Real-World Multimodal Machine Learning for Risk Enrichment Across the Alzheimer’s Disease Spectrum

Bülbül N. G., BAYTAŞ İ. M., KAVALCI E., Karasu E., Okcu Korkmaz B. C., Belen B. G., ...Daha Fazla

Journal of Clinical Medicine, cilt.15, sa.6, 2026 (SCI-Expanded, Scopus) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 15 Sayı: 6
  • Basım Tarihi: 2026
  • Doi Numarası: 10.3390/jcm15062250
  • Dergi Adı: Journal of Clinical Medicine
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, EMBASE
  • Anahtar Kelimeler: Alzheimer's disease, mild cognitive impairment, risk enrichment, real-world data, multimodal machine learning, volumetric MRI, FDG-PET
  • Boğaziçi Üniversitesi Adresli: Evet

Özet

Background and Objectives: Mild cognitive impairment (MCI) is heterogeneous within the Alzheimer’s disease (AD) continuum, and categorical labels may not reflect biological variability. We evaluated whether multimodal machine learning using routine clinical data and neuroimaging could support biologically informed enrichment across MCI and AD in a real-world memory clinic cohort. Methods: We analyzed 474 patients (1547 visits) with clinical and cognitive measures, laboratory parameters, MRI regional volumes, and FDG-PET regional uptake. Elastic Net and gradient boosting models were trained using nested cross-validation with strict patient-level separation. Results: Model discrimination improved as additional data modalities were added, and FDG-PET contributed the largest performance improvement. Hypometabolism in posterior default mode network regions consistently emerged as the most influential predictor. In the MCI subgroup, AD-like scores showed a continuous distribution consistent with biological enrichment. Conclusions: Multimodal models may provide an interpretable enrichment framework in heterogeneous memory clinic populations.