Ng Ted K S, Beck Todd, Liu Xiaoran, Desai Pankaja, Holland Thomas, Dhana Klodian, Krueger Kristin, Wilson Robert S, Evans Denis A, Rajan Kumar B
Rush Institute for Healthy Aging, Department of Internal Medicine, Rush University Medical Center, Chicago, IL, USA.
Rush Institute for Healthy Aging, Department of Internal Medicine, Rush University Medical Center, Chicago, IL, USA.
Arch Gerontol Geriatr. 2025 Jul;134:105825. doi: 10.1016/j.archger.2025.105825. Epub 2025 Mar 18.
There have been contradictory findings on the associations between lipids and cognitive decline (CD), which may be attributed to the heterogeneity in the APOE4 carrier status, given APOE's lipid transportation roles. However, extant studies rarely examined the modifying effects of APOE4 carrier status on the associations between lipids and CD.
We analyzed the Chicago Health and Aging Project, a 20-year cohort study comprising older adults with lipid panel assayed, i.e., total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL), and longitudinal cognitive tests. We ran adjusted linear mixed-effects models, regressing cognitive test composite on each of the four lipids independently, first with the total sample and subsequently using interaction and stratified subgroup analyses, examining the modifying effects of APOE4 carrier status on the associations.
3,496 biracial community-dwelling older adults were recruited from the South side of Chicago (58% African American & 64% women; mean follow-up = 4.6 years). In the total sample, there was a borderline association between TG and CD, estimate (SD, p-value) = 0.0001 (0.0000,0.0565). No associations were detected with other lipids. In the interaction and subgroup analyses, only in ε4 carriers that higher TC levels were significantly associated with accelerated CD, -0.020 (0.009,0.035), whereas higher TG levels were significantly associated with decelerated CD, 0.001 (0.001,0.045). No modifying effects of ε4 carrier status were detected with other lipids.
Specific lipids, i.e., TC and TG, were associated with CD only in the ε4 carriers, highlighting the potential importance of measuring APOE4 status to better inform risk prediction and treatment.
关于脂质与认知功能衰退（CD）之间的关联存在相互矛盾的研究结果，鉴于载脂蛋白E（APOE）在脂质运输中的作用，这可能归因于APOE4携带者状态的异质性。然而，现有研究很少考察APOE4携带者状态对脂质与CD之间关联的调节作用。
我们分析了芝加哥健康与衰老项目，这是一项为期20年的队列研究，纳入了进行过血脂检测（即总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白（HDL）和低密度脂蛋白（LDL））的老年人以及进行了纵向认知测试。我们运行了调整后的线性混合效应模型，分别将四种脂质中的每一种对认知测试综合指标进行回归分析，首先在总样本中进行，随后通过交互作用和分层亚组分析，考察APOE4携带者状态对这些关联的调节作用。
从芝加哥南区招募了3496名居住在社区的不同种族老年人（58%为非裔美国人，64%为女性；平均随访时间 = 4.6年）。在总样本中，TG与CD之间存在临界关联，估计值（标准差，p值） = 0.0001（0.0000，0.0565）。未检测到其他脂质与CD之间的关联。在交互作用和亚组分析中，仅在ε4携带者中，较高的TC水平与加速的CD显著相关，为-0.020（0.009，0.035），而较高的TG水平与减速的CD显著相关，为0.001（0.001，0.045）。未检测到ε4携带者状态对其他脂质有调节作用。
特定的脂质，即TC和TG，仅在ε4携带者中与CD相关，这凸显了检测APOE4状态对于更好地进行风险预测和治疗的潜在重要性。
