Background: Hyperlipidemia has been linked to cognitive impairment (CogI) caused by Alzheimer's disease and vascular disease. Nevertheless the relationship between long-term trajectories of serum lipids and the risk of developing CogI is still lacking.

Methods: Research enrolled participants aged 40 years or older in the suburbs of Xi'an, China and conducted follow-ups every two years from 2014 to 2020. Fasting serum lipid (including total cholesterol, TC; triglyceride, TG; high density lipoprotein, HDL-c; low density lipoprotein, LDL-c) levels were tested. Those with normal cognition at baseline and diagnosed with MCI or dementia during follow-up were defined as having new-onset CogI. We used group-based trajectory model for serum lipid trajectory classification, and multivariable logistic regression models to investigate the relationship between long-term serum lipids trajectories and CogI.

Results: Our final sample included 1268 participants. There were 33 (2.6%) new-onset CogI of whom 20 met the criteria for MCI and 13 met the criteria for dementia during the follow-up. Trajectories of TC and LDL-c were divided into three categories (low, medium and high level) respectively; lgTG and HDL-c were divided into low and high level respectively. Univariate analysis showed that the incidence rate of CogI in low TC group (3.4%) or high TC group (4.3%) was higher than that in medium TC group (1.5%). Multivariable logistic regression analysis showed that compared to medium level, the risk of developing CogI was increased for both low TC level (OR=2.679 [95% CI, 1.140-6.295]) and high TC level (OR=2.828 [95% CI, 0.927-8.624]). Other lipid trajectory levels were not associated with the risk of developing CogI.

Conclusions: Long-term low or high TC levels may be a predictive factor for the risk of CogI.

Keywords: Cognitive impairment; Cohort study; Deterioro cognitivo; Estudio de cohortes; Factor predictivo; Hiperlipidemia; Hyperlipidemia; Predictive factor.

Copyright © 2025 The Authors. Published by Elsevier España, S.L.U. All rights reserved.

背景： 高脂血症与阿尔茨海默病和血管疾病引起的认知障碍（CogI）有关。然而，长期的血脂水平变化轨迹与发生认知障碍风险之间的关系仍然缺乏研究。

方法： 本研究招募了中国西安郊区40岁及以上年龄的人群，并从2014年至2020年每两年进行一次随访。检测空腹血清脂质（包括总胆固醇、TC；甘油三酯、TG；高密度脂蛋白、HDL-c；低密度脂蛋白、LDL-c）水平。基线时认知正常的参与者在随访期间被诊断为轻度认知障碍或痴呆，则定义为新发CogI。我们使用组基轨迹模型对血清脂质变化进行分类，并通过多变量逻辑回归模型研究长期血脂变化与CogI风险之间的关系。

结果： 最终样本包括1268名参与者。其中有33（2.6%）新发认知障碍，其中20人符合轻度认知障碍的标准，13人符合痴呆的标准。TC和LDL-c轨迹分别被分为三类（低、中和高水平），lgTG和HDL-c则分别被分为低和高两类水平。单变量分析显示，在低TC组或高TC组中的CogI发病率（分别为3.4% 和 4.3%）比在中等TC组中的发病风险更高（1.5%）。多变量逻辑回归分析表明，与中等水平相比，低TC水平和高TC水平都增加了新发认知障碍的风险（OR=2.679 [95% CI, 1.140-6.295] 和 OR=2.828 [95% CI, 0.927-8.624]）。其他脂质轨迹水平与新发认知障碍风险无关。

结论： 长期低或高水平的TC可能是认知障碍发生风险的一个预测因素。

关键词： 认知障碍；队列研究；Deterioro cognitivo；Estudio de cohortes；预测因子；Hiperlipidemia；Hyperlipidemia；Predictive factor.