{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T01:18:46Z","timestamp":1790903926365,"version":"4.1.0"},"posted":{"date-parts":[[2024,3,15]]},"group-title":"Neurology","reference-count":67,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,3,15]],"date-time":"2024-03-15T00:00:00Z","timestamp":1710460800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,3,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Alterations in brain iron accumulation, representing both excess or insufficiency of iron, are associated with Parkinson\u2019s disease. Iron is exclusively absorbed from food; therefore, dietary patterns may impact risk.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>Assess associations between dietary preferences, brain iron, and Parkinson\u2019s disease risk.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>This study included 228,653 individuals and utilized dietary surveys, magnetic resonance imaging, and electronic health records of neurological diagnoses. We performed regression analyses using i) estimated dietary nutrient intake, ii) dietary preferences, and iii) a lower-dimensional space factor-loading dietary preferences to predict a novel brain iron accumulation score derived from T2-weighted MRI and Parkinson\u2019s disease diagnosis.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    We found strong positive associations between measures of brain iron accumulation and the alcohol factor (\n                    <jats:italic>t<\/jats:italic>\n                    =4.02,\n                    <jats:italic>\n                      p\n                      <jats:sub>FDR<\/jats:sub>\n                    <\/jats:italic>\n                    &lt;0.001) and significant negative associations between brain iron accumulation and the high-sugar factor (\n                    <jats:italic>t<\/jats:italic>\n                    =-3.73,\n                    <jats:italic>\n                      p\n                      <jats:sub>FDR<\/jats:sub>\n                    <\/jats:italic>\n                    &lt;0.001). Conversely, the alcohol factor was associated with decreased Parkinson\u2019s disease risk (\n                    <jats:italic>t<\/jats:italic>\n                    =-5.83,\n                    <jats:italic>p<\/jats:italic>\n                    &lt;1\u00d710\n                    <jats:sup>\u22128<\/jats:sup>\n                    ) and the high-sugar factor was associated with increased Parkinson\u2019s disease risk (\n                    <jats:italic>t<\/jats:italic>\n                    =6.03,\n                    <jats:italic>p<\/jats:italic>\n                    &lt;1\u00d710\n                    <jats:sup>\u22128<\/jats:sup>\n                    ). Instrumental variable regression revealed that dietary preferences associated with higher brain iron were also associated with lower risk for Parkinson\u2019s disease (\u25a1=-0.247,\n                    <jats:italic>p<\/jats:italic>\n                    =0.004). Voxel-wise imaging analysis displayed iron accumulation patterns consistent with these findings.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Contrary to some prior studies, we find lower central iron levels to be associated with greater Parkinson\u2019s disease risk. Dietary components, especially alcohol and carbohydrates, are related to differences in brain iron accumulation in motor regions of the brain and differences in risk of Parkinson\u2019s disease, suggesting the potential for dietary interventions to influence Parkinson\u2019s disease risk.<\/jats:p>\n                  <jats:fig id=\"ufig1\" position=\"float\" orientation=\"portrait\" fig-type=\"figure\">\n                    <jats:label>Graphical Abstract:<\/jats:label>\n                    <jats:caption>\n                      <jats:title>Dietary and Lifestyle Factors of Brain Iron Accumulation<\/jats:title>\n                      <jats:p>\n                        *Previous research has established that iron overload in the brain is associated with increased risk of movement disorders.\n                        <jats:sup>4\u20137<\/jats:sup>\n                      <\/jats:p>\n                    <\/jats:caption>\n                    <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"24304253v3_ufig1\" position=\"float\" orientation=\"portrait\"\/>\n                  <\/jats:fig>\n                <\/jats:sec>","DOI":"10.1101\/2024.03.13.24304253","type":"posted-content","created":{"date-parts":[[2024,3,15]],"date-time":"2024-03-15T18:25:18Z","timestamp":1710527118000},"source":"Crossref","is-referenced-by-count":6,"title":["Dietary Factors Affect Brain Iron Accumulation and Parkinson\u2019s Disease Risk"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-0115-4527","authenticated-orcid":false,"given":"Jonathan","family":"Ahern","sequence":"first","affiliation":[{"name":"Department of Cognitive Science, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA"},{"name":"Center for Population Neuroscience and Genetics, Laureate Institute for Brain Research, 6655 S Yale Ave, Tulsa, OK 74136, USA"},{"name":"J. Craig Venter Institute, 4120 Capricorn Lane, La Jolla, CA 92037 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary ET","family":"Boyle","sequence":"additional","affiliation":[{"name":"Department of Cognitive Science, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo","family":"Sugrue","sequence":"additional","affiliation":[{"name":"Department of Radiology and Biomedical Imaging, University of California, 505 Parnassus Ave, San Francisco, CA 94143, USA"},{"name":"Department of Psychiatry, University of California, 675 18th St, San Francisco, CA 94107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4461-3568","authenticated-orcid":false,"given":"Ole","family":"Andreassen","sequence":"additional","affiliation":[{"name":"NORMENT Centre, Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Problemveien 11, 0313 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"Dale","sequence":"additional","affiliation":[{"name":"Department of Cognitive Science, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA"},{"name":"J. Craig Venter Institute, 4120 Capricorn Lane, La Jolla, CA 92037 USA"},{"name":"Department of Neuroscience, University of California, San Diego School of Medicine, 9500 Gilman Drive, La Jolla, CA 92037, USA"},{"name":"Department of Radiology, University of California, San Diego School of Medicine, 9500 Gilman Drive, La Jolla, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wesley K.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Center for Population Neuroscience and Genetics, Laureate Institute for Brain Research, 6655 S Yale Ave, Tulsa, OK 74136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9437-2128","authenticated-orcid":false,"given":"Chun Chieh","family":"Fan","sequence":"additional","affiliation":[{"name":"Center for Population Neuroscience and Genetics, Laureate Institute for Brain Research, 6655 S Yale Ave, Tulsa, OK 74136, USA"},{"name":"Department of Radiology, University of California, San Diego School of Medicine, 9500 Gilman Drive, La Jolla, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Loughnan","sequence":"additional","affiliation":[{"name":"Department of Cognitive Science, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA"},{"name":"Center for Population Neuroscience and Genetics, Laureate Institute for Brain Research, 6655 S Yale Ave, Tulsa, OK 74136, USA"},{"name":"J. 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