Metabolic, demographic, and behavioral risk factors predict brain structural variability in the general population:...

Understanding whether commonly available metabolic, demographic, and behavioral factors can explain variability in brain structure may support the development of accessible predictive approaches. This study aims to evaluate the ability of machine learning regression models to predict brain structural measures in young, neurologically healthy adults using clinically accessible risk factors.

Data were drawn from the Human Connectome Project Young Adults dataset, including 1082 participants aged 22-37. Predictors comprised metabolic measures (systolic and diastolic blood pressure, hematocrit, body mass index, hemoglobin A1C, thyroid stimulating hormone) and demographic/behavioral variables (age, gender, race, education level, smoking history, alcohol use). Brain structural parameters from MRI included gray matter (GM) and white matter (WM) volumes, surface areas, and cortical thickness. Distance correlation (dcor) guided feature selection, followed by machine learning modeling. Model performance was evaluated using normalized mean absolute error (NMAE), normalized root-mean-squared error (NRMSE), and coefficient of determination (R²). SHAP values were used for feature interpretation.

XGBoost consistently outperformed other algorithms, showing strong predictive accuracy for total brain segmentation, supratentorial, and total GM volumes (NMAE < 0.35, R² > 0.80). In contrast, cortical surface predictions (left superior frontal) showed moderate performance (NMAE > 0.50, R² < 0.60). SHAP analysis highlighted age, gender, education level, and diastolic and systolic blood pressure as the most influential predictors of brain structure.

The findings highlight the methodological value of regression-based approaches for estimating brain structural variability and support their potential role as complementary tools for brain health research.