Jick H, Zornberg G L, Jick S S, Seshadri S, Drachman D A
Boston Collaborative Drug Surveillance Program, Boston University School of Medicine, Lexington, MA 02421, USA.
Lancet. 2000 Nov 11;356(9242):1627-31. doi: 10.1016/s0140-6736(00)03155-x.
Dementia affects an estimated 10% of the population older than 65 years. Because vascular and lipid-related mechanisms are thought to have a role in the pathogenesis of Alzheimer's disease and vascular dementia, we did an epidemiological study of the potential effect of HMGCoA (3 hydroxy-3methylglutaryl-coenzyme A) reductase inhibitors (statins) and other lipid-lowering agents on dementia.
We used a nested case-control design with information derived from 368 practices which contribute to the UK-based General Practice Research Database. The base study population included three groups of patients age 50 years and older: all individuals who had received lipid-lowering agents (LLAs); all individuals with a clinical diagnosis of untreated hyperlipidaemia; and a randomly selected group of other individuals. From this base population, all cases with a computer-recorded clinical diagnosis of dementia were identified. Each case was matched with up to four controls derived from the base population on age, sex, practice, and index date of case.
The study encompassed 284 cases with dementia and 1080 controls. Among controls 13% had untreated hyperlipidaemia, 11% were prescribed statins, 7% other LLAs, and 69% had no hyperlipidaemia or LLA exposure. The relative risk estimates of dementia adjusted for age, sex, history of coronary-artery disease, hypertension, coronary-bypass surgery and cerebral ischaemia, smoking and body mass index for individuals with untreated hyperlipidaemia (odds ratio 0.72 [95% CI 0.45-1.14]), or treated with nonstatin LLAs (0.96 [0.47-1.97], was close to 1.0 and not significant compared with people who had no diagnosis of hyperlipidaemia or exposure to other lipid-lowering drugs. The adjusted relative risk for those prescribed statins was 0.29 (0.13-0.63; p=0.002).
Individuals of 50 years and older who were prescribed statins had a substantially lowered risk of developing dementia, independent of the presence or absence of untreated hyperlipidaemia, or exposure to nonstatin LLAs. The available data do not distinguish between Alzheimer's disease and other forms of dementia.
据估计，65岁以上人群中10%患有痴呆症。由于血管和脂质相关机制被认为在阿尔茨海默病和血管性痴呆的发病机制中起作用，我们对HMGCoA（3-羟基-3-甲基戊二酰辅酶A）还原酶抑制剂（他汀类药物）和其他降脂药物对痴呆症的潜在影响进行了一项流行病学研究。
我们采用巢式病例对照设计，数据来源于368家参与英国全科医学研究数据库的医疗机构。基础研究人群包括三组50岁及以上的患者：所有接受过降脂药物（LLAs）治疗的个体；所有临床诊断为未经治疗的高脂血症的个体；以及一组随机选择的其他个体。从这个基础人群中，识别出所有计算机记录临床诊断为痴呆症的病例。每个病例与最多四个来自基础人群的对照进行匹配，匹配因素包括年龄、性别、医疗机构和病例的索引日期。
该研究纳入了284例痴呆症病例和1080例对照。在对照中，13%患有未经治疗的高脂血症，11%被处方使用他汀类药物，7%使用其他降脂药物，69%没有高脂血症或未接触过降脂药物。对年龄、性别、冠状动脉疾病史、高血压、冠状动脉搭桥手术和脑缺血、吸烟和体重指数进行调整后，未经治疗的高脂血症患者（比值比0.72 [95%可信区间0.45 - 1.14]）或使用非他汀类降脂药物治疗的患者（0.96 [0.47 - 1.97]）患痴呆症的相对风险估计值接近1.0，与未诊断为高脂血症或未接触过其他降脂药物的人相比无显著差异。使用他汀类药物治疗的患者调整后的相对风险为0.29（0.13 - 0.63；p = 0.002）。
50岁及以上被处方使用他汀类药物的个体患痴呆症的风险大幅降低，与是否存在未经治疗的高脂血症或是否接触非他汀类降脂药物无关。现有数据无法区分阿尔茨海默病和其他形式的痴呆症。
