Ye Zirong, Deng Jiahe, Wu Xiuxia, Cai Jingwen, Li Sicheng, Chen Xiaochun, Xin Jiawei
Department of Neurology, Fujian Medical University Union Hospital, Fujian Key Laboratory of Molecular Neurology and Institute of Neuroscience, Fujian Medical University, No.29, Xinquan Road, Gulou District, Fuzhou, Fujian Province, 350000, China; Key Laboratory of Health Technology Assessment of Fujian Province, School of Public Health, Xiamen University, Xiang'an Nan Road, Xiang'an District, Xiamen, Fujian Province, 361102, China; Institute of Clinical Neurology, Fujian Medical University, No.29 Xinquan Road, Gulou District, Fuzhou, Fujian Province, 350000, China.
School of Clinical Medicine, Fujian Medical University Union Hospital, No.29, Xinquan Road, Gulou District, Fuzhou, Fujian Province, 350000, China.
J Prev Alzheimers Dis. 2025 Feb;12(2):100025. doi: 10.1016/j.tjpad.2024.100025. Epub 2025 Jan 1.
The effect of statins use on the incidence of Alzheimer's disease (AD) is still under debate, and it could be modified by a series of factors.
We aimed to examine the association of statins use with the risk of cognitive impairment and AD, and assess the moderating roles of genetic susceptibility and other individual-related factors.
A longitudinal study was conducted from the UK Biobank where individuals completed baseline surveys (2006-2010) and were followed (mean follow-up period: 9 years).
A population-based study.
A total of 371,019 dementia-free participants (mean age 56.4 years; 53.6% female).
The effects of statins use on cognitive performance and incident AD were examined by using linear regression model and Cox proportional hazards regression model, respectively. We further evaluated the moderating roles of genetic risks and individual-related factors on both multiplicative and additive scales.
The findings showed statins use was associated with an increased risk of AD development [hazard ratio (HR) 1.19 (95% CI: 1.08, 1.30)] compared with no use of statins. We further found significant negative additive interactions of statins use with APOE ε4 allele. Besides, the effects of statins use would be modified by age, sex and cardiovascular diseases (CVDs).
A protective effect of statins use was observed in those who carried two APOE ε4 alleles. Also, sex, age and CVDs could modify the effects of statins use, which would provide insights for the guideline of the statins therapy.
他汀类药物的使用对阿尔茨海默病（AD）发病率的影响仍存在争议，且可能受到一系列因素的影响。
我们旨在研究他汀类药物的使用与认知障碍和AD风险之间的关联，并评估遗传易感性和其他个体相关因素的调节作用。
在英国生物银行进行了一项纵向研究，参与者完成了基线调查（2006 - 2010年）并接受随访（平均随访期：9年）。
一项基于人群的研究。
共有371,019名无痴呆症参与者（平均年龄56.4岁；53.6%为女性）。
分别使用线性回归模型和Cox比例风险回归模型研究他汀类药物使用对认知表现和AD发病的影响。我们进一步在乘法和加法尺度上评估了遗传风险和个体相关因素的调节作用。
研究结果显示，与未使用他汀类药物相比，使用他汀类药物与AD发病风险增加相关[风险比（HR）1.19（95%置信区间：1.08, 1.30）]。我们还发现他汀类药物使用与APOE ε4等位基因之间存在显著的负相加相互作用。此外，他汀类药物使用的效果会因年龄、性别和心血管疾病（CVD）而改变。
在携带两个APOE ε4等位基因的人群中观察到了他汀类药物使用的保护作用。此外，性别、年龄和CVD可改变他汀类药物使用的效果，这将为他汀类药物治疗指南提供参考。
