Location Of White Matter Hyperintensities Research Articles

Strategic white matter hyperintensity locations associated with post-stroke cognitive impairment: a multicenter study in 1568 stroke patients.

Post-stroke cognitive impairment (PSCI) occurs in up to 50% of stroke survivors. Presence of pre-existing vascular brain injury, in particular the extent of white matter hyperintensities (WMH), is associated with worse cognitive outcome after stroke, but the role of WMH location in this association is unclear. We determined if WMH in strategic white matter tracts explain cognitive performance after stroke. Individual patient data from 9 ischemic stroke cohorts with MRI were harmonized through the Meta VCI Map consortium. The association between WMH volumes in strategic tracts and domain-specific cognitive functioning (attention and executive functioning, information processing speed, language and verbal memory) was assessed using linear mixed models and lasso regression. We used a hypothesis-driven design, primarily addressing four white matter tracts known to be strategic in memory clinic patients: the left and right anterior thalamic radiation, forceps major and left inferior fronto-occipital fasciculus. The total study sample consisted of 1568 patients (39.9% female, mean age: 67.3 years). Total WMH volume was strongly related to cognitive performance on all four cognitive domains. WMH volume in the left anterior thalamic radiation was significantly associated with cognitive performance on attention and executive functioning and information processing speed, and WMH volume in the forceps major with information processing speed. The multivariable lasso regression showed that these associations were independent of age, sex, education, and total infarct volume and had larger coefficients than total WMH volume. These results show tract-specific relations between WMH volume and cognitive performance after ischemic stroke, independent of total WMH volume. This implies that the concept of strategic lesions in PSCI extends beyond acute infarcts and also involves pre-existing WMH. The Meta VCI Map consortium is dedicated to data sharing, following our guidelines.

Circulating Exosomal LncRNAs as Novel Diagnostic Predictors of Severity and Sites of White Matter Hyperintensities

ObjectiveExosomal long noncoding RNAs (lncRNAs) are the key to diagnosing and treating various diseases. This study aimed to investigate the diagnostic value of plasma exosomal lncRNAs in white matter hyperintensities (WMH). MethodsWe used high-throughput sequencing to determine the differential expression (DE) profiles of lncRNAs in plasma exosomes from WMH patients and controls. The sequencing results were verified in a validation cohort using qRT-PCR. The diagnostic potential of candidate exosomal lncRNAs was proven by binary logistic analysis and receiver operating characteristic (ROC) curves. The diagnostic value of DE exo-lncRNAs was determined by the area under the curve (AUC). The WMH group was then divided into subgroups according to the Fazekas scale and white matter lesion site, and the correlation of DE exo-lncRNAs in the subgroup was evaluated. ResultsIn our results, four DE exo-lncRNAs were identified, and ROC curve analysis revealed that exo-lnc_011797 and exo-lnc_004326 exhibited diagnostic efficacy for WMH. Furthermore, WMH subgroup analysis showed exo-lnc_011797 expression was significantly increased in Fazekas 3 patients and was significantly elevated in patients with paraventricular matter hyperintensities. ConclusionPlasma exosomal lncRNAs have potential diagnostic value in WMH. Moreover, exo-lnc_011797 is considered to be a predictor of the severity and location of WMH.

Cholinergic white matter hyperintensity volume, cognitive decline, and incident dementia in older adults

AbstractBackgroundWhite matter hyperintensities (WMHs) are frequently observed in the elderly and their severity tends to increase with age. Previous studies have revealed that WMHs are closely related to cognitive dysfunction. However, as inter‐individual variations and a clinicoradiological discrepancy exist, not all individuals with severe WMH burden experience worse cognitive performance. Furthermore, the location of WMHs appears to be a critical factor in the relationship between WMHs and cognitive function. Few studies take both volume and location of white matter hyperintensities (WMHs) into account to explore the association between WMH burden and cognitive impairment. We therefore investigated associations of cholinergic WMH volume (WMHV) with global cognitive function, cognitive decline, and incident dementia in older adults.MethodA total of 752 older adults (mean age 60 years, 50% female) from the Taizhou Imaging Study were involved. Brain magnetic resonance imaging data at baseline and repeated measures of cognition over 5 years were collected and analyzed. WMHV in whole brain, the cholinergic pathways, and different tract classes in the Montreal Neurologic Institute standard space was obtained using the Lesion Segmentation Toolbox and tools from FMRIB Software Library. Multivariable linear regression, Cox regression, and partial correlation tests were performed.ResultOver a median 5.67 (IQR: 2.88‐6.84) years of follow‐up, cholinergic WMHV was associated with annual decline of Mini‐Mental State Examination (MMSE) (β = ‐0.206; P = 0.006), and incident dementia (HR = 3.45; 95%CI: 2.08‐5.74). Within the cholinergic pathways, WMHs in commissural fibers were related to incident dementia. However, greater global WMHV only slightly increased the risk of incident dementia (HR = 1.03; 95%CI: 1.01‐1.06). Neither global nor cholinergic WMHV was associated with MMSE in cross‐sectional analysis.ConclusionCholinergic WMHV is associated with longitudinal cognitive decline and incident dementia in older adults. Within the cholinergic pathways, commissural fiber tracts were strategic locations correlated to incident dementia. Our findings suggest cholinergic WMHV might be a potential indicator of cognitive deterioration.

Impact of White Matter Hyperintensities on domain‐specific cognition in Southeast Asians

AbstractBackgroundDementia affects 55 million people worldwide, with 60% of the burden in Asia. White Matter Hyperintensities (WMH) is a key marker of small vessel disease, with high prevalence in Asian populations with prodromal and clinical dementia. WMH is described as: Deep White Matter Hyperintensities (DWMH), Periventricular Hyperintensities (PVH) or Fazekas‐Total (DWMH and PVH).However, association between WMH topography and performance in specific cognitive domains remains unexplored. Thus, this study aims to characterise the impact of Fazekas‐Total, DWMH and PVH on different cognitive domains.Method304 participants (mean age 60.6, mean education years 14.2, mean Montreal Cognitive Assessment 25.99, 43.8% males) from Biomarkers and Cognition Study, Singapore (Dementia Research Centre (Singapore)) met the inclusion criteria.Eight domains of cognition were tested: global cognition, learning and memory, language, executive function, complex‐attention, perceptual‐motor, social‐cognition, and processing speed.Normality tests, correlation analysis and stepwise regression (with Benjamini and Hochberg False Discovery Rate correction) were performed to understand association between Fazekas‐Total, DWMH, PVH on domains of cognition tested, accounting for age, education, and gender.Two approaches were used for data analysis: (1) by grouping participants as Mild Cognitive Impairment (MCI), Subjective Cognitive Decline (SCD) and Cognitively Normal (CN) as per the National Institute on Aging‐Alzheimer’s Association (NIA‐AA) criteria and (2) by grouping participants’ WMH as confluent (DWMH ≥2 and PVH ≥3) and non‐confluent.ResultHigher Fazekas‐Total was associated with slower processing speed (p = 0.0255, R = ‐0.039) in prodromal participants (MCI and SCD). Higher PVH was associated with slower processing speed in MCI (p = 0.017, R = ‐0.32) and CN (p = 0.017, R = ‐0.663) participants. Higher PVH was significantly associated with poorer learning and memory (p = 0.045, R = ‐0.043) in SCD participants. Higher DWMH was significantly associated with poorer learning and memory (p = 0.017, R = ‐0.765) in CN participants.ConclusionThese results demonstrate differential association between PVH, DWMH and cognitive domains, thus the location of WMH determines the affected cognitive domains. Therefore, it is worthwhile to assess PVH and DWMH in clinical cognitive outcomes separately and to understand the upstream pathobiology of DWMH and PVH.Furthermore, higher Fazekas‐Total was strongly associated with slower processing speed in prodromal participants and could be a marker of cognitive decline.

Neural Substrates of Psychomotor Speed Deficits in Cerebral Small Vessel Disease: A Brain Disconnectome Mapping Study.

It remains unknown which factors influence how brain disconnectivity derived from White Matter Hyperintensity (WMH) lesions leads to psychomotor speed dysfunction, one of the earliest and most common cognitive manifestations in the cerebral Small Vessel Disease (cSVD) population. While the burden of WMH has been strongly linked to psychomotor speed performance, the effect that different locations and volumes of WMH may have on cSVD-related cognitive impairment remains unclear. Therefore, we aimed to explore (1) whether global WMH, deep WMH (DWMH), and periventricular (PVWMH) volumes display different psychomotor speed associations; (2) whether tract-specific WMH volume shows stronger cognitive associations compared with global measures of WMH volume; (3) whether specific patterns of WMH location lead to different degrees of disconnectivity. Using the BCBToolkit, we investigated which pattern of distribution and which locations of WMH lesion result in impaired psychomotor speed in a well-characterized sample (n = 195) of cSVD patients without dementia. Two key findings emerge from our study. First, global (and not tract-specific) measures of WMH volume were associated with psychomotor speed performance. Second, disconnection maps revealed the involvement of callosal tracts, association and projection fibers, and frontal and parietal cortical brain areas related to psychomotor speed, while the lesion location influenced such associations. In conclusion, psychomotor deficits are affected differently by WMH burden and topographic distribution through brain disconnection in non-demented cSVD patients.

Tract-based white matter hyperintensity patterns in patients with systemic lupus erythematosus using an unsupervised machine learning approach.

Currently, little is known about the spatial distribution of white matter hyperintensities (WMH) in the brain of patients with Systemic Lupus erythematosus (SLE). Previous lesion markers, such as number and volume, ignore the strategic location of WMH. The goal of this work was to develop a fully-automated method to identify predominant patterns of WMH across WM tracts based on cluster analysis. A total of 221 SLE patients with and without neuropsychiatric symptoms from two different sites were included in this study. WMH segmentations and lesion locations were acquired automatically. Cluster analysis was performed on the WMH distribution in 20 WM tracts. Our pipeline identified five distinct clusters with predominant involvement of the forceps major, forceps minor, as well as right and left anterior thalamic radiations and the right inferior fronto-occipital fasciculus. The patterns of the affected WM tracts were consistent over the SLE subtypes and sites. Our approach revealed distinct and robust tract-based WMH patterns within SLE patients. This method could provide a basis, to link the location of WMH with clinical symptoms. Furthermore, it could be used for other diseases characterized by presence of WMH to investigate both the clinical relevance of WMH and underlying pathomechanism in the brain.

Association between white matter lesions and Parkinson’s disease: an impact on Postural/Gait difficulty phenotype and cognitive performance

ABSTRACT Background White matter hyperintensities (WMHs) may be observed on Magnetic Resonance Imaging (MRI) in patients with Parkinson disease with or without vascular risk factors. Whether WMHs may influence motor and non-motor aspects of Parkinson disease is a subject of debate. The aim of this study is to evaluate the impact of WMH severity on various aspects of Parkinson disease in combination to the estimation of the impact of cerebrovascular risk factors. Materials and Methods We included a cohort of patients with Parkinson’s disease who underwent MRI examination. The Fazekas visual rating scale was used to assess the severity and location of WMHs, and patient clinical characteristics were correlated with MRI data. Results All vascular risk factors were associated with higher Fazekas score in both periventricular and deep white matter. Periventricular white matter hyperintensities (PWMHs) and deep white matter hyperintensities (DWMHs) were associated with lower scores in the ACE-R cognitive assessment scale (p < 0.001). Furthermore, PWMHs and DWMHs severity was associated with higher UPDRS motor score (p < 0.001), while the Postural Instability Gait Difficulty (PIGD) phenotype was correlated with higher burden of WMHs. Conclusions Comorbid WMHs may contribute to multi-dimension dysfunction in patients with Parkinson disease and consequently the management of vascular risk factors may be crucial to maintain motor and non-motor functions in PD.

The Characteristics of White Matter Hyperintensities in Patients With Migraine.

BackgroundThe presence of white matter hyperintensities (WMHs) in migraine is well-documented, but the location of WMH in patients with migraine is insufficiently researched. This study assessed WMH in patients with migraine using a modified version of the Scheltens visual rating scale, a semiquantitative scale for categorizing WMH in periventricular, lobar, basal ganglia, and infratentorial regions.MethodsIn total, 263 patients with migraine (31 men and232 women) enrolled in the American Registry for Migraine Research (ARMR) from Mayo Clinic Arizona and who had clinical brain magnetic resonance imaging (MRI) were included in this study. Those with imaging evidence for gross anatomical abnormalities other than WMHs were excluded. A board-certified neuroradiologist identified WMHs on axial T2 and fluid-attenuated inversion recovery (FLAIR) sequences. WMHs were characterized via manual inspection and categorized according to the scale's criteria.ResultsResults showed that 95 patients (36.1%, mean age: 41.8 years) had no WMHs on axial T2 and FLAIR imaging and 168 patients (63.9%, mean age: 51.4 year) had WMHs. Of those with WMHs, 94.1% (n = 158) had lobar hyperintensities (frontal: 148/158, 93.7%; parietal: 57/158, 36.1%; temporal: 35/158, 22.1%; and occipital: 9/158, 5.7%), 13/168, 7.7% had basal ganglia WMHs, 49/168, 29.1% had periventricular WMHs, and 17/168, 10.1% had infratentorial WMHs. In addition, 101/168 patients (60.1%) had bilateral WMHs and 67/168 (39.9%) had unilateral WMHs (34 right hemisphere/33 left hemisphere).DiscussionAmong ARMR participants who were enrolled by Mayo Clinic Arizona and who had clinical brain MRIs, nearly two-thirds had WMHs. The WMHs were the most common in the frontal lobes. Describing the features of WMHs in those with migraine, and comparing them with WMHs attributable to other etiologies, might be useful for developing classifiers that differentiate between migraine-specific WMH and other causes of WMH.

Prevalence and Location of White Matter Hyperintensities in Traumatic Brain Injury and Relationship to Outcome (S15.005)

Prevalence and Location of White Matter Hyperintensities in Traumatic Brain Injury and Relationship to Outcome (S15.005)

Frontal White Matter Hyperintensities Effect on Default Mode Network Connectivity in Acute Mild Traumatic Brain Injury.

The functional connectivity of the brain depends not only on the structural integrity of the cortex but also on the white matter pathways between cortical areas. White matter hyperintensities (WMH), caused by chronic hypoperfusion in the white matter, play a role in the outcome of traumatic brain injury (TBI) and other neurodegenerative disorders. Herein, we investigate how the location and volume of WMH affect the default-mode network (DMN) connectivity in acute mild TBI (mTBI) patients. Forty-six patients with acute mTBI and 46 matched healthy controls were enrolled in the study. All participants underwent T2-weighted fluid-attenuated inversion recovery magnetic resonance imaging (MRI), resting-state functional MRI (fMRI),and neuropsychological assessments. The volume and location of WMH were recorded. The relationships between the WMH volume and clinical assessments were evaluated using Spearman’s correlation. Patients with higher frontal lobe WMH volume had more severe post-concussion symptoms and poorer information processing speed. Moreover, these patients had significantly lower functional connectivity in the right middle temporal gyrus, left middle frontal gyrus, right superior frontal gyrus, and left anterior cingulate cortex, compared with patients with low frontal lobe WMH volume. Compared to the controls, the patients with high frontal WMH volume exhibited significantly lower functional connectivity in the right inferior temporal gyrus, left anterior cingulate cortex, and right superior frontal gyrus. These findings suggest that frontal lobe WMH volume may modulate the functional connectivity within the DMN. Therefore, the WMH volume in specific regions of the brain, particularly the frontal and parietal lobes, may accelerate the process of aging and cognitive impairment may be a useful biomarker for the diagnosis and prognosis of acute mTBI.

Comparison of domain adaptation techniques for white matter hyperintensity segmentation in brain MR images.

Robust automated segmentation of white matter hyperintensities (WMHs) in different datasets (domains) is highly challenging due to differences in acquisition (scanner, sequence), population (WMH amount and location) and limited availability of manual segmentations to train supervised algorithms. In this work we explore various domain adaptation techniques such as transfer learning and domain adversarial learning methods, including domain adversarial neural networks and domain unlearning, to improve the generalisability of our recently proposed triplanar ensemble network, which is our baseline model. We used datasets with variations in intensity profile, lesion characteristics and acquired using different scanners. For the source domain, we considered a dataset consisting of data acquired from 3 different scanners, while the target domain consisted of 2 datasets. We evaluated the domain adaptation techniques on the target domain datasets, and additionally evaluated the performance on the source domain test dataset for the adversarial techniques. For transfer learning, we also studied various training options such as minimal number of unfrozen layers and subjects required for fine-tuning in the target domain. On comparing the performance of different techniques on the target dataset, domain adversarial training of neural network gave the best performance, making the technique promising for robust WMH segmentation.

White matter hyperintensities segmentation using an ensemble of neural networks.

White matter hyperintensities (WMHs) represent the most common neuroimaging marker of cerebral small vessel disease (CSVD). The volume and location of WMHs are important clinical measures. We present a pipeline using deep fully convolutional network and ensemble models, combining U‐Net, SE‐Net, and multi‐scale features, to automatically segment WMHs and estimate their volumes and locations. We evaluated our method in two datasets: a clinical routine dataset comprising 60 patients (selected from Chinese National Stroke Registry, CNSR) and a research dataset composed of 60 patients (selected from MICCAI WMH Challenge, MWC). The performance of our pipeline was compared with four freely available methods: LGA, LPA, UBO detector, and U‐Net, in terms of a variety of metrics. Additionally, to access the model generalization ability, another research dataset comprising 40 patients (from Older Australian Twins Study and Sydney Memory and Aging Study, OSM), was selected and tested. The pipeline achieved the best performance in both research dataset and the clinical routine dataset with DSC being significantly higher than other methods (p < .001), reaching .833 and .783, respectively. The results of model generalization ability showed that the model trained on the research dataset (DSC = 0.736) performed higher than that trained on the clinical dataset (DSC = 0.622). Our method outperformed widely used pipelines in WMHs segmentation. This system could generate both image and text outputs for whole brain, lobar and anatomical automatic labeling WMHs. Additionally, software and models of our method are made publicly available at https://www.nitrc.org/projects/what_v1.

The influence of white matter hyperintensity on cognitive impairment in Parkinson's disease.

The aim of this meta‐analysis was to review systematically and to identify the relationship between the severity and location of white matter hyperintensities (WMHs) and the degree of cognitive decline in patients with Parkinson’s disease (PD). We searched the PubMed, EMBASE, Web of Science, Ovid, and Cochrane Library databases for clinical trials of the severity and location of WMHs on the degree of cognitive impairment in PD through October 2020. We conducted the survey to compare the association of WMH burden in patients with PD with mild cognitive impairment (PD‐MCI) versus those with normal cognition (PD‐NC) and in patients with PD with dementia (PDD) versus those with PD without dementia (PD‐ND). Nine studies with PD‐MCI versus PD‐NC and 10 studies with PDD versus PD‐ND comparisons were included. The WMH burden in PD‐MCI patients was significantly different compared to that in PD‐NC patients (standard mean difference, SMD = 0.39, 95% CI: 0.12 to 0.66, p = 0.005), while there was no correlation shown in the age‐matched subgroup of the comparison. In addition, PDD patients had a significantly higher burden of WMHs (SMD = 0.8, 95% CI: 0.44 to 1.71, p < 0.0001), especially deep white matter hyperintensities (SMD = 0.54, 95% CI: 0.36 to 0.73, p < 0.00001) and periventricular hyperintensities (SMD = 0.70, 95% CI: 0.36 to 1.04, p < 0.0001), than PD‐NC patients, regardless of the adjustment of age. WMHs might be imaging markers for cognitive impairment in PDD but not in PD‐MCI, regardless of age, vascular risk factors, or race. Further prospective studies are needed to validate the conclusions.

Cerebral White Matter Hyperintensities in T2 Weighted Magnetic Resonance Images of Elderly Patients- Correlation with their Mental Status

Background: White matter hyperintensities (WMH), focal and/or diffuse areas of hyperintense signals on T2 weighted magnetic resonance imaging (MRI), are the most common incidental finding in elderly patients. However, their clinical significance is usually overlooked. We aimed to find out the correlation between the degree of cerebral WMH in MRI with the mental status of elderly patients, assessed by Mini-Mental Status Examination (MMSE) score.&#x0D; Methods: This cross-sectional study was conducted for two years on eighty eligible elderly patients (&gt; 60 years) referred to the Department of Radiology and Imaging for MRI of the brain. Demographic variables like age and sex, MMSE score, and MRI variables like location and number of WMHs were studied. The Pearson’s correlation coefficient was used to calculate the correlation between the extent of periventricular WMHs and MMSE score.&#x0D; Results: A significant negative correlation (r = -0.78; p &lt; 0.001) was found between decreased MMSE and the extent of periventricular WMH. A significant negative correlation was also found when periventricular hyperintensities were evaluated individually for frontal caps (r = -0.68; p &lt; 0.0001), band opacities (r = -0.55; p&lt;0.0001) and occipital cap (r = -0.59; p &lt; 0.0001). However, subcortical WMH was not significantly corelated with MMSE score (r = +0.018, p = 0.0897).&#x0D; Conclusion: A significant negative correlation exists between the extent of periventricular WMH seen at brain MRI with cognitive decline in elderly subjects. However, no such correlation exists between subcortical WMH and mental status.

Frontal White Matter Hyperintensities and Executive Functioning Performance in Older Adults.

Frontal lobe structures decline faster than most other brain regions in older adults. Age-related change in the frontal lobe is associated with poorer executive function (e.g., working memory, switching/set-shifting, and inhibitory control). The effects and presence of frontal lobe white matter hyperintensities (WMH) on executive function in normal aging is relatively unknown. The current study assessed relationships between region-specific frontal WMH load and cognitive performance in healthy older adults using three executive function tasks from the NIH Toolbox (NIHTB) Cognition Battery. A cohort of 279 healthy older adults ages 65–88 completed NIHTB and 3T T1-weighted and FLAIR MRI. Lesion Segmentation Toolbox quantified WMH volume and generated lesion probability maps. Individual lesion maps were registered to the Desikan-Killiany atlas in FreeSurfer 6.0 to define regions of interest (ROI). Independent linear regressions assessed relationships between executive function performance and region-specific WMH in frontal lobe ROIs. All models included age, sex, education, estimated total intracranial volume, multi-site scanner differences, and cardiovascular disease risk using Framingham criteria as covariates. Poorer set-shifting performance was associated with greater WMH load in three frontal ROIs including bilateral superior frontal (left β = −0.18, FDR-p = 0.02; right β = −0.20, FDR-p = 0.01) and right medial orbitofrontal (β = −0.17, FDR-p = 0.02). Poorer inhibitory performance associated with higher WMH load in one frontal ROI, the right superior frontal (right β = −0.21, FDR-p = 0.01). There were no significant associations between working memory and WMH in frontal ROIs. Our study demonstrates that location and pattern of frontal WMH may be important to assess when examining age-related differences in cognitive functions involving switching/set-shifting and inhibition. On the other hand, working memory performance was not related to presence of frontal WMH in this sample. These data suggest that WMH may contribute selectively to age-related declines in executive function. Findings emerged beyond predictors known to be associated with WMH presence, including age and cardiovascular disease risk. The spread of WMH within the frontal lobes may play a key role in the neuropsychological profile of cognitive aging. Further research should explore whether early intervention on modifiable vascular factors or cognitive interventions targeted for executive abilities may help mitigate the effect of frontal WMH on executive function.

Post-stroke Cognition at 1 and 3 Years Is Influenced by the Location of White Matter Hyperintensities in Patients With Lacunar Stroke.

Lacunar strokes are a common type of ischemic stroke. They are known to have long-term cognitive deficits, but the influencing factors are still largely unknown. We investigated if the location of the index lacunar stroke or regional WMH and their change at 1 year could predict the cognitive performance at 1 and 3 years post-stroke in lacunar stroke patients. We used lacunar lesion location and WMH-segmented data from 118 patients, mean age 64.9 who had a brain MRI scan soon after presenting with symptoms, of which 88 had a repeated scan 12 months later. Premorbid intelligence (National Adult Reading Test) and current intelligence [Addenbrooke's Cognitive Exam-Revised (ACE-R)] were measured at 1, 12, and 36 months after the stroke. ANCOVA analyses adjusting for baseline cognition/premorbid intelligence, vascular risk factors, age, sex and total baseline WMH volume found that the recent small subcortical infarcts (RSSI) in the internal/external capsule/lentiform nucleus and centrum semiovale did not predict cognitive scores at 12 and 36 months. However, RSSI location moderated voxel-based associations of WMH change from baseline to 1 year with cognitive scores at 1 and 3 years. WMH increase in the external capsule, intersection between the anterior limb of the internal and external capsules, and optical radiation, was associated with worsening of ACE-R scores 1 and 3 years post-stroke after accounting for the location of the index infarct, age and baseline cognition.

White matter hyperintensities: a marker for apathy in Parkinson's disease without dementia?

ObjectiveThe objective of this study was to assess the relationship between white matter hyperintensities (WMH) and the occurrence and progression of apathy in Parkinson’s disease (PD).MethodsWe recruited patients with PD who underwent baseline evaluation, which included apathy assessment and magnetic resonance imaging (MRI) head scans. After 2.5 years of follow‐up, we re‐evaluated patient apathy symptoms. The severity and location of WMH were assessed with fluid‐attenuated inversion recovery (FLAIR) sequences using the Fazekas visual rating scale. Logistic regression and linear regression analyses of baseline WMH characteristics were conducted to explore the potential association between apathy and WMH.ResultsA total of 141 PD patients were recruited. The apathy group had a higher proportion of male patients, advanced disease, and depression, which was coupled with a lower quality of life. Morever, higher WMH severity was significantly associated with apathy. Logistic regression analyses demonstrated that WMH severity was a risk factor for apathy. In addition, linear regression analysis also suggests that apathy severity is positively correlated with baseline WMH Fazekas scales (ϐ = 0.959, P < 0.001). Baseline WMH severity was also a risk factor for apathy progression.InterpretationWMH is associated with apathy and could be a promising marker to predict apathy progression in PD.

The Impact of Strategic White Matter Hyperintensity Lesion Location on Language

The impact of white matter hyperintensities (WMH) on language possibly depends on lesion location through disturbance of strategic white matter tracts. We examined the impact of WMH location on language in elderly Asians. Cross-sectional. Population-based. Eight-hundred nineteen residents of Singapore, ages (≥65 years). Clinical, cognitive and 3T magnetic resonance imaging assessments were performed on all participants. Language was assessed using the Modified Boston Naming Test (MBNT) and Verbal Fluency (VF). Hypothesis-free region-of-interest-based (ROI) analyses based on major white matter tracts were used to determine the association between WMH location and language. Conditional dependencies between the regional WMH volumes and language were examined using Bayesian-network analysis. ROI-based analyses showed that WMH located within the anterior thalamic radiation (mean difference: -0.12, 95% confidence interval [CI]: -0.22; -0.02, p = 0.019) and uncinate fasciculus (mean difference: -0.09, 95% CI: -0.18; -0.01, p = 0.022) in the left hemisphere were significantly associated with worse VF but did not survive multiple testing. Conversely, WMH volume in the left cingulum of cingulate gyrus was significantly associated with MBNT performance (mean difference: -0.09, 95% CI: -0.17; -0.02, p = 0.016). Bayesian-network analyses confirmed the left cingulum of cingulate gyrus as a direct determinant of MBNT performance. Our findings identify the left cingulum of cingulate gyrus as a strategic white matter tract for MBNT, suggesting that language - is sensitive to subcortical ischemic damage. Future studies on the role of sporadic ischemic lesions and vascular cognitive impairment should not only focus on total WMH volume but should also take WMH lesion location into account when addressing language.

Spatial distribution and cognitive impact of cerebrovascular risk-related white matter hyperintensities

White matter hyperintensities (WMHs) are considered macroscale markers of cerebrovascular burden and are associated with increased risk of vascular cognitive impairment and dementia. However, the spatial location of WMHs has typically been considered in broad categories of periventricular versus deep white matter. The spatial distribution of WHMs associated with individual cerebrovascular risk factors (CVR), controlling for frequently comorbid risk factors, has not been systematically investigated at the population level in a healthy ageing cohort. Furthermore, there is an inconsistent relationship between total white matter hyperintensity load and cognition, which may be due to the confounding of several simultaneous risk factors in models based on smaller cohorts. We examined trends in individual CVR factors on total WMH burden in 13,680 individuals (aged 45-80) using data from the UK Biobank. We estimated the spatial distribution of white matter hyperintensities associated with each risk factor and their contribution to explaining total WMH load using voxel-wise probit regression and univariate linear regression. Finally, we explored the impact of CVR-related WMHs on speed of processing using regression and mediation analysis. Contrary to the assumed dominance of hypertension as the biggest predictor of WMH burden, we show associations with a number of risk factors including diabetes, heavy smoking, APOE ε4/ε4 status and high waist-to-hip ratio of similar, or greater magnitude to hypertension. The spatial distribution of WMHs varied considerably with individual cerebrovascular risk factors. There were independent effects of visceral adiposity, as measured by waist-to-hip ratio, and carriage of the APOE ε4 allele in terms of the unique spatial distribution of CVR-related WMHs. Importantly, the relationship between total WMH load and speed of processing was mediated by waist-to-hip ratio suggesting cognitive consequences to WMHs associated with excessive visceral fat deposition. Waist-to-hip ratio, diabetes, heavy smoking, hypercholesterolemia and homozygous APOE ε4 status are important risk factors, beyond hypertension, associated with WMH total burden and warrant careful control across ageing. The spatial distribution associated with different risk factors may provide important clues as to the pathogenesis and cognitive consequences of WMHs. High waist-to-hip ratio is a key risk factor associated with slowing in speed of processing. With global obesity levels rising, focused management of visceral adiposity may present a useful strategy for the mitigation of cognitive decline in ageing.

White Matter Hyperintensities Relate to Basal Ganglia Functional Connectivity and Memory Performance in aMCI and SVMCI.

Cerebral small vessel diseases play a crucial role in both vascular and non-vascular dementias. The location of white matter hyperintensities (WMHs), a neuroimaging marker of cerebral small vessel disease, has been found to vary between different types of dementias, and those in the basal ganglia (BG) have been particularly associated with vascular cognitive impairment (VCI). However, anatomical variation of WMHs across BG nuclei and its effect on brain network dysconnectivity has not been clearly elucidated. The study sample consisted of 40 patients with amnestic mild cognitive impairment (aMCI), 40 with subcortical vascular MCI (SVMCI), and 40 healthy control subjects. We examined the volume of WMH using T2-weighted magnetic resonance imaging. We also assessed the disturbances in BG-cortical communication by measuring resting-state functional connectivity (rsFC) from the functional magnetic resonance imaging signal. WMHs were more pronounced in the SVMCI group particularly in the caudate regions. In SVMCI patients, while higher WMHs in the dorsal caudate correlated with weaker FC with executive control regions and worse immediate recall performance, WMHs in the ventral caudate were associated with weaker FC with anterior default mode regions and worse delayed recall performance. In contrast, in aMCI patients, BG WMHs were not correlated with their changes in functional connectivity changes, which showed weaker connectivity with almost all BG structures, rather than restricting to specific BG subdivisions as observed in the SVMCI group. Our findings demonstrate that heterogeneously distributed BG WMHs are associated with changes in functional network interactions and verbal episodic memory performance only in SVMCI patients, which establishes a link between cerebrovascular-related structural abnormality, functional integrity of BG circuits, and episodic memory impairments in SVMCI, and may reflect a differential role of the cerebrovascular pathology in disrupting network-level communications and cognition between Alzheimer’s and subcortical vascular dementia.