ITU-DESC: a missingness-aware machine-learning dementia risk score in the UK Biobank cohort
Background: Existing dementia risk scores rely on fixed, pre-selected features and linear models, or ignore bias from informative missingness in cohort data. Here we introduce the Istanbul Technical University Dementia Risk Score (ITU-DESC), an explainable machine-learning score for incident all-cause dementia that combines broad feature selection across roughly 8,000 candidate features with explicit control of missingness bias. Results: We studied approximately 500,000 UK Biobank participants with a median follow-up of 16.6 years. We withheld missingness patterns from the model using unconditional random hot-deck imputation. We stabilized feature selection by repeating BorutaSHAP-based feature selection with ten random-imputation seeds and selecting predictors chosen in at least eight of the ten seeds, which yielded 38 predictors. We trained a CatBoost gradient-boosted decision-tree model and evaluated it on a holdout test set of 50,041 participants. For all-cause incident dementia, ITU-DESC achieved an average precision of 0.138 (95% confidence interval 0.123-0.156) and an area under the receiver operating characteristic curve (ROC AUC) of 0.853 (0.844-0.863), significantly outperforming other risk scores, including the strongest comparator, the UK Biobank Dementia Risk Prediction model (0.118 and 0.841). We identified dementia risk predictors absent from established scores, including leukocyte telomere length and liver enzymes. Conclusions: ITU-DESC is the first dementia risk score to combine broad feature selection with explicit control of missingness bias.