AUTHOR=Wei Shan , Gao Ling , Jiang Yu , Shang Suhang , Chen Chen , Dang Liangjun , Wang Jin , Huo Kang , Wang Jingyi , Qu Qiumin 

TITLE=The Apolipoprotein E ε4 Allele-Dependent Relationship Between Serum Lipid Levels and Cognitive Function: A Population-Based Cross-sectional Study

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=12

YEAR=2020

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2020.00044

DOI=10.3389/fnagi.2020.00044

ISSN=1663-4365

ABSTRACT=<p><bold>Objectives</bold>: Till now, the effect of serum lipid levels on cognitive function is still controversial. The apolipoprotein E (APOE) ε4 allele is the most critical genetic risk factor for Alzheimer’s disease (AD) and cognitive impairment. Additionally, <italic>APOE</italic> ε4 allele has a major impact on lipid metabolism. The aim of this study was to investigate the <italic>APOE</italic> genotype-dependent relationship between peripheral serum lipid levels and cognitive impairment.</p><p><bold>Methods</bold>: A total of 1,273 subjects aged 40–86 years participated in this cross-sectional study. Serum lipid levels and the <italic>APOE</italic> genotype were detected. Mini-Mental State Examination was used to diagnose the cognitive impairment or not. Univariate and multivariate analyses were used to analyze the relationships between <italic>APOE</italic> genotype, serum lipid levels, and cognition function.</p><p><bold>Results</bold>: After controlling for all possible covariates, a significant interaction between low serum high-density lipoprotein and the <italic>APOE</italic> ε4 allele on cognitive impairment (Wald’s χ<sup>2</sup> = 4.269, <italic>df</italic> = 1, OR = 20.094, <italic>p</italic> = 0.039) was found in the total participants. In <italic>APOE</italic> ε4 carriers, low serum high-density lipoprotein was positively associated with cognitive impairment (Wald’s χ<sup>2</sup> = 8.200, <italic>df</italic> = 1, OR = 60.335, <italic>p</italic> = 0.004) and serum high-density lipoprotein levels were positively correlated with Mini-Mental State Examination score (<italic>r</italic> = 0.217, <italic>df</italic> = 176, <italic>p</italic> = 0.004). There was no significant correlation between serum total cholesterol (TC), low-density lipoprotein, triglycerides (TG) levels, and cognitive impairment in either the total participants or <italic>APOE</italic> ε4 carriers/non-carriers.</p><p><bold>Conclusions</bold>: <italic>APOE</italic> ε4 carriers, but not non-carriers, with lower serum high-density lipoprotein had a higher prevalence of cognitive impairment and a lower Mini-Mental State Examination score. These results suggest that the <italic>APOE</italic> ε4 allele may affect the relationship between serum lipid levels and cognitive impairment. However, the specific mechanism needs to be further elucidated.</p>