{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T23:12:48Z","timestamp":1791673968314,"version":"4.3.4"},"reference-count":26,"publisher":"American Medical Association (AMA)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Neurol"],"published-print":{"date-parts":[[2026,6,1]]},"abstract":"<jats:sec>\n                    <jats:title>Importance<\/jats:title>\n                    <jats:p>Brain imaging biomarkers may (1) identify underlying mechanisms of intervention effects and (2) define brain characteristics of those most likely to benefit cognitively from the intervention.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To test whether (1) a lifestyle intervention is related to brain changes, (2) brain changes are correlated with intervention-specific cognition changes, and (3) brain imaging biomarkers provide information about who is likely to benefit from a lifestyle intervention.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design, Setting, and Participants<\/jats:title>\n                    <jats:p>In this randomized clinical trial, the POINTER Imaging study was an ancillary study of the 2-year, single-blind multicenter US POINTER clinical trial in which neuroimaging data were collected on eligible enrolled participants. The study was conducted from May 2019 to March 2023 (final follow-up, May 14, 2025). Participants were enrolled into the POINTER Imaging study following a standard procedure at 5 clinical sites in the US. Participant eligibility criteria included an age of 60 to 79 years, sedentary lifestyle, and suboptimal diet, plus at least 2 additional risk criteria for cognitive decline and no contraindications for neuroimaging.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interventions<\/jats:title>\n                    <jats:p>Participants were randomly assigned to receive the structured or self-guided intervention. Both interventions emphasized increased physical and cognitive activity, healthy nutrition, social engagement, and cardiovascular health monitoring, but they differed in intensity and accountability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main Outcomes and Measures<\/jats:title>\n                    <jats:p>There were 4 primary imaging outcomes: global \u03b2-amyloid (A\u03b2) burden, tau burden in the entorhinal cortex (ERC), hippocampal (HC) volume, and white matter hyperintensity volume. The primary cognitive measure was a global cognitive composite.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 1943 parent trial participants who were assessed for eligibility, 983 underwent at least 1 magnetic resonance imaging or positron emission tomography scanning session. The mean (SD) age was 68.4 (5.2) years; 605 participants (61.5%) were female and 378 male (38.5%). Five hundred sixteen participants received the structured intervention and 467 the self-guided intervention. There were no intervention group differences in longitudinal cognitive or imaging outcomes. Intervention group differences were not associated with or moderated by A\u03b2 status or accumulation. There was a negative association between change in ERC tau and change in global cognition in the self-guided group that was attenuated in the structured group (difference in association: 0.289; 95% CI, 0.029 to 0.550; interaction\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u2009.03). Lower baseline HC volume was associated with greater cognitive benefit for participants in the structured group vs the self-guided group (lower HC: 0.077 SD; 95% CI, 0.022 to 0.132; higher HC: 0.002 SD; 95% CI, \u22120.037 to 0.041; interaction\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u2009.03).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Relevance<\/jats:title>\n                    <jats:p>This study found that a high-intensity multidomain lifestyle intervention did not affect brain biomarker trajectories and was not associated with A\u03b2 pathology, but older adults with specific at-risk brain characteristics, including lower baseline HC volume, showed a greater cognitive benefit of the structured intervention.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>\n                      ClinicalTrials.gov Identifier:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT03688126\">NCT03688126<\/jats:ext-link>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1001\/jamaneurol.2026.0832","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T15:30:36Z","timestamp":1776699036000},"page":"521","source":"Crossref","is-referenced-by-count":5,"title":["Brain Imaging Biomarkers and Cognitive Outcomes in a Multidomain Lifestyle Intervention"],"prefix":"10.1001","volume":"83","author":[{"given":"Theresa M.","family":"Harrison","sequence":"first","affiliation":[{"name":"University of California, Berkeley"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle 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