Torrandell-Haro Georgina, Branigan Gregory L, Vitali Francesca, Geifman Nophar, Zissimopoulos Julie M, Brinton Roberta Diaz
Center for Innovation in Brain Science University of Arizona Tucson Arizona USA.
Department of Pharmacology University of Arizona College of Medicine Tucson Arizona USA.
Alzheimers Dement (N Y). 2020 Nov 25;6(1):e12108. doi: 10.1002/trc2.12108. eCollection 2020.
Establishing efficacy of and molecular pathways for statins has the potential to impact incidence of Alzheimer's and age-related neurodegenerative diseases (NDD).
This retrospective cohort study surveyed US-based Humana claims, which includes prescription and patient records from private-payer and Medicare insurance. Claims from 288,515 patients, aged 45 years and older, without prior history of NDD or neurological surgery, were surveyed for a diagnosis of NDD starting 1 year following statin exposure. Patients were required to be enrolled with claims data for at least 6 months prior to first statin prescription and at least 3 years thereafter. Computational system biology analysis was conducted to determine unique target engagement for each statin.
Of the 288,515 participants included in the study, 144,214 patients (mean [standard deviation (SD)] age, 67.22 [3.8] years) exposed to statin therapies, and 144,301 patients (65.97 [3.2] years) were not treated with statins. The mean (SD) follow-up time was 5.1 (2.3) years. Exposure to statins was associated with a lower incidence of Alzheimer's disease (1.10% vs 2.37%; relative risk [RR], 0.4643; 95% confidence interval [CI], 0.44-0.49; < .001), dementia 3.03% vs 5.39%; RR, 0.56; 95% CI, 0.54-0.58; < .001), multiple sclerosis (0.08% vs 0.15%; RR, 0.52; 95% CI, 0.41-0.66; < .001), Parkinson's disease (0.48% vs 0.92%; RR, 0.53; 95% CI, 0.48-0.58; < .001), and amyotrophic lateral sclerosis (0.02% vs 0.05%; RR, 0.46; 95% CI, 0.30-0.69; < .001). All NDD incidence for all statins, except for fluvastatin (RR, 0.91; 95% CI, 0.65-1.30; = 0.71), was reduced with variances in individual risk profiles. Pathway analysis indicated unique and common profiles associated with risk reduction efficacy.
Benefits and risks of statins relative to neurological outcomes should be considered when prescribed for at-risk NDD populations. Common statin activated pathways indicate overarching systems required for risk reduction whereas unique targets could advance a precision medicine approach to prevent neurodegenerative diseases.
确定他汀类药物的疗效和分子途径有可能影响阿尔茨海默病及年龄相关神经退行性疾病（NDD）的发病率。
这项回顾性队列研究调查了美国Humana保险公司的理赔数据，其中包括来自私人医疗保险和医疗保险的处方及患者记录。对288,515名年龄在45岁及以上、无NDD或神经外科手术既往史的患者进行了调查，从他汀类药物暴露1年后开始诊断NDD。患者在首次开具他汀类药物处方前至少6个月以及之后至少3年需有理赔数据记录。进行了计算系统生物学分析以确定每种他汀类药物的独特靶点作用。
该研究纳入的288,515名参与者中，144,214名患者（平均[标准差（SD）]年龄为67.22[3.8]岁）接受了他汀类药物治疗，144,301名患者（65.97[3.2]岁）未接受他汀类药物治疗。平均（SD）随访时间为5.1（2.3）年。他汀类药物暴露与阿尔茨海默病发病率较低相关（1.10%对2.37%；相对风险[RR]，0.4643；95%置信区间[CI]，0.44 - 0.49；P <.001），痴呆（3.03%对5.39%；RR，0.56；95% CI，0.54 - 0.58；P <.001），多发性硬化（0.08%对0.15%；RR，0.52；95% CI，0.41 - 0.66；P <.001），帕金森病（0.48%对0.92%；RR，0.53；95% CI，0.48 - 0.58；P <.001）和肌萎缩侧索硬化（0.02%对0.05%；RR，0.46；95% CI，0.30 - 0.69；P <.001）。除氟伐他汀外（RR，0.91；95% CI，0.65 - 1.30；P = 0.71），所有他汀类药物的所有NDD发病率均因个体风险特征的差异而降低。通路分析表明存在与风险降低疗效相关的独特和共同特征。
为有NDD风险的人群开处方时，应考虑他汀类药物相对于神经学结局的益处和风险。常见的他汀类药物激活途径表明了降低风险所需的总体系统，而独特靶点可能推动采用精准医学方法预防神经退行性疾病。
Zotero 插件
