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Background and Objectives: White matter hyperintensities (WMH) are pathologic brain changes that are associated with increased age and cognitive decline. However, the association of WMH burden with amyloid positivity and conversion to dementia in people with mild cognitive impairment (MCI) is unclear. The aim of this study was to expand on this research by examining whether change in WMH burden over time differs in amyloid-negative (Aβ-) and amyloid-positive (Aβ+) people with MCI who either remain stable or convert to dementia. To examine this question, we compared regional WMH burden in 4 groups: Aβ+ progressor, Aβ- progressor, Aβ+ stable, and Aβ- stable., Methods: Participants with MCI from the Alzheimer Disease Neuroimaging Initiative were included if they had APOE ɛ4 status and if amyloid measures were available to determine amyloid status (i.e., Aβ+, or Aβ-). Participants with a baseline diagnosis of MCI and who had APOE ɛ4 information and amyloid measures were included. An average of 5.7 follow-up time points per participant were included, with a total of 5,054 follow-up time points with a maximum follow-up duration of 13 years. Differences in total and regional WMH burden were examined using linear mixed-effects models., Results: A total of 820 participants (55-90 years of age) were included in the study (Aβ+ progressor, n = 239; Aβ- progressor, n = 22; Aβ+ stable, n = 343; Aβ- stable, n = 216). People who were Aβ- stable exhibited reduced baseline WMH compared with Aβ+ progressors and people who were Aβ+ stable at all regions of interest (β belongs to 0.20-0.33, CI belongs to 0.03-0.49, p < 0.02), except deep WMH. When examining longitudinal results, compared with people who were Aβ- stable, all groups had steeper accumulation in WMH burden with Aβ+ progressors (β belongs to -0.03 to 0.06, CI belongs to -0.05 to 0.09, p < 0.01) having the largest increase (i.e., largest increase in WMH accumulation over time)., Discussion: These results indicate that WMH accumulation contributes to conversion to dementia in older adults with MCI who are Aβ+ and Aβ-., (© 2023 American Academy of Neurology.)

White matter hyperintensities (WMHs) are pathological changes that occur with increased age and are associated with cognitive decline. Most WMH research has not examined regional differences and focuses on a whole-brain approach. This study examined regional WMHs between normal controls (NCs), people with mild cognitive impairment (MCI), and Alzheimer's disease (AD). We also examined whether WMHs were associated with cognitive decline. Participants from the Alzheimer's Disease Neuroimaging Initiative were included if they had at least one WMH measurement and cognitive scores examining global cognition, executive functioning, and memory. Only amyloid-positive MCI and AD participants were included. A total of 1573 participants with 7381 timepoints over a maximum period of 13 years were included. Linear mixed-effects models examined group differences in WMH burden and associations between WMH burden and cognition. People with MCI and AD had increased total and regional WMHs compared to NCs. An association between WMHs and cognition was observed for global cognition, executive functioning, and memory in NCs in all regions. A steeper decline (stronger association between WMH and cognition) was observed in MCI compared to NCs for all cognitive domains in all regions. A steeper decline was observed in AD compared to NCs for global cognition in only the temporal region. A strong association is observed between all cognitive domains of interest and WMH burden in healthy aging and MCI, while those with AD only had a few associations between WMH and global cognition. These findings suggest that the WMH burden is associated with changes in cognition in healthy aging and early cognitive decline., (© 2022. The Author(s), under exclusive licence to American Aging Association.)

Some Diffusion Tensor Imaging studies have shown a loss of white matter (WM) integrity linked to impaired cognitive function in obese individuals. However, inconsistent WM integrity changes have been reported. We aimed to identify which WM tracts show consistent changes with obesity. We conducted a systematic search to find studies examining the association between obesity-related measures and Fractional Anisotropy (FA) or Mean Diffusivity. We performed a meta-analysis with FA datasets using Anisotropic Effect Size-Signed Differential Mapping software. The meta-analysis showed that increased obesity measurements were related to reduced FA in the genu of the corpus callosum. We validated our findings using an independent sample from the Human Connectome Project dataset, which supports lower FA in this region in individuals with obesity compared to those with normal weight (p = 0.028). Our findings provide evidence that obesity is associated with reduced WM integrity in the genu of the corpus callosum, a tract linking frontal areas involved in executive function. Future studies are needed on the mechanisms linking obesity with loss of WM integrity., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: MRI studies show that obese adults have reduced grey matter (GM) and white matter (WM) tissue density as well as altered WM integrity. Bariatric surgery can lead to substantial weight loss and improvements in metabolic parameters, but it remains to be examined if it induces structural brain changes. The aim of this study was to characterize GM and WM density changes measured with MRI in a longitudinal setting following sleeve gastrectomy, and to determine whether any changes are related to inflammation and cardiometabolic blood markers., Methods: 29 participants with obesity (age: 45.9 ​± ​7.8 years) scheduled to undergo sleeve gastrectomy were recruited. High-resolution T1-weighted anatomical images were acquired 1 month prior to as well as 4 and 12 months after surgery. GM and WM densities were quantified using voxel-based morphometry (VBM). Circulating lipid profile, glucose, insulin and inflammatory markers (interleukin-6, C-reactive protein and lipopolysaccharide-binding protein) were measured at each time point. A linear mixed effect model was used to compare brain changes before and after SG, controlling for age, sex, initial BMI and diabetic status. To assess the associations between changes in adiposity, metabolism and inflammation and changes in GM or WM density, the mean GM and WM densities were extracted across all the participants using atlas-derived regions of interest, and linear mixed-effect models were used., Results: As expected, weight, BMI, waist circumference and neck circumference significantly decreased after SG compared with baseline (p ​< ​0.001 for all). A widespread increase in WM density was observed after surgery, particularly in the cerebellum, brain stem, cerebellar peduncle, cingulum, corpus callosum and corona radiata (p ​< ​0.05, after FDR correction). Significant increases in GM density were observed 4 months after SG compared to baseline in several brain regions such as the bilateral occipital cortex, temporal cortex, postcentral gyrus, cerebellum, hippocampus and insula as well as right fusiform gyrus, right parahippocampal gyrus, right lingual gyrus and right amygdala. These GM and WM increases were more pronounced and widespread after 12 months and were significantly associated with post-operative weight loss and the improvement of metabolic alterations. A linear mixed-effect model also showed associations between post-operative reductions in lipopolysaccharide-binding protein, a marker of inflammation, and increased WM density. To confirm our results, we tested whether the peak of each significant region showed BMI-related differences in an independent dataset (Human Connectome Project). We matched a group of individuals who were severely obese with a group of individuals who were lean for age, sex and ethnicity. Severe obesity was associated with reduced WM density in the brain stem and cerebellar peduncle as well as reduced GM density in cerebellum, regions that significantly changed after surgery (p ​< ​0.01 for all clusters)., Conclusions: Bariatric surgery-induced weight loss and improvement in metabolic alterations is associated with widespread increases in WM and GM densities. These post-operative changes overlapped with baseline brain differences between participants who were severely obese and those who were normal-weight in a separate dataset, which may suggest a recovery of WM and GM alterations after bariatric surgery., Competing Interests: Declaration of competing interest A. T. and L.B. are recipients of research grant support from Johnson & Johnson Medical Companies and Medtronic for studies on bariatric surgery and the Research Chair in Bariatric and Metabolic Surgery at IUCPQ and Laval University, respectively. No author declared a conflict to interest relevant to the content of the manuscript., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

White Matter Hyperintensities (WMHs) are associated with cognitive decline in aging and Alzheimer's disease. However, the pathogenesis of cognitive decline in Parkinson's disease (PD) is not as clearly related to vascular causes, and therefore the role of WMHs as a marker of small-vessel disease (SVD) in PD is less clear. Currently, SVD in PD is assessed and treated independently of the disease. However, if WMH as the major MRI sign of SVD has a higher impact on cognitive decline in PD patients than in healthy controls, vascular pathology needs to be assessed and treated with a higher priority in this population. Here we investigate whether the presence of WMHs leads to increased cognitive decline in de novo PD, and if these effects relate to cortical atrophy. WMHs and cortical thickness were measured in de novo PD patients and age-matched controls (N PD  = 365, N Control  = 174) from Parkinson's Progression Markers Initiative (PPMI) to study the relationship between baseline WMHs, future cognitive decline (follow-up: 4.09 ± 1.14 years) and cortical atrophy (follow-up: 1.05 ± 0.10 years). PD subjects with high baseline WMH loads had significantly greater cognitive decline than i) PD subjects with low WMH load, and ii) control subjects with high WMH load. Furthermore, in PD subjects, high WMH load resulted in more cortical thinning in the right frontal lobe. Theses results show that the presence of WMHs in de novo PD patients predicts greater future cognitive decline and cortical atrophy than in normal aging., (Copyright © 2018. Published by Elsevier Inc.)