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ABSTRACT: Background
The ε4 allele of the apolipoprotein E (APOE) gene is a strong genetic risk factor for aging-related cognitive decline. However, the causal connection between ε4 alleles and cognition is not well understood. The objective of this study was to identify the roles of cerebral blood flow (CBF) in cognitive-related brain areas in mediating the associations of APOE with cognition.Methods
The multiple linear regression analyses were conducted on 369 subjects (mean age of 68.8 years; 62.9% of women; 29.3% of APOE ε4 allele carriers). Causal mediation analyses with 5,000 bootstrapped iterations were conducted to explore the mediation effects.Result
APOE ε4 allele was negatively associated with cognition (P < 0.05) and CBF in the amygdala, hippocampus, middle temporal gyrus, posterior cingulate, and precuneus (all P < 0.05). The effect of the APOE genotype on cognition was partly mediated by the above CBF (all P < 0.05).Conclusion
CBF partially mediates the potential links between APOE genotype and cognition. Overall, the APOE ε4 allele may lead to a dysregulation of the vascular structure and function with reduced cerebral perfusion, which in turn leads to cognitive impairment.
SUBMITTER: Wang YL
PROVIDER: S-EPMC9279129 | biostudies-literature | 2022
REPOSITORIES: biostudies-literature
Wang Yan-Li YL Sun Mengfan M Wang Fang-Ze FZ Wang Xiaohong X Jia Ziyan Z Zhang Yuan Y Li Runzhi R Jiang Jiwei J Wang Linlin L Li Wenyi W Sun Yongan Y Chen Jinglong J Zhang Cuicui C Shi Baolin B Liu Jianjian J Liu Xiangrong X Xu Jun J
Frontiers in aging neuroscience 20220630
<h4>Background</h4>The ε4 allele of the apolipoprotein E (APOE) gene is a strong genetic risk factor for aging-related cognitive decline. However, the causal connection between ε4 alleles and cognition is not well understood. The objective of this study was to identify the roles of cerebral blood flow (CBF) in cognitive-related brain areas in mediating the associations of APOE with cognition.<h4>Methods</h4>The multiple linear regression analyses were conducted on 369 subjects (mean age of 68.8 ...[more]