain structure, trajectories of vascular risk factors, and cognitive functions in mid-to-late life. Participants were 623 community-dwelling adults from the Whitehall II Imaging Sub-study with multi-modal MRI (mean age 69.96, SD = 5.18, 79% men). We used linear mixed-effects models to investigate associations of SVD burden with up to 25-year retrospective trajectories of vascular risk and cognitive performance. General linear modelling was used to investigate concurrent associations with grey matter (GM) density and white matter (WM) microstructure, and whether these associations were modified by cognitive status (Montreal Cognitive Asessment [MoCA] scores of 〈 26 vs. ≥ 26). Severe SVD burden in older age was associated with higher mean arterial pressure throughout midlife (β = 3.36, 95% CI [0.42-6.30]), and faster cognitive decline in letter fluency (β = −0.07, 95% CI [−0.13–−0.01] ), and verbal reasoning (β = −0.05, 95% CI [−0.11–−0.001]). Moreover, SVD burden was related to lower GM volumes in 9.7% of total GM, and widespread WM microstructural decline (FWE-corrected p  〈  0.05). The latter association was most pronounced in individuals who demonstrated cognitive impairments on MoCA (MoCA 〈 26; F 3,608  = 2.14, p = 0.007). These findings highlight the importance of managing midlife vascular health to preserve brain structure and cognitive function in old age.
    Type of Medium: Online Resource
    ISSN: 0271-678X , 1559-7016
    URL: Article
    DOI: 10.1177/0271678X211048411
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2022
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  • 6
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    Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Triggers, Causes, and Outcome (SECRETO): Rationale and design
    SAGE Publications ; 2017
    In:  European Stroke Journal Vol. 2, No. 2 ( 2017-06), p. 116-125
    Details
    In: European Stroke Journal, SAGE Publications, Vol. 2, No. 2 ( 2017-06), p. 116-125
    Abstract: Worldwide, about 1.3 million annual ischaemic strokes (IS) occur in adults aged 〈 50 years. Of these early-onset strokes, up to 50% can be regarded as cryptogenic or associated with conditions with poorly documented causality like patent foramen ovale and coagulopathies. Key hypotheses/aims (1) Investigate transient triggers and clinical/sub-clinical chronic risk factors associated with cryptogenic IS in the young; (2) use cardiac imaging methods exceeding state-of-the-art to reveal novel sources for embolism; (3) search for covert thrombosis and haemostasis abnormalities; (4) discover new disease pathways using next-generation sequencing and RNA gene expression studies; (5) determine patient prognosis by use of phenotypic and genetic data; and (6) adapt systems medicine approach to investigate complex risk-factor interactions. Design Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome (SECRETO; NCT01934725) is a prospective multi-centre case–control study enrolling patients aged 18–49 years hospitalised due to first-ever imaging-proven IS of undetermined etiology. Patients are examined according to a standardised protocol and followed up for 10 years. Patients are 1:1 age- and sex-matched to stroke-free controls. Key study elements include centralised reading of echocardiography, electrocardiography, and neurovascular imaging, as well as blood samples for genetic, gene-expression, thrombosis and haemostasis and biomarker analysis. We aim to have 600 patient–control pairs enrolled by the end of 2018. Summary SECRETO is aiming to establish novel mechanisms and prognosis of cryptogenic IS in the young and will provide new directions for therapy development for these patients. First results are anticipated in 2019.
    Type of Medium: Online Resource
    ISSN: 2396-9873 , 2396-9881
    URL: Article
    DOI: 10.1177/2396987317703210
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2017
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  • 7
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    Differences in cerebral small vessel disease magnetic resonance imaging markers between lacunar stroke and non–Lobar intracerebral hemorrhage
    SAGE Publications ; 2021
    In:  European Stroke Journal Vol. 6, No. 3 ( 2021-09), p. 236-244
    Details
    In: European Stroke Journal, SAGE Publications, Vol. 6, No. 3 ( 2021-09), p. 236-244
    Abstract: It is unclear why cerebral small vessel disease (SVD) leads to lacunar stroke in some and to non–lobar intracerebral hemorrhage (ICH) in others. We investigated differences in MRI markers of SVD in patients with lacunar stroke or non–lobar ICH. Patients and methods We included patients from two prospective cohort studies with either lacunar stroke (RUN DMC) or non–lobar ICH (FETCH). Differences in SVD markers (white matter hyperintensities [WMH], lacunes, cerebral microbleeds [CMB] ) between groups were investigated with univariable tests; multivariable logistic regression analysis, adjusted for age, sex, and vascular risk factors; spatial correlation analysis and voxel–wise lesion symptom mapping. Results We included 82 patients with lacunar stroke (median age 63, IQR 57–72) and 54 with non-lobar ICH (66, 59–75). WMH volumes and distribution were not different between groups. Lacunes were more frequent in patients with a lacunar stroke (44% vs. 17%, adjusted odds ratio [aOR] 5.69, 95% CI [1.66–22.75] ) compared to patients with a non–lobar ICH. CMB were more frequent in patients with a non–lobar ICH (71% vs. 23%, aOR for lacunar stroke vs non–lobar ICH 0.08 95% CI [0.02–0.26]), and more often located in non–lobar regions compared to CMB in lacunar stroke. Discussion Although we obserd different types of MRI markers of SVD within the same patient, ischemic markers of SVD were more frequent in the ischemic type of lacunar stroke, and hemorrhagic markers were more prevalent in the hemorrhagic phenotype of non-lobar ICH. Conclusion There are differences between MRI markers of SVD between patients with a lacunar stroke and those with a non-lobar ICH.
    Type of Medium: Online Resource
    ISSN: 2396-9873 , 2396-9881
    URL: Article
    DOI: 10.1177/23969873211031753
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2021
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  • 8
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    ESO Guideline on covert cerebral small vessel disease
    SAGE Publications ; 2021
    In:  European Stroke Journal Vol. 6, No. 2 ( 2021-06), p. IV-IV
    Details
    In: European Stroke Journal, SAGE Publications, Vol. 6, No. 2 ( 2021-06), p. IV-IV
    Abstract: ‘Covert’ cerebral small vessel disease (ccSVD) is common on neuroimaging in persons without overt neurological manifestations, and increases the risk of future stroke, cognitive impairment, dependency, and death. These European Stroke Organisation (ESO) guidelines provide evidence-based recommendations to assist with clinical decisions about management of ccSVD, specifically white matter hyperintensities and lacunes, to prevent adverse clinical outcomes. The guidelines were developed according to ESO standard operating procedures and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. We prioritised the clinical outcomes of stroke, cognitive decline or dementia, dependency, death, mobility and mood disorders, and interventions of blood pressure lowering, antiplatelet drugs, lipid lowering, lifestyle modifications, glucose lowering and conventional treatments for dementia. We systematically reviewed the literature, assessed the evidence, formulated evidence-based recommendations where feasible, and expert consensus statements. We found little direct evidence, mostly of low quality. We recommend patients with ccSVD and hypertension to have their blood pressure well controlled; lower blood pressure targets may reduce ccSVD progression. We do not recommend antiplatelet drugs such as aspirin in ccSVD. We found little evidence on lipid lowering in ccSVD. Smoking cessation is a health priority. We recommend regular exercise which may benefit cognition, and a healthy diet, good sleep habits, avoiding obesity and stress for general health reasons. In ccSVD, we found no evidence for glucose control in the absence of diabetes or for conventional Alzheimer dementia treatments. Randomised controlled trials with clinical endpoints are a priority for ccSVD.
    Type of Medium: Online Resource
    ISSN: 2396-9873 , 2396-9881
    URL: Article
    DOI: 10.1177/23969873211027002
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2021
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  • 9
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    Online Resource
    How often does white matter hyperintensity volume regress in cerebral small vessel disease?
    SAGE Publications ; 2023
    In:  International Journal of Stroke Vol. 18, No. 8 ( 2023-10), p. 937-947
    Details
    In: International Journal of Stroke, SAGE Publications, Vol. 18, No. 8 ( 2023-10), p. 937-947
    Abstract: It has been suggested that white matter hyperintensity lesions (WMHs), which typically progress over time, can also regress, and that this might be associated with favorable cognitive performance. We determined the prevalence of WMH regression in patients with cerebral small vessel disease (SVD) and examined which demographic, clinical, and radiological markers were associated with this regression. Methods: We used semi-automated lesion marking methods to quantify WMH volume at multiple timepoints in three cohorts with symptomatic SVD; two with moderate-to-severe symptomatic SVD (the SCANS observational cohort and the control arm of the PRESERVE interventional trial) and one with mild-to-moderate SVD (the RUN DMC observational cohort). Mixed-effects ordered logistic regression models were used to test which factors predicted participants to show WMH regression. Results: No participants (0/98) in SCANS, 6/42 (14.3%) participants in PRESERVE, and 6/276 (2.2%) in RUN DMC showed WMH regression. On multivariate analysis, only lower WMH volume (OR: 0.36, 95% CI: 0.23–0.56) and better white matter microstructural integrity assessed by fractional anisotropy using diffusion tensor imaging (OR: 1.55, 95% CI: 1.07–2.24) predicted participant classification as regressor versus stable or progressor. Discussion: Only a small proportion of participants demonstrated WMH regression across the three cohorts, when a blinded standardized assessment method was used. Subjects who showed regression had less severe imaging markers of disease at baseline. Our results show that lesion regression is uncommon in SVD and unlikely to be a major factor affecting the use of WMH quantification as an outcome for clinical trials.
    Type of Medium: Online Resource
    ISSN: 1747-4930 , 1747-4949
    URL: Article
    DOI: 10.1177/17474930231169132
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2023
    detail.hit.zdb_id: 2211666-7
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  • 10
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    Relation between physical activity and cerebral small vessel disease: A nine-year prospective cohort study
    SAGE Publications ; 2021
    In:  International Journal of Stroke Vol. 16, No. 8 ( 2021-10), p. 962-971
    Details
    In: International Journal of Stroke, SAGE Publications, Vol. 16, No. 8 ( 2021-10), p. 962-971
    Abstract: Given the unexplored potential of physical activity to reduce the progression of cerebral small vessel disease (cSVD, the purpose of this study was to prospectively (across nine-year follow-up) examine the relation between (baseline) physical activity and the (clinical and imaging) consequences of the whole spectrum of cerebral small vessel disease. Methods Five hundred and three patients with cerebral small vessel disease from the RUNDMC study were followed for nine years. Physical activity was assessed using a questionnaire in 2006, 2011, and 2015. Clinical events (i.e. all-cause mortality, cerebrovascular events (by stroke subtype)) were collected with a structured questionnaire. Patients underwent magnetic resonance imaging scanning for the assessment of magnetic resonance imaging markers of cerebral small vessel disease (i.e. white matter hyperintensities, lacunes, and microbleeds) and microstructural integrity of the white matter at three timepoints. Results The mean age at baseline was 66 (SD 9.0) years; 44% were women. A higher baseline physical activity level was independently associated with a lower all-cause mortality (HR: 0.69, 95%CI: 0.49–0.98, p = 0.03) and incidence of cerebrovascular disease (HR: 0.58, 95%CI: 0.36–0.96, p = 0.03). However, we found no relation between physical activity and incident lacunar stroke or progression of magnetic resonance imaging markers of cerebral small vessel disease. Conclusions Whilst regular physical activity was not related to the progression of magnetic resonance imaging markers of cerebral small vessel disease across a nine-year follow-up, results from our study prove that high levels of physical activity in patients with cerebral small vessel disease are associated with a lower all-cause mortality and lower incidence of cerebrovascular events.
    Type of Medium: Online Resource
    ISSN: 1747-4930 , 1747-4949
    URL: Article
    DOI: 10.1177/1747493020984090
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2021
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