TY - UNPB
T1 - Cerebrovascular risk factors impact brain phenotypes and cognitive function in healthy population
AU - Li, Bingli
AU - Wei, Yiran
AU - Zhang, Kaijia
AU - Schonlieb, Carola-Bibiane
AU - Rudd, James
AU - Li, Chao
PY - 2022/4/4
Y1 - 2022/4/4
N2 - 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.
AB - 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.
U2 - 10.1101/2022.03.29.22273047
DO - 10.1101/2022.03.29.22273047
M3 - Preprint
BT - Cerebrovascular risk factors impact brain phenotypes and cognitive function in healthy population
PB - medRxiv
ER -