From the Rush Institute for Healthy Aging (K.B.R., A.D., D.A.E.), Department of Internal Medicine, Rush University Medical Center, Chicago, IL; Division of Endocrinology (E.A.M.), Gerontology and Metabolism, Stanford University Medical Center, CA; Rush Alzheimer's Disease Center (R.S.W.), Rush University Medical Center, Chicago, IL; and Care Policy and Evaluation Centre (S.E.-L.), London School of Economics and Political Science, United Kingdom.
Neurology. 2024 Apr 9;102(7):e209168. doi: 10.1212/WNL.0000000000209168. Epub 2024 Mar 6.
The association of statin initiation with incident Alzheimer disease (AD) dementia and cognitive decline by the ε4 allele is unknown. Our objective was to examine whether the association of statin initiation with incident AD dementia and cognitive decline differs by the ε4 allele.
This population-based longitudinal cohort study was conducted in 4 urban communities in Chicago, IL, United States, consisting of 4,807 participants. Statin initiation is based on the inspection of medications during home assessments. Clinical diagnosis for incident AD used the NINCDS-ADRDA criteria, and longitudinal measurements of global cognition consisted of episodic memory, perceptual speed, and the Mini-Mental State Examination tests.
The study participants had a mean age of 72 years, consisting of 63% female individuals and 61% non-Hispanic Black individuals. During the study period, 1,470 (31%) participants reported statin initiation. In a covariate-adjusted competing risk model, statin initiation was associated with a reduced risk of incident clinical AD [hazard ratio (HR) 0.81 (95% CI 0.70-0.94)] compared with nonusers. This association was statistically significantly lower ( interaction = 0.015) among participants with the ε4 allele [HR 0.60 (95% CI 0.49-0.74)] compared with those without the ε4 allele [HR 0.96 (95% CI 0.82-1.12)]. The annual decline in global cognition (β = 0.021, 95% CI 0.007-0.034) and episodic memory (β = 0.020, 95% CI 0.007-0.033) was also substantially slower among participants with the ε4 allele after statin initiation compared with nonusers. However, the association of statin initiation with cognitive decline was not significant among those without the ε4 allele.
Our findings suggest that statins might be associated with a lower risk of incident AD among individuals with the ε4 allele. The benefits of statin therapy need further consideration in randomized clinical trials, especially among those with the ε4 allele.
This study provides Class II evidence that among those aged 65 years or older, statin initiation was associated with a reduced risk of Alzheimer disease, especially in the presence of an -e4 allele.
尚不清楚他汀类药物起始治疗与载脂蛋白 E ɛ4 等位基因的阿尔茨海默病（AD）痴呆和认知能力下降的相关性。本研究旨在检验他汀类药物起始治疗与载脂蛋白 E ɛ4 等位基因的 AD 痴呆和认知能力下降之间的相关性是否存在差异。
本基于人群的纵向队列研究在美国伊利诺伊州芝加哥的 4 个城市社区进行，共纳入 4807 名参与者。他汀类药物的起始治疗基于家庭评估期间的药物检查。AD 的临床诊断采用 NINCDS-ADRDA 标准，纵向测量的整体认知能力包括情景记忆、知觉速度和简易精神状态检查测试。
研究参与者的平均年龄为 72 岁，其中 63%为女性，61%为非西班牙裔黑人。在研究期间，1470 名（31%）参与者报告了他汀类药物的起始治疗。在调整了混杂因素的竞争风险模型中，与未使用者相比，他汀类药物起始治疗与 AD 临床发病风险降低相关（风险比[HR]0.81[95%置信区间（CI）0.70-0.94]）。与无载脂蛋白 E ɛ4 等位基因的参与者相比（HR0.96[95%CI0.82-1.12]），载脂蛋白 E ɛ4 等位基因的参与者这种关联显著降低（交互作用=0.015，HR0.60[95%CI0.49-0.74]）。与未使用者相比，起始他汀类药物治疗后，载脂蛋白 E ɛ4 等位基因的参与者整体认知能力（β=0.021，95%CI0.007-0.034）和情景记忆（β=0.020，95%CI0.007-0.033）的年下降速度也明显较慢。然而，在无载脂蛋白 E ɛ4 等位基因的参与者中，他汀类药物起始治疗与认知能力下降之间的关联并不显著。
本研究结果表明，他汀类药物可能与载脂蛋白 E ɛ4 等位基因个体 AD 发病风险降低有关。在随机临床试验中，特别是在载脂蛋白 E ɛ4 等位基因个体中，需要进一步考虑他汀类药物治疗的获益。
本研究提供了 II 级证据，表明在年龄 65 岁或以上的人群中，他汀类药物起始治疗与 AD 风险降低相关，特别是在存在载脂蛋白 E ɛ4 等位基因的情况下。
