Distinct effects of cholesterol profile components on amyloid and vascular burdens

초록

Background Cholesterol plays important roles in beta-amyloid (A beta) metabolism and atherosclerosis. However, the relationships of plasma cholesterol levels with A beta and cerebral small vessel disease (CSVD) burdens are not fully understood in Asians. Herein, we investigated the relationships between plasma cholesterol profile components and A beta and CSVD burdens in a large, non-demented Korean cohort.Methods We enrolled 1,175 non-demented participants (456 with unimpaired cognition [CU] and 719 with mild cognitive impairment [MCI]) aged >= 45 years who underwent A beta PET at the Samsung Medical Center in Korea. We performed linear regression analyses with each cholesterol (low-density lipoprotein cholesterol [LDL-c], high-density lipoprotein cholesterol [HDL-c], and triglyceride) level as a predictor and each image marker (A beta uptake on PET, white matter hyperintensity [WMH] volume, and hippocampal volume) as an outcome after controlling for potential confounders.Results Increased LDL-c levels (beta = 0.014 to 0.115, p = 0.013) were associated with greater A beta uptake, independent of the APOE e4 allele genotype and lipid-lowering medication. Decreased HDL-c levels (beta = - 0.133 to - 0.006, p = 0.032) were predictive of higher WMH volumes. Increased LDL-c levels were also associated with decreased hippocampal volume (direct effect beta = - 0.053, p = 0.040), which was partially mediated by A beta uptake (indirect effect beta = - 0.018, p = 0.006).Conclusions Our findings highlight that increased LDL-c and decreased HDL-c levels are important risk factors for A beta and CSVD burdens, respectively. Furthermore, considering that plasma cholesterol profile components are potentially modified by diet, exercise, and pharmacological agents, our results provide evidence that regulating LDL-c and HDL-c levels is a potential strategy to prevent dementia.

키워드