High burden of cerebral white matter lesion in 9 Asian cities.
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ABSTRACT:
SUBMITTER: Lam BYK
PROVIDER: S-EPMC8172636 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:White matter hyperintensities (WMHs) detectable by magnetic resonance imaging are part of the spectrum of vascular injury associated with aging of the brain and are thought to reflect ischemic damage to the small deep cerebral vessels. WMHs are associated with an increased risk of cognitive and motor dysfunction, dementia, depression, and stroke. Despite a significant heritability, few genetic loci influencing WMH burden have been identified.We performed a meta-analysis of genome-wide association studies (GWASs) for WMH burden in 9,361 stroke-free individuals of European descent from 7 community-based cohorts. Significant findings were tested for replication in 3,024 individuals from 2 additional cohorts.We identified 6 novel risk-associated single nucleotide polymorphisms (SNPs) in 1 locus on chromosome 17q25 encompassing 6 known genes including WBP2, TRIM65, TRIM47, MRPL38, FBF1, and ACOX1. The most significant association was for rs3744028 (p(discovery) = 4.0 × 10(-9) ; p(replication) = 1.3 × 10(-7) ; p(combined) = 4.0 × 10(-15) ). Other SNPs in this region also reaching genome-wide significance were rs9894383 (p = 5.3 × 10(-9) ), rs11869977 (p = 5.7 × 10(-9) ), rs936393 (p = 6.8 × 10(-9) ), rs3744017 (p = 7.3 × 10(-9) ), and rs1055129 (p = 4.1 × 10(-8) ). Variant alleles at these loci conferred a small increase in WMH burden (4-8% of the overall mean WMH burden in the sample).This large GWAS of WMH burden in community-based cohorts of individuals of European descent identifies a novel locus on chromosome 17. Further characterization of this locus may provide novel insights into the pathogenesis of cerebral WMH.
| S-EPMC3122147 | biostudies-literature
Project description:IntroductionWhite matter lesions (WMLs), detected as hyperintensities on T2-weighted MRI, represent small vessel disease in the brain and are considered a potential risk factor for memory and cognitive impairment in older adults. The purpose of this study was to evaluate the association between WMLs and cerebral amyloid-β (Aβ) burden in patients with cognitive impairment.MethodsA total of 83 patients with cognitive impairment, who underwent brain MRI and F-18 florbetaben PET, were included prospectively: 19 patients were cognitively unimpaired, 30 exhibited mild cognitive impairment (MCI), and 34 exhibited dementia. The Fazekas scale was used to quantify WMLs on T2-weighted brain MR images. Cerebral Aβ burden was quantitatively estimated using volume-of-interest analysis. Differences in cerebral Aβ burden were evaluated between low-WML (Fazekas scale ≤1) and high-WML (Fazekas scale ≥2) groups. The relationship between the Fazekas rating and cerebral Aβ burden was evaluated using linear regression analysis after adjusting for age and sex.ResultsIn the overall cohort, the high-WML group exhibited significantly higher Aβ burden compared with the low-WML group (P = 0.011) and cerebral Aβ burden was positively correlated with Fazekas rating (β = 0.299, P = 0.006). In patients with MCI, the high-WML group exhibited significantly higher Aβ burden compared with the low-WML group (P = 0.019) and cerebral Aβ burden was positively correlated with Fazekas rating (β = 0.517, P = 0.003).ConclusionThe presence of WMLs was associated with cerebral Aβ burden in patients with MCI. Our findings suggest that small vessel disease in the brain is related to Alzheimer's disease pathology.
| S-EPMC6152974 | biostudies-literature
Project description:White and grey matter lesions are the most prevalent type of injury observable in the Magnetic Resonance Images (MRIs) of children with cerebral palsy (CP). Previous studies investigating the impact of lesions in children with CP have been qualitative, limited by the lack of automated segmentation approaches in this setting. As a result, the quantitative relationship between lesion burden has yet to be established. In this study, we perform automatic lesion segmentation on a large cohort of data (107 children with unilateral CP and 18 healthy children) with a new, validated method for segmenting both white matter (WM) and grey matter (GM) lesions. The method has better accuracy (94%) than the best current methods (73%), and only requires standard structural MRI sequences. Anatomical lesion burdens most predictive of clinical scores of motor, cognitive, visual and communicative function were identified using the Least Absolute Shrinkage and Selection operator (LASSO). The improved segmentations enabled identification of significant correlations between regional lesion burden and clinical performance, which conform to known structure-function relationships. Model performance was validated in an independent test set, with significant correlations observed for both WM and GM regional lesion burden with motor function (p < 0.008), and between WM and GM lesions alone with cognitive and visual function respectively (p < 0.008). The significant correlation of GM lesions with functional outcome highlights the serious implications GM lesions, in addition to WM lesions, have for prognosis, and the utility of structural MRI alone for quantifying lesion burden and planning therapy interventions.
| S-EPMC4908311 | biostudies-literature
Project description:To assess apolipoprotein L1 gene (APOL1) renal-risk-variant effects on the brain, magnetic resonance imaging (MRI)-based cerebral volumes and cognitive function were assessed in 517 African American-Diabetes Heart Study (AA-DHS) Memory IN Diabetes (MIND) and 2568 hypertensive African American Systolic Blood Pressure Intervention Trial (SPRINT) participants without diabetes. Within these cohorts, 483 and 197 had cerebral MRI, respectively. AA-DHS participants were characterized as follows: 60.9% female, mean age of 58.6 years, diabetes duration 13.1 years, estimated glomerular filtration rate of 88.2 ml/min/1.73 m(2), and a median spot urine albumin to creatinine ratio of 10.0 mg/g. In additive genetic models adjusting for age, sex, ancestry, scanner, intracranial volume, body mass index, hemoglobin A1c, statins, nephropathy, smoking, hypertension, and cardiovascular disease, APOL1 renal-risk-variants were positively associated with gray matter volume (β = 3.4 × 10(-3)) and negatively associated with white matter lesion volume (β = -0.303) (an indicator of cerebral small vessel disease) and cerebrospinal fluid volume (β= -30707) (all significant), but not with white matter volume or cognitive function. Significant associations corresponding to adjusted effect sizes (β/SE) were observed with gray matter volume (0.16) and white matter lesion volume (-0.208), but not with cerebrospinal fluid volume (-0.251). Meta-analysis results with SPRINT Memory and Cognition in Decreased Hypertension (MIND) participants who had cerebral MRI were confirmatory. Thus, APOL1 renal-risk-variants are associated with larger gray matter volume and lower white matter lesion volume suggesting lower intracranial small vessel disease.
| S-EPMC4946987 | biostudies-literature
Project description:GoalsThere are no validated biomarkers that allow for reliable distinction between TIA and other transient neurological symptoms that mimic TIA. We sought to determine whether the degree of pre-existing white matter hyperintensity (WMH) lesion burden relates to the diagnostic certainty of TIA in a cohort of patients presenting with transient neurological symptoms.Materials and methodsWe retrospectively analyzed 144 consecutive patients with available brain MRI to quantify and normalize the WMH volume for brain atrophy (adjusted white matter hyperintensity [aWMHV]). We first stratified subjects to probable (n = 62) versus possible (n = 82) TIA as per existing guidelines. Receiver-operating characteristic curves were used to determine a critical aWMHV-threshold (7.8 mL) that best differentiated probable from possible TIA. We then further stratified patients with possible TIA to likely (n = 52) versus unlikely (n = 30) TIA after independent chart review and adjudication. Finally, multivariable logistic and multinomial regression was used to determine whether the defined aWMHV independently related to probable and likely TIA after adjustment for pertinent confounders.FindingsWith the exception of age (P < .001) and use of antiplatelets (P = .017), baseline characteristics were similar between patients with probable, likely, and unlikely TIA. In the fully adjusted multinomial model, the aWMHV cut-off greater than 7.8 mL (odds ratio 3.8, 95% confidence interval 1.3-10.9, P = .012) was significantly more frequent in patients with a probable TIA as compared to those with an unlikely TIA diagnosis.ConclusionsWe provide proof-of-principle that WMH may serve as a neuroimaging marker of diagnostic certainty of TIA after neurological workup has been completed.
| S-EPMC6441369 | biostudies-literature
Project description:IntroductionChronic kidney disease is related to neurodegeneration and structural changes in the brain which might lead to cognitive decline. The Fazekas scale used for assessing white matter hyperintensities (WMHs) was associated with poor cognitive performance. Therefore, this study investigated the associations between the mini-mental status examination (MMSE), Montreal cognitive assessment (MoCA), cognitive abilities screening instrument (CASI), and Fazekas scale in patients under hemodialysis (HD).MethodsThe periventricular (PV) WMHs and deep WMHs (DWMHs) in brain magnetic resonance images of 59 patients under dialysis were graded using the Fazekas scale. Three cognition function tests were also performed, then multivariable ordinal regression and logistic regression were used to identify the associations between cognitive performance and the Fazekas scale.ResultsThere were inverse associations between the three cognitive function tests across the Fazekas scale of PVWMHs (p = .037, .006, and .008 for MMSE, MoCA, and CASI, respectively), but the associations were attenuated in the DWMHs group. In CASI, significant differences were identified in short-term memory, mental manipulation, abstract thinking, language, spatial construction, and name fluency in the PVWMHs group. However, DWMHs were only significantly correlated with abstract thinking and short-term memory.ConclusionAn inverse correlation existed between the Fazekas scale, predominantly in PVWMHs, and cognition in patients undergoing HD. The PVWMHs were associated with cognitive performance assessed by MMSE, MoCA, and CASI, as well as with subdomains of CASI such as memory, language and name fluency in patients undergoing HD.
| S-EPMC10851831 | biostudies-literature
Project description:PurposeHypertension is a risk factor for cognitive impairment; however, the mechanisms leading to cognitive changes remain unclear. In this cross-sectional study, we evaluate the impact of white matter lesion (WML) burden on brain functional connectivity (FC) and cognition in a large cohort of hypertensive patients from the Systolic Blood Pressure Intervention Trial (SPRINT) at baseline.MethodsFunctional networks were identified from baseline resting state functional MRI scans of 660 SPRINT participants using independent component analysis. WML volumes were calculated from structural MRI. Correlation analyses were carried out between mean FC of each functional network and global WML as well as WML within atlas-defined white matter regions. For networks of interest, voxel-wise-adjusted correlation analyses between FC and regional WML volume were performed. Multiple variable linear regression models were built for cognitive test performance as a function of network FC, followed by mediation analysis.ResultsMean FC of the default mode network (DMN) was negatively correlated with global WML volume, and regional WML volume within the precuneus. Voxel-wise correlation analyses revealed that regional WML was negatively correlated with FC of the DMN's left lateral temporal region. FC in this region of the DMN was positively correlated to performance on the Montreal Cognitive Assessment and demonstrated significant mediation effects. Additional networks also demonstrated global and regional WML correlations; however, they did not demonstrate an association with cognition.ConclusionIn hypertensive patients, greater WML volume is associated with lower FC of the DMN, which in turn is related to poorer cognitive test performance.Trial registrationNCT01206062.
| S-EPMC8286444 | biostudies-literature
Project description:Background and purposeWM lesion segmentation is often performed with the use of subjective rating scales because manual methods are laborious and tedious; however, automated methods are now available. We compared the performance of total lesion volume grading computed by use of an automated WM lesion segmentation algorithm with that of subjective rating scales and expert manual segmentation in a cohort of subjects with type 2 diabetes.Materials and methodsStructural T1 and FLAIR MR imaging data from 50 subjects with diabetes (age, 67.7 ± 7.2 years) and 50 nondiabetic sibling pairs (age, 67.5 ± 9.4 years) were evaluated in an institutional review board-approved study. WM lesion segmentation maps and total lesion volume were generated for each subject by means of the Statistical Parametric Mapping (SPM8) Lesion Segmentation Toolbox. Subjective WM lesion grade was determined by means of a 0-9 rating scale by 2 readers. Ground-truth total lesion volume was determined by means of manual segmentation by experienced readers. Correlation analyses compared manual segmentation total lesion volume with automated and subjective evaluation methods.ResultsCorrelation between average lesion segmentation and ground-truth total lesion volume was 0.84. Maximum correlation between the Lesion Segmentation Toolbox and ground-truth total lesion volume (ρ = 0.87) occurred at the segmentation threshold of k = 0.25, whereas maximum correlation between subjective lesion segmentation and the Lesion Segmentation Toolbox (ρ = 0.73) occurred at k = 0.15. The difference between the 2 correlation estimates with ground-truth was not statistically significant. The lower segmentation threshold (0.15 versus 0.25) suggests that subjective raters overestimate WM lesion burden.ConclusionsWe validate the Lesion Segmentation Toolbox for determining total lesion volume in diabetes-enriched populations and compare it with a common subjective WM lesion rating scale. The Lesion Segmentation Toolbox is a readily available substitute for subjective WM lesion scoring in studies of diabetes and other populations with changes of leukoaraiosis.
| S-EPMC4038900 | biostudies-literature
Project description:ObjectivesSmall subcortical infarcts (SSI) frequently coexist with brain white matter hyperintensity (WMH) lesions. We sought to determine whether preexisting WMH burden relates to SSI volume, SSI etiology, and 90-day functional outcome.Materials and methodsWe retrospectively studied 80 consecutive patients with acute SSI. Infarct volume was determined on diffusion weighted imaging, and WMH burden was graded on fluid-attenuated inversion recovery sequences according to the Fazekas scale. SSI etiology was categorized as small vessel disease (SVD) vs non-SVD related. Multivariable linear and logistic regression models were constructed to determine whether WMH burden was independently associated with the SSI volume and a poor 90-day outcome (modified Rankin scale [mRS] score >2), respectively.ResultsIn unadjusted analyses, patients with non-SVD-related SSI were older (P=.002) and more frequently had multiple infarcts (P<.001) than patients with SVD-related SSI. In the fully adjusted model, WMH severity (Coefficient 0.07; 95%-CI 0.029-0.117; P=.002) but not SSI etiology (P>.1) was independently associated with the SSI volume. On multivariable logistic regression, worse WMH (OR 2.28; 95%-CI 1.04-4.99; P=.040), SSI etiology (OR 9.20; 95%-CI 1.04-81.39; P=.046), preadmission mRS (OR 8.96; 95%-CI 2.65-30.27; P<.001), and SSI volume (OR 1.98; 95%-CI 1.14-3.44; P=.016) were associated with a poor 90-day outcome.ConclusionsGreater WMH burden is independently associated with a larger SSI volume and a worse 90-day outcome.
| S-EPMC5332524 | biostudies-literature
Project description:Background and purposeWhite matter lesion (WML) progression on magnetic resonance imaging is related to cognitive decline and stroke, but its determinants besides baseline WML burden are largely unknown. Here, we estimated heritability of WML progression, and sought common genetic variants associated with WML progression in elderly participants from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium.MethodsHeritability of WML progression was calculated in the Framingham Heart Study. The genome-wide association study included 7773 elderly participants from 10 cohorts. To assess the relative contribution of genetic factors to progression of WML, we compared in 7 cohorts risk models including demographics, vascular risk factors plus single-nucleotide polymorphisms that have been shown to be associated cross-sectionally with WML in the current and previous association studies.ResultsA total of 1085 subjects showed WML progression. The heritability estimate for WML progression was low at 6.5%, and no single-nucleotide polymorphisms achieved genome-wide significance (P<5×10(-8)). Four loci were suggestive (P<1×10(-5)) of an association with WML progression: 10q24.32 (rs10883817, P=1.46×10(-6)); 12q13.13 (rs4761974, P=8.71×10(-7)); 20p12.1 (rs6135309, P=3.69×10(-6)); and 4p15.31 (rs7664442, P=2.26×10(-6)). Variants that have been previously related to WML explained only 0.8% to 11.7% more of the variance in WML progression than age, vascular risk factors, and baseline WML burden.ConclusionsCommon genetic factors contribute little to the progression of age-related WML in middle-aged and older adults. Future research on determinants of WML progression should focus more on environmental, lifestyle, or host-related biological factors.
| S-EPMC4749149 | biostudies-literature