血清胆固醇与阿尔茨海默病发病风险：来自思维老化研究的发现。
Serum Cholesterol and Incident Alzheimer's Disease: Findings from the Adult Changes in Thought Study.
机构信息
Department of Pharmacy, School of Pharmacy, University of Washington, Seattle, Washington.
Kaiser Permanente Washington Health Research Institute, Kaiser Permanente Washington, Seattle, Washington.
出版信息
J Am Geriatr Soc. 2018 Dec;66(12):2344-2352. doi: 10.1111/jgs.15581. Epub 2018 Oct 5.
OBJECTIVES
To evaluate associations between high-density lipoprotein cholesterol (HDL) and non-HDL-C levels at specific ages and subsequent Alzheimer's disease (AD) risk.
DESIGN
Prospective population-based cohort study.
SETTING
Adult Changes in Thought (ACT) Study.
PARTICIPANTS
Individuals aged 65 and older with no dementia at ACT Study entry. We identified separate, partially overlapping subcohorts of ACT participants who were eligible for each age band-specific analysis (50-59, n = 1,088; 60-69, n = 2,852; 70-79, n = 2,344; 80-89, n = 537).
MEASUREMENTS
Exposure consisted of clinical measures of total cholesterol (TC) and HDL-C from laboratory data during a given age band. Outcomes of incident AD were assessed post-age band using standard research diagnostic criteria. Statistical analyses used adjusted Cox proportional hazards regression models for each exposure and outcome pair within an age band. Cholesterol exposures were modeled using cubic splines.
RESULTS
For non-HDL-C, we found a statistically significant association with AD risk in the 60 to 69 (omnibus p = .005) and 70 to 79 (omnibus p = .04) age bands, suggesting a potential U-shaped relationship (greater risk at low and high levels). For example, in people aged 60 to 69, those with an average non-HDL-C level of 120 mg/DL had a 29% greater AD hazard (hazard ratio (HR)=1.29, 95% confidence interval (CI)=1.04-1.61) than those with an average non-HDL-C level of 160 mg/dL, whereas those with an average non-HDL-C level of 210 mg/dL had a 16% greater hazard (HR=1.16, 95% CI=1.01-1.33). We did not find a statistically significant association between HDL-C and AD risk.
CONCLUSION
People with low (120 mg/dL) and high (210 mg/dL) non-HDL-C levels during their 60s and 70s had modestly higher risk of AD than those with intermediate (160 mg/dL) levels. The extreme age bands (50s and 80s) had small sample sizes. J Am Geriatr Soc 66:2344-2352, 2018.
目的
评估特定年龄段高密度脂蛋白胆固醇（HDL）和非高密度脂蛋白胆固醇（非 HDL-C）水平与随后发生阿尔茨海默病（AD）风险之间的关联。
设计
前瞻性人群为基础的队列研究。
地点
成人思维变化（ACT）研究。
参与者
在 ACT 研究入组时无痴呆的 65 岁及以上人群。我们确定了 ACT 参与者的单独、部分重叠亚队列，这些亚队列符合每个年龄组特定分析的条件（50-59 岁，n=1088；60-69 岁，n=2852；70-79 岁，n=2344；80-89 岁，n=537）。
测量方法
暴露因素包括特定年龄组内实验室数据中总胆固醇（TC）和 HDL-C 的临床测量值。在年龄组之后，使用标准研究诊断标准评估 AD 事件的发生。在年龄组内，每个暴露和结果对均使用调整后的 Cox 比例风险回归模型进行统计分析。胆固醇暴露用三次样条进行建模。
结果
对于非 HDL-C，我们发现其与 60-69 岁（总体 p=0.005）和 70-79 岁（总体 p=0.04）年龄组的 AD 风险之间存在统计学显著关联，表明存在潜在的 U 型关系（低水平和高水平的风险更高）。例如，在 60-69 岁的人群中，非 HDL-C 平均水平为 120mg/dL 的人发生 AD 的风险增加 29%（风险比（HR）=1.29，95%置信区间（CI）=1.04-1.61），而非 HDL-C 平均水平为 160mg/dL 的人，而非 HDL-C 平均水平为 210mg/dL 的人发生 AD 的风险增加 16%（HR=1.16，95%CI=1.01-1.33）。我们未发现 HDL-C 与 AD 风险之间存在统计学显著关联。
结论
60 多岁和 70 多岁时非 HDL-C 水平较低（120mg/dL）和较高（210mg/dL）的人发生 AD 的风险略高于中等水平（160mg/dL）的人。极端年龄组（50 多岁和 80 多岁）的样本量较小。美国老年学会杂志 66:2344-2352，2018 年。
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