{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T12:17:31Z","timestamp":1791980251355,"version":"4.4.0"},"reference-count":45,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T00:00:00Z","timestamp":1757894400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T00:00:00Z","timestamp":1757894400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["Intramural Research Program"],"award-info":[{"award-number":["Intramural Research Program"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health and Care Research","doi-asserted-by":"publisher","award":["NIHR301844"],"award-info":[{"award-number":["NIHR301844"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Brain iron in specific subcortical regions increases risk of dementia and Parkinson's disease (PD). Genetic and environmental factors affect iron deposition, but underlying mechanisms are unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Identify risk factors and diseases associated with brain iron; assess causality using genetics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>41,581 UK Biobank participants had MRI-estimated brain iron (QSM method) in five dementia or PD-associated subcortical regions (caudate, hippocampus, putamen, substantia nigra, thalamus). We investigated common risk factors (including adiposity, blood pressure, health behaviors, inflammation) and diseases observationally, using covariate-adjusted regression models, and genetically, with Mendelian randomization.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Participants diagnosed with Alzheimer's disease, PD, or other diseases had higher MRI-estimated brain iron. Anemia, osteoporosis, and hyperparathyroidism were associated with lower brain iron. Higher body mass index and blood pressure, smoking history, and self-reported meat consumption, increased brain iron. Hematological parameters, inflammatory and kidney biomarkers, and calcium, were also associated. Genetics support causal effects of depression, type-2 diabetes, and 7 other diseases with increased iron, but not Alzheimer's disease. Evidence supports a causal effect of osteoporosis on lower iron in the substantia nigra. We found causal associations between adiposity and proteins (including IL-6 receptor and transferrin receptor) on subcortical brain iron.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We identified causal effects for liability to type-2 diabetes, depression, and other conditions, on subcortical MRI-estimated brain iron, but not to Alzheimer's disease, supportive of dementia as a consequence of brain iron deposition, not a cause. The role of adiposity reducing interventions on brain iron should be investigated. Relationships between brain iron, osteoporosis, calcium, and hyperparathyroidism warrant further investigation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877251375432","type":"journal-article","created":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T17:26:03Z","timestamp":1757957163000},"page":"107-118","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["Predictors of MRI-estimated brain iron deposition in dementia and Parkinson's disease-associated subcortical regions: Genetic and observational analysis in UK Biobank"],"prefix":"10.1177","volume":"108","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0275-4765","authenticated-orcid":false,"given":"Francesco","family":"Casanova","sequence":"first","affiliation":[{"name":"Department of Clinical and Biomedical Sciences, University of Exeter, Exeter, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qu","family":"Tian","sequence":"additional","affiliation":[{"name":"Translational Gerontology Branch Longitudinal Studies Section, National Institute on Aging, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1152-9755","authenticated-orcid":false,"given":"Daniel S","family":"Williamson","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biomedical Sciences, University of Exeter, Exeter, UK"},{"name":"Department of Health and Care Professions, University of Exeter, Exeter, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0351-4608","authenticated-orcid":false,"given":"Mitchell R","family":"Lucas","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biomedical Sciences, University of Exeter, Exeter, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Zweibaum","sequence":"additional","affiliation":[{"name":"Translational Gerontology Branch Longitudinal Studies Section, National Institute on Aging, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Ding","sequence":"additional","affiliation":[{"name":"Translational Gerontology Branch Longitudinal Studies Section, National Institute on Aging, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janice L","family":"Atkins","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biomedical Sciences, University of Exeter, Exeter, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Melzer","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biomedical Sciences, University of Exeter, Exeter, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Ferrucci","sequence":"additional","affiliation":[{"name":"Translational Gerontology Branch Longitudinal Studies Section, National Institute on Aging, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3332-8454","authenticated-orcid":false,"given":"Luke C","family":"Pilling","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biomedical Sciences, University of Exeter, Exeter, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,9,15]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23137267"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.5045\/br.2013.48.1.10"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2024.106539"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg-2023-109295"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-240605"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-022-01074-w"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-201080"},{"key":"e_1_3_3_9_2","first-page":"644","article-title":"Correlation of cardiovascular risk factors with brain iron deposition: a magnetic resonance imaging study","volume":"48","author":"Hu L","year":"2019","unstructured":"Hu L, Zhang R, Wang S, et al. 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