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Article ; Online: Imaging Biomarkers of VCI: A Focused Update.

Clancy, Una / Kancheva, Angelina K / Valdés Hernández, Maria Del C / Jochems, Angela C C / Muñoz Maniega, Susana / Quinn, Terence J / Wardlaw, Joanna M

Stroke

2024 Volume 55, Issue 4, Page(s) 791–800

Abstract: Vascular cognitive impairment is common after stroke, in memory clinics, medicine for the elderly services, and undiagnosed in the community. Vascular disease is said to be the second most common cause of dementia after Alzheimer disease, yet vascular ... ...

Abstract	Vascular cognitive impairment is common after stroke, in memory clinics, medicine for the elderly services, and undiagnosed in the community. Vascular disease is said to be the second most common cause of dementia after Alzheimer disease, yet vascular dysfunction is now known to predate cognitive decline in Alzheimer disease, and most dementias at older ages are mixed. Neuroimaging has a major role in identifying the proportion of vascular versus other likely pathologies in patients with cognitive impairment. Here, we aim to provide a pragmatic but evidence-based summary of the current state of potential imaging biomarkers, focusing on magnetic resonance imaging and computed tomography, which are relevant to diagnosing, estimating prognosis, monitoring vascular cognitive impairment, and incorporating our own experiences. We focus on markers that are well-established, with a known profile of association with cognitive measures, but also consider more recently described, including quantitative tissue markers of vascular injury. We highlight the gaps in accessibility and translation to more routine clinical practice.
MeSH term(s)	Humans ; Aged ; Alzheimer Disease/diagnostic imaging ; Alzheimer Disease/complications ; Dementia, Vascular/complications ; Cognitive Dysfunction/complications ; Stroke/diagnostic imaging ; Stroke/complications ; Biomarkers
Chemical Substances	Biomarkers
Language	English
Publishing date	2024-03-06
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	80381-9
ISSN	1524-4628 ; 0039-2499 ; 0749-7954
ISSN (online)	1524-4628
ISSN	0039-2499 ; 0749-7954
DOI	10.1161/STROKEAHA.123.044171
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Article ; Online: Neuropsychiatric symptoms associated with cerebral small vessel disease: a systematic review and meta-analysis.

Clancy, Una / Gilmartin, Daniel / Jochems, Angela C C / Knox, Lucy / Doubal, Fergus N / Wardlaw, Joanna M

The lancet. Psychiatry

2021 Volume 8, Issue 3, Page(s) 225–236

Abstract: Background: Cerebral small vessel disease, a common cause of vascular dementia, is often considered clinically silent before dementia or stroke become apparent. However, some individuals have subtle symptoms associated with acute MRI lesions. We aimed ... ...

Abstract	Background: Cerebral small vessel disease, a common cause of vascular dementia, is often considered clinically silent before dementia or stroke become apparent. However, some individuals have subtle symptoms associated with acute MRI lesions. We aimed to determine whether neuropsychiatric and cognitive symptoms vary according to small vessel disease burden. Methods: In this systematic review and meta-analysis, we searched MEDLINE, EMBASE, and PsycINFO for articles published in any language from database inception to Jan 24, 2020. We searched for studies assessing anxiety, apathy, delirium, emotional lability, fatigue, personality change, psychosis, dementia-related behavioural symptoms or cognitive symptoms (including subjective memory complaints), and radiological features of cerebral small vessel disease. We extracted reported odds ratios (OR), standardised mean differences (SMD), and correlations, stratified outcomes by disease severity or symptom presence or absence, and pooled data using random-effects meta-analyses, reporting adjusted findings when possible. We assessed the bias on included studies using the Risk of Bias for Non-randomized Studies tool. This study is registered with PROSPERO, CRD42018096673. Findings: Of 7119 papers identified, 81 studies including 79 cohorts in total were eligible for inclusion (n=21 730 participants, mean age 69·2 years). Of these 81 studies, 45 (8120 participants) reported effect estimates. We found associations between worse white matter hyperintensity (WMH) severity and apathy (OR 1·41, 95% CI 1·05-1·89) and the adjusted SMD in apathy score between WMH severities was 0·38 (95% CI 0·15-0·61). Worse WMH severity was also associated with delirium (adjusted OR 2·9, 95% CI 1·12-7·55) and fatigue (unadjusted OR 1·63, 95% CI 1·20-2·22). WMHs were not consistently associated with subjective memory complaints (OR 1·34, 95% CI 0·61-2·94) and unadjusted SMD for WMH severity between these groups was 0·08 (95% CI -0·31 to 0·47). Anxiety, dementia-related behaviours, emotional lability, and psychosis were too varied or sparse for meta-analysis; these factors were reviewed narratively. Overall heterogeneity varied from 0% to 79%. Only five studies had a low risk of bias across all domains. Interpretation: Apathy, fatigue, and delirium associated independently with worse WMH, whereas subjective cognitive complaints did not. The association of anxiety, dementia-related behaviours, emotional lability, and psychosis with cerebral small vessel disease require further investigation. These symptoms should be assessed longitudinally to improve early clinical detection of small vessel disease and enable prevention trials to happen early in the disease course, long before cognition declines. Funding: Chief Scientist Office of the Scottish Government, UK Dementia Research Institute, Fondation Leducq, Stroke Association Garfield-Weston Foundation, Alzheimer's Society, and National Health Service Research Scotland.
MeSH term(s)	Cerebral Small Vessel Diseases/complications ; Cost of Illness ; Fatigue/etiology ; Humans ; Mental Disorders/etiology
Language	English
Publishing date	2021-02-01
Publishing country	England
Document type	Journal Article ; Meta-Analysis ; Research Support, Non-U.S. Gov't ; Systematic Review
ISSN	2215-0374
ISSN (online)	2215-0374
DOI	10.1016/S2215-0366(20)30431-4
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Article ; Online: Longitudinal Changes of White Matter Hyperintensities in Sporadic Small Vessel Disease: A Systematic Review and Meta-analysis.

Jochems, Angela C C / Arteaga, Carmen / Chappell, Francesca / Ritakari, Tuula / Hooley, Monique / Doubal, Fergus / Muñoz Maniega, Susana / Wardlaw, Joanna M

Neurology

2022 Volume 99, Issue 22, Page(s) e2454–e2463

Abstract: Background and objectives: White matter hyperintensities (WMHs) are frequent imaging features of small vessel disease (SVD) and related to poor clinical outcomes. WMH progression over time is well described, but regression was also noted recently, ... ...

Abstract	Background and objectives: White matter hyperintensities (WMHs) are frequent imaging features of small vessel disease (SVD) and related to poor clinical outcomes. WMH progression over time is well described, but regression was also noted recently, although the frequency and associated factors are unknown. This systematic review and meta-analysis aims to assess longitudinal intraindividual WMH volume changes in sporadic SVD. Methods: We searched EMBASE and MEDLINE for articles up to 28 January 2022 on WMH volume changes using MRI on ≥2 time points in adults with sporadic SVD. We classified populations (healthy/community-dwelling, stroke, cognitive, other vascular risk factors, and depression) based on study characteristics. We performed random-effects meta-analyses with Knapp-Hartung adjustment to determine mean WMH volume change (change in milliliters, percentage of intracranial volume [%ICV], or milliliters per year), 95% CI, and prediction intervals (PIs, limits of increase and decrease) using unadjusted data. Risk of bias assessment tool for nonrandomized studies was used to assess risk of bias. We followed Preferred Reporting in Systematic Review and Meta-Analysis guidelines. Results: Forty-one articles, 12,284 participants, met the inclusion criteria. Thirteen articles had low risk of bias across all domains. Mean WMH volume increased over time by 1.74 mL (95% CI 1.23-2.26; PI -1.24 to 4.73 mL; 27 articles, N = 7,411, mean time interval 2.7 years, SD = 1.65); 0.25 %ICV (95% CI 0.14-0.36; PI -0.06 to 0.56; 6 articles, N = 1,071, mean time interval 3.5 years, SD = 1.54); or 0.58 mL/y (95% CI 0.35-0.81; PI -0.26 to 1.41; 8 articles, N = 3,802). In addition, 13 articles specifically mentioned and/or provided data on WMH regression, which occurred in asymptomatic, stroke, and cognitive disorders related to SVD. Discussion: Net mean WMH volume increases over time mask wide-ranging change (e.g., mean increase of 1.75 mL ranging from 1.25 mL decrease to 4.75 mL increase), with regression documented explicitly in up to one-third of participants. More knowledge on underlying mechanisms, associated factors, and clinical correlates is needed, as WMH regression could be an important intervention target.
MeSH term(s)	Adult ; Humans ; Cerebral Small Vessel Diseases/diagnostic imaging ; Cerebral Small Vessel Diseases/psychology ; White Matter/diagnostic imaging ; Leukoaraiosis/diagnostic imaging ; Magnetic Resonance Imaging/methods ; Stroke
Language	English
Publishing date	2022-09-19
Publishing country	United States
Document type	Meta-Analysis ; Systematic Review ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	207147-2
ISSN	1526-632X ; 0028-3878
ISSN (online)	1526-632X
ISSN	0028-3878
DOI	10.1212/WNL.0000000000201205
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Article ; Online: Magnetic Resonance Imaging Tissue Signatures Associated With White Matter Changes Due to Sporadic Cerebral Small Vessel Disease Indicate That White Matter Hyperintensities Can Regress.

Journal of the American Heart Association

2024 Volume 13, Issue 3, Page(s) e032259

Abstract: Background: White matter hyperintensities (WMHs) might regress and progress contemporaneously, but we know little about underlying mechanisms. We examined WMH change and underlying quantitative magnetic resonance imaging tissue measures over 1 year in ... ...

Abstract	Background: White matter hyperintensities (WMHs) might regress and progress contemporaneously, but we know little about underlying mechanisms. We examined WMH change and underlying quantitative magnetic resonance imaging tissue measures over 1 year in patients with minor ischemic stroke with sporadic cerebral small vessel disease. Methods and results: We defined areas of stable normal-appearing white matter, stable WMHs, progressing and regressing WMHs based on baseline and 1-year brain magnetic resonance imaging. In these areas we assessed tissue characteristics with quantitative T1, fractional anisotropy (FA), mean diffusivity (MD), and neurite orientation dispersion and density imaging (baseline only). We compared tissue signatures cross-sectionally between areas, and longitudinally within each area. WMH change masks were available for N=197. Participants' mean age was 65.61 years (SD, 11.10), 59% had a lacunar infarct, and 68% were men. FA and MD were available for N=195, quantitative T1 for N=182, and neurite orientation dispersion and density imaging for N=174. Cross-sectionally, all 4 tissue classes differed for FA, MD, T1, and Neurite Density Index. Longitudinally, in regressing WMHs, FA increased with little change in MD and T1 (difference estimate, 0.011 [95% CI, 0.006-0.017]; -0.002 [95% CI, -0.008 to 0.003] and -0.003 [95% CI, -0.009 to 0.004]); in progressing and stable WMHs, FA decreased (-0.022 [95% CI, -0.027 to -0.017] and -0.009 [95% CI, -0.011 to -0.006]), whereas MD and T1 increased (progressing WMHs, 0.057 [95% CI, 0.050-0.063], 0.058 [95% CI, 0.050 -0.066]; stable WMHs, 0.054 [95% CI, 0.045-0.063], 0.049 [95% CI, 0.039-0.058]); and in stable normal-appearing white matter, MD increased (0.004 [95% CI, 0.003-0.005]), whereas FA and T1 slightly decreased and increased (-0.002 [95% CI, -0.004 to -0.000] and 0.005 [95% CI, 0.001-0.009]). Conclusions: Quantitative magnetic resonance imaging shows that WMHs that regress have less abnormal microstructure at baseline than stable WMHs and follow trajectories indicating tissue improvement compared with stable and progressing WMHs.
MeSH term(s)	Male ; Humans ; Aged ; Female ; White Matter/diagnostic imaging ; White Matter/pathology ; Magnetic Resonance Imaging/methods ; Brain/diagnostic imaging ; Brain/pathology ; Diffusion Magnetic Resonance Imaging ; Cerebral Small Vessel Diseases/diagnostic imaging
Language	English
Publishing date	2024-01-31
Publishing country	England
Document type	Journal Article
ZDB-ID	2653953-6
ISSN	2047-9980 ; 2047-9980
ISSN (online)	2047-9980
ISSN	2047-9980
DOI	10.1161/JAHA.123.032259
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Article ; Online: Impact of long-term white matter hyperintensity changes on mobility and dexterity.

Jochems, Angela C C / Muñoz Maniega, Susana / Chappell, Francesca M / Clancy, Una / Arteaga, Carmen / Jaime Garcia, Daniela / Hamilton, Olivia K L / Hewins, Will / Locherty, Rachel / Backhouse, Ellen V / Barclay, Gayle / Jardine, Charlotte / McIntyre, Donna / Gerrish, Iona / Cheng, Yajun / Liu, Xiaodi / Zhang, Junfang / Kampaite, Agniete / Sakka, Eleni /

Valdés Hernández, Maria / Wiseman, Stewart / Stringer, Michael S / Thrippleton, Michael J / Doubal, Fergus N / Wardlaw, Joanna M

Brain communications

2024 Volume 6, Issue 3, Page(s) fcae133

Abstract: White matter hyperintensities (WMH), a common feature of cerebral small vessel disease, are related to worse clinical outcomes after stroke. We assessed the impact of white matter hyperintensity changes over 1 year after minor stroke on change in ... ...

Abstract	White matter hyperintensities (WMH), a common feature of cerebral small vessel disease, are related to worse clinical outcomes after stroke. We assessed the impact of white matter hyperintensity changes over 1 year after minor stroke on change in mobility and dexterity, including differences between the dominant and non-dominant hands and objective in-person assessment versus patient-reported experience. We recruited participants with lacunar or minor cortical ischaemic stroke, performed medical and cognitive assessments and brain MRI at presentation and at 1 year. At both time points, we used the timed-up and go test and the 9-hole peg test to assess mobility and dexterity. At 1 year, participants completed the Stroke Impact Scale. We ran two linear mixed models to assess change in timed-up and go and 9-hole peg test, adjusted for age, sex, stroke severity (National Institutes of Health Stroke Scale), dependency (modified Rankin Score), vascular risk factor score, white matter hyperintensity volume (as % intracranial volume) and additionally for 9-hole peg test: Montreal cognitive assessment, hand (dominant/non-dominant), National Adult Reading Test (premorbid IQ), index lesion side. We performed ordinal logistic regression, corrected for age and sex, to assess relations between timed-up and go and Stroke Impact Scale mobility, and 9-hole peg test and Stroke Impact Scale hand function. We included 229 participants, mean age 65.9 (standard deviation = 11.13); 66% male. 215/229 attended 1-year follow-up. Over 1 year, timed-up and go time increased with aging (standardized β [standardized 95% Confidence Interval]: 0.124[0.011, 0.238]), increasing National Institutes of Health Stroke Scale (0.106[0.032, 0.180]), increasing modified Rankin Score (0.152[0.073, 0.231]) and increasing white matter hyperintensity volume (0.176[0.061, 0.291]). Men were faster than women (-0.306[0.011, 0.238]). Over 1 year, slower 9-hole peg test was related to use of non-dominant hand (0.290[0.155, 0.424]), aging (0.102[0.012, 0.192]), male sex (0.182[0.008, 0.356]), increasing National Institutes of Health Stroke Scale (0.160 [0.094, 0.226]), increasing modified Rankin Score (0.100[0.032, 0.169]), decreasing Montreal cognitive assessment score (-0.090[-0.167, -0.014]) and increasing white matter hyperintensity volume (0.104[0.015, 0.193]). One year post-stroke, Stroke Impact Scale mobility worsened per second increase on timed-up and go, odds ratio 0.67 [95% confidence interval 0.60, 0.75]. Stroke Impact Scale hand function worsened per second increase on the 9-hole peg test for the dominant hand (odds ratio 0.79 [0.71, 0.86]) and for the non-dominant hand (odds ratio 0.88 [0.83, 0.93]). Decline in mobility and dexterity is associated with white matter hyperintensity volume increase, independently of stroke severity. Mobility and dexterity declined more gradually for stable and regressing white matter hyperintensity volume. Dominant and non-dominant hands might be affected differently. In-person measures of dexterity and mobility are associated with self-reported experience 1-year post-stroke.
Language	English
Publishing date	2024-05-07
Publishing country	England
Document type	Journal Article
ISSN	2632-1297
ISSN (online)	2632-1297
DOI	10.1093/braincomms/fcae133
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Article ; Online: Cognitive impairment in sporadic cerebral small vessel disease: A systematic review and meta-analysis.

Hamilton, Olivia K L / Backhouse, Ellen V / Janssen, Esther / Jochems, Angela C C / Maher, Caragh / Ritakari, Tuula E / Stevenson, Anna J / Xia, Lihua / Deary, Ian J / Wardlaw, Joanna M

Alzheimer's & dementia : the journal of the Alzheimer's Association

2020 Volume 17, Issue 4, Page(s) 665–685

Abstract: This paper is a proposal for an update on the characterization of cognitive impairments associated with sporadic cerebral small vessel disease (SVD). We pose a series of questions about the nature of SVD-related cognitive impairments and provide answers ... ...

Abstract	This paper is a proposal for an update on the characterization of cognitive impairments associated with sporadic cerebral small vessel disease (SVD). We pose a series of questions about the nature of SVD-related cognitive impairments and provide answers based on a comprehensive review and meta-analysis of published data from 69 studies. Although SVD is thought primarily to affect executive function and processing speed, we hypothesize that SVD affects all major domains of cognitive ability. We also identify low levels of education as a potentially modifiable risk factor for SVD-related cognitive impairment. Therefore, we propose the use of comprehensive cognitive assessments and the measurement of educational level both in clinics and research settings, and suggest several recommendations for future research.
MeSH term(s)	Aging/physiology ; Cerebral Small Vessel Diseases/complications ; Cognition ; Cognitive Dysfunction/etiology ; Educational Status ; Executive Function ; Humans ; Magnetic Resonance Imaging ; Neuropsychological Tests ; Stroke/complications
Language	English
Publishing date	2020-11-13
Publishing country	United States
Document type	Journal Article ; Meta-Analysis ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Systematic Review
ZDB-ID	2211627-8
ISSN	1552-5279 ; 1552-5260
ISSN (online)	1552-5279
ISSN	1552-5260
DOI	10.1002/alz.12221
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Zs.A 6316: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
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Article: Associations of Peak-Width Skeletonized Mean Diffusivity and Post-Stroke Cognition.

Jochems, Angela C C / Muñoz Maniega, Susana / Clancy, Una / Jaime Garcia, Daniela / Arteaga, Carmen / Hewins, Will / Penman, Rachel / Hamilton, Olivia K L / Czechoń, Agnieszka / Backhouse, Ellen V / Thrippleton, Michael J / Stringer, Michael S / Bastin, Mark E / Valdés Hernández, Maria Del C / Wiseman, Stewart / Chappell, Francesca M / Doubal, Fergus N / Wardlaw, Joanna M

Life (Basel, Switzerland)

2022 Volume 12, Issue 9

Abstract: Post-stroke cognitive impairment is common and can have major impact on life after stroke. Peak-width of Skeletonized Mean Diffusivity (PSMD) is a diffusion imaging marker of white matter microstructure and is also associated with cognition. Here, we ... ...

Abstract	Post-stroke cognitive impairment is common and can have major impact on life after stroke. Peak-width of Skeletonized Mean Diffusivity (PSMD) is a diffusion imaging marker of white matter microstructure and is also associated with cognition. Here, we examined associations between PSMD and post-stroke global cognition in an ongoing study of mild ischemic stroke patients. We studied cross-sectional associations between PSMD and cognition at both 3-months (N = 229) and 1-year (N = 173) post-stroke, adjusted for premorbid IQ, sex, age, stroke severity and disability, as well as the association between baseline PSMD and 1-year cognition. At baseline, (mean age = 65.9 years (SD = 11.1); 34% female), lower Montreal Cognitive Assessment (MoCA) scores were associated with older age, lower premorbid IQ and higher stroke severity, but not with PSMD (βstandardized = −0.116, 95% CI −0.241, 0.009; p = 0.069). At 1-year, premorbid IQ, older age, higher stroke severity and higher PSMD (βstandardized = −0.301, 95% CI −0.434, −0.168; p < 0.001) were associated with lower MoCA. Higher baseline PSMD was associated with lower 1-year MoCA (βstandardized = −0.182, 95% CI −0.308, −0.056; p = 0.005). PSMD becomes more associated with global cognition at 1-year post-stroke, possibly once acute effects have settled. Additionally, PSMD in the subacute phase after a mild stroke could help predict long-term cognitive impairment.
Language	English
Publishing date	2022-08-31
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662250-6
ISSN	2075-1729
ISSN	2075-1729
DOI	10.3390/life12091362
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Article ; Online: Contribution of white matter hyperintensities to ventricular enlargement in older adults.

Jochems, Angela C C / Muñoz Maniega, Susana / Del C Valdés Hernández, Maria / Barclay, Gayle / Anblagan, Devasuda / Ballerini, Lucia / Meijboom, Rozanna / Wiseman, Stewart / Taylor, Adele M / Corley, Janie / Chappell, Francesca M / Backhouse, Ellen V / Stringer, Michael S / Dickie, David Alexander / Bastin, Mark E / Deary, Ian J / Cox, Simon R / Wardlaw, Joanna M

NeuroImage. Clinical

2022 Volume 34, Page(s) 103019

Abstract: Lateral ventricles might increase due to generalized tissue loss related to brain atrophy. Alternatively, they may expand into areas of tissue loss related to white matter hyperintensities (WMH). We assessed longitudinal associations between lateral ... ...

Abstract	Lateral ventricles might increase due to generalized tissue loss related to brain atrophy. Alternatively, they may expand into areas of tissue loss related to white matter hyperintensities (WMH). We assessed longitudinal associations between lateral ventricle and WMH volumes, accounting for total brain volume, blood pressure, history of stroke, cardiovascular disease, diabetes and smoking at ages 73, 76 and 79, in participants from the Lothian Birth Cohort 1936, including MRI data from all available time points. Lateral ventricle volume increased steadily with age, WMH volume change was more variable. WMH volume decreased in 20% and increased in remaining subjects. Over 6 years, lateral ventricle volume increased by 3% per year of age, 0.1% per mm Hg increase in blood pressure, 3.2% per 1% decrease of total brain volume, and 4.5% per 1% increase of WMH volume. Over time, lateral ventricle volumes were 19% smaller in women than men. Ventricular and WMH volume changes are modestly associated and independent of general brain atrophy, suggesting that their underlying processes do not fully overlap.
MeSH term(s)	Aged ; Atrophy/pathology ; Brain ; Female ; Humans ; Infant, Newborn ; Leukoaraiosis ; Magnetic Resonance Imaging ; Male ; Neurodegenerative Diseases/pathology ; White Matter/pathology
Language	English
Publishing date	2022-04-26
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2701571-3
ISSN	2213-1582 ; 2213-1582
ISSN (online)	2213-1582
ISSN	2213-1582
DOI	10.1016/j.nicl.2022.103019
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Article ; Online: Cerebrovascular Reactivity in Patients With Small Vessel Disease: A Cross-Sectional Study.

Sleight, Emilie / Stringer, Michael S / Clancy, Una / Arteaga, Carmen / Jaime Garcia, Daniela / Hewins, Will / Jochems, Angela C C / Hamilton, Olivia K L / Manning, Cameron / Morgan, Alasdair G / Locherty, Rachel / Cheng, Yajun / Liu, Xiaodi / Zhang, Junfang / Hamilton, Iona / Jardine, Charlotte / Brown, Rosalind / Sakka, Eleni / Kampaite, Agniete /

Wiseman, Stewart / Valdés-Hernández, Maria C / Chappell, Francesca M / Doubal, Fergus N / Marshall, Ian / Thrippleton, Michael J / Wardlaw, Joanna M

Stroke

2023 Volume 54, Issue 11, Page(s) 2776–2784

Abstract: Background: Cerebrovascular reactivity (CVR) is inversely related to white matter hyperintensity severity, a marker of cerebral small vessel disease (SVD). Less is known about the relationship between CVR and other SVD imaging features or cognition. We ... ...

Abstract	Background: Cerebrovascular reactivity (CVR) is inversely related to white matter hyperintensity severity, a marker of cerebral small vessel disease (SVD). Less is known about the relationship between CVR and other SVD imaging features or cognition. We aimed to investigate these cross-sectional relationships. Methods: Between 2018 and 2021 in Edinburgh, we recruited patients presenting with lacunar or cortical ischemic stroke, whom we characterized for SVD features. We measured CVR in subcortical gray matter, normal-appearing white matter, and white matter hyperintensity using 3T magnetic resonance imaging. We assessed cognition using Montreal Cognitive Assessment. Statistical analyses included linear regression models with CVR as outcome, adjusted for age, sex, and vascular risk factors. We reported regression coefficients with 95% CIs. Results: Of 208 patients, 182 had processable CVR data sets (median age, 68.2 years; 68% men). Although the strength of association depended on tissue type, lower CVR in normal-appearing tissues and white matter hyperintensity was associated with larger white matter hyperintensity volume (B Conclusions: Lower CVR in patients with SVD was related to more severe SVD burden and worse cognition in this cross-sectional analysis. Longitudinal analysis will help determine whether lower CVR predicts worsening SVD severity or vice versa. Registration: URL: https://www.isrctn.com; Unique identifier: ISRCTN12113543.
MeSH term(s)	Male ; Humans ; Aged ; Female ; Cross-Sectional Studies ; Cerebral Small Vessel Diseases/complications ; Magnetic Resonance Imaging/methods ; Cognition ; White Matter/pathology
Language	English
Publishing date	2023-10-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	80381-9
ISSN	1524-4628 ; 0039-2499 ; 0749-7954
ISSN (online)	1524-4628
ISSN	0039-2499 ; 0749-7954
DOI	10.1161/STROKEAHA.123.042656
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Article ; Online: Relationship Between Venules and Perivascular Spaces in Sporadic Small Vessel Diseases.

Jochems, Angela C C / Blair, Gordon W / Stringer, Michael S / Thrippleton, Michael J / Clancy, Una / Chappell, Francesca M / Brown, Rosalind / Jaime Garcia, Daniela / Hamilton, Olivia K L / Morgan, Alasdair G / Marshall, Ian / Hetherington, Kirstie / Wiseman, Stewart / MacGillivray, Tom / Valdés-Hernández, Maria C / Doubal, Fergus N / Wardlaw, Joanna M

Stroke

2020 Volume 51, Issue 5, Page(s) 1503–1506

Abstract: Background and Purpose- Perivascular spaces (PVS) around venules may help drain interstitial fluid from the brain. We examined relationships between suspected venules and PVS visible on brain magnetic resonance imaging. Methods- We developed a visual ... ...

Abstract	Background and Purpose- Perivascular spaces (PVS) around venules may help drain interstitial fluid from the brain. We examined relationships between suspected venules and PVS visible on brain magnetic resonance imaging. Methods- We developed a visual venular quantification method to examine the spatial relationship between venules and PVS. We recruited patients with lacunar stroke or minor nondisabling ischemic stroke and performed brain magnetic resonance imaging and retinal imaging. We quantified venules on gradient echo or susceptibility-weighted imaging and PVS on T2-weighted magnetic resonance imaging in the centrum semiovale and then determined overlap between venules and PVS. We assessed associations between venular count and patient demographic characteristics, vascular risk factors, small vessel disease features, retinal vessels, and venous sinus pulsatility. Results- Among 67 patients (69% men, 69.0±9.8 years), only 4.6% (range, 0%-18%) of venules overlapped with PVS. Total venular count increased with total centrum semiovale PVS count in 55 patients after accounting for venule-PVS overlap (β=0.468 [95% CI, 0.187-0.750]) and transverse sinus pulsatility (β=0.547 [95% CI, 0.309-0.786]) and adjusting for age, sex, and systolic blood pressure. Conclusions- Despite increases in both visible PVS and suspected venules, we found minimal spatial overlap between them in patients with sporadic small vessel disease, suggesting that most magnetic resonance imaging-visible centrum semiovale PVS are periarteriolar rather than perivenular.
MeSH term(s)	Aged ; Brain/diagnostic imaging ; Brain Ischemia/diagnostic imaging ; Cerebral Small Vessel Diseases/diagnostic imaging ; Female ; Glymphatic System/diagnostic imaging ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Stroke/diagnostic imaging ; Stroke, Lacunar/diagnostic imaging ; Transverse Sinuses ; Venules/diagnostic imaging
Language	English
Publishing date	2020-04-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80381-9
ISSN	1524-4628 ; 0039-2499 ; 0749-7954
ISSN (online)	1524-4628
ISSN	0039-2499 ; 0749-7954
DOI	10.1161/STROKEAHA.120.029163
Database	MEDical Literature Analysis and Retrieval System OnLINE

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