{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T12:08:16Z","timestamp":1790683696217,"version":"4.1.0"},"reference-count":58,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["2022\u201001608 to SH"],"award-info":[{"award-number":["2022\u201001608 to SH"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG067996\u201001A1 to SH"],"award-info":[{"award-number":["R01AG067996\u201001A1 to SH"]}],"id":[{"id":"10.13039\/100000049","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":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>We tested whether combining Alzheimer's disease and related dementias (ADRD) polygenic risk scores (PRS) with biological aging markers improves ADRD risk prediction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      In 16,215 UK Biobank (UKB) participants free of ADRD at baseline (median follow\u2010up: 10.08 years), 397 incident diagnoses were identified. Biological aging measures included clinical, telomere, proteomic, and metabolomic aging markers. External validation\/replication was performed in TwinGene (\n                      <jats:italic>N<\/jats:italic>\n                      \u00a0=\u00a03772; 331 cases).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>The fully integrated model achieved area under the curve (AUC)\u00a0=\u00a00.90 and area under the precision\u2010recall curve (AUPRC)\u00a0=\u00a00.24 in the UKB held\u2010out test set. PRS was the strongest predictor (subdistribution hazard ratio [sHR]\u00a0=\u00a02.24, 95% CI: 2.02\u20132.48), followed by ProtAge (sHR\u00a0=\u00a02.01, 95% CI: 1.13\u20133.58). The top predicted\u2010risk quartile showed higher ADRD incidence (sHR\u00a0=\u00a016.73, 95% CI: 6.49\u201343.11). TwinGene showed moderate transportability (AUC\u00a0=\u00a00.757; AUPRC\u00a0=\u00a00.223) and preserved risk stratification (sHR\u00a0=\u00a04.02, 95% CI: 3.25\u20135.02).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Integrating PRS and biological aging measures improved ADRD risk stratification.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71869","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T02:53:48Z","timestamp":1790650428000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrative prediction of Alzheimer's disease and related dementias using multi\u2010omics aging clocks and genetic data"],"prefix":"10.1002","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1966-1306","authenticated-orcid":false,"given":"Shayan","family":"Mostafaei","sequence":"first","affiliation":[{"name":"Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karolina","family":"Gustavsson","sequence":"additional","affiliation":[{"name":"Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hampus","family":"Hagelin","sequence":"additional","affiliation":[{"name":"Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan K. L.","family":"Mak","sequence":"additional","affiliation":[{"name":"Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm Sweden"},{"name":"Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine The University of Hong Kong  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trung Nghia","family":"Vu","sequence":"additional","affiliation":[{"name":"Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ida K.","family":"Karlsson","sequence":"additional","affiliation":[{"name":"Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"H\u00e4gg","sequence":"additional","affiliation":[{"name":"Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.11.001"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-025-00958-3"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.51507"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-023-02288-w"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awad252"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2023-331917"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11606-020-05895-y"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/svn-2025-004048"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.12.032"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.26508\/lsa.201900303"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-022-01024-z"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(24)01296-0"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-024-01939-9"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-023-00565-0"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-022-02449-3"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-022-00511-7"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fninf.2024.1443865"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-025-00928-9"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1101\/2025.05.31.25328688"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-025-00951-w"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-026-02011-w"},{"key":"e_1_2_11_23_1","article-title":"Alzheimer's disease drug development pipeline: 2025","volume":"11","author":"Cummings JL","year":"2025","journal-title":"Alzheimers Dement"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13859"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.70535"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.g7594"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-12391-2"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0579-z"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0311-9"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2005.10.004"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.101414"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2013.01.004"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwab281"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-021-00480-5"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2318-8-24"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-023-00783-9"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-021-00166-9"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-52310-9"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adp3743"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-03164-7"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-019-00499-1"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.02.016"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00521-023-09359-2"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1093\/geroni\/igab046.2436"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1017\/thg.2012.104"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.21203\/rs.3.rs-9600666\/v1"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-12-77"},{"key":"e_1_2_11_48_1","unstructured":"GrayB GrayMB Package \u2018cmprsk\u2019. Subdistribution analysis of competing risks R package version.2014;2:2\u20107."},{"key":"e_1_2_11_49_1","doi-asserted-by":"crossref","unstructured":"WickhamH ggplot2. Wiley interdisciplinary reviews: computational statistics.2011;3:180\u2010185.","DOI":"10.1002\/wics.147"},{"key":"e_1_2_11_50_1","doi-asserted-by":"crossref","unstructured":"TherneauTM LumleyT Package \u2018survival\u2019. R Top Doc.2015;128:28\u201033.","DOI":"10.1017\/S0305862X00023499"},{"key":"e_1_2_11_51_1","unstructured":"ChenT HeT BenestyM et\u00a0al.Xgboost: extreme gradient boosting. R package version 04\u20102.2015;1:1\u20104."},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-021-02492-y"},{"key":"e_1_2_11_53_1","unstructured":"FriedmanJ HastieT TibshiraniR et\u00a0al.Package \u2018glmnet\u2019. CRAN R repositary.2021;595:874."},{"key":"e_1_2_11_54_1","unstructured":"FoxJ WeisbergS AdlerD et\u00a0al.Package \u2018car\u2019. Vienna: R Foundation for statistical computing.2012;16:333."},{"key":"e_1_2_11_55_1","unstructured":"CortesMD Package \u2018isotree\u2019.2025."},{"key":"e_1_2_11_56_1","volume-title":"Python machine learning: machine learning and deep learning with Python, scikit\u2010learn, and TensorFlow 2","author":"Raschka S","year":"2019"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2517-6161.1995.tb02031.x"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-024-03418-8"},{"key":"e_1_2_11_59_1","first-page":"1","article-title":"Dementia risk across distinct metabolic profiles in the UK Biobank","author":"Lumsden AL","year":"2025","journal-title":"GeroScience"}],"container-title":["Alzheimer's &amp; Dementia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.71869","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/alz.71869","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.71869","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T11:39:44Z","timestamp":1790681984000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1002\/alz.71869"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,28]]},"references-count":58,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1002\/alz.71869"],"URL":"https:\/\/doi.org\/10.1002\/alz.71869","archive":["Portico"],"relation":{},"ISSN":["1552-5260","1552-5279"],"issn-type":[{"value":"1552-5260","type":"print"},{"value":"1552-5279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,28]]},"assertion":[{"value":"2026-02-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-26","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e71869"}}