Introduction: As a structural proxy for evaluating brain health, neuroimaging-based brain age gap (BAG) is presumed to link the dementia risks to cognitive changes in the premorbid phase, but this remains unclear. Methods: Brain age prediction models were constructed and applied to a population-based cohort (N=371) to estimate their BAG. Further, structural equation modeling was employed to investigate the mediation effect of BAG between risk levels (assessed by 2 dementia-related risk scores) and cognitive changes (examined by 4 cognitive assessments). Results: A higher burden of modifiable dementia risk factors was causally associated with a greater cognitive decline, and this was significantly mediated (P=0.017) by a larger multimodal BAG, which indicated an older brain. Moreover, a steeper slope (P=0.020) of association between cognitive decline and multimodal BAG was observed when individuals had higher dementia risks. Discussion: Multimodal BAG is a potential mediating indicator to reflect the changes in the pathophysiological mechanism of cognitive aging.
bioRxiv Subject Collection: Neuroscience