{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T20:32:30Z","timestamp":1786480350857,"version":"build-2736575974"},"reference-count":36,"publisher":"Wiley","issue":"10-12","license":[{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"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\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG064803"],"award-info":[{"award-number":["R01AG064803"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["P30AG072958"],"award-info":[{"award-number":["P30AG072958"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Statistics in Medicine"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Alzheimer's disease (AD) is a progressive neurodegenerative disorder whose molecular mechanisms involve multiple biological pathways. Longitudinal blood\u2010based omics data, such as lipidomics and metabolomics profiles, offer promising noninvasive biomarkers for early detection and prognosis, yet they are high\u2010dimensional, sparse, and exhibit complex temporal and cross\u2010feature correlations. The primary goal of this study is to identify which omics data types are most strongly associated with time to dementia onset in patients with mild cognitive impairment (MCI) at baseline. To address this, we propose a longitudinal sparse single\u2010omics factor analysis (LS\u2010SOFA) framework that models each omics view through view\u2010specific latent factors and feature\u2010weight matrices, with temporal dynamics captured by functional principal component analysis (FPCA). The resulting functional principal component (FPC) scores are incorporated into a survival model to test whether each omics view is associated with time to dementia onset. An efficient covariance\u2010based estimation algorithm substantially reduces computational and memory cost, enabling large\u2010scale application in the Alzheimer's Disease Neuroimaging Initiative (ADNI) study. In simulations, LS\u2010SOFA achieves higher longitudinal estimation accuracy and more stable hypothesis testing than competing methods. Applied to five blood\u2010based omics views from ADNI, LS\u2010SOFA identified plasma lipidomics and serum metabolomics from FIA and UPLC as significantly associated with dementia risk after FDR adjustment, with nominal evidence of association for gut microbial metabolomics from serum. The top features within each omics view reveal biologically interpretable metabolic pathways that may serve as blood\u2010based biomarkers for AD progression.<\/jats:p>","DOI":"10.1002\/sim.70601","type":"journal-article","created":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T05:55:29Z","timestamp":1778824529000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Longitudinal Sparse Single\u2010Omics Factor Analysis for High\u2010Dimensional Blood Biomarkers in Alzheimer's Disease"],"prefix":"10.1002","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3595-8716","authenticated-orcid":false,"given":"Haotian","family":"Zou","sequence":"first","affiliation":[{"name":"Department of Biostatistics and Bioinformatics Duke University  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rima","family":"Kaddurah\u2010Daouk","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences Duke University  Durham North Carolina USA"},{"name":"Duke Institute of Brain Sciences Duke University  Durham North Carolina USA"},{"name":"Department of Medicine Duke University  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4214-5809","authenticated-orcid":false,"given":"Sheng","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Bioinformatics Duke University  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Alzheimer's Disease Neuroimaging Initiative","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,14]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)32205-4"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25245789"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-022-00645-6"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13449"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/WAD.0000000000000279"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-024-00731-y"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/sdata.2017.140"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41597-019-0181-8"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19473-7"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-0755-1"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2022.5272"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-230039"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2012.12.006"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.70105"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaa399"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2023.5319"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-021-01343-9"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btab664"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-37432-w"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1198\/016214504000001745"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1214\/08-AOAS206"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/biom.13427"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1214\/23-AOAS1733"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1214\/24-AOAS1970"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1214\/ss\/1038425655"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/1467-9868.00374"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1080\/01621459.2022.2153689"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1137\/07070111X"},{"issue":"2","key":"e_1_2_12_30_1","article-title":"Serum Bile Acids Improve Prediction of Alzheimer's Progression in a Sex\u2010Dependent Manner. 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