Sparks D Larry, Sabbagh Marwan N, Connor Donald J, Lopez Jean, Launer Lenore J, Browne Patrick, Wasser Dawn, Johnson-Traver Sherry, Lochhead Jeff, Ziolwolski Chuck
Author Affiliations: Sun Health Research Institute, Sun City, AZ 85351, USA.
Arch Neurol. 2005 May;62(5):753-7. doi: 10.1001/archneur.62.5.753.
Laboratory evidence of cholesterol-induced production of amyloid beta as a putative neurotoxin precipitating Alzheimer disease, along with epidemiological evidence, suggests that cholesterol-lowering statin drugs may favorably influence the progression of the disorder.
To determine if treatment with atorvastatin calcium affects the cognitive and/or behavioral decline in patients with mild to moderate Alzheimer disease.
Pilot intention-to-treat, proof-of-concept, double-blind, placebo-controlled, randomized (1:1) trial with a 1-year exposure to once-daily atorvastatin calcium (80 mg; two 40-mg tablets) or placebo using last observation carried forward analysis of covariance as the primary method of statistical assessment.
Individuals with mild to moderate Alzheimer disease (Mini-Mental State Examination score of 12-28) were recruited. Of the 98 participants providing informed consent, 71 were eligible for randomization, 67 were randomized, and 63 subjects completed the 3-month visit and were considered evaluable.
The primary outcome measures were change in Alzheimer's Disease Assessment Scale-cognitive subscale and the Clinical Global Impression of Change Scale scores. The secondary outcome measures included scores on the Mini-Mental State Examination, Geriatric Depression Scale, the Neuropsychiatric Inventory Scale, and the Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory. The tertiary outcome measures included total cholesterol, low-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol levels.
Atorvastatin reduced circulating cholesterol levels and produced a positive signal on each of the clinical outcome measures compared with placebo. This beneficial effect reached significance for the Geriatric Depression Scale and the Alzheimer's Disease Assessment Scale-cognitive subscale at 6 months and was significant at the level of a trend for the Alzheimer's Disease Assessment Scale-cognitive subscale, Clinical Global Impression of Change Scale, and Neuropsychiatric Inventory Scale at 12 months assessed by analysis of covariance with last observation carried forward.
Atorvastatin treatment may be of some clinical benefit and could be established as an effective therapy for Alzheimer disease if the current findings are substantiated by a much larger multicenter trial.
胆固醇诱导产生β淀粉样蛋白作为一种可能引发阿尔茨海默病的神经毒素的实验室证据，以及流行病学证据表明，降低胆固醇的他汀类药物可能对该疾病的进展产生有利影响。
确定阿托伐他汀钙治疗是否会影响轻至中度阿尔茨海默病患者的认知和/或行为衰退。
意向性治疗的先导性概念验证双盲安慰剂对照随机（1:1）试验，每日一次给予阿托伐他汀钙（80毫克；两片40毫克片剂）或安慰剂，为期1年，采用末次观察结转协方差分析作为主要统计评估方法。
招募轻至中度阿尔茨海默病患者（简易精神状态检查表评分12 - 28分）。在98名提供知情同意书的参与者中，71名符合随机分组条件，67名被随机分组，63名受试者完成了3个月的访视并被视为可评估对象。
主要结局指标为阿尔茨海默病评估量表认知子量表和临床总体印象变化量表评分的变化。次要结局指标包括简易精神状态检查表、老年抑郁量表、神经精神科问卷量表以及阿尔茨海默病协作研究日常生活活动量表的评分。三级结局指标包括总胆固醇、低密度脂蛋白胆固醇和极低密度脂蛋白胆固醇水平。
与安慰剂相比，阿托伐他汀降低了循环胆固醇水平，并在各项临床结局指标上产生了积极信号。这种有益效果在6个月时对于老年抑郁量表和阿尔茨海默病评估量表认知子量表达到显著水平，在12个月时，通过末次观察结转协方差分析评估，阿尔茨海默病评估量表认知子量表、临床总体印象变化量表和神经精神科问卷量表在趋势水平上具有显著意义。
阿托伐他汀治疗可能具有一定的临床益处，如果当前研究结果能被更大规模的多中心试验所证实，那么它可能被确立为治疗阿尔茨海默病的有效疗法。
