Table1_Association between calculated remnant cholesterol levels and incident risks of Alzheimer’s disease among elderly patients with type 2 diabetes: a real-world study.docx

ObjectiveAlzheimer’s disease (AD) is a leading cause of dementia, with a rising global burden. Remnant cholesterol (RC), a component of triglyceride-rich lipoproteins, has been implicated in cardiovascular diseases and metabolic disorders, but its role in AD remains unclear. This study investigated the association between RC levels and the risk of AD among elderly patients with type 2 diabetes (T2D) in a real-world clinical setting.
MethodsWe conducted a retrospective cohort study using electronic medical records from Gongli Hospital of Shanghai Pudong New Area, covering the period from 2013 to 2023. The study included 15,364 elderly patients aged 65-80 years with T2D. RC levels were calculated using the equation. The primary outcome was the diagnosis of AD, validated by neurologists using ICD-10-CM code G30. Cox proportional hazards models were employed to estimate hazard ratios (HRs) for AD across quartiles of RC levels, adjusting for potential confounders.
ResultsOver a mean follow-up of 3.69 ± 1.33 years, 312 new cases of AD were identified. A U-shaped relationship was observed between RC levels and AD risk, with the lowest risk associated with RC levels between 0.58-0.64 mmol/L. Both lower (<0.52 mmol/L) and higher (≥0.77 mmol/L) RC levels were linked to increased AD risk. Compared to the reference group (Q2: 0.52-0.64 mmol/L), the adjusted HRs (95% CI) for the lowest and highest quartiles were 1.891 (1.368-2.613) and 1.891 (1.363-2.622), respectively. Each 1 mmol/L increase in RC was associated with a 3.47-fold higher risk of AD (HR=4.474, 95% CI 2.330-8.592).
ConclusionRC levels may serve as a predictive biomarker for AD risk, with both extremes posing a higher risk. Future studies should explore the mechanistic pathways and potential interventions targeting RC to prevent AD in high-risk populations.

研究目的：阿尔茨海默病（Alzheimer’s disease, AD）是引发痴呆的首要病因，全球疾病负担逐年加重。残余胆固醇（Remnant cholesterol, RC）是富含甘油三酯脂蛋白的组成成分，既往研究已证实其与心血管疾病及代谢紊乱密切相关，但其在阿尔茨海默病中的作用机制尚未明确。本研究于真实世界临床场景中，探究2型糖尿病（type 2 diabetes, T2D）老年患者体内残余胆固醇水平与阿尔茨海默病发病风险的关联。

研究方法：本研究采用回顾性队列研究设计，使用上海浦东新区公利医院2013年至2023年的电子病历数据。研究纳入15364名年龄介于65至80岁的2型糖尿病老年患者。残余胆固醇水平通过特定计算公式得出。本研究的主要结局为阿尔茨海默病确诊病例，由神经内科医师依据ICD-10-CM编码G30进行验证。本研究采用Cox比例风险模型（Cox proportional hazards models），针对不同四分位分组的残余胆固醇水平估算阿尔茨海默病的风险比（hazard ratios, HRs），并校正潜在混杂因素。

研究结果：平均随访时长为3.69±1.33年，期间共确诊312例新发阿尔茨海默病病例。研究观察到残余胆固醇水平与阿尔茨海默病发病风险呈U型关联：当残余胆固醇水平处于0.58~0.64 mmol/L区间时，发病风险最低。当残余胆固醇水平过低（<0.52 mmol/L）或过高（≥0.77 mmol/L）时，阿尔茨海默病发病风险均显著升高。以参考组（Q2：0.52~0.64 mmol/L）为参照，最低四分位组和最高四分位组的校正后风险比（95%置信区间，95% CI）分别为1.891（1.368~2.613）和1.891（1.363~2.622）。残余胆固醇水平每升高1 mmol/L，阿尔茨海默病发病风险升高3.47倍（HR=4.474，95%CI 2.330~8.592）。

研究结论：残余胆固醇水平可作为阿尔茨海默病发病风险的预测生物标志物，其水平过高或过低均会增加发病风险。未来研究应进一步探索残余胆固醇相关的分子机制通路，并针对高危人群开发以残余胆固醇为靶点的阿尔茨海默病预防干预手段。