{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T11:16:23Z","timestamp":1793531783727,"version":"4.5.0"},"reference-count":39,"publisher":"American Medical Association (AMA)","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA"],"published-print":{"date-parts":[[2025,8,26]]},"abstract":"\n Importance<\/jats:title>\n Identifying new interventions to slow and prevent cognitive decline associated with dementia is critical. Nonpharmacological interventions targeting modifiable risk factors are promising, relatively low-cost, accessible, and safe approaches.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To compare the effects of two 2-year lifestyle interventions on cognitive trajectory in older adults at risk of cognitive decline and dementia.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n Single-blind, multicenter randomized clinical trial enrolling 2111 participants from May 2019 to March 2023 (final follow-up, May 14, 2025) at 5 clinical sites in the US. Participant inclusion criteria enriched risk of cognitive decline and included age 60 to 79 years, sedentary lifestyle, and suboptimal diet plus at least 2 additional criteria related to family history of memory impairment, cardiometabolic risk, race and ethnicity, older age, and sex.<\/jats:p>\n <\/jats:sec>\n \n Interventions<\/jats:title>\n Participants were randomly assigned with equal probability to structured (n\u2009=\u20091056) or self-guided (n\u2009=\u20091055) interventions. Both interventions encouraged increased physical and cognitive activity, healthy diet, social engagement, and cardiovascular health monitoring, but differed in structure, intensity, and accountability.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n The primary comparison was difference between intervention groups in annual rate of change in global cognitive function, assessed by a composite measure of executive function, episodic memory, and processing speed, over 2 years.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Among the 2111 individuals enrolled (mean age, 68.2 [SD, 5.2] years; 1455 [68.9%] female), 89% completed the year 2 assessment. The mean global cognitive composite\n z<\/jats:italic>\n score increased from baseline over time in both groups, with a mean rate of increase per year of 0.243 SD (95% CI, 0.227-0.258) for the structured intervention and 0.213 SD (95% CI, 0.198-0.229) for the self-guided intervention. The mean rate of increase per year was statistically significantly greater for the structured group than the self-guided group by 0.029 SD (95% CI, 0.008-0.050;\n P<\/jats:italic>\n \u2009=\u2009.008). Based on prespecified secondary subgroup comparisons, the structured intervention benefit was consistent for\n APOE<\/jats:italic>\n \u03b54 carriers and noncarriers (\n P<\/jats:italic>\n \u2009=\u2009.95 for interaction) but appeared greater for adults with lower vs higher baseline cognition (\n P<\/jats:italic>\n \u2009=\u2009.02 for interaction). Fewer ascertained adverse events were reported in the structured group (serious: 151; nonserious: 1091) vs the self-guided group (serious: 190; nonserious: 1225), with a positive COVID-19 test result being the most common adverse event overall and more frequent in the structured group.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n Among older adults at risk of cognitive decline and dementia, a structured, higher-intensity intervention had a statistically significant greater benefit on global cognition compared with an unstructured, self-guided intervention. Further investigation of functional outcomes, biomarkers, and ongoing extended follow-up will help address clinical relevance and sustainability of the observed cognitive benefits.<\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n ClinicalTrials.gov Identifier:\n NCT03688126<\/jats:ext-link>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jama.2025.12923","type":"journal-article","created":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T18:30:17Z","timestamp":1753727417000},"page":"681","source":"Crossref","is-referenced-by-count":296,"title":["Structured vs Self-Guided Multidomain Lifestyle Interventions for Global Cognitive Function"],"prefix":"10.1001","volume":"334","author":[{"given":"Laura D.","family":"Baker","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark 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