Abstract
Objectives: 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, APOE ε4 allele has a major impact on lipid metabolism. The aim of this study was to investigate the APOE genotype-dependent relationship between peripheral serum lipid levels and cognitive impairment.Methods: A total of 1,273 subjects aged 40–86 years participated in this cross-sectional study. Serum lipid levels and the APOE 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 APOE genotype, serum lipid levels, and cognition function.Results: After controlling for all possible covariates, a significant interaction between low serum high-density lipoprotein and the APOE ε4 allele on cognitive impairment (Wald’s χ2 = 4.269, df = 1, OR = 20.094, p = 0.039) was found in the total participants. In APOE ε4 carriers, low serum high-density lipoprotein was positively associated with cognitive impairment (Wald’s χ2 = 8.200, df = 1, OR = 60.335, p = 0.004) and serum high-density lipoprotein levels were positively correlated with Mini-Mental State Examination score (r = 0.217, df = 176, p = 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 APOE ε4 carriers/non-carriers.Conclusions: APOE 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 APOE ε4 allele may affect the relationship between serum lipid levels and cognitive impairment. However, the specific mechanism needs to be further elucidated.
Highlights
Alzheimer’s disease (AD) is the most common type of dementia, and its prevalence has been increasing rapidly in China (Jia et al, 2014)
Considering that the Apolipoprotein E (APOE) genotype plays an important role in both AD pathogenesis and lipid metabolism, we investigated the effects of the APOE genotype on the relationships between peripheral serum lipid levels and cognitive impairment in Chinese middle-aged and elderly subjects from Qubao village in the suburbs of Xi’an, northwest China
The exclusion criteria were as follows: (1) participants who had used lipid-lowering drugs in the last 3 months; (2) participants who had severe liver, kidney, thyroid, and hematopoietic system diseases; (3) participants who had suffered from a clear history of acute cerebrovascular disease, including stroke; (4) participants who had suffered from severe nervous system diseases that can cause cognitive impairment, including infection, Parkinson’s disease, epilepsy, congenital intellectual disability, and craniocerebral operations; (5) participants who had suffered from other physical and chemical factors that led to cognitive impairment; (6) participants who had suffered from severe psychopathy, including schizophrenia, bipolar disorder, severe depression or anxiety; and (7) participants without a complete Mini-Mental State Examination (MMSE) score, biomarkers, or covariates
Summary
Alzheimer’s disease (AD) is the most common type of dementia, and its prevalence has been increasing rapidly in China (Jia et al, 2014). When cleaved by β-secretase and γ-secretase, APP is mainly hydrolyzed into the 38–43 amino acid residue Aβ peptide (De Felice and Ferreira, 2002), and senile plaques are mainly composed of amyloid Aβ40 and amyloid Aβ42 (Masters et al, 1985). The responsiveness of Aβ production to cholesterol levels suggests that cholesterol metabolism plays an essential role in the pathogenesis of AD (Hartmann et al, 2007). There are still no consistent results of epidemiological studies concerning the role of cholesterol as a risk factor for AD, some studies have demonstrated that elevated cholesterol increases the risk of AD development, in middle-aged individuals (Kivipelto et al, 2001; Whitmer et al, 2005). Other researchers have failed to confirm this result (Reitz et al, 2004; Tukiainen et al, 2012)
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