Risk factors associated with brain aging in the 7th Tromsø study

Abstract

Introduction: Aging is a natural biological process characterized by a deterioration of functions on multiple levels: molecular, cellular, organ-specific, and systemic. There is considerable variation between individuals in aging based on biological and functional markers. This variation forms the basis for the idea of "biological age," which measures a more representative age than chronological age. Biological age is clinically and scientifically interesting as it summarizes a complex aging process into a single number that can be a valuable instrument to assess an individual's health risks and conditions. A novel marker for biological age is "Brain age,” which estimates the age of the brain based on MRI images. The difference between a person's brain age and chronological age is referred to as the "brain age gap" (BAG; brain age minus chronological age). A positive BAG indicates that a brain resembles an older average brain, while a negative BAG suggests that the brain resembles a younger average brain. BAG is what is scientifically relevant in this study, regardless of whether an individual's biological age is greater or less than their chronological age.

Methods: We analyzed data from the 7th Tromsø survey including 1.864 MRI scans. The data set consisted of people between 40 - 87 years, an average age of 65 years, and about the same number of participants from both sexes. Amongst exclusion criteria were people with infarction, tumors, and other major structural malformations in the brain that may affect the brain age estimate. We investigated how brain age could be associated with different variables. We corrected for education and socioeconomic status associated with brain health.

Results: Multiple regression model was applied to see what factors are associated with brain age. Resting heart rate, sex-differences, HDL cholesterol, diabetes, and smoking were significantly associated with BAG.

Conclusion: Our findings suggest that males are likely to have higher brain age compared to females. In addition, resting heart rate, HDL-C, smoking and diabetes were significantly associated with BAG. Smoking, whether previous or current was found to accelerate brain age significantly. Also, having diabetes increased brain age by 2.4 years. Our study found none of the interaction terms for sex differences to be significant. Confounding variables such as education or economic status were not significantly associated with BAG. Despite previously contradictory findings, neither hypertension nor self-reported cardiovascular disease was significantly associated with BAG in this study. A low heart rate may be advantageous for healthy brain aging. In addition, self-reported physical activity and self-reported sleep problems were not associated with BAG.