Associations between white matter lesions, adiposity, and systemic inflammation in late adulthood: Results from the IGNITE study

Shivangi Jain; Patricio Solis-Urra; Alina Lesnovskaya; Lu Wan; Cristina Molina-Hidalgo; Audrey Collins; Haiqing Huang; Kelsey R. Sewell; Rebecca Reed; Renee J. Rogers; Anna L. Marsland; George Grove; Lauren E. Oberlin; Chaeryon Kang; John M. Jakicic; Lauren Raine; Joseph Mettenburg; Lauren M. Sparks; Arthur F. Kramer; Charles Hillman; Edward McAuley; Jeffrey M. Burns; Eric D. Vidoni; Bradley P. Sutton; Kirk I. Erickson

doi:10.1016/j.bbi.2025.106223

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Associations between white matter lesions, adiposity, and systemic inflammation in late adulthood: Results from the IGNITE study

Journal article

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Associations between white matter lesions, adiposity, and systemic inflammation in late adulthood: Results from the IGNITE study

Shivangi Jain, Patricio Solis-Urra, Alina Lesnovskaya, Lu Wan, Cristina Molina-Hidalgo, Audrey Collins, Haiqing Huang, Kelsey R. Sewell, Rebecca Reed, Renee J. Rogers, …

Brain, behavior, and immunity, Vol.132, 106223

2026

DOI: https://doi.org/10.1016/j.bbi.2025.106223

PMID: 41421734

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Abstract

Inflammatory cytokines

Path analyses

Subcutaneous adipose tissue

Visceral adipose tissue

White matter lesions

White matter hyperintensities or lesions (WMLs) increase the risk for cognitive impairment and dementia. Cardiometabolic factors (e.g., excess adiposity) and markers of systemic inflammation relate to greater WML volume, but few studies have examined whether specific compartments of adipose tissue (e.g., visceral adipose tissue (VAT), and abdominal subcutaneous adipose tissue (ASAT)) relative to total body adiposity (TBA) differentially relate to WML volume or whether these patterns could be statistically mediated by inflammation. We examined associations between markers of low-grade systemic inflammation and compartments of adipose tissue relative to total body adiposity (rVAT or rASAT respectively), measured by dual-energy x-ray absorptiometry (DXA), and WML volume. We hypothesized that higher rVAT and not rASAT would be associated with greater WML volume, and that this association would be statistically mediated by concentrations of inflammatory cytokines. We used baseline data (n = 648) from the multisite study “Investigating Gains in Neurocognition in an Intervention Trial of Exercise” (IGNITE; mean age = 69.9 ± 3.8 years, 70.5 % females). IL-6, IL-1RA, and TNF-α were included as markers of systemic inflammation and age, sex, years of education, hypertension status, and study site were included as covariates. Our hypotheses were partially supported such that the relationship between rVAT and WMLs, as well as between rASAT and WMLs, were statistically mediated by IL-6 and TNF-α. These findings suggest that both higher rVAT and rASAT, are associated with higher WML burden through an elevated inflammatory state. These results set a testable mechanistic pathway for future longitudinal and intervention studies examining whether managing low-grade systemic inflammation and intentional weight loss would be beneficial for supporting brain health in older adults.

Details

Title: Associations between white matter lesions, adiposity, and systemic inflammation in late adulthood: Results from the IGNITE study
Authors/Creators: Shivangi Jain - Neuroscience Institute
Patricio Solis-Urra - Neuroscience Institute
Alina Lesnovskaya - University of Pittsburgh
Lu Wan - Neuroscience Institute
Cristina Molina-Hidalgo - Neuroscience Institute
Audrey Collins - Neuroscience Institute
Haiqing Huang - Neuroscience Institute
Kelsey R. Sewell - Neuroscience Institute
Rebecca Reed - University of Pittsburgh
Renee J. Rogers - University of Kansas Medical Center
Anna L. Marsland - University of Pittsburgh
George Grove - University of Pittsburgh
Lauren E. Oberlin - Neuroscience Institute
Chaeryon Kang - University of Pittsburgh
John M. Jakicic - University of Kansas Medical Center
Lauren Raine - Department of Psychology, Northeastern University, USA
Joseph Mettenburg - University of Pittsburgh
Lauren M. Sparks - Neuroscience Institute
Arthur F. Kramer - Northeastern University
Charles Hillman - Northeastern University
Edward McAuley - University of Illinois Urbana-Champaign
Jeffrey M. Burns - University of Kansas
Eric D. Vidoni - University of Kansas Medical Center
Bradley P. Sutton - University of Illinois Urbana-Champaign
Kirk I. Erickson - Neuroscience Institute
Publication Details: Brain, behavior, and immunity, Vol.132, 106223
Publisher: Elsevier Inc.
Number of pages: 8
Identifiers: 991005845959707891
Murdoch Affiliation: Centre for Healthy Ageing
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.21 Psychiatry; 1.21.1828 Neuroinflammation
Web Of Science research areas: Immunology; Neurosciences; Psychiatry
ESI research areas: Neuroscience & Behavior