Associations of Accelerated Biological Aging With Dementia and the Mediation Role of Brain Structure

BACKGROUND AND OBJECTIVES: The association between biological aging and dementia, as well as the underlying mechanism, remains limited. The aim of this study was to investigate the relationships of biological age (BA) with incident dementia and examine the underlying neurobiological mechanisms. METHODS: This study used data from the UK Biobank, a prospective longitudinal study. We included participants free of diagnosed dementia at baseline. BA was evaluated from clinical traits using the Klemera-Doubal method biological age (KDM-BA) and PhenoAge algorithms. Genetic risk of dementia was assessed using the apolipoprotein E (APOE) ε4 genotype and polygenic risk scores (PRSs). Cox proportional hazard regression models were used to estimate the associations of BA and the combined effect of genetic risk and BA with dementia. In addition, the potential roles of brain structures (gray matter volume [GMV], cortical mean thickness, and cortical surface area) in the associations between BA and dementia were evaluated using mediation analysis. RESULTS: = 0.212). Mediation analysis showed that the identified GMV, cortical mean thickness, and cortical surface area partly mediated the association between BA accelerations and incident dementia, with proportion-mediated percentage ranging from 6.64% to 17.98%. DISCUSSION: Advanced BA may be a potential risk factor of incident dementia. The risk is possibly mediated through the widespread reduction of brain structures.