{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:28:11Z","timestamp":1786976891515,"version":"build-2736575974"},"reference-count":33,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100019111","name":"Perron Institute for Neurological and Translational Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100019111","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>\n                      Identifying individuals at risk of dementia is essential for prevention and targeted disease\u2010modifying strategies. We investigated whether mid\u2010life metabolomic ageing is associated with incident dementia and its age of onset and assessed joint associations and interactions with\n                      <jats:italic>APOE<\/jats:italic>\n                      genotype and dementia polygenic scores.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>In the UK Biobank, plasma metabolites were quantified at baseline. Metabolomic age (MileAge) delta reflects the difference between metabolite\u2010predicted and chronological age. Dementia was identified via health records.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Amongst 223,496 participants, 3976 developed dementia. A higher MileAge delta was associated with higher hazards of all\u2010cause, unspecified and vascular dementia (HR\u00a0=\u00a01.61, 95% CI 1.28\u20132.02,\n                      <jats:italic>p\u00a0<\/jats:italic>\n                      =\u00a00.001) and earlier onset. Key metabolites were lipids, lipoproteins and amino acids. MileAge delta and genetic risk were jointly associated with dementia. Individuals with a high MileAge delta and two\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54 alleles had a 10.30\u2010fold higher all\u2010cause dementia risk (95% CI 7.95\u201013.34,\n                      <jats:italic>p\u00a0<\/jats:italic>\n                      &lt;\u00a00.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Metabolomic ageing and genetic risk likely represent independent biological pathways contributing to dementia risk.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71280","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T11:01:30Z","timestamp":1778670090000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Metabolomic ageing (MileAge) in mid\u2010life predicts incident vascular, unspecified and all\u2010cause dementia"],"prefix":"10.1002","volume":"22","author":[{"given":"Julian","family":"Mutz","sequence":"first","affiliation":[{"name":"Social, Genetic and Developmental Psychiatry Centre Institute of Psychiatry, Psychology &amp; Neuroscience, King's College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lachlan","family":"Gilchrist","sequence":"additional","affiliation":[{"name":"Social, Genetic and Developmental Psychiatry Centre Institute of Psychiatry, Psychology &amp; Neuroscience, King's College London  London UK"},{"name":"Perron Institute for Neurological and Translational Science  Perth Australia"},{"name":"Centre for Preventive Neurology Wolfson Institute of Population Health, Queen Mary's University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Pain","sequence":"additional","affiliation":[{"name":"Maurice Wohl Clinical Neuroscience Institute Department of Basic and Clinical Neuroscience Institute of Psychiatry, Psychology &amp; Neuroscience, King's College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petroula","family":"Proitsi","sequence":"additional","affiliation":[{"name":"Centre for Preventive Neurology Wolfson Institute of Population Health, Queen Mary's University of London  London UK"},{"name":"Maurice Wohl Clinical Neuroscience Institute Department of Basic and Clinical Neuroscience Institute of Psychiatry, Psychology &amp; Neuroscience, King's College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cathryn M.","family":"Lewis","sequence":"additional","affiliation":[{"name":"Social, Genetic and Developmental Psychiatry Centre Institute of Psychiatry, Psychology &amp; Neuroscience, King's College London  London UK"},{"name":"Department of Medical and Molecular Genetics Faculty of Life Sciences &amp; Medicine King's College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,13]]},"reference":[{"key":"e_1_2_12_2_1","volume-title":"Projections of older people with dementia and costs of dementia care in the United Kingdom, 2019\u20102040","author":"Wittenberg R","year":"2019"},{"key":"e_1_2_12_3_1","unstructured":"Alzheimer's Research UK.Prevalence and incidence.https:\/\/dementiastatistics.org\/about\u2010dementia\/prevalence\u2010and\u2010incidence\/"},{"key":"e_1_2_12_4_1","unstructured":"Office for National Statistics.Deaths registered in England and Wales:2023. Accessed 25.04.2025.https:\/\/www.ons.gov.uk\/peoplepopulationandcommunity\/birthsdeathsandmarriages\/deaths\/bulletins\/deathsregistrationsummarytables\/2023"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(24)01296\u20100"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41576\u2010022\u201000511\u20107"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010021\u201001266\u20100"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.add6155"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12916\u2010022\u201002519\u20106"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010022\u201001980\u20103"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010024\u201054357\u20100"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adp3743"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2666\u20107568(20)30007\u20106"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010018\u20100579\u2010z"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwx016"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41597\u2010023\u201001949\u2010y"},{"key":"e_1_2_12_17_1","first-page":"343","volume-title":"Learning with continuous classes","author":"Quinlan JR","year":"1992"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4614-6849-3_8"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13742\u2010015\u20100047\u20108"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2020.102954"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btae551"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature15393"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aay5012"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010021\u201024485\u2010y"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1009021"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380\u2010019\u20100546\u20106"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.01.003"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.16344"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.101414"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.13258"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13016"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13859"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2024.3770"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1212\/cpj.0000000000000566"}],"container-title":["Alzheimer's &amp; Dementia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.71280","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/alz.71280","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.71280","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T05:24:21Z","timestamp":1785475461000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1002\/alz.71280"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5]]},"references-count":33,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1002\/alz.71280"],"URL":"https:\/\/doi.org\/10.1002\/alz.71280","archive":["Portico"],"relation":{},"ISSN":["1552-5260","1552-5279"],"issn-type":[{"value":"1552-5260","type":"print"},{"value":"1552-5279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5]]},"assertion":[{"value":"2025-07-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e71280"}}