BACKGROUND Previous studies regarding the cholesterol-cognition relationship in midlife have generated conflicting results. We thus investigated whether dietary and blood cholesterol were associated with cognitive decline. METHODS Participants were drawn from a large cohort study entitled the Effects and Mechanism Investigation of Cholesterol and Oxysterol on Alzheimer's disease (EMCOA) study. We included 2514 participants who completed a selection of comprehensive cognitive tests and were followed for an average of 2.3 years. Blood concentrations of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) were assessed and dietary intakes were investigated by food frequency questionnaire (FFQ) at baseline. Apolipoprotein E (APOE) was genotyped by Kompetitive Allele Specific PCR (KASP) sequencing. Non-high-density lipoprotein cholesterol (Non-HDL-C) and LDL-C/HDL-C ratio were calculated. The longitudinal effects of dietary and blood cholesterol on risk of global cognitive decline (decrease in Montreal Cognitive Assessment (MoCA) > 2 points) were examined using Cox proportional hazards models. The nonlinear associations with global and domain-specific cognitive decline was evaluated with mixed effect linear models. RESULTS In Cox proportional hazards models, neither cholesterol nor egg intake was associated with a higher risk of accelerated global cognitive decline. In contrast, the higher serum concentrations of TC, LDL-C, non-HDL-C and LDL-C/HDL-C ratio were positively associated with accelerated global cognitive decline regardless of being evaluated continuously or categorically while higher HDL-C was positively associated with accelerated global cognitive decline only when being evaluated categorically (all P < 0.05). In mixed effect linear models, quadratic and longitudinal relations of dietary cholesterol and egg intakes to global cognition, processing speed and executive function were observed. Moreover, there were inverted U-shaped relations of HDL-C, with processing speed and executive function but U-shaped relations of HDL-C and LDL-C/HDL-C ratio with verbal memory. Adverse linear associations of higher LDL-C and LDL-C/HDL-C ratio with multiple cognitive comes were also revealed. Additionally adjusting for APOE genotype did not modify cholesterol-cognition associations. Dietary and serum cholesterol had variable associations with global and domain-specific cognitive decline across educational groups. CONCLUSION Differential associations between dietary/serum cholesterol and cognitive decline across different domains of function were observed in a particular population of middle-aged and elderly Chinese. Interventions to improve cognitive reserve regarding dietary instruction and lipid management should be tailored according to specific target. TRIAL REGISTRATION EMCOA, ChiCTR-OOC-17011882, Registered 5th, July 2017-Retrospectively registered, http://www.medresman.org/uc/project/projectedit.aspx?proj=2610.

中文翻译：

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中年饮食和血清胆固醇与认知能力下降的纵向和非线性关系：EMCAA研究的结果。

背景技术先前关于中年胆固醇-认知关系的研究产生了矛盾的结果。因此，我们调查了饮食和血液中的胆固醇是否与认知能力下降有关。方法参与者来自一项名为胆固醇和氧固醇对阿尔茨海默病（EMCOA）研究的作用和机制研究的大型队列研究。我们纳入了2514名参与者，他们完成了一系列综合认知测试，平均随访了2.3年。评估总胆固醇（TC），高密度脂蛋白胆固醇（HDL-C），低密度脂蛋白胆固醇（LDL-C）和甘油三酸酯（TG）的血药浓度，并通过食物频率调查表（FFQ）对饮食摄入量进行调查基线。通过竞争性等位基因特异性PCR（KASP）测序对载脂蛋白E（APOE）进行基因分型。计算非高密度脂蛋白胆固醇（Non-HDL-C）和LDL-C / HDL-C之比。使用Cox比例风险模型检查了饮食和胆固醇水平对总体认知下降风险的纵向影响（蒙特利尔认知评估（MoCA）下降> 2分）。用混合效应线性模型评估了与整体认知障碍和特定领域认知障碍的非线性关联。结果在Cox比例风险模型中，胆固醇和鸡蛋摄入均与加速全球认知功能下降的较高风险无关。相反，TC，LDL-C，非HDL-C和LDL-C / HDL-C比率与加速的总体认知能力下降呈正相关，而不论连续或分类评估，而较高的HDL-C与加速的整体认知能力下降呈正相关（仅当进行分类评估时（所有P <0.05）。在混合效应线性模型中，观察到膳食胆固醇和鸡蛋摄入量与总体认知，加工速度和执行功能的二次和纵向关系。此外，HDL-C呈倒U形关系，具有处理速度和执行功能，而HDL-C和LDL-C / HDL-C比的U形关系具有言语记忆。还揭示了较高的LDL-C和LDL-C / HDL-C比与多种认知障碍的不良线性关联。此外，调整APOE基因型不会改变胆固醇认知关联。饮食和血清胆固醇与各个教育群体的整体和特定领域的认知能力下降具有可变的关联。结论在特定的中老年人群中，饮食/血清胆固醇与认知功能下降之间跨不同功能域的差异相关。应根据具体目标量身定制用于改善饮食指导和脂质管理的认知储备的干预措施。试用注册EMCOA，ChiCTR-OOC-17011882，2017年7月5日注册-追溯注册，http：//www.medresman.org/uc/project/projectedit.aspx？proj = 2610。饮食和血清胆固醇与各个教育群体的整体认知障碍和特定领域认知障碍之间存在可变的关联。结论在特定的中老年人群中，饮食/血清胆固醇与认知功能下降之间跨不同功能域的差异相关。应根据具体目标量身定制旨在改善饮食指导和脂质管理的认知储备的干预措施。试用注册EMCOA，ChiCTR-OOC-17011882，2017年7月5日注册-追溯注册，http：//www.medresman.org/uc/project/projectedit.aspx？proj = 2610。饮食和血清胆固醇与各个教育群体的整体认知障碍和特定领域认知障碍之间存在可变的关联。结论在特定的中老年人群中，饮食/血清胆固醇与认知功能下降之间跨不同功能域的差异相关。应根据具体目标量身定制旨在改善饮食指导和脂质管理的认知储备的干预措施。试用注册EMCOA，ChiCTR-OOC-17011882，2017年7月5日注册-追溯注册，http：//www.medresman.org/uc/project/projectedit.aspx？proj = 2610。结论在特定的中老年人群中，饮食/血清胆固醇与认知功能下降之间跨不同功能域的差异相关。应根据具体目标量身定制旨在改善饮食指导和脂质管理的认知储备的干预措施。试用注册EMCOA，ChiCTR-OOC-17011882，2017年7月5日注册-追溯注册，http：//www.medresman.org/uc/project/projectedit.aspx？proj = 2610。结论在特定的中老年人群中，饮食/血清胆固醇与认知功能下降之间跨不同功能域的差异相关。应根据具体目标量身定制旨在改善饮食指导和脂质管理的认知储备的干预措施。试用注册EMCOA，ChiCTR-OOC-17011882，2017年7月5日注册-追溯注册，http：//www.medresman.org/uc/project/projectedit.aspx？proj = 2610。