white matter hyperintensity
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2022 ◽  
Vol 12 ◽  
Author(s):  
Yilei Zhao ◽  
Jingfeng Xu ◽  
Zhan Feng ◽  
Jincheng Wang

Some studies show that low serum vitamin D levels are associated with white matter hyperintensity (WMH), while other studies report no association. This meta-analysis aimed to investigate the presence of an association between serum 25-hydroxy vitamin D [25(OH)D] levels and WMH. PubMed, Embase, the Cochrane Library, CNKI, WANFANG, and VIP were searched for available papers published up to December 2020. The outcomes were the odds ratios (ORs) with 95% confidence intervals (CIs) for the association between different vitamin D statuses and WMH. All meta-analyses were performed using a random-effects model. Five studies (4393 patients) were included. Compared with sufficient 25(OH)D levels, 25(OH)D deficiency was not associated with WMH (OR = 1.67, 95%CI: 0.92–3.04; I2 = 70.2%, Pheterogeneity = 0.009), nor was 25(OH)D insufficiency (OR = 1.21, 95%CI: 0.89–1.65; I2 = 48.1%, Pheterogeneity = 0.103). A decrease of 25 nmol/L in 25(OH)D levels was associated with WMH (OR = 1.83, 95%CI: 1.34-2.49; I2 = 0%, Pheterogeneity= 0.512). The sensitivity analyses showed that the results were robust. 25(OH)D deficiency and insufficiency are not associated with WMH. A decrease of 25 nmol/L in 25(OH)D levels was associated with WMH, but this result will have to be confirmed. Prospective trials, both cross-sectional and longitudinal, are necessary to examine the association between 25(OH)D levels and WMH.


2022 ◽  
Vol 13 ◽  
Author(s):  
Niklas Wulms ◽  
Lea Redmann ◽  
Christine Herpertz ◽  
Nadine Bonberg ◽  
Klaus Berger ◽  
...  

Introduction: White matter hyperintensities of presumed vascular origin (WMH) are an important magnetic resonance imaging marker of cerebral small vessel disease and are associated with cognitive decline, stroke, and mortality. Their relevance in healthy individuals, however, is less clear. This is partly due to the methodological challenge of accurately measuring rare and small WMH with automated segmentation programs. In this study, we tested whether WMH volumetry with FMRIB software library v6.0 (FSL; https://fsl.fmrib.ox.ac.uk/fsl/fslwiki) Brain Intensity AbNormality Classification Algorithm (BIANCA), a customizable and trainable algorithm that quantifies WMH volume based on individual data training sets, can be optimized for a normal aging population.Methods: We evaluated the effect of varying training sample sizes on the accuracy and the robustness of the predicted white matter hyperintensity volume in a population (n = 201) with a low prevalence of confluent WMH and a substantial proportion of participants without WMH. BIANCA was trained with seven different sample sizes between 10 and 40 with increments of 5. For each sample size, 100 random samples of T1w and FLAIR images were drawn and trained with manually delineated masks. For validation, we defined an internal and external validation set and compared the mean absolute error, resulting from the difference between manually delineated and predicted WMH volumes for each set. For spatial overlap, we calculated the Dice similarity index (SI) for the external validation cohort.Results: The study population had a median WMH volume of 0.34 ml (IQR of 1.6 ml) and included n = 28 (18%) participants without any WMH. The mean absolute error of the difference between BIANCA prediction and manually delineated masks was minimized and became more robust with an increasing number of training participants. The lowest mean absolute error of 0.05 ml (SD of 0.24 ml) was identified in the external validation set with a training sample size of 35. Compared to the volumetric overlap, the spatial overlap was poor with an average Dice similarity index of 0.14 (SD 0.16) in the external cohort, driven by subjects with very low lesion volumes.Discussion: We found that the performance of BIANCA, particularly the robustness of predictions, could be optimized for use in populations with a low WMH load by enlargement of the training sample size. Further work is needed to evaluate and potentially improve the prediction accuracy for low lesion volumes. These findings are important for current and future population-based studies with the majority of participants being normal aging people.


2022 ◽  
Vol 12 ◽  
Author(s):  
Weihang Guo ◽  
Baolei Xu ◽  
Hong Sun ◽  
Jinghong Ma ◽  
ShanShan Mei ◽  
...  

Parkinsonism is a rare phenotype of cerebral autosomal dominant arteriopathy with subcortical infarction and leukoencephalopathy (CADASIL), all of which involve cognitive decline. Normal cognition has not been reported in previous disease studies. Here we report the case of a 60-year-old female patient with a 2-year history of progressive asymmetric parkinsonism. On examination, she showed severe parkinsonism featuring bradykinesia and axial and limb rigidity with preserved cognition. Magnetic resonance imaging (MRI) revealed white matter hyperintensity in the external capsule and periventricular region. Dopaminergic response was limited. A missense mutation c.1630C>T (p.R544C) on the NOTCH3 gene was identified on whole-exome sequencing, which confirmed the diagnosis of vascular parkinsonism secondary to CADASIL. A diagnosis of CADASIL should be considered in asymmetric parkinsonism without dementia. Characteristic MRI findings support the diagnosis.


Author(s):  
Enrica Cavedo ◽  
Philippe Tran ◽  
Urielle Thoprakarn ◽  
Jean-Baptiste Martini ◽  
Antoine Movschin ◽  
...  

Abstract Objectives QyScore® is an imaging analysis tool certified in Europe (CE marked) and the US (FDA cleared) for the automatic volumetry of grey and white matter (GM and WM respectively), hippocampus (HP), amygdala (AM), and white matter hyperintensity (WMH). Here we compare QyScore® performances with the consensus of expert neuroradiologists. Methods Dice similarity coefficient (DSC) and the relative volume difference (RVD) for GM, WM volumes were calculated on 50 3DT1 images. DSC and the F1 metrics were calculated for WMH on 130 3DT1 and FLAIR images. For each index, we identified thresholds of reliability based on current literature review results. We hypothesized that DSC/F1 scores obtained using QyScore® markers would be higher than the threshold. In contrast, RVD scores would be lower. Regression analysis and Bland–Altman plots were obtained to evaluate QyScore® performance in comparison to the consensus of three expert neuroradiologists. Results The lower bound of the DSC/F1 confidence intervals was higher than the threshold for the GM, WM, HP, AM, and WMH, and the higher bounds of the RVD confidence interval were below the threshold for the WM, GM, HP, and AM. QyScore®, compared with the consensus of three expert neuroradiologists, provides reliable performance for the automatic segmentation of the GM and WM volumes, and HP and AM volumes, as well as WMH volumes. Conclusions QyScore® represents a reliable medical device in comparison with the consensus of expert neuroradiologists. Therefore, QyScore® could be implemented in clinical trials and clinical routine to support the diagnosis and longitudinal monitoring of neurological diseases. Key Points • QyScore® provides reliable automatic segmentation of brain structures in comparison with the consensus of three expert neuroradiologists. • QyScore® automatic segmentation could be performed on MRI images using different vendors and protocols of acquisition. In addition, the fast segmentation process saves time over manual and semi-automatic methods. • QyScore® could be implemented in clinical trials and clinical routine to support the diagnosis and longitudinal monitoring of neurological diseases.


2021 ◽  
Vol 13 (2) ◽  
pp. 55-63
Author(s):  
Ki-Woong Nam ◽  
Hyung-Min Kwon ◽  
Jin-Ho Park ◽  
Hyuktae Kwon

Background: Arterial stiffness has been suggested as one of the major pathological mechanisms of cerebral small vessel diseases (cSVDs). In this study, we confirmed this hypothesis by evaluating the association between vascular overload index (VOI), which is a physiologically good indicator of arterial stiffness, and cSVD.Methods: We evaluated participants who visited Seoul National University Hospital Health Promotion Center for health check-ups between 2006 and 2013. VOI was calculated by the following formula: VOI (mmHg)=1.33×systolic blood pressure -0.33×diastolic blood pressure-133.3. cSVDs were measured including white matter hyperintensity (WMH), lacunes, and cerebral microbleeds (CMBs). We quantitatively measured the WMH volume and rated the presence and number of lacunes and CMBs qualitatively.Results: A total of 3,231 participants were evaluated (mean age 57±9 years, male sex 53.9%). In multivariable linear regression analysis, VOI was significantly associated with WMH volume after adjusting confounders (β=0.004, 95% confidence interval=0.002–0.006). VOI also showed a close association with lacunes in multivariable logistic regression analysis (adjusted odds ratio=1.01, 95% confidence interval=1.00–1.02). There was no statistical association with CMBs. In subgroup analysis according to the presence of hypertension, VOI was closely associated with WMH volume/lacunes only in patients without hypertension. In patients with hypertension, these statistical associations disappeared.Conclusion: A high VOI was associated with cSVD in a neurologically healthy population, especially in patients without hypertension. This marker of arterial stiffness could be convenient and useful predictor of cSVD.


2021 ◽  
Vol 19 ◽  
Author(s):  
Lulu Yu ◽  
Yusheng Li ◽  
Yunchao Wang ◽  
Yuan Gao ◽  
Shanshan Li ◽  
...  

Background: Age and hypertension are widely considered to be the main risk factors for white matter hyperintensity (WMH), but they do not account for all the pathophysiological mechanisms of WMH.Therefore, identifying novel risk factors is significant to improve our understanding of the etiology and consequences of WMH. Objective: To examine the association of heart rate(HR) and common vascular risk factors with WMH burden in patients hospitalized for Cerebral Small Vessel Disease(CSVD) Method: The study consisted of 778 patients who underwent 24-hour ambulatory blood pressure and HR monitoring and brain magnetic resonance imaging(MRI). The relationship of HR measures and vascular risk factors with the presence of log WMHV4 was analyzed.Univariable and multivariable analysis was carried out to investigate the relationship of incidence of severe WMH (4th quartile, ≥19.64 ml) and HR measures and common vascular risk factors. Results: Multivariate analysis showed that WMHV was independently predicted by nighttime HR ( OR (95% CI): 1.041(1.02~1.062), P<0.001),Homocysteine ( OR (95% CI): 1.019(1.005~1.033), P=0.009), and cerebral infarction ( OR (95% CI): 0.463(0.31~0.691), P<0.001), No similar association was observed for daytime HR、HR variability and other vascular risk factors . Conclusion: As nighttime HR、Hcy increased, log WMHV increased accordingly; furthermore, patients with cerebral infarction were more likely to have higher levels of WMHV. nighttime HR 、Hcy、cerebral infarction was associated with WMHV, suggesting independent roles of their in WMHV. The influence of HRV on WMHV needs to be addressed by further studies.


2021 ◽  
Author(s):  
Julie Ottoy ◽  
Miracle Ozzoude ◽  
Katherine Zukotynski ◽  
Sabrina Adamo ◽  
Christopher Scott ◽  
...  

INTRODUCTION: It remains unclear to which extent vascular burden promotes neurodegeneration and cognitive dysfunction in a cohort spanning low-to-severe small vessel disease (SVD) and amyloid-beta pathology. METHODS: In 120 subjects, we investigated 1) whether vascular burden, quantified as total or lobar white matter hyperintensity (WMH) volumes, is associated with different cognitive domains; and 2) whether the total WMH effect on cognition is mediated by amyloid (18F-AV45-PET), glucose metabolism (18F-FDG-PET), and/or cortical atrophy. RESULTS: Increased total WMH volume was associated with poorer performance in all cognitive domains tested, with the strongest effects observed for semantic fluency. These relationships were mediated mainly through cortical atrophy, particularly in the temporal lobe, and to a lesser extent through amyloid and metabolism. WMH volumes differentially impacted cognition depending on lobar location and amyloid status. DISCUSSION: Our study suggests mainly an amyloid-dependent pathway in which vascular burden affects cognitive impairment through temporal lobe atrophy.


2021 ◽  
Vol 19 ◽  
Author(s):  
Alexandra L. Clark ◽  
Seraphina K. Solders ◽  
Kelsey R. Thomas ◽  
Katherine J. Bangen

Background: Although clusterin-a protein involved in lipid metabolism, amyloid beta clearance, and myelination-has been linked to gray matter atrophy within samples of older adults at risk for Alzheimer’s disease, research exploring associations with white matter (WM) micro- and macro- structural markers are largely limited. Objective:: The current study [1] explored associations between serum clusterin protein levels and WM micro- and macro- structural markers, and [2] clarified whether variations in WM fractional anisotropy (FA) were associated with functional abilities within in a racially homogenous sample of relatively well-educated older adults free of dementia. Methods: Participants underwent magnetic resonance imaging (MRI) brain exams and a blood draw and completed a performance-based measure of everyday functioning. Multiple linear regression adjusting for age, sex, APOE e4 positivity, and vascular risk were used to explore serum clusterin associations with WM metrics, as well clarify potential links between WM microstructure and everyday functioning. Results: Higher serum clusterin was associated with lower FA in several thalamocortical (anterior and posterior internal capsule, posterior thalamic radiation; ßs = -.32 to -.37, ps = .01 to .02) and association fiber tracts (external capsule, superior longitudinal fasciculus; ßs = -.32 to -.40, ps = .02). Serum clusterin was not associated with white matter hyperintensity volume (ß = .14, p = .28), but higher FA of several WM tracts was associated with better performance on the Independent Living Scale (ßs = .37 to .53, ps = .006 to .03). Conclusion: Serum clusterin is differentially associated with WM metrics, and WM microstructure is associated with everyday functioning.


2021 ◽  
pp. jnnp-2021-326677
Author(s):  
Rebecca Koncz ◽  
Anbupalam Thalamuthu ◽  
Wei Wen ◽  
Vibeke S Catts ◽  
Vincent Dore ◽  
...  

ObjectiveTo determine the proportional genetic contribution to the variability of cerebral β-amyloid load in older adults using the classic twin design.MethodsParticipants (n=206) comprising 61 monozygotic (MZ) twin pairs (68 (55.74%) females; mean age (SD): 71.98 (6.43) years), and 42 dizygotic (DZ) twin pairs (56 (66.67%) females; mean age: 71.14 (5.15) years) were drawn from the Older Australian Twins Study. Participants underwent detailed clinical and neuropsychological evaluations, as well as MRI, diffusion tensor imaging (DTI) and amyloid PET scans. Fifty-eight participants (17 MZ pairs, 12 DZ pairs) had PET scans with 11Carbon-Pittsburgh Compound B, and 148 participants (44 MZ pairs, 30 DZ pairs) with 18Fluorine-NAV4694. Cortical amyloid burden was quantified using the centiloid scale globally, as well as the standardised uptake value ratio (SUVR) globally and in specific brain regions. Small vessel disease (SVD) was quantified using total white matter hyperintensity volume on MRI, and peak width of skeletonised mean diffusivity on DTI. Heritability (h2) and genetic correlations were measured with structural equation modelling under the best fit model, controlling for age, sex, tracer and scanner.ResultsThe heritability of global amyloid burden was moderate (0.41 using SUVR; 0.52 using the centiloid scale) and ranged from 0.20 to 0.54 across different brain regions. There were no significant genetic or environmental correlations between global amyloid burden and markers of SVD.ConclusionAmyloid deposition, the hallmark early feature of Alzheimer’s disease, is under moderate genetic influence, suggesting a major environmental contribution that may be amenable to intervention.


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