Enlarged perivascular spaces and cognitive impairment after stroke and transient ischemic attack

Background Previous studies suggested that enlarged perivascular spaces are neuroimaging markers of cerebral small vessel disease. However, it is not clear whether enlarged perivascular spaces are associated with cognitive impairment. We aimed to determine the cross-sectional relationship between enlarged perivascular spaces and small vessel disease, and to investigate the relationship between enlarged perivascular spaces and subsequent cognitive impairment in patients with recent cerebral ischemic event. Methods Anonymized data were accessed from the virtual international stroke trial archive. We rated number of lacunes, white matter hyperintensities, brain atrophy, and enlarged perivascular spaces with validated scales on magnetic resonance brain images after the index stroke. We defined cognitive impairment as a mini mental state examination score of ≤26, recorded at one year post stroke. We examined the associations between enlarged perivascular spaces and clinical and imaging markers of small vessel disease at presentation and clinical evidence of cognitive impairment at one year using linear and logistic regression models. Results We analyzed data on 430 patients with mean (±SD) age 64.7 (±12.7) years, 276 (64%) males. In linear regression analysis, age (β = 0.24; p < 0.001), hypertension (β = 0.09; p = 0.025), and deep white matter hyperintensities (β = 0.31; p < 0.001) were associated with enlarged perivascular spaces. In logistic regression analysis, basal ganglia enlarged perivascular spaces were independently associated with cognitive impairment at one year after adjusting for clinical confounders (OR = 1.72, 95% CI = 1.22–2.42) and for clinical and imaging confounders (OR = 1.54; 95% CI = 1.03–2.31). Conclusions Our data show that in patients with ischemic cerebral events, enlarged perivascular spaces are cross-sectionally associated with age, hypertension, and white matter hyperintensities and suggest that enlarged perivascular spaces in the basal ganglia are associated with cognitive impairment after one year.

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Collateral Recruitment Is Impaired by Cerebral Small Vessel Disease

Stroke ◽

10.1161/strokeaha.119.027661 ◽

2020 ◽

Vol 51 (5) ◽

pp. 1404-1410 ◽

Cited By ~ 3

Author(s):

Michelle P. Lin ◽

Thomas G. Brott ◽

David S. Liebeskind ◽

James F. Meschia ◽

Kevin Sam ◽

...

Keyword(s):

White Matter ◽

White Matter Hyperintensities ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Cerebral Microbleeds ◽

Large Vessel ◽

Small Vessel ◽

Perivascular Spaces ◽

Vessel Disease ◽

Poor Recruitment

Background and Purpose— Cerebral small vessel disease (SVD) is associated with increased stroke risk and poor stroke outcomes. We aimed to evaluate whether chronic SVD burden is associated with poor recruitment of collaterals in large-vessel occlusive stroke. Methods— Consecutive patients with middle cerebral artery or internal carotid artery occlusion presenting within 6 hours after stroke symptom onset who underwent thrombectomy from 2012 to 2017 were included. The prespecified primary outcome was poor collateral flow, which was assessed on baseline computed tomographic angiography (poor, ≤50% filling; good, >50% filling). Markers of chronic SVD on brain magnetic resonance imaging were rated for the extent of white matter hyperintensities, enlarged perivascular spaces, chronic lacunar infarctions and cerebral microbleeds using the Standards for Reporting Vascular Changes on Neuroimaging criteria. Severity of SVD was quantified by adding the presence of each SVD feature, with a total possible score of 0 to 4; each SVD type was also evaluated separately. Multivariable logistic regression analyses were performed to evaluate the relationships between SVD and poor collaterals, with adjustment for potential confounders. Results— Of the 100 eligible patients, the mean age was 65±16 years, median National Institutes of Health Stroke Scale score was 15, and 68% had any SVD. Poor collaterals were observed in 46%, and those with SVD were more likely to have poor collaterals than patients without SVD (aOR, 1.9 [95% CI, 1.1–3.2]). Of the SVD types, poor collaterals were significantly associated with white matter hyperintensities (aOR, 2.9 per Fazekas increment [95% CI, 1.6–5.3]) but not with enlarged perivascular spaces (adjusted odds ratio [aOR], 1.3 [95% CI, 0.4–4.0]), lacunae (aOR, 2.1 [95% CI, 0.6–7.1]), or cerebral microbleeds (aOR, 2.1 [95% CI, 0.6–7.8]). Having a greater number of different SVD markers was associated with a higher odds of poor collaterals (crude trend P <0.001; adjusted P =0.056). There was a dose-dependent relationship between white matter hyperintensity burden and poor collaterals: adjusted odds of poor collaterals were 1.5, 3.0, and 9.7 across Fazekas scores of 1 to 3 ( P trend=0.015). No patient with an SVD score of 4 had good collaterals. Conclusions— Chronic cerebral SVD is associated with poor recruitment of collaterals in large vessel occlusive stroke. A prospective study to elucidate the potential mechanism of how SVD may impair the recruitment of collaterals is ongoing.

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Higher white matter hyperintensity lesion load is associated with reduced long-range functional connectivity

Brain Communications ◽

10.1093/braincomms/fcaa111 ◽

2020 ◽

Vol 2 (2) ◽

Author(s):

Fanny Quandt ◽

Felix Fischer ◽

Julian Schröder ◽

Marlene Heinze ◽

Iris Lettow ◽

...

Keyword(s):

Cognitive Impairment ◽

White Matter ◽

Functional Connectivity ◽

White Matter Hyperintensities ◽

Small Vessel Disease ◽

White Matter Lesion ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Lesion Load ◽

Vessel Disease

Abstract Cerebral small vessel disease is a common disease in the older population and is recognized as a major risk factor for cognitive decline and stroke. Small vessel disease is considered a global brain disease impacting the integrity of neuronal networks resulting in disturbances of structural and functional connectivity. A core feature of cerebral small vessel disease commonly present on neuroimaging is white matter hyperintensities. We studied high-resolution resting-state EEG, leveraging source reconstruction methods, in 35 participants with varying degree of white matter hyperintensities without clinically evident cognitive impairment in an observational study. In patients with increasing white matter lesion load, global theta power was increased independently of age. Whole-brain functional connectivity revealed a disrupted network confined to the alpha band in participants with higher white matter hyperintensities lesion load. The decrease of functional connectivity was evident in long-range connections, mostly originating or terminating in the frontal lobe. Cognitive testing revealed no global cognitive impairment; however, some participants revealed deficits of executive functions that were related to larger white matter hyperintensities lesion load. In summary, participants without clinical signs of mild cognitive impairment or dementia showed oscillatory changes that were significantly related to white matter lesion load. Hence, oscillatory neuronal network changes due to white matter lesions might act as biomarker prior to clinically relevant behavioural impairment.

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Association of total cerebral small vessel disease burden with the cavitation of recent small subcortical infarcts

Acta Radiologica ◽

10.1177/02841851211066583 ◽

2021 ◽

pp. 028418512110665

Author(s):

Meimei Wang ◽

Yunfei Li ◽

Yingjie Song ◽

Yingyu Zhao ◽

Xiaohu Zhao

Keyword(s):

White Matter ◽

White Matter Hyperintensities ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Perivascular Spaces ◽

Vessel Disease ◽

Multivariable Regression ◽

Total Burden

Background Recent small subcortical infarcts (RSSIs) could evolve into cavitation (lacunes) or non-cavitation (white matter hyperintensities or disappearance) during the chronic period, but the factors involved remain unclear. Purpose To explore the association between total cerebral small vessel disease (CSVD) burden and lesion cavitation. Material and Methods We retrospectively selected 202 inpatients with an isolated RSSI who underwent baseline and follow-up magnetic resonance imaging (median interval = 16.6 months; interquartile range [IQR]=8.2–30.1). Inpatients were divided into cavitation and non-cavitation groups depending on whether a fluid-filled cavity formed. Data including demographic, clinical, and radiological features were collected and analyzed. To determine total CSVD burden, four imaging markers, including lacunes, microbleeds, white matter hyperintensities, and enlarged perivascular spaces, were rated and summed as a final practical score between 0 and 4. Results Overall, 137 (67.8%) patients progressed to cavitation and 65 (32.2%) to non-cavitation. Binary multivariable regression analysis showed that the baseline total CSVD burden ( P = 0.005) and infarct diameter ( P = 0.002) were independent risk factors for cavitation. A severe total burden (scores of 3–4) at baseline was independently related to cavitation ( P = 0.001). Moreover, the total CSVD burden score varied from 2 (IQR=1–3) at baseline to 3 (IQR=2–4) at follow-up. The extent of the increase in total burden was correlated with cavitation ( r = 0.201; P = 0.004). Conclusion Total CSVD burden, both the baseline value and extent of increase, was positively associated with cavitation. RSSIs with severe total CSVD burden at baseline have a greater potential to become cavitated.

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Nonfocal Transient Neurological Attacks Are Associated With Cerebral Small Vessel Disease

Stroke ◽

10.1161/strokeaha.119.025328 ◽

2019 ◽

Vol 50 (12) ◽

pp. 3540-3544 ◽

Cited By ~ 1

Author(s):

Eline A. Oudeman ◽

Jacoba P. Greving ◽

Renske M. Van den Berg-Vos ◽

Geert Jan Biessels ◽

Esther E. Bron ◽

...

Keyword(s):

Cognitive Impairment ◽

White Matter ◽

Odds Ratio ◽

Adjusted Odds Ratio ◽

White Matter Hyperintensities ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Vessel Disease ◽

Increased Risk

Background and Purpose— Nonfocal transient neurological attacks (TNAs), such as unsteadiness, bilateral weakness, or confusion, are associated with an increased risk of stroke and dementia. Cerebral ischemia plays a role in their pathogenesis, but the precise mechanisms are unknown. We hypothesized that cerebral small vessel disease is involved in the pathogenesis of TNAs and assessed the relation between TNAs and manifestations of cerebral small vessel disease on magnetic resonance imaging. Methods— We included participants from the HBC (Heart-Brain Connection) study. In this study, hemodynamic and cardiovascular contributions to cognitive impairment have been studied in patients with heart failure, carotid artery occlusion, or possible vascular cognitive impairment, as well as in a reference group. We excluded participants with a history of stroke or transient ischemic attacks. The occurrence of the following 8 TNAs was assessed with a standardized interview: unconsciousness, confusion, amnesia, unsteadiness, bilateral leg weakness, blurred vision, nonrotatory dizziness, and paresthesias. The occurrence of TNAs was related to the presence of lacunes or white matter hyperintensities (Fazekas score, ≥2; early confluent or confluent lesions) in logistic regression analysis, adjusted for age, sex, and hypertension. Results— Of 304 participants (60% men; mean age, 67±9 years), 63 participants (21%) experienced ≥1 TNAs. Lacunes and early confluent or confluent white matter hyperintensities were more common in participants with TNAs than in participants without TNAs (35% versus 20%; adjusted odds ratio, 2.32 [95% CI, 1.22–4.40] and 48% versus 27%; adjusted odds ratio, 2.65 [95% CI, 1.44–4.90], respectively). Conclusions— In our study, TNAs are associated with the presence of lacunes and early confluent or confluent white matter hyperintensities of presumed vascular origin, which indicates that cerebral small vessel disease might play a role in the pathogenesis of TNAs.

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Cerebral Small Vessel Disease Associated With Atrial Fibrillation Among Older Adults: A Population-Based Study

Stroke ◽

10.1161/strokeaha.120.031573 ◽

2021 ◽

Author(s):

Mozhu Ding ◽

Rui Wang ◽

Grégoria Kalpouzos ◽

Erika J. Laukka ◽

Yuanjing Li ◽

...

Keyword(s):

Older Adults ◽

White Matter ◽

White Matter Hyperintensities ◽

Small Vessel Disease ◽

Population Based ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Perivascular Spaces ◽

Resonance Imaging ◽

Vessel Disease

Background and Purpose: Cerebral small vessel disease, as a potential mechanism underlying the association between atrial fibrillation (AF) and dementia, remains poorly investigated. In this cohort study, we sought to examine the association between AF and cerebral small vessel disease markers among older adults. Methods: Data on 336 participants (age ≥60 years, mean 70.2 years; 60.2% women) free of dementia, disability, and cerebral infarcts were derived from the population-based Swedish National Study on Aging and Care in Kungsholmen. Structural brain magnetic resonance imaging examinations were performed at baseline (2001–2004) and follow-ups (2004–2007 and 2007–2010). Magnetic resonance imaging markers of cerebral small vessel disease included perivascular spaces, lacunes, and volumes of white matter hyperintensities, lateral ventricles, and total brain tissue. AF was assessed at baseline and follow-ups through clinical examinations, electrocardiogram, and medical records. Data were analyzed using linear mixed-effects models. Results: At baseline, 18 persons (5.4%) were identified to have prevalent AF and 17 (5.6%) developed incident AF over the 6-year follow-up. After multivariable adjustment, AF was significantly associated with a faster annual increase in white matter hyperintensities volume (β coefficient=0.45 [95% CI, 0.04–0.86]) and lateral ventricular volume (0.58 [0.13–1.02]). There was no significant association of AF with annual changes in perivascular spaces number (β coefficient=0.53 [95% CI, −0.27 to 1.34]) or lacune number (−0.01 [−0.07 to 0.05]). Conclusions: Independent of cerebral infarcts, AF is associated with accelerated progression of white matter lesions and ventricular enlargement among older adults.

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Cerebral Small Vessel Disease and the Risk of Dementia and Cognition Decline

Vascular Disease, Alzheimer's Disease, and Mild Cognitive Impairment ◽

10.1093/oso/9780190634230.003.0009 ◽

2020 ◽

pp. 187-207

Author(s):

Emilia Salvadori ◽

Fabio Fierini ◽

Leonardo Pantoni

Keyword(s):

White Matter ◽

Cognitive Decline ◽

White Matter Hyperintensities ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Perivascular Spaces ◽

Lacunar Infarcts ◽

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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Suffering from cerebral small vessel disease with and without metabolic syndrome

Open Medicine ◽

10.1515/med-2019-0051 ◽

2019 ◽

Vol 14 (1) ◽

pp. 479-484

Author(s):

Tatjana Bošković Matić ◽

Gordana Toncev ◽

Aleksandar Gavrilović ◽

Dejan Aleksić

Keyword(s):

Metabolic Syndrome ◽

Cognitive Impairment ◽

White Matter ◽

White Matter Hyperintensities ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Cognitively Impaired ◽

Vessel Disease ◽

Neurology Clinic

AbstractBackgroundCerebral small vessel disease (CSVD) and metabolic syndrome were separately associated with cognitive impairment and depression. However, whether metabolic syndrome adds to cognitive impairment and depression in patients who already have CSVD remained unanswered.ObjectiveThe aim of our study was to investigate the association of metabolic syndrome with cognitive impairment and depression in patients with CSVD who have lacunar lesions or white matter hyperintensities.MethodsThis prospective cohort study was conducted at Neurology Clinic, Clinical Center, Kragujevac, Serbia. Main outcomes of the study were cognitive assessment, and assessment of depression among hospitalized patients with or without CSVD.ResultsThe study included 74 inpatients, 25 of them having lacunary infarctions, 24 with the white matter hyperintensities, and 25 control patients without CSVD. The CSVD was accompanied by impairment of cognition and depression, the patients with lacunary lesions being more cognitively impaired and more depressive than the patients with the white matter hyperintensities. The patients with CSVD who also had metabolic syndrome were more cognitively impaired and depressed than the patients with CSVD alone.ConclusionsIn conclusion, our study showed that metabolic syndrome is associated with further worsening of already impaired cognition and existing depression in patients with CSVD.

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CNS small vessel disease

Neurology ◽

10.1212/wnl.0000000000007654 ◽

2019 ◽

Vol 92 (24) ◽

pp. 1146-1156 ◽

Cited By ~ 31

Author(s):

Rocco J. Cannistraro ◽

Mohammed Badi ◽

Benjamin H. Eidelman ◽

Dennis W. Dickson ◽

Erik H. Middlebrooks ◽

...

Keyword(s):

Risk Factors ◽

White Matter ◽

Small Vessel Disease ◽

Blood Oxygenation ◽

Small Vessel ◽

Imaging Biomarkers ◽

Amyloid Angiopathy ◽

Perivascular Spaces ◽

Advanced Imaging ◽

Vessel Disease

CNS small vessel disease (CSVD) causes 25% of strokes and contributes to 45% of dementia cases. Prevalence increases with age, affecting about 5% of people aged 50 years to almost 100% of people older than 90 years. Known causes and risk factors include age, hypertension, branch atheromatous disease, cerebral amyloid angiopathy, radiation exposure, immune-mediated vasculitides, certain infections, and several genetic diseases. CSVD can be asymptomatic; however, depending on location, lesions can cause mild cognitive dysfunction, dementia, mood disorders, motor and gait dysfunction, and urinary incontinence. CSVD is diagnosed on the basis of brain imaging biomarkers, including recent small subcortical infarcts, white matter hyperintensities, lacunes, cerebral microbleeds, enlarged perivascular spaces, and cerebral atrophy. Advanced imaging modalities can detect signs of disease even earlier than current standard imaging techniques. Diffusion tensor imaging can identify altered white matter connectivity, and blood oxygenation level-dependent imaging can identify decreased vascular reactivity. Pathogenesis is thought to begin with an etiologically specific insult, with or without genetic predisposition, which results in dysfunction of the neurovascular unit. Uncertainties regarding pathogenesis have delayed development of effective treatment. The most widely accepted approach to treatment is to intensively control well-established vascular risk factors, of which hypertension is the most important. With better understanding of pathogenesis, specific therapies may emerge. Early identification of pathologic characteristics with advanced imaging provides an opportunity to forestall progression before emergence of symptoms.

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Microstructural Predictors of Cognitive Impairment in Cerebral Small Vessel Disease and the Conditions of Their Formation

Diagnostics ◽

10.3390/diagnostics10090720 ◽

2020 ◽

Vol 10 (9) ◽

pp. 720

Author(s):

Larisa A. Dobrynina ◽

Zukhra Sh. Gadzhieva ◽

Kamila V. Shamtieva ◽

Elena I. Kremneva ◽

Bulat M. Akhmetzyanov ◽

...

Keyword(s):

Blood Flow ◽

Cognitive Impairment ◽

White Matter ◽

Diffusion Tensor ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Venous Blood Flow ◽

Csf Flow ◽

Vessel Disease

Introduction: Cerebral small vessel disease (CSVD) is the leading cause of vascular and mixed degenerative cognitive impairment (CI). The variability in the rate of progression of CSVD justifies the search for sensitive predictors of CI. Materials: A total of 74 patients (48 women, average age 60.6 ± 6.9 years) with CSVD and CI of varying severity were examined using 3T MRI. The results of diffusion tensor imaging with a region of interest (ROI) analysis were used to construct a predictive model of CI using binary logistic regression, while phase-contrast magnetic resonance imaging and voxel-based morphometry were used to clarify the conditions for the formation of CI predictors. Results: According to the constructed model, the predictors of CI are axial diffusivity (AD) of the posterior frontal periventricular normal-appearing white matter (pvNAWM), right middle cingulum bundle (CB), and mid-posterior corpus callosum (CC). These predictors showed a significant correlation with the volume of white matter hyperintensity; arterial and venous blood flow, pulsatility index, and aqueduct cerebrospinal fluid (CSF) flow; and surface area of the aqueduct, volume of the lateral ventricles and CSF, and gray matter volume. Conclusion: Disturbances in the AD of pvNAWM, CB, and CC, associated with axonal damage, are a predominant factor in the development of CI in CSVD. The relationship between AD predictors and both blood flow and CSF flow indicates a disturbance in their relationship, while their location near the floor of the lateral ventricle and their link with indicators of internal atrophy, CSF volume, and aqueduct CSF flow suggest the importance of transependymal CSF transudation when these regions are damaged.

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Cognitive consequences of regression of cerebral small vessel disease

European Stroke Journal ◽

10.1177/2396987318820790 ◽

2018 ◽

Vol 4 (1) ◽

pp. 85-89 ◽

Cited By ~ 6

Author(s):

Esther MC van Leijsen ◽

Mayra I Bergkamp ◽

Ingeborg WM van Uden ◽

Sjacky Cooijmans ◽

Mohsen Ghafoorian ◽

...

Keyword(s):

Executive Function ◽

White Matter ◽

Cognitive Decline ◽

White Matter Hyperintensities ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Vessel Disease ◽

Disease Markers ◽

Total Brain

Introduction Recent studies have shown that neuroimaging markers of cerebral small vessel disease can also regress over time. We investigated the cognitive consequences of regression of small vessel disease markers. Patients and methods Two hundred and seventy-six participants of the RUNDMC study underwent neuroimaging and cognitive assessments at three time-points over 8.7 years. We semi-automatically assessed white matter hyperintensities volumes and manually rated lacunes and microbleeds. We analysed differences in cognitive decline and accompanying brain atrophy between participants with regression, progression and stable small vessel disease by analysis of variance. Results Fifty-six participants (20.3%) showed regression of small vessel disease markers: 31 (11.2%) white matter hyperintensities regression, 10 (3.6%) vanishing lacunes and 27 (9.8%) vanishing microbleeds. Participants with regression showed a decline in overall cognition, memory, psychomotor speed and executive function similar to stable small vessel disease. Participants with small vessel disease progression showed more cognitive decline compared with stable small vessel disease (p < 0.001 for cognitive index and memory; p < 0.01 for executive function), although significance disappeared after adjusting for age and sex. Loss of total brain, gray matter and white matter volume did not differ between participants with small vessel disease regression and stable small vessel disease, while participants with small vessel disease progression showed more volume loss of total brain and gray matter compared to those with stable small vessel disease (p < 0.05), although significance disappeared after adjustments. Discussion Regression of small vessel disease markers was associated with similar cognitive decline compared to stable small vessel disease and did not accompany brain atrophy, suggesting that small vessel disease regression follows a relatively benign clinical course. Future studies are required to validate these findings and to assess the role of vascular risk factor control on small vessel disease regression and possible recovery of clinical symptoms. Conclusion Our findings of comparable cognitive decline between participants with regression and stable small vessel disease might suggest that small vessel disease regression has a relative benign cognitive outcome.

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