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Journal article
Inflammatory, metabolic, and vascular pathways linking cardiorespiratory fitness to cognition: Results from the IGNITE study
Brain, behavior, & immunity. Health, Vol.55, 101291
2026
PMID: 42395032
Abstract
Objectives: This study examined whether peripheral biological pathways including inflammation, insulin resistance, and arterial stiffness, partially explain the link between cardiorespiratory fitness (CRF) and cognitive function in older adults.
Methods: In a cross-sectional sample of cognitively unimpaired older adults (N = 648, 71% female, M age = 69.88 ± 3.75 years), participants completed a comprehensive cognitive battery assessing executive function (EF)/Attentional control, episodic memory, processing speed, working memory, and visuospatial abilities. CRF was measured using a maximal graded exercise test performed on a motorized treadmill. Peripheral biomarkers included low-grade systemic inflammation (Interleukin-6; IL-6), insulin resistance (Homeostatic Model Assessment for Insulin Resistance; HOMA-IR) and arterial stiffness (carotid-femoral pulse wave velocity; cfPWV). Parallel mediation models, adjusted for age, sex, APOE4 carriage, body fat percentage, study site and years of education, tested whether these biomarkers statistically mediated associations between CRF and cognitive performance.
Results: IL-6 emerged as a consistent significant mediator of the relationship between CRF and EF, episodic memory, visuospatial processing and working memory. HOMA-IR statistically mediated the association between CRF and both EF and processing speed. In contrast, cfPWV did not statistically mediate an association between CRF and performance in any cognitive domain.
Conclusion: These findings suggest that low-grade systemic inflammation broadly mediates the relationship between CRF and cognitive function, while metabolic pathways show more domain-specific associations. Together, these results highlight the need for understanding the plural, yet distinct, biological mechanisms by which higher CRF relates to better cognitive performance, with the goal of identifying potential targets for interventions aimed at preserving cognitive health in older adulthood.
Details
- Title
- Inflammatory, metabolic, and vascular pathways linking cardiorespiratory fitness to cognition: Results from the IGNITE study
- Authors/Creators
- Patricio Solis-Urra - Viña del Mar UniversityKelsey R. Sewell - Murdoch UniversityAudrey M. Collins - Translational Research Institute for Metabolism and DiabetesChaeryon Kang - University of PittsburghHaiqing Huang - Translational Research Institute for Metabolism and DiabetesGeorge Grove - University of PittsburghLu Wan - Translational Research Institute for Metabolism and DiabetesAmani M. Norling - Harvard UniversityArthur F. Kramer - University of Illinois Urbana-ChampaignEdward McAuley - University of Illinois Urbana-ChampaignJeffrey M. Burns - University of Kansas Medical CenterCharles H. Hillman - Northeastern UniversityEric D. Vidoni - University of Kansas Medical CenterAnna L. Marsland - University of PittsburghM. Ilyas Kamboh - University of PittsburghAmanda Szabo-Reed - University of Kansas Medical CenterRenee J. Rogers - University of Kansas Medical CenterDaniel E. Forman - Geriatric Research Education and Clinical CenterSandra A. Billinger - University of Kansas Medical CenterKirk I. Erickson - Translational Research Institute for Metabolism and DiabetesJohn M. Jakicic - University of Kansas Medical CenterLauren E. Oberlin - Cornell University
- Publication Details
- Brain, behavior, & immunity. Health, Vol.55, 101291
- Publisher
- Elsevier Inc.
- Identifiers
- 991005902123007891
- Copyright
- © 2026 The Author(s).
- Murdoch Affiliation
- School of Psychology
- Language
- English
- Resource Type
- Journal article
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