Association of accelerated biological aging with brain volumes: A cross-sectional study

Multiple epidemiological studies have observed the connection between aging and brain volumes. The concept of accelerated biological aging (BA) is more powerful for observing the degree of aging of an individual than chronologic age (CA). The objective of this study is to explore the relationship between BA and brain volumes.

BA was measured from clinical traits using two blood-chemistry algorithms, the Klemera-Doubal method (KDM) and the PhenoAge. The two age acceleration biomarkers were calculated by the residuals from regressing CA, termed "KDM-acceleration" and "PhenoAge-acceleration". Brain volumes were from brain magnetic resonance imaging (MRI) data. After adjustment for confounding factors, general linear regression models were used to examine associations between KDM-acceleration and PhenoAge-acceleration and brain volumes, respectively. Additionally, we stratified participants by sex, age, and the four quartiles of the Townsend Deprivation Index (TDI) for extra subgroup analysis.

14,725 participants with available information were enrolled. After full adjustment, we observed negative associations between KDM-acceleration and brain volumes, such as gray matter (β = -0.029), white matter (β = -0.021), gray and white matter (β = -0.026), and hippocampus (β = -0.011 for left and β = -0.014 for right). There were also negative associations between PhenoAge-acceleration and brain volumes, such as white matter (β = -0.008), gray and white matter (β = -0.010), thalamus (β = -0.012 for left and β = -0.012 for right). In the subgroup analysis stratified by sex, age, and the four quartiles of TDI, the association between KDM-acceleration and PhenoAge-acceleration and brain volumes still existed. In subgroup analyses, the variation in associations suggests that socioeconomic and biological factors may differentially influence brain aging.

Our research indicated that more advanced BA was associated with less brain tissue.