Discovery of High-Risk Clinical Factors That Accelerate Brain Aging in Adults: A Population-Based Machine Learning Study.

Brain age prediction using neuroimaging data and machine learning algorithms holds significant promise for gaining insights into the development of neurodegenerative diseases. The estimation of brain age may be influenced not only by the imaging modality but also by multidomain clinical factors. However, the degree to which various clinical factors in individuals are associated with brain structure, as well as the comprehensive relationship between these factors and brain aging, is not yet clear. In this study, multimodal brain magnetic resonance imaging data and longitudinal clinical information were collected from 964 participants in a population-based cohort with 16 years of follow-up in northern China. We developed a machine learning-based algorithm to predict multimodal brain age and compared the estimated brain age gap (BAG) differences among the 5 groups characterized by varying exposures to these high-risk clinical factors. We then estimated modality-specific brain age in the hypertension group based on hypertension-related regional imaging metrics. The results revealed a significantly larger BAG estimated from multimodal neuroimaging in subjects with 4 or 5 risk factors compared to other groups, suggesting an acceleration of brain aging under cumulative exposure to multiple risk factors. The estimated T1-based BAG exhibited a significantly higher level in the hypertensive subjects compared to the normotensive individuals. Our study provides valuable insights into a range of health factors across lifestyle, metabolism, and social context that are reflective of brain aging and also contributes to the advancement of interventions and public health initiatives targeted at the general population aimed at promoting brain health.