{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T22:10:09Z","timestamp":1793916609187,"version":"4.8.0"},"reference-count":77,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T00:00:00Z","timestamp":1775952000000},"content-version":"vor","delay-in-days":11,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Brain imaging markers may help detect early cognitive decline and Alzheimer\u2019s disease (AD). Although exercise-related effects on AD-specific brain signatures remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To examine the effects of a 24-week resistance exercise (RE) program on AD brain signatures in cognitively unimpaired older adults, to explore potential moderators and to assess associations with cognition, including mediation effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This secondary analysis of a single-site, two-arm, single-blinded randomized controlled trial included 90 participants (72\u2009\u00b1\u20094\u00a0years; 58% female) randomly assigned by a blind external researcher to an RE group (3 sessions\/week, 60\u00a0min\/session, n\u2009=\u200946) or a wait-list control group (CG, n\u2009=\u200944). T1- and diffusion-weighted MRI were acquired at baseline and post-intervention. Primary outcomes were thickness\/volume and grey matter mean diffusivity (GMMD) signatures, derived from cortical and hippocampal regions. Moderators included age, sex, education, multimorbidity, apolipoprotein E \u03f54 status, amyloid beta (A\u03b2) status and baseline AD brain signatures. Secondary outcomes included cognitive function. Outcome measures and analyses were conducted by staff blinded to intervention assignment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Compared with the CG, the RE group showed a reduction in the thickness\/volume signature (\u22120.23 standardized mean difference [SMD]; 95% CI, \u22120.43 to \u22120.02), but no effect on the GMMD signature (0.08 SMD; 95% CI, \u22120.13 to 0.29). A\u03b2-status moderated the effect, as A\u03b2-positive participants in the RE group showed a larger reduction in the thickness\/volume signature than those in the CG (\u22120.64 SMD; 95% CI, \u22121.09 to \u22120.18), whereas no effect was observed in A\u03b2-negative participants. Thickness\/volume and GMMD reductions were associated with improvements in executive function and attentional\/inhibitory control, respectively. Changes in AD signatures did not mediate cognitive outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings suggest that reductions in the macrostructural AD signature following a 24-week RE program may reflect adaptive, rather than detrimental, brain changes, particularly in A\u03b2-positive older adults, as these changes were associated with improved executive function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>Registered on Clinicaltrials.gov (Identifier: NCT05186090).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ageing\/afag086","type":"journal-article","created":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T12:50:13Z","timestamp":1774529413000},"source":"Crossref","is-referenced-by-count":4,"title":["Effects of a 24-week resistance exercise program on Alzheimer\u2019s disease brain signatures in cognitively unimpaired older adults: a secondary analysis of the AGUEDA randomized controlled trial"],"prefix":"10.1093","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9451-8454","authenticated-orcid":false,"given":"Javier","family":"Sanchez-Martinez","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 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2493-9528","authenticated-orcid":false,"given":"Patricio","family":"Solis-Urra","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 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University Research Institute (iMUDS), University of Granada , Granada ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0234-8751","authenticated-orcid":false,"given":"Luc\u00eda","family":"S\u00e1nchez-Aranda","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 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8736-981X","authenticated-orcid":false,"given":"Kirk I","family":"Erickson","sequence":"additional","affiliation":[{"name":"Neuroscience Institute Orlando, AdventHealth Research Institute , Orlando, FL ,","place":["USA"]},{"name":"Department of Psychology, University of Pittsburgh , Pittsburgh, PA 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