White matter microstructure mediates the association between cardiorespiratory fitness and cognitive performance in older adults

IF 4.9 Q1 CLINICAL NEUROLOGY

Alzheimer''s and Dementia: Translational Research and Clinical Interventions Pub Date : 2025-07-24 DOI:10.1002/trc2.70125

Emma M. Tinney, Aaron E. L. Warren, Amanda O'Brien, Hannah Odom, Meishan Ai, Bradley P. Sutton, Shivangi Jain, Chaeryon Kang, Haiqing Huang, Lu Wan, Lauren E. Oberlin, George Grove, John M. Jakicic, Audrey M. Collins, Kelsey R. Sewell, Jeffrey M. Burns, Eric D. Vidoni, Edward McAuley, Arthur F. Kramer, Kirk I. Erickson, Charles H. Hillman

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引用次数: 0

Abstract

INTRODUCTION

Age-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.

METHODS

Here, 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.

RESULTS

In 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.

Abstract Image

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白质微结构介导老年人心肺健康和认知表现之间的关联

与年龄相关的认知能力下降，部分是由于白质完整性的减少。较高的心肺适能（CRF）与较好的认知能力相关，但这种关联背后的神经生物学机制尚不清楚。先前的磁共振成像（MRI）研究表明，crf相关的白质微结构变化可能会预防或减缓与年龄相关的认知能力下降，但受限于小样本量和方法的限制。具体来说，大多数先前的研究使用基于张量的扩散加权MRI指标，这对复杂的白质结构不敏感，包括交叉纤维。在这里，我们利用了一种新的分析框架，能够在体素级基于固定的分析（FBA）上解析单个纤维种群，以分析弥散加权MRI扫描中白质组织的三个指标：纤维密度（FD）、纤维横截面（FC）和它们的联合测量（FDC）。使用636名年龄在65至80岁(平均年龄= 69.8岁；（71%女性），我们假设FBA指标与CRF相关，FBA指标的这种变化将介导CRF和认知表现之间的关联。结果在全脑分析中，较高的CRF与较高的FD、FC和FDC相关。此外，这些fba衍生的指标在视觉空间能力、加工速度、工作记忆和执行功能/注意控制等领域对CRF和认知表现之间的关系进行了统计调解，但对情景记忆没有影响。这些发现强调了CRF作为白质微观和宏观结构特性的功能，在保存认知的多个方面的潜力。我们的研究结果为健身相关认知弹性的神经生物学机制提供了新的见解。老年人较高的心肺健康（CRF）与更好的白质完整性有关。基于固定的分析显示CRF与纤维密度和截面有关。白质特性介导CRF对认知的影响，不包括情景记忆。研究结果表明，CRF通过白质组织支持认知弹性。

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来源期刊

Alzheimer''s and Dementia: Translational Research and Clinical Interventions Medicine-Psychiatry and Mental Health

CiteScore

10.10

自引率

2.10%

发文量

134

审稿时长

10 weeks

期刊介绍： Alzheimer''s & Dementia: Translational Research & Clinical Interventions (TRCI) is a peer-reviewed, open access,journal from the Alzheimer''s Association®. The journal seeks to bridge the full scope of explorations between basic research on drug discovery and clinical studies, validating putative therapies for aging-related chronic brain conditions that affect cognition, motor functions, and other behavioral or clinical symptoms associated with all forms dementia and Alzheimer''s disease. The journal will publish findings from diverse domains of research and disciplines to accelerate the conversion of abstract facts into practical knowledge: specifically, to translate what is learned at the bench into bedside applications. The journal seeks to publish articles that go beyond a singular emphasis on either basic drug discovery research or clinical research. Rather, an important theme of articles will be the linkages between and among the various discrete steps in the complex continuum of therapy development. For rapid communication among a multidisciplinary research audience involving the range of therapeutic interventions, TRCI will consider only original contributions that include feature length research articles, systematic reviews, meta-analyses, brief reports, narrative reviews, commentaries, letters, perspectives, and research news that would advance wide range of interventions to ameliorate symptoms or alter the progression of chronic neurocognitive disorders such as dementia and Alzheimer''s disease. The journal will publish on topics related to medicine, geriatrics, neuroscience, neurophysiology, neurology, psychiatry, clinical psychology, bioinformatics, pharmaco-genetics, regulatory issues, health economics, pharmacoeconomics, and public health policy as these apply to preclinical and clinical research on therapeutics.