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We evaluated cognitively unimpaired older adults to identify specific GM patterns, their clinical and cognitive profiles, and longitudinal trajectories.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We analysed 746 participants from the Gothenburg H70 study using random forest cross-sectional clustering based on MRI measures of cortical thickness and subcortical volume across 41 regions. Using regression-based models, we examined associations with clinical, MRI variables, biochemical, and CSF Alzheimer biomarkers (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009286) and assessed 5-year longitudinal cognitive and brain trajectories.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Five clusters emerged, mainly differing in frontoparietal regions. Compared to Cluster 1 (reference), Cluster 2 showed diffuse GM loss, higher odds of diabetes (\n                      <jats:italic>OR<\/jats:italic>\n                      \u2009=\u20092.54, 95%\n                      <jats:italic>CI<\/jats:italic>\n                      [1.27\u20135.06]) and at-risk alcohol consumption (\n                      <jats:italic>OR<\/jats:italic>\n                      \u2009=\u20091.83, 95%\n                      <jats:italic>CI<\/jats:italic>\n                      [1.13\u20132.97]), poorer episodic memory (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2009=\u2009\u2009\u2212\u20090.19,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.014) and visuospatial abilities (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2009=\u2009\u2009\u2212\u20090.21,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.044), and greater longitudinal decline in MMSE (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      <jats:sub>slope<\/jats:sub>\n                      \u2009=\u2009\u2009\u2212\u20090.45,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.035) and increase in white matter hyperintensity volume (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      <jats:sub>slope<\/jats:sub>\n                      \u2009=\u20091.84,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.004). Cluster 3 showed thicker GM and lower BMI (\n                      <jats:italic>OR<\/jats:italic>\n                      \u2009=\u20090.57, 95%\n                      <jats:italic>CI<\/jats:italic>\n                      [0.35\u20130.94]). Cluster 4 had preserved GM, lower smoking habits (\n                      <jats:italic>OR<\/jats:italic>\n                      \u2009=\u20090.62, 95%\n                      <jats:italic>CI<\/jats:italic>\n                      [0.40\u20130.95]), triglyceride levels (\n                      <jats:italic>OR<\/jats:italic>\n                      \u2009=\u20090.55, 95%\n                      <jats:italic>CI<\/jats:italic>\n                      [0.32\u20130.95]) and depression (\n                      <jats:italic>OR<\/jats:italic>\n                      \u2009=\u20090.17, 95%\n                      <jats:italic>CI<\/jats:italic>\n                      [0.05\u20130.56]), higher education (\n                      <jats:italic>OR<\/jats:italic>\n                      \u2009=\u20092.52, 95%\n                      <jats:italic>CI<\/jats:italic>\n                      [1.08\u20135.87]), and better cognition in multiple domains. Cluster 5 had a mixed GM pattern and higher odds of heart disease (\n                      <jats:italic>OR<\/jats:italic>\n                      \u2009=\u20093.44, 95%\n                      <jats:italic>CI<\/jats:italic>\n                      [1.48\u20138.01]).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Cardiovascular and psychosocial factors influence GM integrity, which in turn relates to cognition. Targeting these risk factors may preserve brain health in late life.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12916-025-04583-0","type":"journal-article","created":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T08:05:16Z","timestamp":1765958716000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Risk and protective factors associated with brain grey matter patterns in a population-based cohort of cognitively unimpaired 70\u00a0years old"],"prefix":"10.1186","volume":"24","author":[{"given":"Giulia","family":"Lorenzon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Marseglia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos","family":"Poulakis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camillo","family":"Imbimbo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Ryd\u00e9n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evangelos","family":"Galaris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olof","family":"Lindberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Shams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosaleena","family":"Mohanty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Ferreira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miia","family":"Kivipelto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Eriksdotter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silke","family":"Kern","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingmar","family":"Skoog","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Westman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,17]]},"reference":[{"key":"4583_CR1","first-page":"1","volume":"2022","author":"S Gauthier","year":"2022","unstructured":"Gauthier S, Webster C, Servaes S, Morais J. 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