Choe Young Min, Choi Hye Ji, Keum Musung, Lee Boung Chul, Suh Guk-Hee, Kim Shin Gyeom, Kim Hyun Soo, Hwang Jaeuk, Yi Dahyun, Kim Jee Wook
Department of Neuropsychiatry, Hallym University Dongtan Sacred Heart Hospital, 7 Keunjaebong-gil, Hwaseong 18450, Gyeonggi, Republic of Korea.
Department of Psychiatry, College of Medicine, Hallym University, Chuncheon 24252, Gangwon, Republic of Korea.
Nutrients. 2025 Jul 14;17(14):2321. doi: 10.3390/nu17142321.
High-density lipoprotein cholesterol (HDL-C) is known for its cardiovascular and neuroprotective effects, but its association with cognitive function remains unclear, particularly in relation to genetic factors such as apolipoprotein E ε4 (APOE4). We aimed to investigate the association between serum HDL-C levels and cognition and to examine the moderating effect of APOE4 on this relationship. This cross-sectional study included 196 dementia-free older adults (aged 65-90) recruited from a memory clinic and the community. Cognitive function was assessed across multiple domains using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) battery. Serum HDL-C levels were measured, and APOE4 genotyping was performed. Multiple linear regression analyses were conducted, adjusting for age, sex, APOE4 status, education, diagnosis, vascular risk, nutritional status, physical activity, and blood biomarkers. Higher HDL-C levels were significantly associated with better episodic memory (B = 0.109, 95% confidence interval [CI]: 0.029-0.189, = 0.008) and global cognition (B = 0.130, 95% CI: 0.001-0.261, = 0.049). These associations were significantly moderated by APOE4 status. In APOE4-positive individuals, HDL-C was strongly associated with both episodic memory (B = 0.357, 95% CI: 0.138-0.575, = 0.003) and global cognition (B = 0.519, 95% CI: 0.220-0.818, = 0.002), but no such associations were observed in APOE4-negative participants. This study indicates a significant association between serum HDL-C levels and cognitive function, particularly in episodic memory and global cognition, with APOE4 status potentially moderating this relationship. While these findings may suggest a protective role of HDL-C in individuals at increased genetic risk due to APOE4, they should be interpreted with caution given the cross-sectional design. Future longitudinal and mechanistic studies are warranted to clarify causality and potential clinical implications.
高密度脂蛋白胆固醇（HDL-C）以其心血管保护和神经保护作用而闻名，但其与认知功能的关联仍不明确，尤其是与载脂蛋白Eε4（APOE4）等遗传因素的关系。我们旨在研究血清HDL-C水平与认知之间的关联，并检验APOE4对这种关系的调节作用。这项横断面研究纳入了196名从记忆诊所和社区招募的无痴呆症老年人（年龄在65 - 90岁之间）。使用阿尔茨海默病注册协会（CERAD）成套测试在多个领域评估认知功能。测量血清HDL-C水平，并进行APOE4基因分型。进行了多元线性回归分析，对年龄、性别、APOE4状态、教育程度、诊断、血管风险、营养状况、身体活动和血液生物标志物进行了调整。较高的HDL-C水平与较好的情景记忆（B = 0.109，95%置信区间[CI]：0.029 - 0.189，P = 0.008）和整体认知（B = 0.130，95%CI：0.001 - 0.261，P = 0.049）显著相关。这些关联受到APOE4状态的显著调节。在APOE4阳性个体中，HDL-C与情景记忆（B = 0.357，95%CI：0.138 - 0.575，P = 0.0
