{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T14:55:40Z","timestamp":1791557740045,"version":"4.3.4"},"reference-count":34,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T00:00:00Z","timestamp":1748995200000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["NSTC 112\u20102321\u2010B\u2010075\u2010004"],"award-info":[{"award-number":["NSTC 112\u20102321\u2010B\u2010075\u2010004"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["NSTC 112\u20102321\u2010B\u2010A49\u2010006"],"award-info":[{"award-number":["NSTC 112\u20102321\u2010B\u2010A49\u2010006"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>While multidomain interventions show promise for promoting healthy aging, their impact on brain structure remains unclear. This randomized controlled trial (ENHANCE) assessed the efficacy of a 12\u2010month group\u2010based multidomain intervention on brain structure and function in community\u2010dwelling older adults, with particular attention to urban\u2013rural disparities.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The ENHANCE trial delivered twice\u2010weekly group\u2010based multidomain sessions (physical exercise, cognitive training and nutrition education) in urban and rural communities for 12\u2009months, while the control group received quarterly telephone education. A total of 88 participants completed the trial (attendance rates &gt;\u200960% across all sites), with 76 completing longitudinal MRI assessments (intervention: <jats:italic>n<\/jats:italic>\u2009=\u200935; control: <jats:italic>n<\/jats:italic>\u2009=\u200941). The intervention group (<jats:italic>n<\/jats:italic>\u2009=\u200944; 75.0% female) was significantly older than the control group (<jats:italic>n<\/jats:italic>\u2009=\u200944; 70.5% female) (75.0\u2009\u00b1\u20096.6 vs. 72.3\u2009\u00b1\u20095.0\u2009years, <jats:italic>p<\/jats:italic>\u2009=\u20090.035) and had lower BMI (23.4 vs. 25.2\u2009kg\/m<jats:sup>2<\/jats:sup>, <jats:italic>p<\/jats:italic>\u2009=\u20090.016) at baseline. The primary outcomes were brain structures (voxel\u2010based changes in brain grey matter volume [GMV]), while secondary outcomes were functional outcomes (physical performance, nutritional status, cognitive function, psychosocial assessments and cardiometabolic biomarkers).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Using two\u2010stage tensor\u2010based morphometry analysis, the intervention group demonstrated significantly less GMV reduction in regions over the left inferior temporal lobe compared with controls over 12\u2009months (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). Using generalized estimating equation (GEE) model, the intervention group showed enhanced physical performance at 6\u2009months (5\u2010time chair rise test: \u22121.19\u2009s; 95% CI, \u22122.24 to \u22120.13; <jats:italic>p<\/jats:italic>\u2009=\u20090.028) and improved cognitive function by 12\u2009months (Montreal Cognitive Assessment: +1.32 points; 95% CI, 0.10\u20132.54; <jats:italic>p<\/jats:italic>\u2009=\u20090.034). Cardiometabolic improvements included increased HDL\u2010C (+6.65\u2009mg\/dL, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) and decreased triglycerides (\u221216.07\u2009mg\/dL, <jats:italic>p<\/jats:italic>\u2009=\u20090.025) at 12\u2009months in GEE models. In subgroup analyses, rural participants showed preserved GMV in additional regions including the cerebellum (Crus I and II) and occipital cortex with greater cognitive improvements (MoCA: +3.06 points; 95% CI, 0.84\u20135.27; <jats:italic>p<\/jats:italic>\u2009=\u20090.007), while urban participants showed greater GMV reduction in the left temporal\u2010occipital fusiform cortex but achieved superior physical performance gains (5\u2010time chair rise test: \u22121.85\u2009s; 95% CI, \u22123.07 to \u22120.64; <jats:italic>p<\/jats:italic>\u2009=\u20090.003).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study demonstrates that multidomain interventions can induce neuroplasticity in older adults, with differential effects on brain structure and function between urban and rural participants, emphasizing the need for tailored approaches that consider sociocultural factors to optimize healthy aging across diverse populations.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.13830","type":"journal-article","created":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T11:04:45Z","timestamp":1749726285000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Enhancing Neurocognitive Health via Activity, Nutrition and Cognitive Exercise (ENHANCE): A Randomized Controlled Trial"],"prefix":"10.1002","volume":"16","author":[{"given":"Li\u2010Ning","family":"Peng","sequence":"first","affiliation":[{"name":"Center for Geriatric and Gerontology Taipei Veterans General Hospital  Taipei City Taiwan"},{"name":"Center for Healthy Longevity and Aging Sciences National Yang Ming Chiao Tung University  Taipei City Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei\u2010Lin","family":"Lee","sequence":"additional","affiliation":[{"name":"Center for Healthy Longevity and Aging Sciences National Yang Ming Chiao Tung University  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