ArticleAlzheimer's & dementia (New York, N. Y.)
White matter microstructure mediates the association between cardiorespiratory fitness and cognitive performance in older adults.
Article in Alzheimer's & dementia (New York, N. Y.). The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Inflammatory, metabolic, and vascular pathways linking cardiorespiratory fitness to cognition: Results from the IGNITE study.Brain, behavior, & immunity - health · 2026Article
- Physical activity, aerobic fitness, and AD blood biomarkers: The IGNITE study.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Association between 24-h time-use composition and brain age: The IGNITE study.Alzheimer's & dementia (New York, N. Y.)Article
- White matter microstructure mediates the association between cardiorespiratory fitness and cognitive performance in older adults.Alzheimer's & dementia (New York, N. Y.)Article
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Authors and funding
21 authors.
Funding
Abstract
introductionAge-related cognitive decline occurs, in part, due to diminishing white matter integrity. Higher cardiorespiratory fitness (CRF) is associated with better cognitive performance, but the neurobiological mechanisms underlying this association remain uncertain. Previous magnetic resonance imaging (MRI) studies have suggested that CRF-related changes in white matter microstructure might prevent or slow age-related cognitive decline, but have been limited by small sample sizes and methodological limitations. Specifically, most prior studies used tensor-based diffusion-weighted MRI metrics, which are insensitive to complex white matter architectures, including crossing fibers.
methodsHere, we leveraged a novel analysis framework capable of resolving individual fiber populations at the within-voxel level-fixel-based analysis (FBA)-to analyze three metrics of white matter organization from diffusion-weighted MRI scans: fiber density (FD), fiber cross-section (FC), and their combined measure (FDC). Using a cross-sectional sample of 636 cognitively unimpaired older adults aged 65 to 80 years (mean age = 69.8 years; 71% female), we hypothesized that FBA metrics would be associated with CRF and that this variation in FBA metrics would mediate associations between CRF and cognitive performance.
resultsIn whole-brain analyses, higher CRF was associated with greater FD, FC, and FDC. Furthermore, these FBA-derived metrics statistically mediated the relationship between CRF and cognitive performance in the domains of visuospatial abilities, processing speed, working memory, and executive function/attentional control, but not episodic memory. DISCUSSION: These findings highlight the potential for CRF in the preservation of multiple aspects of cognition as a function of white matter micro- and macro-structural properties. Our results provide novel insights into the neurobiological mechanisms of fitness-related cognitive resilience. Highlights: Higher cardiorespiratory fitness (CRF) is linked to better white matter integrity in older adults.Fixel-based analysis reveals CRF associations with fiber density and cross-section.White matter properties mediate CRF effects on cognition, excluding episodic memory.Findings suggest CRF supports cognitive resilience via white matter organization.
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