Incremental Value of Multidomain Risk Factors for Dementia Prediction: A Machine Learning Approach.

Objective: The current evidence regarding how different predictor domains contributes to predicting incident dementia remains unclear. This study aims to assess the incremental value of five predictor domains when added to a simple dementia risk prediction model (DRPM) for predicting incident dementia in older adults.

Design: Population-based, prospective cohort study.

Setting: UK Biobank study.

Participants: Individuals aged 60 or older without dementia.

Measurements: Fifty-five dementia-related predictors were gathered and categorized into clinical and medical history, questionnaire, cognition, polygenetic risk, and neuroimaging domains. Incident dementia (all-cause) and the subtypes, Alzheimer's disease (AD) and vascular dementia (VaD), were determined through hospital and death registries. Ensemble machine learning (ML) DRPMs were employed for prediction. The incremental values of risk predictors were assessed using the percent change in Area Under the Curve (∆AUC%) and the net reclassification index (NRI).

Results: The simple DRPM which included age, body mass index, sex, education, diabetes, hyperlipidaemia, hypertension, depression, smoking, and alcohol consumption yielded an AUC of 0.711 (± 0.008 SD). The five predictor domains exhibited varying levels of incremental value over the basic model when predicting all-cause dementia and the two subtypes. Neuroimaging markers provided the highest incremental value in predicting all-cause dementia (∆AUC% +9.6%) and AD (∆AUC% +16.5%) while clinical and medical history data performed the best at predicting VaD (∆AUC% +12.2%). Combining clinical and medical history, and questionnaire data synergistically enhanced ML DRPM performance.

Conclusion: Combining predictors from different domains generally results in better predictive performance. Selecting predictors involves trade-offs, and while neuroimaging markers can significantly enhance predictive accuracy, they may pose challenges in terms of cost or accessibility.