Low-frequency oscillations in the brain show differential regional associations with severity of cerebral small vessel disease: a systematic review
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SUBMITTER: Thomas J
PROVIDER: S-EPMC10501452 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
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Project description:Background and purposeCerebral large artery and small vessel diseases are related to different pathogenetic mechanisms and have different risk factor profile. Lipoprotein(a) (Lp(a)) was shown to promote atherosclerosis but data was limited on its association with cerebral small vessel diseases (cSVD). The objective of this study was to assess the associations of Lp(a) level with the two types of cerebrovascular diseases.MethodsCommunity-dwelling subjects aged 50-75 years from the baseline survey of The PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events study were included. Lp(a) concentrations was measured and categorised into three groups according to the tertiles. Eligible participants were scanned by a 3.0T MRI scanner and assessed for intracranial atherosclerosis and cSVD burden based on four imaging markers.ResultsThis study included 3059 subjects. The average age of the participants was 61.2±6.7 years, and 53.5% (1636) were female. Compared with the first tertile, subjects with the second and third tertiles of Lp(a) concentrations were associated with an increased odds of presence of intracranial plaque (18.7% vs 15.4%, adj.OR 1.37, 95% CI 1.08 to 1.75; 18.9% vs 15.4%, adj.OR 1.34, 95% CI 1.05 to 1.72). Similar associations were observed for intracranial atherosclerotic burden. Whereas, subjects with the third tertile of Lp(a) level had a decreased odds of presence of cSVD (25.9% vs 31.7%, adj.OR 0.74, 95% CI 0.60 to 0.92) and lower cSVD burden (adj.cOR 0.76, 95% CI 0.62 to 0.94).ConclusionsIn this study, Lp(a) concentrations were positively associated with presence and burden of intracranial atherosclerosis, but was inversely associated with cSVD.Trial registration numberNCT03178448.
| S-EPMC9811597 | biostudies-literature
Project description:The link between white matter hyperintensities (WMH) and cortical thinning is thought to be an important pathway by which WMH contributes to cognitive deficits in cerebral small vessel disease (SVD). However, the mechanism behind this association and the underlying tissue composition abnormalities are unclear. The objective of this study is to determine the association between WMH and cortical thickness, and the in vivo tissue composition abnormalities in the WMH-connected cortical regions. In this cross-sectional study, we included 213 participants with SVD who underwent standardized protocol including multimodal neuroimaging scans and cognitive assessment (i.e. processing speed, executive function and memory). We identified the cortex connected to WMH using probabilistic tractography starting from the WMH and defined the WMH-connected regions at three connectivity levels (low, medium and high connectivity level). We calculated the cortical thickness, myelin and iron of the cortex based on T1-weighted, quantitative R1, R2* and susceptibility maps. We used diffusion-weighted imaging to estimate the mean diffusivity of the connecting white matter tracts. We found that cortical thickness, R1, R2* and susceptibility values in the WMH-connected regions were significantly lower than in the WMH-unconnected regions (all Pcorrected < 0.001). Linear regression analyses showed that higher mean diffusivity of the connecting white matter tracts were related to lower thickness (β = -0.30, Pcorrected < 0.001), lower R1 (β = -0.26, Pcorrected = 0.001), lower R2* (β = -0.32, Pcorrected < 0.001) and lower susceptibility values (β = -0.39, Pcorrected < 0.001) of WMH-connected cortical regions at high connectivity level. In addition, lower scores on processing speed were significantly related to lower cortical thickness (β = 0.20, Pcorrected = 0.030), lower R1 values (β = 0.20, Pcorrected = 0.006), lower R2* values (β = 0.29, Pcorrected = 0.006) and lower susceptibility values (β = 0.19, Pcorrected = 0.024) of the WMH-connected regions at high connectivity level, independent of WMH volumes and the cortical measures of WMH-unconnected regions. Together, our study demonstrated that the microstructural integrity of white matter tracts passing through WMH is related to the regional cortical abnormalities as measured by thickness, R1, R2* and susceptibility values in the connected cortical regions. These findings are indicative of cortical thinning, demyelination and iron loss in the cortex, which is most likely through the disruption of the connecting white matter tracts and may contribute to processing speed impairment in SVD, a key clinical feature of SVD. These findings may have implications for finding intervention targets for the treatment of cognitive impairment in SVD by preventing secondary degeneration.
| S-EPMC10629800 | biostudies-literature
Project description:It remains unclear if and how the interactions between APOE genotypes and cerebral small-vessel diseases (CSVD) lead to cognitive decline in the long term. Based on ADNI cohort, this longitudinal study aimed to clarify the potential relationship among APOE genotype, CSVD and cognition by integrating multi-level data.There were 135 healthy elderly (including ε2, ε4 allele carriers and ε3 homozygotes) who had completed two years' follow-up. MRI markers of CSVD, including white matter hyperintensities (WMH), dilated perivascular space (dPVS), microbleeds and lacune, were assessed. Besides, neuropathological factors including Alzheimer's disease-related pathology measured by CSF and PiB-PET were assessed. Repeated measurements ANOVAs were performed to test impact of different APOE genotypes on CSVD.We found that APOE ε4 carriers had significantly more frontal WMH burden and basal ganglia dPVS at baseline and faster progression of frontal WMH burden during follow-up. Furthermore, our results showed that APOE ε4 carriers had significantly decreased Aβ1-42 level, and its level was negatively related with baseline and progressive total WMH burden. Then, general linear modals indicated interaction between basal frontal WMH burden and ε4 allele was related with declining trend of cognition.Our findings suggested APOE ε4 allele was associated with increased Aβ deposition, which may lead to the formation and progression of WMH, especially in frontal lobe. Besides, interaction between the increased frontal WMH burden and ε4 allele can exert long-term detrimental effects on individual's trajectory of cognition.
| S-EPMC5546495 | biostudies-other
Project description:BackgroundA low serum total bilirubin (T-bil) level is associated with an increased risk of atherosclerosis. However, the differential impact of the serum T-bil level on cerebral atherosclerosis and cerebral small vessel disease (SVD) is still unclear.MethodsWe evaluated serum T-bil levels from 1,128 neurologically healthy subjects. Indices of cerebral atherosclerosis (extracranial arterial stenosis [ECAS] and intracranial arterial stenosis [ICAS]), and indices of SVD (silent lacunar infarct [SLI], and moderate-to-severe white matter hyperintensities [msWMH]) were evaluated by the use of brain magnetic resonance imaging (MRI) and MR angiography.ResultsIn logistic regression analysis after adjusting for confounding variables, subjects within middle T-bil (odds ratio [OR]: 0.63; 95% CI: 0.41-0.97) and high T-bil tertiles (OR: 0.54; 95% CI: 0.33-0.86) showed a lower prevalence of ECAS than those in a low T-bil tertile. Although subjects with a high T-bil tertile had a lower prevalence of ICAS than those with a low T-bil tertile, the statistical significance was marginal after adjusting for confounding variables. There were no significant differences in the proportions of subjects with SLI and msWMH across serum T-bil tertile groups.ConclusionsThe serum T-bil level is negatively associated with cerebral atherosclerosis, especially extracranial atherosclerosis, but not with SVD.
| S-EPMC5358834 | biostudies-literature
Project description:Cerebral small vessel disease is a major cause of vascular cognitive impairment and dementia. There are few treatments, largely reflecting limited understanding of the underlying pathophysiology. Metabolomics can be used to identify novel risk factors to better understand pathogenesis and to predict disease progression and severity. We analysed data from 624 patients with symptomatic cerebral small vessel disease from two prospective cohort studies. Serum samples were collected at baseline and patients underwent MRI scans and cognitive testing at regular intervals with up to 14 years of follow-up. Using ultra-performance liquid chromatography-mass spectrometry and nuclear magnetic resonance spectroscopy, we obtained metabolic and lipidomic profiles from 369 annotated metabolites and 54 764 unannotated features and examined their association with respect to disease severity, assessed using MRI small vessel disease markers, cognition and future risk of all-cause dementia. Our analysis identified 28 metabolites that were significantly associated with small vessel disease imaging markers and cognition. Decreased levels of multiple glycerophospholipids and sphingolipids were associated with increased small vessel disease load as evidenced by higher white matter hyperintensity volume, lower mean diffusivity normalized peak height, greater brain atrophy and impaired cognition. Higher levels of creatine, FA(18:2(OH)) and SM(d18:2/24:1) were associated with increased lacune count, higher white matter hyperintensity volume and impaired cognition. Lower baseline levels of carnitines and creatinine were associated with higher annualized change in peak width of skeletonized mean diffusivity, and 25 metabolites, including lipoprotein subclasses, amino acids and xenobiotics, were associated with future dementia incidence. Our results show multiple distinct metabolic signatures that are associated with imaging markers of small vessel disease, cognition and conversion to dementia. Further research should assess causality and the use of metabolomic screening to improve the ability to predict future disease severity and dementia risk in small vessel disease. The metabolomic profiles may also provide novel insights into disease pathogenesis and help identify novel treatment approaches.
| S-EPMC9337813 | biostudies-literature
Project description:The factors and mechanisms underlying the heterogeneous cognitive outcomes of cerebral small vessel disease are largely unknown. Brain biological age can be estimated by machine learning algorithms that use large brain MRI data sets to integrate and compute neuroimaging-derived age-related features. Predicted and chronological ages difference (brain-age gap) reflects advanced or delayed brain aging in an individual. The present study firstly reports the brain aging status of cerebral small vessel disease. In addition, we investigated whether global or certain regional brain age could mediate the cognitive functions in cerebral small vessel disease. Global and regional (400 cortical, 14 subcortical and 28 cerebellum regions of interest) brain-age prediction models were constructed using grey matter features from MRI of 1482 healthy individuals (age: 18-92 years). Predicted and chronological ages differences were obtained and then applied to non-stroke, non-demented individuals, aged ≥50 years, from another community-dwelling population (I-Lan Longitudinal Aging Study cohort). Among the 734 participants from the I-Lan Longitudinal Aging Study cohort, 124 were classified into the cerebral small vessel disease group. The cerebral small vessel disease group demonstrated significantly poorer performances in global cognitive, verbal memory and executive functions than that of non-cerebral small vessel disease group. Global brain-age gap was significantly higher in the cerebral small vessel disease (3.71 ± 7.60 years) than that in non-cerebral small vessel disease (-0.43 ± 9.47 years) group (P = 0.003, η2 = 0.012). There were 82 cerebral cortical, 3 subcortical and 4 cerebellar regions showing significantly different brain-age gap between the cerebral small vessel disease and non-cerebral small vessel disease groups. Global brain-age gap failed to mediate the relationship between cerebral small vessel disease and any of the cognitive domains. In 89 regions with increased brain-age gap in the cerebral small vessel disease group, seven regional brain-age gaps were able to show significant mediation effects in cerebral small vessel disease-related cognitive impairment (we set the statistical significance P < 0.05 uncorrected in 89 mediation models). Of these, the left thalamus and left hippocampus brain-age gap explained poorer global cognitive performance in cerebral small vessel disease. We demonstrated the interconnections between cerebral small vessel disease and brain age. Strategic brain aging, i.e. advanced brain aging in critical regions, may be involved in the pathophysiology of cerebral small vessel disease-related cognitive impairment. Regional rather than global brain-age gap could potentially serve as a biomarker for predicting heterogeneous cognitive outcomes in patients with cerebral small vessel disease.
| S-EPMC9525017 | biostudies-literature
Project description:AimsCerebral small vessel disease (CSVD) is characterized by functional and structural changes in small vessels. We aimed to elucidate the relationship between dynamic cerebral autoregulation (dCA) and neuroimaging characteristics of CSVD.MethodsA case-control study was performed. Cerebral blood flow velocity (CBFV) of bilateral middle cerebral arteries and spontaneous arterial blood pressure were simultaneously recorded. Transfer function analysis was used to calculate dCA parameters (phase, gain, and the rate of recovery of CBFV [RoRc]). Neuroimaging characteristics of CSVD patients were evaluated, including lacunes, white matter hyperintensities (WMH), cerebral microbleeds (CMBs), perivascular spaces (PVS), and the total CSVD burden.ResultsOverall, 113 patients and 83 controls were enrolled. Compared with the control group, the phase at low frequency and the RoRc in CSVD patients were lower, and the gain at very low and low frequencies were higher, indicating bilaterally impaired dCA. Total CSVD burden, WMH (total, periventricular and deep), severe PVS, and lobar CMBs were independently correlated with the phase at low frequency.ConclusionsOur findings suggested that dCA was compromised in CSVD patients, and some specific neuroimaging characteristics (the total CSVD burden, WMH, severe PVS and lobar CMBs) might indicate more severe dCA impairment in CSVD patients.
| S-EPMC8739047 | biostudies-literature
Project description:ObjectiveOur aim was to investigate the relationship of carotid structure and function with MRI markers of cerebral ischemic small-vessel disease.MethodsThe study comprised 1,800 participants (aged 72.5 ± 4.1 years, 59.4% women) from the 3C-Dijon Study, a population-based, prospective cohort study, who had undergone quantitative brain MRI and carotid ultrasound. We used multivariable logistic and linear regression adjusted for age, sex, and vascular risk factors.ResultsPresence of carotid plaque and increasing carotid lumen diameter (but not common carotid artery intima-media thickness) were associated with higher prevalence of lacunar infarcts: odds ratio (OR) = 1.60 (95% confidence interval [CI]: 1.09-2.35), p = 0.02 and OR = 1.24 (95% CI: 1.02-1.50), p = 0.03 (by SD increase). Carotid plaque was also associated with large white matter hyperintensity volume (WMHV) (age-specific top quartile of WMHV distribution): OR = 1.32 (95% CI: 1.04-1.67), p = 0.02, independently of vascular risk factors. Increasing Young elastic modulus and higher circumferential wall stress, reflecting augmented carotid stiffness, were associated with increasing WMHV (effect estimate [β] ± standard error: 0.0003 ± 0.0001, p = 0.024; β ± standard error: 0.005 ± 0.002, p = 0.008). Large WMHV was also associated with increasing Young elastic modulus (OR = 1.22 [95% CI: 1.04-1.42], p = 0.01) and with decreasing distensibility coefficient (OR = 0.83 [95% CI: 0.69-0.99], p = 0.04), independently of vascular risk factors. Associations of carotid lumen diameter with lacunar infarcts and of carotid stiffness markers with WMHV were independent of carotid plaque.ConclusionsIn addition to and independently of carotid plaque, increasing carotid lumen diameter and markers of carotid stiffness were associated with increasing prevalence of lacunar infarcts and increasing WMHV, respectively.
| S-EPMC3590057 | biostudies-literature
Project description:Slowed processing speed is common in elderly subjects and frequently related to cerebral small vessel disease. Previous studies have demonstrated associations between processing speed and subcortical ischemic lesions as well as cortical alterations but the precise functional-anatomical relationships remain poorly understood. Here we assessed the impact of both cortical and subcortical changes on processing speed by measuring regional cortical thickness and regional lesion volumes within distinct white-matter tracts. To limit confounding effects from age-related pathologies we studied patients with CADASIL, a genetic small vessel disease. General linear model analysis revealed significant associations between cortical thickness in the medial frontal and occipito-temporal cortex and processing speed. Bayesian network analysis showed a robust conditional dependency between the volume of lacunar lesions in the left anterior thalamic radiation and cortical thickness of the left medial frontal cortex, and between thickness of the left medial frontal cortex and processing speed, whereas there was no direct dependency between lesion volumes in the left anterior thalamic radiation and processing speed. Our results suggest that the medial frontal cortex has an intermediate position between lacunar lesions in the anterior thalamic radiation and deficits in processing speed. In contrast, we did not observe such a relationship for the occipito-temporal region. These findings reinforce the key role of frontal-subcortical circuits in cognitive impairment resulting from cerebral small vessel disease.
| S-EPMC3777834 | biostudies-other
Project description:BackgroundCerebral small vessel disease (SVD) commonly coexists with large artery atherosclerosis (LAA).AimWe evaluate the effect of SVD on stroke recurrence in patients for ischemic stroke with LAA.MethodsWe consecutively collected first-ever ischemic stroke patients who were classified as LAA mechanism between Jan 2010 and Dec 2013. Univariate and multivariate Cox analyses were performed to evaluate the association between the 2-year recurrence and demographic, clinical, and radiological factors. To evaluate the impact of SVD and its components on recurrent stroke, we used the Kaplan-Meier analysis. SVD was defined as the presence of severe white matter hyperintensity (WMH) or old lacunar infarction (OLI) or cerebral microbleeds (CMB). We also compared frequency and burden of SVD among recurrent stroke groups with different mechanisms.ResultsAmong a total of 956 participants, 92 patients had recurrent events. Recurrence group showed a higher frequency of severe WMH, OLI, asymptomatic territorial infarction, and severe stenosis on the relevant vessel in multivariate analysis. The impact of SVD and its components on recurrent stroke was significant in any ischemic recurrent stroke, and the presence of SVD was continuously important in stroke recurrence regardless of its mechanism, including recurrent LAA stroke, recurrent small vessel occlusion stroke, and even recurrent cardioembolic stroke. Additionally, the recurrence rate increased in dose-response manner with the increased number of SVD components.ConclusionsCerebral SVD is associated with recurrent stroke in patients with LAA. Additionally, it may affect any mechanisms of recurrent stroke and even with a dose response manner.
| S-EPMC5633141 | biostudies-literature