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A total of 91 participants were enrolled in the AGUEDA trial (NCT05186090), with 89 included in this cross\u2010sectional analysis (mean age\u2009=\u200971.61\u2009\u00b1\u20093.85\u2009years; 56.2% females). Moderate\u2010to\u2010vigorous physical activity (MVPA), light physical activity (LPA), sedentary behavior (SB), and sleep were objectively assessed using 9\u2010day wrist\u2010worn accelerometry. Cognitive function was assessed across attention\/inhibitory control, episodic memory, processing speed, visuospatial processing, and working memory. Thickness\/volume and GMMD signatures were derived from cortical and hippocampal regions. Compositional linear regression models (CoDA) examined associations, adjusting for age, sex, and education, and tested interactions between movement behaviors and Alzheimer's disease brain signatures. No direct associations were observed between 24\u2010h movement behaviors and cognitive domains (all\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&gt;\u20090.05). However, GMMD signature, but not thickness\/volume signature, moderated several movement behavior\u2010cognition associations. Moderation was most evident for episodic memory, with significant interactions for MVPA, LPA, and sleep, while LPA exhibited the broadest pattern of moderation across cognitive domains, interacting with attention\/inhibitory control, episodic memory, processing speed, and working memory (all\n                    <jats:italic>p<\/jats:italic>\n                    for interaction \u2264\u20090.04). In conclusion, the associations between 24\u2010h movement behaviors and cognitive function may depend on microstructural brain integrity (i.e., GMMD). These findings highlight the importance of considering Alzheimer's disease\u2010related brain signatures when investigating lifestyle\u2013cognition associations and support a more personalized approach to promoting cognitive health in older adults. Future prospective longitudinal studies and CoDA interventional trials are needed to establish temporal precedence and evaluate whether targeted time reallocations can actively attenuate cognitive trajectories across distinct microstructural vulnerability profiles.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Trial Registration:<\/jats:bold>\n                    NCT05186090\n                  <\/jats:p>","DOI":"10.1111\/sms.70360","type":"journal-article","created":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T09:09:56Z","timestamp":1788685796000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Microstructural Brain Reserve Moderates the Associations Between 24\u2010h Movement Behaviors and Cognition in Older Adults: Cross\u2010Sectional Findings From the\n                    <scp>AGUEDA<\/scp>\n                    Trial"],"prefix":"10.1111","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8987-9925","authenticated-orcid":false,"given":"Beatriz","family":"Fernandez\u2010Gamez","sequence":"first","affiliation":[{"name":"Department of Physical Education and Sports, Faculty of Sport Sciences, Sport and Health University Research Institute (iMUDS) University of Granada  Granada Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2493-9528","authenticated-orcid":false,"given":"Patricio","family":"Solis\u2010Urra","sequence":"additional","affiliation":[{"name":"Department of Physical Education and Sports, Faculty of Sport Sciences, Sport and Health University Research Institute (iMUDS) University of Granada  Granada Spain"},{"name":"AdventHealth Research Institute Neuroscience Institute  Orlando Florida USA"},{"name":"Faculty of Education and Social Sciences Universidad Andres Bello  Vi\u00f1a del Mar Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Sanchez\u2010Martinez","sequence":"additional","affiliation":[{"name":"Department of Physical Education and Sports, Faculty of Sport Sciences, Sport and Health University Research Institute (iMUDS) University of Granada  Granada Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6573-6867","authenticated-orcid":false,"given":"Alessandro","family":"Sclafani","sequence":"additional","affiliation":[{"name":"Department of Physical Education and Sports, Faculty of Sport Sciences, Sport and Health University Research Institute (iMUDS) University of Granada  Granada Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7922-1647","authenticated-orcid":false,"given":"Marcos","family":"Olvera\u2010Rojas","sequence":"additional","affiliation":[{"name":"Department of Physical Education and Sports, Faculty of Sport Sciences, Sport and Health University Research Institute (iMUDS) University of Granada  Granada Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Teresa","family":"Rodr\u00edguez\u2010Palacios","sequence":"additional","affiliation":[{"name":"Department of Physical Education and Sports, Faculty of Sport Sciences, Sport and Health University Research Institute (iMUDS) University of Granada  Granada Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maddison L.","family":"Mellow","sequence":"additional","affiliation":[{"name":"Alliance for Research in Exercise, Nutrition and Activity, Allied Health and Human Performance, College of Health Adelaide University  Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorothea","family":"Dumuid","sequence":"additional","affiliation":[{"name":"Alliance for Research in Exercise, Nutrition and Activity, Allied Health and Human Performance, 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