Evidence for benefit of statins to modify cognitive decline and risk in Alzheimer's disease.
Evidence for benefit of statins to modify cognitive decline and risk in Alzheimer's disease.
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DOI：
10.1186/s13195-017-0237-y
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发表时间：
2017-02-17
期刊：
影响因子：
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通讯作者：
Butte AJ
中科院分区：
文献类型：
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作者：
Geifman N;Brinton RD;Kennedy RE;Schneider LS;Butte AJ
尽管对阿尔茨海默病（AD）进行了大量的研究和开发投资，但有效的治疗方法仍然难以捉摸。大量新出现的证据将胆固醇、β-淀粉样蛋白和AD联系起来，几项研究表明，接受他汀类药物治疗的人群患AD和痴呆症的风险降低。然而，虽然已经进行了一些评估他汀类药物在一般AD人群中的临床试验，但这些试验没有产生显著的治疗益处。通过关注AD人群的亚组，有可能检测对他汀类药物治疗有反应的内型。在这里，我们调查可能的保护和治疗作用，他汀类药物在AD通过分析数据集的综合临床试验，前瞻性观察研究。对来自失败临床试验的AD患者水平数据的重新分析表明，辛伐他汀的使用可能会减缓认知功能下降的进展，并且在ApoE 4纯合子中的程度更大。在基线时对多项研究参与者连续长期使用各种他汀类药物的评估显示，他汀类药物使用者的认知表现更好。这些结果得到了一个额外的观察性队列的支持，其中他汀类药物使用者的AD发生率显著较低，接受他汀类药物治疗的ApoE 4/ApoE 4基因型AD患者在10年随访期间表现出更好的认知功能。这些结果表明，使用他汀类药物可能使所有AD患者受益，在ApoE 4纯合子患者中可能具有更高的治疗疗效。
Despite substantial research and development investment in Alzheimer’s disease (AD), effective therapeutics remain elusive. Significant emerging evidence has linked cholesterol, β-amyloid and AD, and several studies have shown a reduced risk for AD and dementia in populations treated with statins. However, while some clinical trials evaluating statins in general AD populations have been conducted, these resulted in no significant therapeutic benefit. By focusing on subgroups of the AD population, it may be possible to detect endotypes responsive to statin therapy. Here we investigate the possible protective and therapeutic effect of statins in AD through the analysis of datasets of integrated clinical trials, and prospective observational studies. Re-analysis of AD patient-level data from failed clinical trials suggested by trend that use of simvastatin may slow the progression of cognitive decline, and to a greater extent in ApoE4 homozygotes. Evaluation of continual long-term use of various statins, in participants from multiple studies at baseline, revealed better cognitive performance in statin users. These findings were supported in an additional, observational cohort where the incidence of AD was significantly lower in statin users, and ApoE4/ApoE4-genotyped AD patients treated with statins showed better cognitive function over the course of 10-year follow-up. These results indicate that the use of statins may benefit all AD patients with potentially greater therapeutic efficacy in those homozygous for ApoE4.