| الوصف: |
Cognitive decline is a major characteristic of ageing. Studies show that cardiovascular risk factors (CVR) are associated with cognitive declines and brain phenotypes, but the causality between CVR and cognitive function needs further understanding. In this study, we seek to investigate the causalities between CVR, brain phenotypes and cognitive function. We first generate a general factor (gCVR) representing common CVR and a score representing the polygenic risk (PRS). We then identify phenotypes of brain and cognitive functions associated with gCVR and PRS. Moreover, we conduct causal mediation analysis to evaluate the indirect effect of PRS through CVR, which infers the causality of gCVR on brain phenotypes and cognition. Further, we test the mediation effect of gCVR on the total effect of brain phenotypes on cognitive function. Finally, the causality between CVR and brain phenotypes is cross validated using Mendelian randomization (MR) with genetic instruments. The results show that CVR mediates the effect of PRS on brain phenotypes and cognitive function, and CVR also mediates the effect of brain phenotypes on cognitive changes. Additionally, we validate that the variation in a few brain phenotypes., e.g., volume of grey matter, are caused by CVR. |
