A link between frontal white matter integrity and dizziness in cerebral small vessel disease.
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ABSTRACT:
SUBMITTER: Ibitoye RT
PROVIDER: S-EPMC9253455 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Cerebral small vessel disease (CSVD) is a widespread condition associated to stroke, dementia and depression. To shed light on its opaque pathophysiology, we conducted a neuroimaging study aiming to assess the location of CSVD-induced damage in the human brain network. Structural connectomes of 930 subjects of the Hamburg City Health Study were reconstructed from diffusion weighted imaging. The connectome edges were partitioned into groups according to specific schemes: (1) connection to grey matter regions, (2) course and length of underlying streamlines. Peak-width of skeletonised mean diffusivity (PSMD) - a surrogate marker for CSVD - was related to each edge group's connectivity in a linear regression analysis allowing localisation of CSVD-induced effects. PSMD was associated with statistically significant decreases in connectivity of most investigated edge groups except those involved in connecting limbic, insular, temporal or cerebellar regions. Connectivity of interhemispheric and long intrahemispheric edges as well as edges connecting subcortical and frontal brain regions decreased most severely with increasing PSMD. In conclusion, MRI findings of CSVD are associated with widespread impairment of structural brain network connectivity, which supports the understanding of CSVD as a global brain disease. The pattern of regional preference might provide a link to clinical phenotypes of CSVD.
| S-EPMC7280237 | biostudies-literature
Project description:It is currently unclear whether midlife systemic inflammation promotes the development of white matter (WM) abnormalities and small vessel disease in the elderly. We examined the association of midlife systemic inflammation with late-life WM hyperintensity volume, deep and periventricular WM microstructural integrity (fractional anisotropy and mean diffusivity [MD]), cerebral infarcts, and microbleeds in a biracial prospective cohort study.Linear and logistic regression examined the relation between midlife high-sensitivity C-reactive protein (CRP)-a nonspecific marker of inflammation-and brain magnetic resonance imaging markers assessed 21 years later in the Atherosclerosis Risk in Communities Study.We included 1485 participants (baseline age, 56[5]; 28% black). After adjusting for demographic factors and cardiovascular disease, each SD increase in midlife CRP was associated with lower fractional anisotropy (-0.09 SD; 95% confidence interval, -0.15 to -0.02) and greater MD (0.08 SD; 95% confidence interval, 0.03-0.15) in deep WM and lower fractional anisotropy (-0.07 SD; 95% confidence interval, -0.13 to 0.00) in periventricular WM. We found stronger associations between CRP and periventricular WM microstructural integrity among black participants (P interaction=0.011). Although an association between higher CRP levels and greater WM hyperintensity volume was found only among APOE ?4-positive participants in our primary analysis (0.14 SD; 95% confidence interval, 0.01-0.26; P interaction=0.028), this relationship extended to the entire sample after accounting for differential attrition. Midlife CRP was not associated with the presence of cerebral infarcts or microbleeds in late life.Our findings support the hypothesis that midlife systemic inflammation may promote the development of chronic microangiopathic structural WM abnormalities in the elderly.
| S-EPMC5705320 | biostudies-literature
Project description:To explore the correlation between the number of lenticulostriate arteries (LSAs) and the white matter features in cerebral small vessel diseases (CSVD) by 3T magnetic resonance imaging (MRI). Seventy-one patients with diagnoses of CSVD were prospectively enrolled to undergo 3T MRI examination, including high-resolution vascular wall imaging (VWI) and diffusion tensor imaging (DTI). The LSAs were observed and counted on VWI, and the patients were divided into three groups according to the LSA counts. The presence of white matter hyperintensities (WMHs), lacunes, cerebral microbleeds (CMBs), and enlarged perivascular spaces (EPVS) was assessed in each patient, and a composite CSVD score was calculated. Periventricular and deep white matter hyperintensity (PVWMH, DWMH) volume ratios were obtained based on automatic segmentation. Fractional anisotropy (FA) and mean diffusivity (MD) were processed by using tract-based spatial statistics (TBSS) analysis. These parameters were compared among the three groups. Correlations between the LSA counts and white matter features were also analyzed. There were differences in WMHs (P = 0.001), CMBs (P < 0.001), EPVS (P = 0.017), composite CSVD scores (P < 0.001), PVWMH volume ratios (P = 0.001), DWMH volume ratios (P < 0.001), global FA (P = 0.001), and global MD (P = 0.002) among the three groups. There were correlations between the LSA counts and WMHs (r = -0.45, P < 0.001), CMBs (r = -0.44, P < 0.001), EPVS (r = -0.28, P = 0.020), the composite CSVD score (r = -0.52, P < 0.001), DWMH volume ratio (r = -0.47, P < 0.001), PWMH volume ratio (r = -0.34, P = 0.004), global FA (r = 0.36, P = 0.002), and global MD (r = -0.33, P = 0.005). Diabetes mellitus (OR 3.36, 95% CI 1.06-10.63; P = 0.039) and increased DWMH volume ratios (OR 1.04, 95% CI 1.00-1.08; P = 0.048) were independent risk factors for a decrease in LSA counts. TBSS analysis showed differences among the three groups in global FA and MD after adjusting for age and sex (P < 0.05). The LSA counts was associated with white matter microstructure changes in CSVD and has the potential to represent the extent of subcortical microvascular damage in CSVD patients.
| S-EPMC10560852 | biostudies-literature
Project description:Cerebral small vessel disease (CSVD) is a common cause of morbidity and cognitive decline in the elderly population. However, characterizing the disease pathophysiology and its association with potential clinical sequelae in early stages is less well explored. We applied fixel-based analysis (FBA), a novel framework of investigating microstructural white matter integrity by diffusion-weighted imaging, to data of 921 participants of the Hamburg City Health Study, comprising middle-aged individuals with increased cerebrovascular risk in early stages of CSVD. In individuals in the highest quartile of white matter hyperintensity loads (n = 232, median age 63 years; IQR 15.3 years), FBA detected significantly reduced axonal density and increased atrophy of transcallosal fiber tracts, the bilateral superior longitudinal fasciculus, and corticospinal tracts compared to participants in the lowest quartile of white matter hyperintensities (n = 228, mean age 55 years; IQR 10 years). Analysis of all participants (N = 921) demonstrated a significant association between reduced fiber density and worse executive functions operationalized by the Trail Making Test. Findings were confirmed by complementary analysis of diffusion tensor metrics.
| S-EPMC8799636 | biostudies-literature
Project description:BACKGROUND:Although schizophrenia patients are at high risk for tobacco use, the neurobiological basis of this comorbid association is not clear. White matter abnormalities have been described independently in schizophrenia and smoking cohorts. We sought to determine whether smoking and schizophrenia are associated with similar white matter abnormalities that could be biomarkers for the high risk of smoking in schizophrenia. METHODS:Whole brain white matter integrity (fractional anisotropy) was measured in 46 schizophrenia patients (32 smokers and 14 nonsmokers) and 69 healthy age-matched control subjects (48 smokers and 21 nonsmokers). RESULTS:Schizophrenia and smoking status were independently and additively associated with reduced fractional anisotropy in left anterior thalamic radiation/anterior limb of the internal capsule, and significant fractional anisotropy decreases were identified in the bilateral uncinate fasciculus/inferior fronto-occipital fasciculus in schizophrenia and the left prefrontal area in smoking status separately. CONCLUSIONS:Common and distinct patterns of impaired white matter are associated with schizophrenia and smoking. Particularly, the anatomic congruence of an additive white matter abnormality in the anterior thalamic radiation/anterior limb of the internal capsule suggests that this abnormal fiber connectivity between frontal cortex and striatum/thalamus may be a biomarker for the increased comorbid smoking in schizophrenia patients.
| S-EPMC3065776 | biostudies-literature
Project description:In this study, we performed the first genome-wide expression profiling of post-mortem brains of a cohort of patients deceased from SVD and compared them to age-matched normal controls. Normal-appearing frontal temporal and occipital cortical and subcortical brain samples were dissected at autopsy from 5 patients diagnosed with pure SVD and 5 control patients without neurological disease and immediately frozen.
2015-03-11 | E-MTAB-3408 | biostudies-arrayexpress
Project description:Background and Purpose- The role of inflammation in ischemic white matter disease is increasingly recognized, and further understanding of the pathophysiology might inform future treatment strategies. Multiple sclerosis (MS) is a chronic autoimmune condition in which inflammation plays a central role that also affects the white matter. We hypothesized that white matter injury might share common mechanisms and used statistical genetics techniques to assess whether having genetically elevated white matter hyperintensity (WMH) volume was associated with increased MS risk. Methods- We investigated the genetic association in 2 cohorts with magnetic resonance imaging-quantified ischemic white matter lesion volume (WMH in stroke; n=2797 and UK Biobank; n=8353) and 14?802 cases of MS and 26?703 controls from the International Multiple Sclerosis Genetics Consortium. We further performed individual-level polygenic risk score calculations for MS and measures of structural white matter disease in UK Biobank. Finally, we looked for evidence of overlapping risk across the whole genome. Results- There was no association of genetic variants influencing MS with WMH volume using summary statistics in the WMH in stroke cohort (relative risk score =1.014; 95% CI, 0.936-1.110) or in the UK Biobank cohort (relative risk score =1.030; 95% CI, 0.932-1.117). Conversely, assessing the contribution of single nucleotide polymorphisms significantly associated with WMH on the risk of MS there was no significant association (relative risk score =0.930; 95% CI, 0.736-1.191). There were no significant associations between polygenic risk scores calculations; these results were robust to the selection of single nucleotide polymorphisms at a range of significance thresholds. Whole genome analysis did not reveal any overlap of risk between the traits. Conclusions- Our results do not provide evidence to suggest a shared mechanism of white matter damage in ischemia and MS. We propose that inflammation acts in distinct pathways because of the differing nature of the primary insult.
| S-EPMC6661245 | biostudies-literature
Project description:AimBrain clusterin is known to be associated with the amyloid-? deposits in Alzheimer's disease (AD). We assessed the distribution of clusterin immunoreactivity in cerebrovascular disorders, particularly focusing on white matter changes in small vessel diseases.MethodsPost-mortem brain tissues from the frontal or temporal lobes of a total of 70 subjects with various disorders including cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), cerebral amyloid angiopathy (CAA) and AD were examined using immunohistochemistry and immunofluorescence. We further used immunogold electron microscopy to study clusterin immunoreactivity in extracellular deposits in CADASIL.ResultsImmunostaining with clusterin antibodies revealed strong localization in arterioles and capillaries, besides cortical neurones. We found that clusterin immunostaining was significantly increased in the frontal white matter of CADASIL and pontine autosomal dominant microangiopathy and leukoencephalopathy subjects. In addition, clusterin immunostaining correlated with white matter pathology severity scores. Immunostaining in axons ranged from fine punctate deposits in single axons to larger confluent areas with numerous swollen axon bulbs, similar to that observed with known axon damage markers such as non-phosphorylated neurofilament H and the amyloid precursor protein. Immunofluorescence and immunogold electron microscopy experiments showed that whereas clusterin immunoreactivity was closely associated with vascular amyloid-? in CAA, it was lacking within the granular osmiophilic material immunolabelled by NOTCH3 extracelluar domain aggregates found in CADASIL.ConclusionsOur results suggest a wider role for clusterin associated with white matter damage in addition to its ability to chaperone proteins for clearance via the perivascular drainage pathways in several disease states.
| S-EPMC4949672 | biostudies-literature
Project description:Cerebral small-vessel damage manifests as white matter hyperintensities and cerebral atrophy on brain MRI and is associated with aging, cognitive decline and dementia. We sought to examine the interrelationship of these imaging biomarkers and the influence of hypertension in older individuals. We used a multivariate spatial covariance neuroimaging technique to localize the effects of white matter lesion load on regional gray matter volume and assessed the role of blood pressure control, age and education on this relationship. Using a case-control design matching for age, gender, and educational attainment we selected 64 participants with normal blood pressure, controlled hypertension or uncontrolled hypertension from the Northern Manhattan Study cohort. We applied gray matter voxel-based morphometry with the scaled subprofile model to (1) identify regional covariance patterns of gray matter volume differences associated with white matter lesion load, (2) compare this relationship across blood pressure groups, and (3) relate it to cognitive performance. In this group of participants aged 60-86 years, we identified a pattern of reduced gray matter volume associated with white matter lesion load in bilateral temporal-parietal regions with relative preservation of volume in the basal forebrain, thalami and cingulate cortex. This pattern was expressed most in the uncontrolled hypertension group and least in the normotensives, but was also more evident in older and more educated individuals. Expression of this pattern was associated with worse performance in executive function and memory. In summary, white matter lesions from small-vessel disease are associated with a regional pattern of gray matter atrophy that is mitigated by blood pressure control, exacerbated by aging, and associated with cognitive performance.
| S-EPMC5430031 | biostudies-literature
Project description:Objective: Reliable quantification of white matter hyperintensities (WHMs) resulting from cerebral small vessel diseases (CSVD) is essential for understanding their clinical impact. We aim to develop and clinically validate a deep learning system for automatic segmentation of CSVD-WMH from fluid-attenuated inversion recovery (FLAIR) imaging using large multicenter data. Method: A FLAIR imaging dataset of 1,156 patients diagnosed with CSVD associated WMH (median age, 54 years; 653 males) obtained between September 2018 and September 2019 from Beijing Tiantan Hospital was retrospectively analyzed in this study. Locations of CSVD-WMH on the FLAIR scans were manually marked by two experienced neurologists. Using the manually labeled data of 996 patients (development set), a U-shaped novel 2D convolutional neural network (CNN) architecture was trained for automatic segmentation of CSVD-WMH. The segmentation performance of the network was evaluated with per pixel and lesion level dice scores using an independent internal test set (n = 160) and a multi-center external test set (n = 90, three medical centers). The clinical suitability of the segmentation results, classified as acceptable, acceptable with minor revision, acceptable with major revision, and not acceptable, was analyzed by three independent neuroradiologists. The inter-neuroradiologists agreement rate was assessed by the Kendall-W test. Results: On the internal and external test sets, the proposed CNN architecture achieved per pixel and lesion level dice scores of 0.72 (external test set), and they were significantly better than the state-of-the-art deep learning architectures proposed for WMH segmentation. In the clinical evaluation, neuroradiologists observed the segmentation results for 95% of the patients were acceptable or acceptable with a minor revision. Conclusions: A deep learning system can be used for automated, objective, and clinically meaningful segmentation of CSVD-WMH with high accuracy.
| S-EPMC8656685 | biostudies-literature