Machine learning-based LASSO-Cox model for dementia prediction: the role of midlife cardiometabolic, inflammatory, and genetic risk factors in a US cohort
Published, Version of Record (VoR)Open Access via Drexel Libraries Read and Publish Program 2026CC BY V4.0, Open
Abstract
Midlife Features and Dementia Risk LASSO-Cox Modeling Machine Learning
We aimed to identify key midlife dementia predictors and develop a novel machine learning (ML) -enabled risk prediction model.
Using data from 9,266 Atherosclerosis Risk in Communities study participants (aged 45-64 years at baseline, 1987-1989). Incident dementia was ascertained through December 2019. A ML-based LASSO-Cox model was applied to develop the risk prediction model.
Over a 25-year mean follow-up, 2,010 participants developed dementia. The LASSO-Cox model identified 12 key predictors and achieved C-indices (95%CI) of 0.77 (0.75-0.79) in the training set (n = 6,182) and 0.78 (0.76-0.81) in the test set (n = 3,084). Predictors included age, Digit Symbol Substitution Test, apolipoprotein E ε4, HbA1c, brachial blood pressure, Factor VIII, Delayed Word Recall Test, hypertension, stroke history, C-reactive protein, white blood cell count, and apolipoprotein B. The resulting nomogram demonstrated strong discrimination (AUC 0.77-0.86) and good calibration. LASSO-Cox risk score quartiles effectively stratified participants into low, moderate, high, and very high dementia risk groups.
The findings demonstrate that the newly developed machine learning-based LASSO-Cox model provides a robust method to predict individuals at high risk of dementia.
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Title
Machine learning-based LASSO-Cox model for dementia prediction: the role of midlife cardiometabolic, inflammatory, and genetic risk factors in a US cohort
Creators
Longjian Liu (Corresponding Author) - Drexel University