These health risk factors are accelerating brain aging

On October 21, 2024, the research team led by Professor Lv Han from Capital Medical University Affiliated Beijing Friendship Hospital, in collaboration with the team led by Professor Jiang Jiehui from Shanghai University, conducted a population-based cohort study to investigate the long-term effects of unhealthy lifestyles, metabolic abnormalities, and other risk factors on brain aging. The results demonstrated that these risk factors significantly accelerate brain aging, and the researchers proposed key strategies to promote brain health. The study was published in the Research under the title "Discovery of High-Risk Clinical Factors That Accelerate Brain Aging in Adults: A Population-Based Machine Learning Study" (Research 2024; 7: Article 0500. DOI: 10.34133/research.0500).

Background

As individuals age, the brain undergoes a series of structural changes related to brain aging, including cerebral atrophy, damage to white matter microstructure, and increased white matter hyperintensities. These changes are closely linked to the development and progression of cognitive impairment and neurodegenerative diseases. Brain age, calculated based on brain magnetic resonance imaging (MRI) features, serves as a critical biomarker for assessing brain aging.

However, previous brain age prediction models have typically been constructed using a single neuroimaging modality. In contrast, multi-modal brain imaging data can provide a more comprehensive characterization of individual brain aging traits and improve the accuracy of brain age prediction. Additionally, substantial evidence indicates that a variety of health risk factors, such as hypertension, hyperglycemia, and smoking, may contribute to alterations in brain structure. However, the relationship between these risk factors and brain aging remains poorly understood. Thus, identifying the key risk factors that accelerate brain aging is essential for promoting brain health.

Research progress

This study, utilizing a 16-year clinical follow-up cohort of the Kailuan population, elucidated that long-term adverse lifestyle, metabolic abnormalities, and other risk factors significantly accelerate brain aging.

First, the authors constructed a matrix dataset integrating multi-dimensional health risk factors and multi-modal brain imaging features. By applying correlation analysis correcting for multiple comparisons, they investigated the associations between multi-dimensional risk factors and multi-modal brain imaging features. They further identified the five risk factors most strongly associated with brain imaging features: hypertension, hyperglycemia, hypercreatinemia, smoking, and relatively low educational level. This finding preliminarily provides key insights into the risk factors that accelerate brain aging (Figure 1).

Subsequently, the participants were stratified into five groups based on the number of high-risk factors they exhibited: 0 (healthy control), 1, 2, 3, and 4-5 high-risk factor groups. The brain age prediction model was trained on the healthy group and subsequently applied to the five risk exposure groups to predict their brain ages and compare the differences in brain aging. The results indicate that individuals with 4-5 high-risk factors exhibit a significantly greater brain age gap (BAG) compared to the healthy group and other risk exposure groups (Figure 2). This suggests that a range of health factors across unhealthy lifestyles, metabolic abnormalities, and other risk factors may collectively contribute to the accelerated aging process of the brain.

A further in-depth analysis revealed that the BAG predicted by T1-weighted imaging was significantly higher in the hypertensive subjects compared to those normotensive subjects (Figure 3). This indicates that hypertension exerts a pivotal influence on the structural degeneration of brain tissue and is a key factor in accelerating brain aging.

Suggestions for Future Research

This study, based on a long-term longitudinal follow-up of a large population, reveals that the five risk factors—hypertension, hyperglycemia, hypercreatinemia, smoking, and low educational attainment—accelerate brain aging, with hypertension causing the most significant brain damage. Future research will incorporate longitudinal brain imaging data to assess the dynamic progression pattern of brain aging. In addition, future research is warranted to fully excavate high-dimensional information from multi-modal images, thereby enhancing the predictive and generalization capabilities of the models.

In summary, this study elucidates that a range of health risk factors contribute to the acceleration of brain aging, and effective management of blood pressure, blood glucose, and creatinine levels, along with reduced smoking and improved educational attainment, are essential for promoting brain health.