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  Visceral obesity relates to deep white matter hyperintensities via inflammation

Lampe, L., Zhang, R., Beyer, F., Huhn, S., Kharabian, S., Preusser, S., et al. (2019). Visceral obesity relates to deep white matter hyperintensities via inflammation. Annals of Neurology, 85(2), 194-203. doi:10.1002/ana.25396.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0002-D00C-6 Version Permalink: http://hdl.handle.net/21.11116/0000-0005-0F21-6
Genre: Journal Article

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 Creators:
Lampe, Leonie1, 2, Author              
Zhang, Rui1, Author              
Beyer, Frauke1, Author              
Huhn, Sebastian1, Author              
Kharabian, Shahrzad1, 3, Author              
Preusser, Sven1, Author              
Bazin, Pierre-Louis1, 4, 5, Author              
Schroeter, Matthias L.1, 2, Author              
Villringer, Arno1, 2, Author              
Witte, A. Veronica1, Author              
Affiliations:
1Department Neurology, MPI for Human Cognitive and Brain Sciences, Max Planck Society, ou_634549              
2Clinic for Cognitive Neurology, University of Leipzig, Germany, ou_persistent22              
3Institute of Neuroscience and Medicine, Research Center Jülich, Germany, ou_persistent22              
4The Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Amsterdam, the Netherlands, ou_persistent22              
5Spinoza Centre for Neuroimaging, University of Amsterdam, the Netherlands, ou_persistent22              

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Free keywords: Cerebral small vessel disease; Brain atrophy; IL6; CRP; Cytokines
 Abstract: Objective: White matter hyperintensities (WMH) are linked to vascular risk factors and increase the risk of cognitive decline, dementia and stroke. We here aimed to determine if obesity contributes to regional WMH using a whole‐brain approach in a well‐characterized population‐based cohort. Methods: Waist‐to‐hip 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 1825 participants of the LIFE‐adult study (age 20‐82 years; BMI 18.4 ‐ 55.4 kg/m2) using high‐resolution 3‐Tesla MRI. Voxel‐wise analyses tested if obesity predicts regional probability of WMH. Additionally, mediation effects of high‐sensitive C‐reactive protein (CRP) and interleukin‐6 (IL6) measured in blood were related to obesity and WMH using linear regression and structural equation models. Results: 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 ß=0.0043 (0.0008 SE), 95%CI [0.00427, 0.0043], TFCE/FWE‐corrected p<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‐to‐periventricular WMH‐ratio through elevated IL6. Interpretation: 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 co‐morbidities such as hypertension. Mediation analyses proposed hat visceral obesity contributed to deep white matter lesions through increases in pro‐inflammatory cytokines, suggesting a pathomechanistic link. Longitudinal studies need to confirm this hypothesis.

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Language(s): eng - English
 Dates: 2018-12-122018-08-212018-12-132018-12-172019-02
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1002/ana.25396
PMID: 30556596
 Degree: -

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Funding organization : European Union (EU)
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Funding program : European Regional Development Fund
Funding organization : European Commission (EC)
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Funding organization : Free State of Saxony
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Grant ID : 713‐241202 ; 14505/2470 ; 14575/2470
Funding program : -
Funding organization : LIFE–Leipzig Research Center for Civilization Diseases, University of Leipzig
Project name : Obesity Mechanisms” / SFB 1052
Grant ID : -
Funding program : -
Funding organization : German Research Foundation (DFG)
Project name : -
Grant ID : WI 3342/3‐1
Funding program : -
Funding organization : German Research Foundation (DFG)

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Title: Annals of Neurology
Source Genre: Journal
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Publ. Info: Boston : American Neurological Association
Pages: - Volume / Issue: 85 (2) Sequence Number: - Start / End Page: 194 - 203 Identifier: ISSN: 0364-5134
CoNE: https://pure.mpg.de/cone/journals/resource/954925523748