Effect of reductions in amyloid levels on cognitive change in randomized trials: instrumental variable meta-analysis.
Effect of reductions in amyloid levels on cognitive change in randomized trials: instrumental variable meta-analysis.
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DOI：
10.1136/bmj.n156
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发表时间：
2021-02-25
期刊：
影响因子：
--
通讯作者：
Glymour MM
中科院分区：
文献类型：
--
作者：
Ackley SF;Zimmerman SC;Brenowitz WD;Tchetgen Tchetgen EJ;Gold AL;Manly JJ;Mayeda ER;Filshtein TJ;Power MC;Elahi FM;Brickman AM;Glymour MM
评估针对淀粉样蛋白的药物试验，以确定淀粉样蛋白水平的降低是否可能改善认知。工具变量荟萃分析。14项针对淀粉样蛋白机制的预防或治疗阿尔茨海默病药物的随机对照试验，来自ClinicalTrials.gov。试验的入选标准各不相同，但通常包括50岁或以上的成年人，诊断为轻度认知障碍或阿尔茨海默病，基线时淀粉样蛋白阳性。分析包括的试验，可以获得的信息都在大脑淀粉样蛋白水平的变化与淀粉样蛋白正电子发射断层扫描和变化，至少有一个认知测试评分报告为每个随机arm. Pool结果从14个随机对照试验比任何单一的试验估计更精确。将淀粉样蛋白水平降低0.1个标准化摄取值比率单位的效果的合并估计值是简易精神状态检查评分改善0.03（95%置信区间-0.06至0.1）分。这项研究提供了一个网络应用程序，允许在新数据可用时重新估计结果，并说明了实现支持降低淀粉样蛋白水平获益的汇总估计所需的新证据的数量。现有的试验报告了淀粉样蛋白水平降低和认知改变的汇总证据表明，淀粉样蛋白减少策略不会显著改善认知。
To evaluate trials of drugs that target amyloid to determine whether reductions in amyloid levels are likely to improve cognition. Instrumental variable meta-analysis. 14 randomized controlled trials of drugs for the prevention or treatment of Alzheimer’s disease that targeted an amyloid mechanism, identified from ClinicalTrials.gov. Adults enrolled in randomized controlled trials of amyloid targeting drugs. Inclusion criteria for trials vary, but typically include adults aged 50 years or older with a diagnosis of mild cognitive impairment or Alzheimer’s disease, and amyloid positivity at baseline. Analyses included trials for which information could be obtained on both change in brain amyloid levels measured with amyloid positron emission tomography and change in at least one cognitive test score reported for each randomization arm. Pooled results from the 14 randomized controlled trials were more precise than estimates from any single trial. The pooled estimate for the effect of reducing amyloid levels by 0.1 standardized uptake value ratio units was an improvement in the mini-mental state examination score of 0.03 (95% confidence interval −0.06 to 0.1) points. This study provides a web application that allows for the re-estimation of the results when new data become available and illustrates the magnitude of the new evidence that would be necessary to achieve a pooled estimate supporting the benefit of reducing amyloid levels. Pooled evidence from available trials reporting both reduction in amyloid levels and change in cognition suggests that amyloid reduction strategies do not substantially improve cognition.
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DOI：
10.3233/jad-179901
发表时间：
2018
期刊：
Journal of Alzheimer's disease : JAD
影响因子：
--
作者：
Cummings J;Ritter A;Zhong K
通讯作者：
Zhong K
影响因子：
2.6
作者：
Abushouk AI;Elmaraezy A;Aglan A;Salama R;Fouda S;Fouda R;AlSafadi AM
通讯作者：
AlSafadi AM
影响因子：
120.7
作者：
Näslund, J;Haroutunian, V;Buxbaum, JD
通讯作者：
Buxbaum, JD
DOI：
10.1056/nejmoa1304839
发表时间：
2014-01-23
期刊：
The New England journal of medicine
影响因子：
--
作者：
Salloway S;Sperling R;Fox NC;Blennow K;Klunk W;Raskind M;Sabbagh M;Honig LS;Porsteinsson AP;Ferris S;Reichert M;Ketter N;Nejadnik B;Guenzler V;Miloslavsky M;Wang D;Lu Y;Lull J;Tudor IC;Liu E;Grundman M;Yuen E;Black R;Brashear HR;Bapineuzumab 301 and 302 Clinical Trial Investigators
通讯作者：
Bapineuzumab 301 and 302 Clinical Trial Investigators
DOI：
10.1097/nen.0b013e31825018f7
发表时间：
2012-05
影响因子：
3.2
作者：
Nelson PT;Alafuzoff I;Bigio EH;Bouras C;Braak H;Cairns NJ;Castellani RJ;Crain BJ;Davies P;Del Tredici K;Duyckaerts C;Frosch MP;Haroutunian V;Hof PR;Hulette CM;Hyman BT;Iwatsubo T;Jellinger KA;Jicha GA;Kövari E;Kukull WA;Leverenz JB;Love S;Mackenzie IR;Mann DM;Masliah E;McKee AC;Montine TJ;Morris JC;Schneider JA;Sonnen JA;Thal DR;Trojanowski JQ;Troncoso JC;Wisniewski T;Woltjer RL;Beach TG
通讯作者：
Beach TG