{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T23:21:30Z","timestamp":1791933690037,"version":"4.3.4"},"reference-count":40,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T00:00:00Z","timestamp":1770940800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"crossref","award":["22-15-00155-\u220f"],"award-info":[{"award-number":["22-15-00155-\u220f"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Vascular and metabolic disorders in the elderly\u2014including acute ischemic stroke (AIS), chronic cerebral circulation insufficiency (CCCI), type 2 diabetes mellitus (DM), and subcortical ischemic vascular dementia (SIVD)\u2014pose a major diagnostic challenge due to their reliance on multi-parameter blood chemistry. In this study, 49 biochemical features were analyzed within a cohort of 120 patients. The application of variance-aware statistical testing revealed that several features (e.g., Fe, Transf, RDW%, LDL) exhibited statistically significant heterogeneity of variance (p &lt; 0.05), which is known to distort standard ANOVA inference. While standard machine-learning (ML) classifiers demonstrated variable performance across clinical groups, a gradient boosting model with restricted tree depth (max depth = 3) achieved high discriminative accuracy, yielding F1-scores between 0.87 and 0.96 across all five clinical classes. Through the use of Shapley Additive Explanations (SHAP), key stable biomarkers including iron (Fe), transferrin, and glucose were identified as having synergistic interactions in model predictions. A comparative analysis of feature importance ranks indicated consistency between statistical significance and SHAP values, with Spearman correlation coefficients reaching 0.53 for groups 1\u20132 and 0.59 for groups 1\u20135. Conversely, unsupervised KMeans clustering (k = 5) revealed a poor correspondence with clinical labels, yielding an Adjusted Rand Index (ARI) of 0.198 and Normalized Mutual Information (NMI) of 0.286. These results underscore that statistical structures in biochemical data do not always map to meaningful clinical categories and advocate for the adoption of variance-aware workflows and interpretable ML to enhance diagnostic reliability in aging populations.<\/jats:p>","DOI":"10.3390\/ijms27041805","type":"journal-article","created":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T12:06:59Z","timestamp":1770984419000},"page":"1805","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Interpretable Machine Learning with SHAP Identifies Key Biomarkers in a Multi-Factorial Spectrum of Age-Related Neurological and Metabolic Conditions"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-0858-8098","authenticated-orcid":false,"given":"Daniil V.","family":"Artamonov","sequence":"first","affiliation":[{"name":"Group of Theoretical Chemistry, N.D. Zelinsky Institute of Organic Chemistry of Russian Academy of Sciences, Leninsky Prospect 47, Moscow 119991, Russia"},{"name":"Infochemistry Scientific Center, National Research University ITMO, Kronverksky Ave. 49, Building A, St. Petersburg 197101, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Polina I.","family":"Popova","sequence":"additional","affiliation":[{"name":"St. Petersburg State Budgetary Healthcare Institution \u201cCity Polyclinic No. 107\u201d, St. Petersburg 195030, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina A.","family":"Korf","sequence":"additional","affiliation":[{"name":"Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, pr. Torez 44, St. Petersburg 194223, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3164-4971","authenticated-orcid":false,"given":"Natalia G.","family":"Voitenko","sequence":"additional","affiliation":[{"name":"Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, pr. Torez 44, St. Petersburg 194223, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alisa A.","family":"Chernysheva","sequence":"additional","affiliation":[{"name":"Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, pr. Torez 44, St. Petersburg 194223, Russia"},{"name":"Department of Computational Biology, Sirius University of Science and Technology, Olympic Ave. 1, Sirius 354340, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4138-1589","authenticated-orcid":false,"given":"Pavel V.","family":"Avdonin","sequence":"additional","affiliation":[{"name":"Koltsov Institute of Developmental Biology, Russian Academy of Sciences, 26 Vavilov St., Moscow 119334, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard O.","family":"Jenkins","sequence":"additional","affiliation":[{"name":"Leicester School of Allied Health Sciences, De Montfort University, The Gateway, Leicester LE1 9BH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolay V.","family":"Goncharov","sequence":"additional","affiliation":[{"name":"Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, pr. Torez 44, St. Petersburg 194223, Russia"},{"name":"Research Institute of Hygiene, Occupational Pathology and Human Ecology of the Federal Medical Biological Agency, p.o. Kuz\u2019molovsky bld.93, St. Petersburg 188663, Russia"},{"name":"Department of Biological Chemistry, Petersburg State Pediatric Medical University, Ministry of Health of the Russian Federation, Litovskaya St. 2, St. Petersburg 194100, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1136\/bmjqs-2019-010822","article-title":"Prevalence of Harmful Diagnostic Errors in Hospitalised Adults: A Systematic Review and Meta-Analysis","volume":"29","author":"Gunderson","year":"2020","journal-title":"BMJ Qual. 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