{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T13:01:59Z","timestamp":1790859719832,"version":"4.1.0"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Repeated serum metabolite measurements may contribute to predicting clinical progression, but their incremental value requires evaluation beyond established clinical predictors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We linked Alzheimer\u2019s Disease Neuroimaging Initiative (ADNI) clinical data to Biocrates Quant 500 serum measurements. Annualized metabolite slopes were estimated from baseline through month 12, usually from two observations. At the month-12 landmark, participants without dementia were characterized by diagnosis, memory performance, and APOE \u03b54 status; progression was assessed at approximately month 36. Models were developed in ADNI1 (225 participants; 26 events) and applied without refitting to ADNI-GO\/2 (269 participants; 50 events). We compared a clinical logistic model with a model that added a data-derived phosphatidylcholine (PC) aa C42:1 candidate slope. Models using 88 phosphatidylcholine-family metabolite slopes or 598 full-panel slopes were exploratory.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The clinical model achieved an area under the receiver operating characteristic curve (AUROC) of 0.758 (95% CI, 0.675\u20130.838). Adding PC aa C42:1 changed the AUROC by +0.0004 (\u22120.013 to 0.017). Both partially penalized lasso models retained no metabolite slopes at the selected penalty. A\n                      <jats:italic>post-hoc<\/jats:italic>\n                      evaluation restricted to 233 participants with mild cognitive impairment, including 38 events, also found no evidence of incremental discrimination. Other sensitivity analyses yielded similar results.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We found no evidence that annualized serum metabolite slopes improved held-out prediction in this sample. The 26 development events limited estimation and feature selection, so these results cannot distinguish between a lack of incremental prognostic information and insufficient data to identify such information. Larger development samples and independent validation are needed to assess the value of serial metabolomics.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnagi.2026.1942662","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T12:45:56Z","timestamp":1790858756000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["No evidence that serum metabolite slopes improve held-out prediction of clinical progression in the Alzheimer\u2019s disease neuroimaging initiative"],"prefix":"10.3389","volume":"18","author":[{"given":"Tia","family":"Warrick","sequence":"first","affiliation":[{"name":"Department of Health Sciences, Juniata College","place":["Huntingdon, PA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manali","family":"Misra","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, Juniata College","place":["Huntingdon, PA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Kataria","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, Juniata College","place":["Huntingdon, PA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jahnavi","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, Juniata College","place":["Huntingdon, PA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhuvi","family":"Ajmera","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, Juniata College","place":["Huntingdon, PA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,1]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"7361","DOI":"10.1002\/alz.14167","article-title":"The Alzheimer\u2019s Disease Neuroimaging Initiative clinical Core","volume":"20","author":"Aisen","year":"2024","journal-title":"Alzheimers Dement."},{"key":"ref2","year":"2026"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1016\/j.dadm.2019.07.002","article-title":"Sets of coregulated serum lipids are associated with Alzheimer\u2019s disease pathophysiology","volume":"11","author":"Barupal","year":"2019","journal-title":"Alzheimers Dement (Amst)."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1023\/A:1010933404324","article-title":"Random forests","volume":"45","author":"Breiman","year":"2001","journal-title":"Mach. 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