Cardiorespiratory fitness is associated with white matter integrity in aging
Open accessAbstract
OBJECTIVE: Aging is associated with reduced neural integrity, yet there are remarkable individual differences in brain health among older adults (OA). One factor that may attenuate age-related neural decline is cardiorespiratory fitness (CRF). The primary aim of this study was to link CRF to neural white matter microstructure using diffusion tensor imaging in OA. METHODS: Young adults (YA; n = 32) and OA (n = 27) completed a graded maximal exercise test to evaluate CRF and diffusion tensor magnetic resonance imaging to examine neural white matter integrity. RESULTS: As expected, pervasive age-related declines in white matter integrity were observed when OA were compared to YA. Further, peak VO2 was positively associated with fractional anisotropy (FA), an indicator of white matter integrity, in multiple brain regions in OA, but not YA. In multiple posterior regions such as the splenium, sagittal stratum, posterior corona radiata, and superior parietal white matter, FA values were similar in YA and OA classified as higher fit, with both groups having greater FA than lower fit OA. However, age-related differences in FA values remained in other regions, including the body and genu of the corpus callosum, precuneus, and superior frontal gyrus. INTERPRETATION: CRF is positively associated with neural white matter microstructure in aging. The relationship between peak VO2 and FA appears to be tract-specific, as equivalent FA values were observed in higher fit OA and YA in some white matter tracts, but not others. Further, the association between peak VO2 and FA appears to be age-dependent.
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Cardiorespiratory fitness and aerobic exercise have been positively associated with fronto-parietal and medial temporal lobe white matter tracts including the fornix, cingulum bundle, and superior longitudinal fasciculus.
“Cardiorespiratory fitness and aerobic exercise have been positively associated with fronto-parietal and medial temporal lobe white matter tracts including the fornix, cingulum bundle and superior longitudinal fasciculus”
From Exercise Intervention in PTSD: A Narrative Review and Rationale for Implementation (2019) · cites this paper as [101]
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“Our moderation findings are also consistent with the age-dependent hypothesis, which suggests that reserve factors tend to have greater protective effects in older age, when neurocognitive declines become more apparent (Gold et al. 2013; Hötting and Röder, 2013; Hayes et al. 2015).”
Hayes, S. M., Hayes, J. P., Williams, V. J., Liu, H., & Verfaellie, M. H. (2017) · Cortex · doi:10.1016/j.cortex.2017.01.002 · Cited by 28 · see citing works
Sbardelotto, M. L., Costa, R. R., Malysz, K. A., Pedroso, G. S., Pereira, B. C., Sorato, H. R., Silveira, P. C. L., Nesi, R. T., Grande, A. J., & Pinho, R. A. (2019) · Clinics · doi:10.6061/clinics/2019/e833 · Cited by 27 · see citing works
“Aging is associated with decreased neural integrity, whereas cardiovascular fitness, which can potentially improve the quality of life, delay cognitive decline, and prolong functional fitness in elderly people by ensuring functional independence, is a factor that might mitigate the neural decline in neural integrity r…”
BackgroundPani, J., Eikenes, L., Reitlo, L. S., Stensvold, D., Wisløff, U., & Haberg, A. K. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.859383 · Cited by 24 · see citing works
“Our results are consistent with previous studies, which report positive associations between FA and CRF in the corpus callosum (Johnson et al., 2012; Hayes et al., 2015; Oberlin et al., 2016; Tarumi et al., 2020b), the inferior longitudinal fasciculus (Tseng et al., 2013), the internal capsule…”
ResultCardiorespiratory fitness and white matter integrity in Alzheimer’s disease
Perea, R. D., Vidoni, E. D., Morris, J. K., Graves, R. S., Burns, J. M., & Honea, R. A. (2015) · Brain Imaging and Behavior · doi:10.1007/s11682-015-9431-3 · Cited by 24 · see citing works
“Hayes et al. identified white matter regions where VO2peak was associated with increased FA in older adults, namely the right temporal pole, right fornix, left sagittal striatum, right posterior corona radiate, and the corpus callosum (Hayes et al. 2015).”
BackgroundResultInfluentialCallow, D. D., Purcell, J. J., Won, J., & Smith, J. C. (2022) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2022.108207 · Cited by 23 · see citing works
Faulkner, M. E., Gong, Z., Bilgel, M., Laporte, J. P., Guo, A., Bae, J., Elango, P., Kaileh, M., Bergeron, C. M., Bergeron, J., et al. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2402813121 · Cited by 23 · see citing works
“As a modifiable lifestyle factor, CRF can be enhanced through various aerobic fitness activities including walking, running, swimming, and biking (6).”
BackgroundAerobic Fitness Is Associated with Cerebral μ-Opioid Receptor Activation in Healthy Humans
Saanijoki, T., Kantonen, T., Pekkarinen, L., Kalliokoski, K. K., Hirvonen, J., Malén, T., Tuominen, L. J., Tuulari, J. J., Arponen, E., Nuutila, P., et al. (2022) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000002895 · Cited by 23 · see citing works
Hackney, M. E., Bay, A. A., Jackson, J. M., Nocera, J. R., Krishnamurthy, V., Crosson, B., Evatt, M. L., Langley, J. A., Cui, X., McKay, J. L., et al. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.00943 · Cited by 22 · see citing works
“AE is also associated with improved hippocampal function in older adults (36) and spared age-related deterioration of white matter tracts (37).”
BackgroundPredovan, D., Gazes, Y., Lee, S., Li, P., Sloan, R. P., & Stern, Y. (2021) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2021.681634 · Cited by 15 · see citing works
“The association between CRF and WMM might be age-dependent, as CRF was positively associated with WMM in older adults (age 55–82), but not in younger adults (age 18–31) (Hayes et al., 2015).”
BackgroundWATER-BASED EXERCISE AND RESISTANCE TRAINING IMPROVE COGNITION IN OLDER ADULTS
Bento-Torres, N. V. O., Bento‐Torres, J., Tomás, A. M., de Souza, L. G. T., de Freitas, J. O., Pantoja, J. A. D. S., & Diniz, C. W. P. (2019) · Revista Brasileira de Medicina do Esporte · doi:10.1590/1517-869220192501190627 · Cited by 15 · see citing works
Chen, F., Erickson, K. I., Huang, H., & Chang, Y. (2020) · Psychophysiology · doi:10.1111/psyp.13539 · Cited by 12 · see citing works
Exercise ameliorates deficits in neural microstructure in a Disc1 model of psychiatric illness
Barnett, B. R., Anderson, J. E., Torres-Velázquez, M., Yi, S. Y., Rowley, P. A., & Yu, J. J. (2019) · Magnetic Resonance Imaging · doi:10.1016/j.mri.2019.05.021 · Cited by 10 · see citing works
“Previous studies on aerobic exercise and white matter microstructural change have largely focused on long-term exercise regimes in aging clinical cohorts, where exercise has been found to have a neuroprotective effect on white matter microstructural integrity [4-14].”
BackgroundAge-dependent relationship of cardiorespiratory fitness and white matter integrity
Mace, R. A., Gansler, D. A., Sawyer, K. S., & Suvak, M. K. (2021) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2021.04.006 · Cited by 8 · see citing works
Olson, K. L., Houston, D. K., Ross, J., Wing, R. R., Simpson, F. R., Pandey, A., Walkup, M. P., Yang, M., & Espeland, M. A. (2023) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000003353 · Cited by 8 · see citing works
“Poorer fitness based on exercise tests is associated with increased vascular aging (30), greater levels of multimorbidity (4), poorer profiles of brain structure and function (31 – 33), and poorer biomarkers of aging (5).”
BackgroundWhite matter pathways as both a target and mediator of health behaviors
Porter, A., Leckie, R. L., & Verstynen, T. (2018) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.13708 · Cited by 8 · see citing works
Chen, F., Soya, H., Yassa, M. A., Li, R., Chu, C., Chen, A., Hung, C., & Chang, Y. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.943992 · Cited by 8 · see citing works
“Previous studies have reported that several brain regions are sensitive to aerobic fitness, including the cingulum bundle, the corpus callosum, the anterior internal capsule, the fornix, and the anterior corona radiata (Johnson et al., 2012; Tseng et al., 2013; Hayes et al., 2015; Oberlin et al., 2016), and the presen…”
BackgroundCaron, B., Bullock, D., Kitchell, L., McPherson, B., Kellar, D. A., Cheng, H., Newman, S. D., Port, N. L., & Pestilli, F. (2020) · doi:10.31234/osf.io/dxaqp · Cited by 9 · see citing works
Clements, G. M., Camacho, P., Bowie, D. C., Low, K. A., Sutton, B. P., Gratton, G., & Fabiani, M. (2025) · Human Brain Mapping · doi:10.1002/hbm.70168 · Cited by 5 · see citing works
“…adult lifespan, instead focusing either on older adults only (Johnson et al. 2012; Liu et al. 2012; Marks et al. 2011; Oberlin et al. 2016; Tian et al. 2014), younger adults only (Herting et al. 2014; Zhu et al. 2015), or comparing extreme groups of younger and older adults (Hayes et al. 2015).”
Xie, Y., Cai, K., Dai, J., & Wei, G. (2023) · Brain Sciences · doi:10.3390/brainsci13040691 · Cited by 4 · see citing works
“It has been reported that FX undergoes age-related decline [53] and is sensitive to aerobic fitness.”
BackgroundMean arterial pressure, fitness, and executive function in middle age and older adults
Gogniat, M. A., Won, J., Callow, D. D., & Smith, J. C. (2022) · Cerebral Circulation - Cognition and Behavior · doi:10.1016/j.cccb.2022.100135 · Cited by 4 · see citing works
Won, J., Tarumi, T., Tomoto, T., Shan, K., Rodrigue, K. M., Kennedy, K. M., Park, D. C., & Zhang, R. (2025) · GeroScience · doi:10.1007/s11357-025-01664-z · Cited by 3 · see citing works
Clinical and Treatment Considerations for the Pediatric and Aging Patients with Multiple Sclerosis
Siddiqui, A., Yang, J. H., Hua, L. H., & Graves, J. S. (2023) · Neurologic Clinics · doi:10.1016/j.ncl.2023.07.003 · Cited by 3 · see citing works
Wang, Y. R., Lefebvre, G., Picard, M., Lamoureux-Andrichuk, A., Ferland, M. C., Therrien-Blanchet, J.-M., Boré, A., Tremblay, J., Descoteaux, M., Champoux, F., et al. (2023) · Neuroscience · doi:10.1016/j.neuroscience.2023.03.007 · Cited by 3 · see citing works
Hegberg, N. J., Dev, S. I., & Hayes, S. M. (2020) · Cambridge University Press eBooks · doi:10.1017/9781108552684.040 · Cited by 2 · see citing works
Markovic, S. J., Hellewell, S. C., Doré, V., Xia, Y., Scott, B. R., Peiffer, J. J., Fitzgerald, M., & Brown, B. M. (2022) · Gerontology · doi:10.1159/000526297 · Cited by 2 · see citing works
Tractography: Applications to neurodevelopment, aging, and plasticity
Lebel, C. A., Salat, D. H., & Yeatman, J. D. (2025) · Elsevier eBooks · doi:10.1016/b978-0-12-818894-1.00009-4 · Cited by 1 · see citing works
Tarumi, T., Won, J., Tomoto, T., Scheel, N., Zhu, D. C., Ashley, J., Rodrigue, K. M., Kennedy, K. M., Park, D. C., & Zhang, R. (2025) · GeroScience · doi:10.1007/s11357-025-01709-3 · Cited by 1 · see citing works
Smith, J. C., Callow, D. D., Pena, G. S., & Purcell, J. J. (2025) · Advances in neurobiology · doi:10.1007/978-981-95-0066-6_14 · Cited by 1 · see citing works
Aging with Parkinson’s Disease
Nocera, J. R., & McGregor, K. (2018) · Handbooks in health, work, and disability · doi:10.1007/978-3-030-03916-5_8 · Cited by 1 · see citing works
Future directions in clinical application of gait, balance and mobility analysis
Mason, R., Tait, P., Morris, R., & Stuart, S. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-21484-4.00017-x · Cited by 1 · see citing works
Campos, D. P., Carbonell-Hernández, L., & Gimeno, E. M. C. (2017) · Dialnet (Universidad de la Rioja) · Cited by 1 · see citing works
Effects of Aging, Fitness, and Cerebrovascular Status on White Matter Microstructural HealthPreprint
Clements, G. M., Camacho, P., Bowie, D. C., Low, K. A., Sutton, B. P., Gratton, G., & Fabiani, M. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.08.04.606520 · Cited by 1 · see citing works
“…as well as cross-sectional and longitudinal studies, supports the positive impact of fitness on white matter integrity in aging (cross-sectional: Hayes et al., 2015; Oberlin et al., 2016; Tarumi et al., 2021b; Tian et al., 2014; Longitudinal: Burzynska et al., 2017; Clark et al., 2019; Mendez…”
BackgroundResultAfonso, A. D. Q., SILVA, D. J. F. D., & Barreto, J. G. (2023) · doi:10.22533/at.ed.54123270611
OCLUSÃO VASCULAR: APTIDÃO E REABILITAÇÃO
Júnior, D. B. L., de MORAES, L. C. P., & SILVA, M. P. M. E. (2023) · doi:10.22533/at.ed.5412327069
Moraes, A. A. D. C., Almeida, G. C. D. S., Duarte, M. B., & Callegari, B. (2023) · doi:10.22533/at.ed.5412327068
Gaia, J. W. P., Ferreira, R. W., & Pires, D. A. (2023) · doi:10.22533/at.ed.54123270610 · Cited by 1 · see citing works
Tópicos em ciências do movimento humano
Penna, E. M., & Coswig, V. S. (2023) · doi:10.22533/at.ed.541232706
AVALIAÇÕES OBJETIVAS DO NÍVEL DE ATIVIDADE FÍSICA
de Sá, K. S. G., Santos, F. G. D., & SILVA, A. D. A. C. E. (2023) · doi:10.22533/at.ed.5412327062
COSTA, N. S. D., Costa, T. D. L., & Neto, J. S. D. M. (2023) · doi:10.22533/at.ed.54123270612
TRINDADE, F. P. P., SILVA, L. M. D., & NETO, J. B.-T. (2023) · doi:10.22533/at.ed.5412327066
VARIÁVEIS DE PRESCRIÇÃO DE EXERCÍCIO
Castanheira, L. F. D. S., Moda, T. E. D. R., FARACHE, W. L. P., & Coswig, V. S. (2023) · doi:10.22533/at.ed.5412327063
Penna, E. M., & Coswig, V. S. (2023) · doi:10.22533/at.ed.5412327061
Tomás, A. M., Moraes, P. M., & Bento-Torres, N. V. O. (2023) · doi:10.22533/at.ed.5412327067
MÉTODOS DE AVALIAÇÃO NEUROMUSCULAR
Noronha, Á. S. N., de Azevedo, A. B. C., Dias, R. K. N., & Coswig, V. S. (2023) · doi:10.22533/at.ed.5412327065
MÉTODOS DE AVALIAÇÃO CARDIORRESPIRATÓRIA
Cruz, S. D. J. V., Moraes, W. R. A., de Castro, V. L., Almeida, C. N. S., Ribeiro, B. C., & Neves, L. M. T. (2023) · doi:10.22533/at.ed.5412327064
Koevoets, E. W., Schagen, S. B., May, A. M., Geerlings, M. I., Witlox, L., van der Wall, E., Stuiver, M. M., Sonke, G. S., Velthuis, M. J., Jobsen, J. J., et al. (2025) · Brain Imaging and Behavior · doi:10.1007/s11682-024-00965-9
“…studies performed in healthy (older adult) and patient populations reported a positive association between (regional) FA and cardiovascular fitness measures (Fissler et al., 2017; Hayes et al., 2015; Johnson et al., 2012; Liu et al., 2012; Opel et al., 2019; Perea et al., 2016; Tseng et al., 2013).”
Smith, S. G., Bharadwaj, P. K., Raichlen, D. A., Grilli, M. D., Andrews‐Hanna, J. R., Hishaw, G. A., Huentelman, M. J., Trouard, T. P., & Alexander, G. E. (2025) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2025.1542458
“…have also involved white matter tracts connected to anterior brain regions, including the genu of the corpus callosum, superior longitudinal fasciculus, inferior longitudinal fasciculus, and uncinate fasciculus (Johnson et al., 2012; Hayes et al., 2015; Oberlin et al., 2016; Ding et al., 2018).”
Elder, M. M., & Ellmore, T. (2025) · bioRxiv · doi:10.1101/2025.07.17.665387
“These patterns align with models of adaptive neuroplasticity (Bennett & Madden, 2014; Fjell & Walhovd, 2010) and are consistent with evidence that aerobic fitness and cognitive engagement can bolster white matter integrity in aging (Hayes et al., 2015; Lee et al., 2024).”
Cloud, J. A., Howe, I., Kraemer, W. J., Volek, J. S., Hayes, J. P., & Hayes, S. M. (2026) · Scientific Reports · doi:10.1038/s41598-026-43466-z
Ukropcova, K., Deckers, K., Koster, A., de Jong, J. J. A., Jansen, J. F. A., Backes, W. H., Savelberg, H. H. C. M., Kallen, C., Schram, M. T., Köhler, S., et al. (2026) · GeroScience · doi:10.1007/s11357-026-02329-1
- Authors
- Hayes, S. M., Salat, D. H., Forman, D. E., Sperling, R. A., & Verfaellie, M.
- Affiliations
- Boston University (US)
- VA Boston Healthcare System (US)
- Geriatric Research Education and Clinical Center (US)
- Brigham and Women's Hospital (US)
- Corresponding author
- Hayes, Scott M.
- Venue
- Annals of Clinical and Translational Neurology
- Publisher
- Wiley
- Published
- 2015-04-24
- Volume
- 2
- Issue
- 6
- Pages
- 688-698
- ISSN
- 2328-9503 (ISSN-L)
- PMC
- PMC4479528
- OpenAlex
- W2133821918
- Cited by
- 75
- References
- 43
- Citations by year
- 2026: 2 · 2025: 9 · 2024: 2 · 2023: 17 · 2022: 7 · 2021: 4 · 2020: 10 · 2019: 8 · 2018: 5 · 2017: 5 · 2016: 2 · 2015: 4
- FWCI
- 4.32
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Annals of Clinical and Translational Neurology (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Department of Veterans Affairs, Rehabilitation Research & Development Service (e7822w)
- Department of Veterans Affairs, Clinical Science Research & Development Service
- National Institute on Aging (K24AG035007)
- Massachusetts Alzheimer's Disease Research Center (P50-AG005134)
- Boston University Alzheimer's Disease Center (P30-AG13846)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Health Sciences › Medicine › Physiology › Physical Activity and Health
- Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Keywords
- cardiorespiratory fitness, white matter integrity, aging, fractional anisotropy, peak oxygen uptake, older adults, corpus callosum, white matter microstructure
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