Letter by Feng et al Regarding Article, “Lacunar Infarcts, but Not Perivascular Spaces, Are Predictors of Cognitive Decline in Cerebral Small-Vessel Disease”

Cerebral small vessel disease (SVD) is well recognized as a highly prevalent disorder that plays an important role in stroke and cognitive impairment. This chapter deals with the relationship between SVD and cognition in longitudinal studies and aims at clarifying the role of SVD as a marker and determinant of neurocognitive impairment. This chapter discusses the prognostic role of magnetic resonance imaging (MRI)-based SVD features (i.e., white matter hyperintensities, small lacunar infarcts, microbleeds, and perivascular spaces) as predictors of dementia or cognitive decline. The evidence reviewed in this chapter provides strong supports for the impact of white matter hyperintensities and small lacunar infarcts in increasing the risk of dementia and cognitive decline. Microbleeds and perivascular spaces have been more recently targeted as MRI features of SVD, and this chapter will review the increasing evidence of their role in cognitive decline.

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Circulating biologic markers of endothelial dysfunction in cerebral small vessel disease: A review

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2015.116 ◽

2015 ◽

Vol 36 (1) ◽

pp. 72-94 ◽

Cited By ~ 98

Author(s):

Anna Poggesi ◽

Marco Pasi ◽

Francesca Pescini ◽

Leonardo Pantoni ◽

Domenico Inzitari

Keyword(s):

Endothelial Dysfunction ◽

Endothelial Function ◽

Small Vessel Disease ◽

Brain Magnetic Resonance Imaging ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Perivascular Spaces ◽

Vessel Disease ◽

Brain Changes

The term cerebral small vessel disease (SVD) refers to a group of pathologic processes with various etiologies that affect small arteries, arterioles, venules, and capillaries of the brain. Magnetic resonance imaging (MRI) correlates of SVD are lacunes, recent small subcortical infarcts, white-matter hyperintensities, enlarged perivascular spaces, microbleeds, and brain atrophy. Endothelial dysfunction is thought to have a role in the mechanisms leading to SVD-related brain changes, and the study of endothelial dysfunction has been proposed as an important step for a better comprehension of cerebral SVD. Among available methods to assess endothelial function in vivo, measurement of molecules of endothelial origin in peripheral blood is currently receiving selective attention. These molecules include products of endothelial cells that change when the endothelium is activated, as well as molecules that reflect endothelial damage and repair. This review examines the main molecular factors involved in both endothelial function and dysfunction, and the evidence linking endothelial dysfunction with cerebral SVD, and gives an overview of clinical studies that have investigated the possible association between endothelial circulating biomarkers and SVD-related brain changes.

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Abstract P332: Cerebral Small Vessel Disease Score in CADASIL: Relationships to Cognitive Dysfunctions

Stroke ◽

10.1161/str.52.suppl_1.p332 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Dorothee Schoemaker ◽

Yesica Zuluaga ◽

Lina Velilla ◽

Carolina Ospina ◽

Francisco Lopera ◽

...

Keyword(s):

Small Vessel Disease ◽

Structural Mri ◽

Vascular Cognitive Impairment ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

White Matter Hyperintensity ◽

Perivascular Spaces ◽

Cerebrovascular Injury ◽

Vessel Disease ◽

History Of

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary cerebral small vessel disease (cSVD) linked to NOTCH3 mutations and leading to the early onset of stroke and vascular cognitive impairment. Neuroimaging features of CADASIL include extensive white matter hyperintensity, lacunes, cerebral microbleeds and enlarged perivascular spaces. Researchers from the Rotterdam study recently proposed a MRI-based cSVD Score reflecting the overall burden of cerebrovascular injury (Yilmaz et al., 2018). Here, we explored the relevance of this cSVD Score in distinguishing CADASIL subjects from non-carriers and its relationships to cognition. We evaluated 26 NOTCH3 mutation carriers and 25 non-carriers from large Colombian families. Of the CADASIL subjects, 4 had previous strokes (symptomatic) and 22 had no history of strokes (asymptomatic). All subjects underwent a 3T MRI and a neuropsychological evaluation. Structural MRI markers of cSVD, as well as the cSVD Score, were quantified in each subject following established protocols. Demographic, cognitive and neuroimaging features across groups are presented in Table 1. The cSVD Score significantly differed between groups, after adjusting for age (Figure 1-A). In CADASIL subjects, the cSVD Score was negatively related to performance in Memory, Processing Speed, Executive Function, after accounting for age and education (Figure 1-B). These results suggest that the cSVD Score could be a useful marker of disease severity in CADASIL. Longitudinal studies are now needed to determine if this score allows predicting clinical outcomes in CADASIL, such as stroke or dementia.

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Total Cerebral Small Vessel Disease Burden on MRI Correlates With Cognitive Impairment in Outpatients With Amnestic Disorders

Frontiers in Neurology ◽

10.3389/fneur.2021.747115 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yangyi Fan ◽

Yicheng Xu ◽

Ming Shen ◽

Huailian Guo ◽

Zhaoxu Zhang

Keyword(s):

Linear Regression ◽

Regression Model ◽

Linear Regression Model ◽

Small Vessel Disease ◽

Multiple Linear Regression Model ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Perivascular Spaces ◽

Vessel Disease ◽

Moca Score

Objectives: The main markers of cerebral small vessel disease (cSVD) on MRI may be entered into a scoring system, with the total score representing the overall burden of cSVD. An association between total cSVD score and cognitive dysfunction has been reported in several cohorts. The present study aimed to investigate this association in outpatients with amnestic disorders.Materials and Methods: Outpatients with amnestic complaints in a memory clinic (n = 289) were recruited retrospectively. All the patients had undergone clinical and cognitive evaluation at first presentation. Cognitive function was assessed by Montreal Cognitive Assessment (MoCA) scale. The total cSVD score was based on the following markers on MRI: lacune; white matter hyperintensities, microbleed, and enlarged perivascular spaces. The association between total cSVD score and MoCA score was tested via Spearman's analysis and a linear regression model.Results: Among the 289 patients, rates for 0–4 cSVD markers respectively ranged from 30.4 to 2.8%. A multiple linear regression model revealed an inverse correlation between the total cSVD score and MoCA score. The association remained significant after adjusting for gender, age, education, levels of medial temporal lobe atrophy, and classical vascular risk factors [β = −0.729, 95% CI (−1.244, −0.213); P = 0.006]. When individual markers were individually analyzed after adjusting for the same factors, only microbleed associated with MoCA score [β = −3.007, 95% CI (−4.533, −1.480), P < 0.001].Conclusions: A significant association was demonstrated between total cSVD score and cognitive performance in the outpatients with amnestic disorders.

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Enlarged Perivascular Spaces on MRI Are a Feature of Cerebral Small Vessel Disease

Stroke ◽

10.1161/strokeaha.109.564914 ◽

2010 ◽

Vol 41 (3) ◽

pp. 450-454 ◽

Cited By ~ 275

Author(s):

Fergus N. Doubal ◽

Alasdair M.J. MacLullich ◽

Karen J. Ferguson ◽

Martin S. Dennis ◽

Joanna M. Wardlaw

Keyword(s):

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Perivascular Spaces ◽

Vessel Disease

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Lacunar Syndromes, Lacunar Infarcts, and Cerebral Small-vessel Disease

Stroke ◽

10.1016/b978-0-323-29544-4.00027-x ◽

2016 ◽

pp. 449-465.e4

Author(s):

Bo Norrving

Keyword(s):

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Lacunar Infarcts ◽

Vessel Disease

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Arterial Stiffness Is Associated With Basal Ganglia Enlarged Perivascular Spaces and Cerebral Small Vessel Disease Load

Stroke ◽

10.1161/strokeaha.118.020163 ◽

2018 ◽

Vol 49 (5) ◽

pp. 1279-1281 ◽

Cited By ~ 15

Author(s):

Iolanda Riba-Llena ◽

Joan Jiménez-Balado ◽

Xavier Castañé ◽

Anna Girona ◽

Antonio López-Rueda ◽

...

Keyword(s):

Basal Ganglia ◽

Arterial Stiffness ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Perivascular Spaces ◽

Vessel Disease

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Abstract WMP59: White Matter Hyperintensities Play a Pivotal Role in Progression of Cerebral Small Vessel Disease: A 7-Year Chinese Urban Community Study

Stroke ◽

10.1161/str.51.suppl_1.wmp59 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Yiwei Xia ◽

Yi Shen ◽

Yi Wang ◽

Lumeng Yang ◽

Yiqing Wang ◽

...

Keyword(s):

Executive Function ◽

Small Vessel Disease ◽

Urban Community ◽

Cerebral Small Vessel Disease ◽

Pivotal Role ◽

Small Vessel ◽

Community Study ◽

Perivascular Spaces ◽

Vessel Disease ◽

Increased Risk

Objective: To explore the role of WMH in progression of CSVD in an urban community in China over a period of 7 years, and to investigate associations between WMH volume (baseline & progression) and cognitive impairment. Methods: CSVD markers and neuropsychological tests at baseline and follow-up of 191 participants of the Shanghai Aging Study (SAS) were assessed. WMH volume were assessed by automatic segmentation based on U-net model. Lacunes, cerebral microbleeds (CMBs) and enlarged perivascular spaces (ePVS) were rated manually. SVD score was rated as the total burden of CSVD markers. We performed multivariate linear regression and binominal logistic regression. We plotted progression of markers by baseline WMH volume in tertile. Results: Participants with higher baseline WMH volume developed more progression of WMH volume, increased risk of incident lacunes, incident CMBs, and ePVS progression. Mean change of WMH volume over 7 years was 4.27mL (0.62mL/y) for all participants, 3.21mL for participants with 1st tertile WMH volume at baseline, 4.19mL for those with 2nd tertile WMH, and 5.43mL for those with 3rd tertile WMH. Incident lacunes and incident CMBs were predominantly seen in participants with 2nd and 3rd tertile WMH. WMH (baseline & progression) were associated with decline of executive function. Conclusions: WMH play a pivotal role in progression of cerebral small vessel disease and are associated with decline of executive function in a Chinese urban community study over a period of 7 years.

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Relationship Between Step Counts and Cerebral Small Vessel Disease in Japanese Men

Stroke ◽

10.1161/strokeaha.120.030141 ◽

2020 ◽

Vol 51 (12) ◽

pp. 3584-3591

Author(s):

Mohammad Moniruzzaman ◽

Aya Kadota ◽

Hiroyoshi Segawa ◽

Keiko Kondo ◽

Sayuki Torii ◽

...

Keyword(s):

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Cerebral Microbleeds ◽

Small Vessel ◽

Odds Ratios ◽

Japanese Men ◽

Lacunar Infarcts ◽

Step Counts ◽

Vessel Disease ◽

Steps Per Day

Background and Purpose: Cerebral small vessel disease (CSVD) is a common subclinical feature of the aging brain. Steps per day may contribute to its prevention. We herein investigated the association between step counts and CSVD in a healthy Japanese male population. Methods: We analyzed data from 680 men who were free of stroke and participated in this observational study. Seven-day step counts were assessed at baseline (2006–2008) using a pedometer. CSVD was assessed at follow-ups (2012–2015) based on deep and subcortical white matter hyperintensities (WMHs), periventricular hyperintensities, lacunar infarcts, and cerebral microbleeds on magnetic resonance imaging. Using a logistic regression analysis, we computed the adjusted odds ratios, with 95% CIs, of prevalent CSVD according to quartiles of step counts (reference: Q1). We also investigated the association between step counts and WMH volumes using a quantile regression. Results: Steps per day were significantly associated with lower odds ratios, with the lowest at Q3 (8175–10 614 steps/day), of higher (versus low or no burden) deep and subcortical WMHs (odds ratio, 0.52 [95% CI, 0.30–0.89]), periventricular hyperintensities (0.50 [95% CI, 0.29–0.86]), and lacunar infarcts (0.52 [95% CI, 0.30–0.91]) compared with Q1 (≤6060 steps/day) but not cerebral microbleeds. An inverse linear association was observed between step counts and WMH volumes. These associations were independent of age and smoking and drinking status and remained consistent when adjusted for vascular risk factors. Conclusions: We found a J-shaped relationship between step counts and prevalent CSVD in healthy Japanese men, with the lowest risk being observed among participants with ≈8000 to 10 000 steps/day. Higher steps were also associated with lower WMH volumes.

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