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We here aimed to determine whether obesity contributes to regional WMHs using a whole\u2010brain approach in a well\u2010characterized population\u2010based cohort.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Waist\u2010to\u2010hip ratio (WHR), body mass index (BMI), systolic\/diastolic blood pressure, hypertension, diabetes and smoking status, blood glucose and inflammatory markers, as well as distribution of WMH were assessed in 1,825 participants of the LIFE\u2010adult study (age, 20\u201382 years; BMI, 18.4\u201355.4 kg\/m<jats:sup>2<\/jats:sup>) using high\u2010resolution 3\u2010Tesla magnetic resonance imaging. Voxel\u2010wise analyses tested if obesity predicts regional probability of WMH. Additionally, mediation effects of high\u2010sensitive C\u2010reactive protein and interleukin\u20106 (IL6) measured in blood were related to obesity and WMH using linear regression and structural equation models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>WHR related to higher WMH probability predominantly in the deep white matter, even after adjusting for effects of age, sex, and systolic blood pressure (mean \u00df = 0.0043 [0.0008 SE], 95% confidence interval, [0.00427, 0.0043]; threshold\u2010free cluster enhancement, family\u2010wise error\u2010corrected <jats:italic>p<\/jats:italic> &lt; 0.05). Conversely, higher systolic blood pressure was associated with WMH in periventricular white matter regions. Mediation analyses indicated that both higher WHR and higher BMI contributed to increased deep\u2010to\u2010periventricular WMH ratio through elevated IL6.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Our results indicate an increased WMH burden selectively in the deep white matter in obese subjects with high visceral fat accumulation, independent of common obesity comorbidities such as hypertension. Mediation analyses proposed that visceral obesity contributes to deep white matter lesions through increases in proinflammatory cytokines, suggesting a pathomechanistic link. Longitudinal studies need to confirm this hypothesis. <jats:bold>ANN NEUROL 2019;85:194\u2013203.<\/jats:bold><\/jats:p><\/jats:sec>","DOI":"10.1002\/ana.25396","type":"journal-article","created":{"date-parts":[[2018,12,17]],"date-time":"2018-12-17T08:09:55Z","timestamp":1545034195000},"page":"194-203","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":182,"title":["Visceral obesity relates to deep white matter hyperintensities via inflammation"],"prefix":"10.1002","volume":"85","author":[{"given":"Leonie","family":"Lampe","sequence":"first","affiliation":[{"name":"Department of Neurology Max\u2010Planck\u2010Institute for Human Cognitive and Brain Sciences  Leipzig Germany"},{"name":"Clinic of Cognitive Neurology University Hospital Leipzig  Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology Max\u2010Planck\u2010Institute for Human Cognitive and Brain Sciences  Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frauke","family":"Beyer","sequence":"additional","affiliation":[{"name":"Department of Neurology Max\u2010Planck\u2010Institute for Human Cognitive and Brain Sciences  Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Huhn","sequence":"additional","affiliation":[{"name":"Department of Neurology Max\u2010Planck\u2010Institute for Human Cognitive and Brain Sciences  Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahrzad","family":"Kharabian Masouleh","sequence":"additional","affiliation":[{"name":"Department of Neurology Max\u2010Planck\u2010Institute for Human Cognitive and Brain Sciences  Leipzig Germany"},{"name":"Research Center J\u00fclich Institute of Neuroscience and Medicine (INM\u20107)  J\u00fclich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven","family":"Preusser","sequence":"additional","affiliation":[{"name":"Department of Neurology Max\u2010Planck\u2010Institute for Human Cognitive and Brain Sciences  Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre\u2010Louis","family":"Bazin","sequence":"additional","affiliation":[{"name":"Department of Neurology Max\u2010Planck\u2010Institute for Human Cognitive and Brain Sciences  Leipzig Germany"},{"name":"Netherlands Institute for Neuroscience  Amsterdam The Netherlands"},{"name":"Spinoza Centre for Neuroimaging  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias L.","family":"Schroeter","sequence":"additional","affiliation":[{"name":"Department of Neurology Max\u2010Planck\u2010Institute for Human Cognitive and Brain Sciences  Leipzig Germany"},{"name":"Clinic of Cognitive Neurology University Hospital Leipzig  Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arno","family":"Villringer","sequence":"additional","affiliation":[{"name":"Department of Neurology Max\u2010Planck\u2010Institute for Human Cognitive and Brain Sciences  Leipzig Germany"},{"name":"Clinic of Cognitive Neurology University Hospital Leipzig  Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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