Relationship between white matter hyperintensities and chronic kidney disease in patients with acute lacunar stroke.

BACKGROUND AND PURPOSE: Previous studies have revealed a relationship between chronic kidney disease (CKD) and white matter hyperintensities (WMH). However, studies on the WMH and CKD in acute stroke patients are rare, and the conclusion is consistent. Our study aimed to investigate the relationship between the severity of WMH and CKD in acute lacunar infarction patients. METHODS: Consecutive acute lacunar infarction patients were recruited in this cross-sectional study. All patients were divided into two groups according to the severity of periventricular WMH (PVWMH) and deep WMH (DWMH). We dichotomized the severity of WMH (PVWMH and DWMH, separately) into mild group (Fazekas scores 0-1) and moderate-severe group (Fazekas scores 2-3). Estimated glomerular filtration rate (eGFR), proteinuria, vascular risk factors, and clinical features were compared between these two groups. Multivariable logistic regression analysis was used to investigate the association between the severity of WMH and risk factors. RESULTS: A total of 993 acute lacunar infarction patients aged 25-95 years were enrolled. The proportions of participants presenting moderate-severe group PVWMH and DWMH were 46.6% and 38.6%, respectively. Patients with moderate-severe PVWMH had higher age (P < 0.001) and higher incidence of stroke history (P < 0.001) than those in mild group. The level of serum creatinine and the presence of CKD were significantly higher while the eGFR was significantly lower in patients with moderate-severe PVWMH than those with mild PVWMH. Patients with moderate-severe DWMH (n = 383) also had higher age (P < 0.001) and often had a history of stroke (P < 0.001). But the association between the severity of DWMH and eGFR was not found. Multivariable logistic regression analyses showed stage 2 CKD and stage 3 CKD were independently associated with moderate-severe PVWMH, but not DWMH. CONCLUSIONS: Our study demonstrates that CKD was independently associated with moderate-severe PVWMH in patients with acute lacunar infarction, but not DWMH. PVWMH and DWMH may have distinct pathophysiology.

Hyperhomocysteinemia can predict the severity of white matter hyperintensities in elderly lacunar infarction patients.

Background and Purpose: Hyperhomocysteinemia (Hhcy) is a risk factor for stroke. Several studies have demonstrated that Hhcy was more closely linked to small vessel occlusive disease and white matter hyperintensities (WMH) in general and elderly population. Studies on WMH and homocysteine in elderly subjects are rare, and the results were inconsistent. Our study aimed to investigate the relationship between the serum homocysteine (HCY) and the severity of WMH in elderly lacunar stroke patients.Methods: Consecutive elderly (≥60 years old) lacunar infarction patients were recruited in this cross-sectional study. All patients were divided into two groups according to periventricular WMH (PVWMH) and deep WMH (DWMH) Fazekas scores. Patients with a Fazekas score (PVWMH or DWMH) of 0, 1, 2 were in mild-moderate group and 3 were in severe group. Vascular risk factors and clinical features were compared between these two groups. Multiple logistic regression analysis was used to determine the relationship between severity of WMH and vascular risk factors.Results: A total of 587 participants aged 60-95 years were enrolled. Patients with severe PVWMH (n = 178) had higher age (p = 0.030) and higher incidence of stroke history (p<0.001) than those in mild-moderate group. The level of serum HCY was significantly higher in patients with severe PVWMH (p ＝ 0.002). Patients with severe DWMH (n = 142) had higher age (p<0.001) and often had a history of stroke (p<0.001). The level of HCY was higher in patients with severe degree of DWMH, but had no significance (p ＝ 0.153). Multivariable logistic regression analyses showed Hhcy were independently associated with severe PVWMH after adjusted for age and vascular risk factors (p ＝ 0.014).Conclusions: Hhcy was independently associated with severe PVWMH of elderly lacunar stroke patients, but not DWMH.

Prevalence of carotid artery stenosis and intra-cranial lesions in patients with aortic arch aneurysm and its association with intraoperative regional cerebral oxygen saturation and postoperative neurological outcomes.

Background: Although aortic aneurysm is associated with vascular aging and atherosclerosis, carotid and intracranial vascular disease prevalence in patients with aortic arch aneurysm remains unclear. Similarly, the effect of carotid and intracranial lesions on postoperative outcomes is unknown. This study aimed to investigate the prevalence of carotid artery stenosis and intracranial lesions in patients with aortic arch aneurysm and its association with intraoperative regional cerebral oxygen saturation (rScO2) and postoperative neurological outcomes, including delirium and cerebral infarction. Methods: This retrospective observational study included 133 patients with true aortic arch aneurysm who underwent preoperative magnetic resonance imaging (MRI). We evaluated the prevalence of carotid and intracranial arterial lesions. Symptomatic cerebral infarction and delirium, defined by the confusion assessment method for the intensive care unit, were evaluated for their association with preoperative cerebrovascular lesions. Additionally, changes in regional saturation of the cerebral tissue at different surgical phases were evaluated for patients with and without cerebrovascular lesions. Results: Fifteen (11.3%) patients experienced symptomatic cerebral infarction, and 64 (48.1%) had postoperative delirium. Preoperative MRI showed old infarction, microbleeds, significant carotid artery stenosis, and intracranial lesions in 21.1%, 14.3%, 10.5%, and 7.5% of the patients, respectively. White matter hyperintensities with Fazekas scale 2 were observed in 40.6% of the patients, while Fazekas scale 3 were observed in 18.8% of the patients. Preoperative MRI findings and postoperative neurological outcomes were not significantly different. Seventy-six patients underwent rScO2 monitoring intraoperatively. Changes in rScO2 in patients with and without carotid/cerebrovascular lesions were not significantly different. However, rScO2 was significantly lower in patients who developed cerebral infarction. Conclusions: Significant carotid artery stenosis and intracranial lesions were observed in 10.5% and 7.5% of the patients, respectively. Although preoperative MRI findings and changes in rScO2 or postoperative outcomes showed no significant association, patients with postoperative cerebral infarction showed significantly lower rScO2 intraoperatively.

Pathways linking pulse pressure to dementia in adults with Down syndrome.

Individuals with Down syndrome (DS) are less likely to have hypertension than neurotypical adults. However, whether blood pressure measures are associated with brain health and clinical outcomes in this population has not been studied in detail. Here, we assessed whether pulse pressure is associated with markers of cerebrovascular disease, entorhinal cortical atrophy, and diagnosis of dementia in adults with DS. Participants with DS from the Biomarkers of Alzheimer's Disease in Adults with Down Syndrome study (ADDS; n=195, age=50.6±7.2 years, 44% women, 18% diagnosed with dementia) were included. Higher pulse pressure was associated with greater global, parietal, and occipital WMH volume. Pulse pressure was not related to enlarged PVS, microbleeds, infarcts, entorhinal cortical thickness, or dementia diagnosis. However, in a serial mediation model, we found that pulse pressure was indirectly related to dementia diagnosis through parieto-occipital WMH and, subsequently through entorhinal cortical thickness. Higher pulse pressure may be a risk factor for dementia in people with DS by promoting cerebrovascular disease, which in turn affects neurodegeneration. Pulse pressure is an important determinant of brain health and clinical outcomes in individuals with Down syndrome despite the low likelihood of frank hypertension.

Associations between sleep-related symptoms, obesity, cardiometabolic conditions, brain structural alterations and cognition in the UK biobank.

OBJECTIVES: Sleep disturbances are increasingly recognized as adversely affecting brain health in aging. Our aim was to investigate interrelations between subjective sleep-related symptoms, obesity, cardiometabolic disorders, brain structure and cognitive decline in a population-based aging sample. METHODS: Data were extracted from the UK Biobank for anthropometric and demographic information, self-reported sleep behaviours, cardiometabolic measures, structural brain magnetic resonance imaging and cognitive test scores. "Sleep-related symptoms" (SRS) were measured using four questionnaire items: loud snoring, daytime sleepiness, likelihood to nap and difficulty getting up in the morning. Associations were tested using a structural equation model (SEM), adjusted for confounders. Further, multiple regression analysis was used to test for direct relationships between SRS and specific cognitive domains. RESULTS: Among 36,468 participants with an average age of 63.6 (SD 7.5) years and 46.7% male, we found that SRS were associated with obesity and several pre-existing cardiometabolic disturbances. In turn, cardiometabolic disorders were associated with increased white matter hyperintensities and cortical thinning, which were related to cognitive dysfunction. SRS were also directly related to several structural brain changes and to cognitive dysfunction. Regression analyses showed that SRS were directly associated with slower reaction times, and lower scores in fluid intelligence, working memory and executive function. CONCLUSIONS: Self-reported sleep-related symptoms were associated with cognitive dysfunction directly and through pre-existing cardiometabolic disorders and brain structural alterations. These findings provide evidence that symptoms of sleep disturbances, here defined primarily by hypersomnolence and snoring, are important risk factors or markers for cognitive dysfunction in an aging population.

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

Objective: Exosomal 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). Methods: We 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. Results: In 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. Conclusion: Plasma 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.

Relationship between chronic kidney disease and cerebral white matter hyperintensities: a systematic review.

Background: This systematic review summarizes available evidence on the relationship between white matter hyperintensities (WMH) volumetric quantification on brain MRI scans and chronic kidney disease (CKD). Methods: The literature search was performed in March 2022 using MEDLINE PubMed Central, Scopus and Web of Science - Publons as search engines. Relevant articles investigating, with a quantitative volumetric approach, the link between WMH and CKD patients were selected. Results: The database search strategy found 987 articles, after excluding duplicates, the titles and abstracts of the remaining 320 articles were examined. Subsequently 276 articles were excluded as they were not relevant to the topic. Of the 44 articles evaluated for eligibility, 36 were excluded because the quantitative analysis of WMH was not volumetric. Finally, 8 articles were included in this systematic review. Conclusions: Literature on this topic is extremely heterogeneous in terms of methodology and samples. However, evidence shows that there is a relationship between CKD and WMH volume of the brain. We recommend that quantifiable biomarkers such as estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (UACR) should be included in studies dealing with cerebrovascular disease. The biological and molecular mechanisms underlying cerebrovascular damage in patients with chronic renal failure deserve to be further explored.

Amyloid-PET and White Matter Hyperintensities Have Independent Effects on Baseline Cognitive Function and Synergistic Effects on Longitudinal Executive Function.

Co-occurrence of beta amyloid (Aß) and white matter hyperintensities (WMHs) increase the risk of dementia and both are considered biomarkers of preclinical dementia. Moderation and mediation modeling were used to define the interplay between global and regional Aß and WMHs measures in relation to executive function (EF) and memory composite scores outcomes at baseline and after approximately 2 years across a sample of 714 clinically normal participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI 2). The moderation regression analysis showed additive effects of Aß and WMHs over baseline memory and EF scores (p = 0.401 and 0.061, respectively) and synergistic effects over follow-up EF (p < 0.05). Through mediation analysis, the data presented demonstrate that WMHs effects, mediated by global and regional amyloid burden, are responsible for baseline cognitive performance deficits in memory and EF. These findings suggest that Aß and WMHs contribute to baseline cognition independently while WMHs volumes exert effects on baseline cognitive performance directly and through influences on Aß accumulation.

Sex-Specific Causes and Consequences of White Matter Damage in a Middle-Aged Cohort.

Objective: To evaluate potential sex-specific effects of multiple cardiovascular risk factors on white matter pathology in normal aging men and women, as well as potential sex-differences in the association of white matter pathology and cognitive functions. Methods: We analyzed cross-sectional data of 581 participants (median age: 53 years, 54% women) of the population-based cohort of the BiDirect Study who completed clinical examinations, five neuropsychological tests, and an 3T MRI examination. White matter pathology was determined by the extent of white matter hyperintensities (WMH) on FLAIR images as well as the magnitude of global fractional anisotropy (FA) based on diffusion tensor imaging. Main effects, interaction as well as sex-stratified generalized linear regression models were used to evaluate the moderating effect of sex on the association of hypertension, diabetes mellitus, smoking, and obesity with WMH and FA, respectively. Associations of imaging markers with cognitive test results were determined with linear regression models. Results: Hypertension showed stronger associations with more extensive WMH and less FA in women compared to men. Current smoking was associated with more severe WMH in women only. Adjusted for age and education, WMH were not significantly associated with cognitive tests, but higher FA was associated with better performance in motor function in both sexes and with executive functions in men, even after adjustment for cardiovascular risk factors. Conclusion: We observed a stronger association of hypertension and smoking with white matter damage in women, suggesting a higher susceptibility for vascular pathology in women. However, there was no association of WMH with cognition, and FA was associated with executive function tests only in men, suggesting a higher cognitive reserve in women.

Differential effects of white matter hyperintensities and regional amyloid deposition on regional cortical thickness.

White matter hyperintensities (WMH) and ß-amyloid (Aß) accumulation have both been linked to neurodegeneration in Alzheimer's disease (AD). However, the independent effects of global WMH and regional Aß on the corresponding regional cortical thickness have not been investigated. Here, we evaluated 280 cognitively normal (CN), 450 mild cognitive impairment (MCI), and 63 individuals with AD dementia separately. In CN individuals, only WMH was associated with lower cortical thickness in fronto-temporal regions, independent of regional Aß deposition in the corresponding cortical regions. In MCI individuals, the spatial pattern of independent WMH associations was predominantly in temporal and cingulate regions, while independent regional Aß associations were now evident in temporal regions. No regional interactions were found. In non-demented individuals and MCI individuals alone, we found that global WMH, composite regional Aß burden and cortical thickness in AD-associated regions all independently predicted progression to AD dementia. Our findings suggest that the independent effects of global WMH and regional Aß on regional cortical thickness are spatially different, converging in temporal regions in MCI individuals.

Accelerated vascular aging: Ethnic differences in basilar artery length and diameter, and its association with cardiovascular risk factors and cerebral small vessel disease.

Background and aims: Risk of stroke and dementia is markedly higher in people of South Asian and African Caribbean descent than white Europeans in the UK. This is unexplained by cardiovascular risk factors (CVRF). We hypothesized this might indicate accelerated early vascular aging (EVA) and that EVA might account for stronger associations between cerebral large artery characteristics and markers of small vessel disease. Methods: 360 participants in a tri-ethnic population-based study (120 per ethnic group) underwent cerebral and vertebral MRI. Length and median diameter of the basilar artery (BA) were derived from Time of Flight images, while white matter hyperintensities (WMH) volumes were obtained from T1 and FLAIR images. Associations between BA characteristics and CVRF were assessed using multivariable linear regression. Partial correlation coefficients between WMH load and BA characteristics were calculated after adjustment for CVRF and other potential confounders. Results: BA diameter was strongly associated with age in South Asians (+11.3 µm/year 95% CI = [3.05; 19.62]; p = 0.008), with unconvincing relationships in African Caribbeans (3.4 µm/year [-5.26, 12.12]; p = 0.436) or Europeans (2.6 µm/year [-5.75, 10.87]; p = 0.543). BA length was associated with age in South Asians (+0.34 mm/year [0.02; 0.65]; p = 0.037) and African Caribbeans (+0.39 mm/year [0.12; 0.65]; p = 0.005) but not Europeans (+0.08 mm/year [-0.26; 0.41]; p = 0.653). BA diameter (rho = 0.210; p = 0.022) and length (rho = 0.261; p = 0.004) were associated with frontal WMH load in South Asians (persisting after multivariable adjustment for CVRF). Conclusions: Compared with Europeans, the basilar artery undergoes more accelerated EVA in South Asians and in African Caribbeans, albeit to a lesser extent. Such EVA may contribute to the higher burden of CSVD observed in South Asians and excess risk of stroke, vascular cognitive impairment and dementia observed in these ethnic groups.

Advances in the Role of Endothelial Cells in Cerebral Small Vessel Disease.

Cerebral small vessel disease (CSVD) poses a serious socio-economic burden due to its high prevalence and severe impact on the quality of life of elderly patients. Pathological changes in CSVD mainly influence small cerebral arteries, microarteries, capillaries, and small veins, which are usually caused by multiple vascular risk factors. CSVD is often identified on brain magnetic resonance imaging (MRI) by recent small subcortical infarcts, white matter hyperintensities, lacune, cerebral microbleeds (CMBs), enlarged perivascular spaces (ePVSs), and brain atrophy. Endothelial cell (EC) dysfunction is earlier than clinical symptoms. Immune activation, inflammation, and oxidative stress may be potential mechanisms of EC injury. ECs of the blood-brain-barrier (BBB) are the most important part of the neurovascular unit (NVU) that ensures constant blood flow to the brain. Impaired cerebral vascular autoregulation and disrupted BBB cause cumulative brain damage. This review will focus on the role of EC injury in CSVD. Furthermore, several specific biomarkers will be discussed, which may be useful for us to assess the endothelial dysfunction and explore new therapeutic directions.

Enlarged Perivascular Spaces Are Negatively Associated With Montreal Cognitive Assessment Scores in Older Adults.

Emerging evidence suggests that enlarged perivascular spaces (ePVS) may be a clinically significant neuroimaging marker of global cognitive function related to cerebral small vessel disease (cSVD). We tested this possibility by assessing the relationship between ePVS and both a standardized measure of global cognitive function, the Montreal Cognitive Assessment (MoCA), and an established marker of cSVD, white matter hyperintensity volume (WMH) volume. One hundred and eleven community-dwelling older adults (56-86) underwent neuroimaging and MoCA testing. Quantification of region-specific ePVS burden was performed using a previously validated visual rating method and WMH volumes were computed using the standard ADNI pipeline. Separate linear regression models were run with ePVS as a predictor of MoCA scores and whole brain WMH volume. Results indicated a negative association between MoCA scores and both total ePVS counts (P ≤ 0.001) and centrum semiovale ePVS counts (P ≤ 0.001), after controlling for other relevant cSVD variables. Further, WMH volumes were positively associated with total ePVS (P = 0.010), basal ganglia ePVS (P ≤ 0.001), and centrum semiovale ePVS (P = 0.027). Our results suggest that ePVS burden, particularly in the centrum semiovale, may be a clinically significant neuroimaging marker of global cognitive dysfunction related to cSVD.

The potential role of leukoaraiosis in remodeling the brain network to buffer cognitive decline: a Leukoaraiosis And Disability study from Alzheimer's Disease Neuroimaging Initiative.

BACKGROUND: Leukoaraiosis (LA) is a phenomenon of the brain that is often observed in elderly people. However, little is known about the role of LA in cognitive impairment in neurodegeneration and disease. This cross-sectional, retrospective Leukoaraiosis And Disability (LADIS) study aimed to characterize the relationship between brain white matter connectivity properties with LA ratings in patients with Alzheimer's disease (AD) as compared with age-matched cognitively normal controls. METHODS: Patients with AD (n=76) and elderly individuals with normal cognitive (NC) function (n=82) were classified into 3 groups, LA1, LA2, and LA3, according to the rating of their white matter changes (WMCs). Diffusion tensor imaging (DTI) data were analyzed by quantifying and comparing the white matter connectivity properties and gray matter (GM) volume of brain regions of interest (ROIs). RESULTS: The rich-club network properties in the AD LA1 and LA2 groups showed significant patterns of disrupted peripheral regions and reduced connectivity compared to those in the NC LA1 and LA2 groups, respectively. However, the rich-club network properties in the AD LA3 group showed similar patterns of disrupted peripheral regions and reduced connectivity compared to those in the NC LA3 group, despite there being significant hippocampal and amygdala atrophic differences between AD patients and NC elders. Compared to the NC LA1 group, the characteristic path length of white matter fiber connectivity in the NC LA3 group was significantly increased, and the brain's global efficiency, clustering coefficient, and network connectivity strength were significantly reduced (P<0.05, respectively). However, no significant differences (P>0.05) were observed in characteristic path length, reduced global efficiency, or the clustering coefficient between the NC LA3 and AD LA1 groups, or between the NC LA3 and AD LA2 groups. CONCLUSIONS: Our findings offer some insights into a potential role of LA in cognitive impairment that may predict the development of disability in older adults. The occurrence of LA, an intermediate degenerative change, during neurodegeneration and disease may potentially lead to the remodeling of the brain network through brain plasticity. LA, therefore, representing a possible compensatory mechanism to buffer cognitive decline.

Changes Over Time of Diffusion MRI in the White Matter of Aging Brain, a Good Predictor of Verbal Recall.

Objective: Extensive research using water-diffusion MRI reported age-related modifications of cerebral White Matter (WM). Moreover, water-diffusion parameter modifications have been frequently associated with cognitive performances in the elderly sample, reinforcing the idea of aging inducing microstructural disconnection of the brain which in turn impacts cognition. However, only few studies really assessed over-time modifications of these parameters and their relationship with episodic memory outcome of elderly. Materials and Methods: One-hundred and thirty elderly subjects without dementia (74.1 ± 4.1 years; 47% female) were included in this study. Diffusion tensor imaging (DTI) was performed at two-time points (3.49 ± 0.68 years apart), allowing the assessment of changes in water-diffusion parameters over time using a specific longitudinal pipeline. White matter hyperintensity (WMH) burden and gray matter (GM) atrophy were also measured on FLAIR and T1-weighted sequences collected during these two MRI sessions. Free and cued verbal recall scores assessed at the last follow-up of the cohort were used as episodic memory outcome. Changes in water-diffusion parameters over time were included in serial linear regression models to predict retrieval or storage ability of elderly. Results: GM atrophy and an increase in mean diffusivity (MD) and WMH load between the two-time points were observed. The increase in MD was significantly correlated with WMH load and the different memory scores. In models accounting for the baseline cognitive score, GM atrophy, or WMH load, MD changes still significantly predict free verbal recall, and not total verbal recall, suggesting the specific association with the retrieval deficit in healthy aging. Conclusion: In elderly, microstructural WM changes are good predictors of lower free verbal recall performances. Moreover, this contribution is not only driven by WMH load increase. This last observation is in line with studies reporting early water-diffusion modification in WM tissue during aging, resulting lately in the appearance of WMH on conventional MRI.

The relation between APOE genotype and cerebral microbleeds in cognitively unimpaired middle- and old-aged individuals.

Positive associations between cerebral microbleeds (CMBs) and APOE-ε4 (apolipoprotein E) genotype have been reported in Alzheimer's disease, but show conflicting results. We investigated the effect of APOE genotype on CMBs in a cohort of cognitively unimpaired middle- and old-aged individuals enriched for APOE-ε4 genotype. Participants from ALFA (Alzheimer and Families) cohort were included and their magnetic resonance scans assessed (n = 564, 50% APOE-ε4 carriers). Quantitative magnetic resonance analyses included visual ratings, atrophy measures, and white matter hyperintensity (WMH) segmentations. The prevalence of CMBs was 17%, increased with age (p < 0.05), and followed an increasing trend paralleling APOE-ε4 dose. The number of CMBs was significantly higher in APOE-ε4 homozygotes compared to heterozygotes and non-carriers (p < 0.05). This association was driven by lobar CMBs (p < 0.05). CMBs co-localized with WMH (p < 0.05). No associations between CMBs and APOE-ε2, gray matter volumes, and cognitive performance were found. Our results suggest that cerebral vessels of APOE-ε4 homozygous are more fragile, especially in lobar locations. Co-occurrence of CMBs and WMH suggests that such changes localize in areas with increased vascular vulnerability.

Subclinical Cognitive and Neuropsychiatric Correlates and Hippocampal Volume Features of Brain White Matter Hyperintensity in Healthy People.

White matter hyperintensities (WMH) are associated with brain aging and behavioral symptoms as a possible consequence of disrupted white matter pathways. In this study, we investigated, in a cohort of asymptomatic subjects aged 50 to 80, the relationship between WMH, hippocampal atrophy, and subtle, preclinical cognitive and neuropsychiatric phenomenology. Thirty healthy subjects with WMH (WMH+) and thirty individuals without (WMH-) underwent comprehensive neuropsychological and neuropsychiatric evaluations and 3 Tesla Magnetic Resonance Imaging scan. The presence, degree of severity, and distribution of WMH were evaluated with a semi-automated algorithm. Volumetric analysis of hippocampal structure was performed through voxel-based morphometry. A multivariable logistic regression analysis indicated that phenomenology of subclinical apathy and anxiety was associated with the presence of WMH. ROI-based analyses showed a volume reduction in the right hippocampus of WMH+. In healthy individuals, WMH are associated with significant preclinical neuropsychiatric phenomenology, as well as hippocampal atrophy, which are considered as risk factors to develop cognitive impairment and dementia.

Limited One-time Sampling Irregularity Map (LOTS-IM) for Automatic Unsupervised Assessment of White Matter Hyperintensities and Multiple Sclerosis Lesions in Structural Brain Magnetic Resonance Images.

We present the application of limited one-time sampling irregularity map (LOTS-IM): a fully automatic unsupervised approach to extract brain tissue irregularities in magnetic resonance images (MRI), for quantitatively assessing white matter hyperintensities (WMH) of presumed vascular origin, and multiple sclerosis (MS) lesions and their progression. LOTS-IM generates an irregularity map (IM) that represents all voxels as irregularity values with respect to the ones considered "normal". Unlike probability values, IM represents both regular and irregular regions in the brain based on the original MRI's texture information. We evaluated and compared the use of IM for WMH and MS lesions segmentation on T2-FLAIR MRI with the state-of-the-art unsupervised lesions' segmentation method, Lesion Growth Algorithm from the public toolbox Lesion Segmentation Toolbox (LST-LGA), with several well established conventional supervised machine learning schemes and with state-of-the-art supervised deep learning methods for WMH segmentation. In our experiments, LOTS-IM outperformed unsupervised method LST-LGA on WMH segmentation, both in performance and processing speed, thanks to the limited one-time sampling scheme and its implementation on GPU. Our method also outperformed supervised conventional machine learning algorithms (i.e., support vector machine (SVM) and random forest (RF)) and deep learning algorithms (i.e., deep Boltzmann machine (DBM) and convolutional encoder network (CEN)), while yielding comparable results to the convolutional neural network schemes that rank top of the algorithms developed up to date for this purpose (i.e., UResNet and UNet). LOTS-IM also performed well on MS lesions segmentation, performing similar to LST-LGA. On the other hand, the high sensitivity of IM on depicting signal change deems suitable for assessing MS progression, although care must be taken with signal changes not reflective of a true pathology.

Automatic spatial estimation of white matter hyperintensities evolution in brain MRI using disease evolution predictor deep neural networks.

Previous studies have indicated that white matter hyperintensities (WMH), the main radiological feature of small vessel disease, may evolve (i.e., shrink, grow) or stay stable over a period of time. Predicting these changes are challenging because it involves some unknown clinical risk factors that leads to a non-deterministic prediction task. In this study, we propose a deep learning model to predict the evolution of WMH from baseline to follow-up (i.e., 1-year later), namely "Disease Evolution Predictor" (DEP) model, which can be adjusted to become a non-deterministic model. The DEP model receives a baseline image as input and produces a map called "Disease Evolution Map" (DEM), which represents the evolution of WMH from baseline to follow-up. Two DEP models are proposed, namely DEP-UResNet and DEP-GAN, which are representatives of the supervised (i.e., need expert-generated manual labels to generate the output) and unsupervised (i.e., do not require manual labels produced by experts) deep learning algorithms respectively. To simulate the non-deterministic and unknown parameters involved in WMH evolution, we modulate a Gaussian noise array to the DEP model as auxiliary input. This forces the DEP model to imitate a wider spectrum of alternatives in the prediction results. The alternatives of using other types of auxiliary input instead, such as baseline WMH and stroke lesion loads are also proposed and tested. Based on our experiments, the fully supervised machine learning scheme DEP-UResNet regularly performed better than the DEP-GAN which works in principle without using any expert-generated label (i.e., unsupervised). However, a semi-supervised DEP-GAN model, which uses probability maps produced by a supervised segmentation method in the learning process, yielded similar performances to the DEP-UResNet and performed best in the clinical evaluation. Furthermore, an ablation study showed that an auxiliary input, especially the Gaussian noise, improved the performance of DEP models compared to DEP models that lacked the auxiliary input regardless of the model's architecture. To the best of our knowledge, this is the first extensive study on modelling WMH evolution using deep learning algorithms, which deals with the non-deterministic nature of WMH evolution.

Risk Factors for Aphasia in Cerebral Small Vessel Diseases.

BACKGROUND: Lacunes and white matter hyperintensities (WMH) are two common findings seen on neuroimaging in patients with cerebral small vessel disease (cSVD). Clinically we observed that some patients with cSVD have aphasia through the language assessment scale. Our study aimed to explore the underlying risk factors for aphasia in cSVD patients. METHODS: This study retrospectively analyzed 38 patients, with and without aphasia, aged 50 or over, Chinese Han population, diagnosed as cSVD with lacunes and/or WMH. We collected demographic characteristics and vascular risk factors. The severity of WMH was assessed by the age related white matter changes (ARWMC) rating scale. RESULTS: Risk factors associated with aphasia were: lower education (p = 0.029), higher total cholesterol (TC) levels (p = 0.023), and higher low-density lipoprotein cholesterol (LDL-C) levels (p = 0.027). After controlling for age and sex, levels of TC (odds ratios, 1.96; 95% confidence interval, 1.06-3.62; p = 0.032) remained associated with aphasia independently. CONCLUSION: High level of TC was significantly associated with a higher risk of aphasia in clinically silent cSVD patients. Early interventions including lipid-lowering treatment, cranial magnetic resonance imaging (MRI) and ARWMC rating scale should be performed. Further studies are needed to explore proper methods of prevention and treatment for aphasia in clinically silent cSVD patients, in addition to understanding the pathophysiological mechanism.