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Regular physical activity is known to mitigate cognitive decline; whether the degree of benefit differs by\n                      <jats:italic>APOE<\/jats:italic>\n                      genotype, sex, and race remains unknown.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Analyses utilized data from 2,985 participants in the Health, Aging, and Body Composition (HABC) cohort, comprising community-dwelling black and white older adults followed for 10 years. Cognitive performance was assessed multiple times across the 10 years using the Digit Symbol Substitution Test (DSST) for executive functions and processing speed and the Modified Mini-Mental State Examination (3MS) for global cognition.\n                      <jats:italic>APOE<\/jats:italic>\n                      genotypes were categorized into \u03b52, \u03b53, and \u03b54 groups. Annual self-reported walking time was used to quantify physical activity. Linear mixed models and latent growth curve modeling examined the interactions between\n                      <jats:italic>APOE<\/jats:italic>\n                      genotype, sex, and walking on cognitive trajectories with adjustments for race, study location, health score, age, education attained, and body mass index.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54 carriers demonstrated steeper declines in both DSST and 3MS scores compared to \u03b53 carriers, irrespective of sex (all \u03b2&lt;-0.13, all\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.004).\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b52 was protective longitudinally for 3MS in females only (\u03b2\u2009=\u20090.15,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.002). Walking showed the strongest protective effect in\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54 carriers for females and males in the rate of change of DSST and 3MS scores (all \u03b2\u2009&gt;\u20090.27, all\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.044).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings underscore the importance of public messaging about the benefits of regular physical activity for retaining cognitive function especially for persons genetically at heightened risk.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13293-026-00860-6","type":"journal-article","created":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T11:23:40Z","timestamp":1771673020000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Walking to protect against cognitive decline: the role of APOE genotype and sex"],"prefix":"10.1186","volume":"17","author":[{"given":"Joel S.","family":"Burma","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caterina","family":"Rosano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John R.","family":"Best","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eleanor M.","family":"Simonsick","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teresa","family":"Liu-Ambrose","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cindy K.","family":"Barha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,2,21]]},"reference":[{"key":"860_CR1","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1055\/s-0035-1555115","volume":"36","author":"DL Murman","year":"2015","unstructured":"Murman DL. 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