{
  "abstract": "Cross-sectional studies suggest associations between physical exercise and white matter in older adults, but evidence from randomized controlled trials is scarce. Neurite orientation dispersion and density imaging indices are biophysically informed metrics of white matter microstructure. Here, we tested whether a remotely delivered, 8-week multicomponent physical exercise intervention impacts neurite density (NDI) and orientation dispersion (ODI) across major white matter tracts in older adults. This secondary analysis of a randomized controlled trial included participants with available diffusion MRI data (n = 66; age: 66.4 {+/-} 3.6 y; 43 females). Participants were randomized to a multicomponent exercise (PAG, n = 34) or an active control (CON, n = 32) intervention. Intervention effects on NDI/ODI were tested using linear mixed-effects and Bayesian multilevel models adjusted for age and sex. A significant Timepoint x Group interaction was observed for NDI (p = 0.003) but not for ODI (p = 0.785), further confirmed in Bayesian analyses for 22 white matter tracts, indicating a greater increase in NDI in the PAG. The standardized composite VO2max score increased from pre- to post-intervention within the PAG, although the Timepoint x Group interaction was not significant (p = 0.079). Across all participants, pre-to-post changes in mean NDI were positively correlated with changes in VO2max, but this association did not differ between groups. Our results indicate that white matter microstructure remains responsive to short-term, multicomponent physical exercise in older adults.\n\nSignificance statementWhite matter microstructure deteriorates with aging. Given the ample health benefits of physical exercise, we investigated whether it can also improve white matter microstructural indices. In this randomized controlled trial, an 8-week remotely delivered multicomponent exercise program increased an MRI-based index of white matter tissue density across major tracts in older adults. These changes were not observed in an active control group. An index of white matter tissue orientation did not show intervention-related changes. Our findings provide experimental evidence that white matter microstructure remains sensitive and responsive to short-term multicomponent physical exercise in later life.",
  "abstract_shown": true,
  "affiliations": [
    "Jena University Hospital"
  ],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "A. L. Ruiz-Rizzo"
    },
    {
      "name": "S. J. Schrenk"
    },
    {
      "name": "S. Brodoehl"
    },
    {
      "name": "C. Frahm"
    },
    {
      "name": "C. Gaser"
    },
    {
      "name": "M. Herbsleb"
    },
    {
      "name": "C. Puta"
    },
    {
      "name": "O. W. Witte"
    },
    {
      "name": "K. Finke"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/c5zz6bvvf3qfh.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.08.31.26361810",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.08.31.26361810v1.full",
  "id": "c5zz6bvvf3qfh",
  "issns": [],
  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.08.31.26361810v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "medrxiv",
      "neurology"
    ],
    [
      "openalex",
      "2741|Advanced Neuroimaging Techniques and Applications"
    ]
  ],
  "openalex": "W7208740018",
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.08.31.26361810v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-08-31",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/c5zz6bvvf3qfh.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:47Z",
      "native_id": "10.64898/2026.08.31.26361810",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.08.31.26361810v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "medrxiv:neurology",
      "subfield": "neurology"
    }
  ],
  "title": "Physical exercise increases the NODDI-derived neurite density index across white matter tracts in healthy older adults: results from the FIT4BRAIN randomized controlled trial",
  "title_text": "Physical exercise increases the NODDI-derived neurite density index across white matter tracts in healthy older adults: results from the FIT4BRAIN randomized controlled trial",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:47Z",
  "url": "https://research.draconitic.com/paper/c5zz6bvvf3qfh",
  "venue": "medRxiv",
  "versions": []
}