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oai:figshare.com:article/34045752 2026-10-01T12:36:53Z category_15 portal_316 item_type_3 month_year_10_2026

Supplementary file 1_No evidence that serum metabolite slopes improve held-out prediction of clinical progression in the Alzheimer’s disease neuroimaging initiative.zip Tia Warrick (25156542) Manali Misra (25156545) Stephen Kataria (25156548) Jahnavi Patel (25156551) Bhuvi Ajmera (25156554) Neuroscience ADNI Alzheimer’s disease APOE clinical progression longitudinal biomarkers metabolomics prediction model validation Background<p>Repeated serum metabolite measurements may contribute to predicting clinical progression, but their incremental value requires evaluation beyond established clinical predictors.</p>Methods<p>We linked Alzheimer’s 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 ε4 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.</p>Results<p>The clinical model achieved an area under the receiver operating characteristic curve (AUROC) of 0.758 (95% CI, 0.675–0.838). Adding PC aa C42:1 changed the AUROC by +0.0004 (−0.013 to 0.017). Both partially penalized lasso models retained no metabolite slopes at the selected penalty. A post-hoc 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.</p>Conclusion<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.</p> 2026-10-01T12:36:53Z Dataset Dataset 10.3389/fnagi.2026.1942662.s002 https://figshare.com/articles/dataset/Supplementary_file_1_No_evidence_that_serum_metabolite_slopes_improve_held-out_prediction_of_clinical_progression_in_the_Alzheimer_s_disease_neuroimaging_initiative_zip/34045752 CC BY 4.0