An empirically derived composite cognitive test score with improved power to track and evaluate treatments for preclinical Alzheimer's disease
An empirically derived composite cognitive test score with improved power to track and evaluate treatments for preclinical Alzheimer's disease
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DOI：
10.1016/j.jalz.2014.02.002
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发表时间：
2014-11-01
影响因子：
14
通讯作者：
Reiman, Eric M.
中科院分区：
文献类型：
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作者：
Langbaum, Jessica B.;Hendrix, Suzanne B.;Reiman, Eric M.
背景：临床前阿尔茨海默病（AD）治疗的评价越来越受到关注。因此，有必要确定一种认知复合材料，它对跟踪临床前AD下降敏感，可用作治疗试验的主要终点。方法：从最初认知正常，70- 85岁来自拉什阿尔茨海默病中心的三项关于衰老和痴呆的队列研究的老年参与者被检查，以经验性地定义一个复合认知终点，在认知障碍发作之前检测和跟踪认知能力下降。计算随时间变化的平均标准差比（MSDR），以寻找认知测试/子测试的最佳组合，这些测试/子测试来自认知正常参与者的神经心理电池，随后在2年和5年期间进展到AD的临床阶段，使用同期未受损的数据来校正老化和实践影响。表现良好的组合，然后进行了评估的代表性相关的认知领域，稳健性在个别年前的诊断，并发生选定的项目内的最佳执行combinations.Results：最佳的复合认知测试分数包括7个认知测试/子测试的MSDR = 0.964。通过比较，最敏感的个人测试分数是逻辑记忆延迟回忆，MSDR = 0.64。结论：我们已经确定了一个复合认知测试分数代表多个认知领域，具有改善的权力相比，最敏感的单一测试项目，以跟踪临床前AD下降和评估临床前AD治疗。我们正在确认复合材料在独立队列中的功效，并与其他可能导致改进的分析方法一起，将其指定为阿尔茨海默病预防计划临床前治疗试验的主要终点，用于因迟发性AD而出现症状的高危个体。(C)2014年，阿尔茨海默氏症协会。All rights reserved.
Background: There is growing interest in the evaluation of preclinical Alzheimer's disease (AD) treatments. As a result, there is a need to identify a cognitive composite that is sensitive to track preclinical AD decline to be used as a primary endpoint in treatment trials.Methods: Longitudinal data from initially cognitively normal, 70- to 85-year-old participants in three cohort studies of aging and dementia from the Rush Alzheimer's Disease Center were examined to empirically define a composite cognitive endpoint that is sensitive to detect and track cognitive decline before the onset of cognitive impairment. The mean-to-standard deviation ratios (MSDRs) of change over time were calculated in a search for the optimal combination of cognitive tests/subtests drawn from the neuropsychological battery in cognitively normal participants who subsequently progressed to clinical stages of AD during 2- and 5-year periods, using data from those who remained unimpaired during the same period to correct for aging and practice effects. Combinations that performed well were then evaluated for representation of relevant cognitive domains, robustness across individual years before diagnosis, and occurrence of selected items within top performing combinations.Results: The optimal composite cognitive test score comprised seven cognitive tests/subtests with an MSDR = 0.964. By comparison, the most sensitive individual test score was Logical Memory Delayed Recall with an MSDR = 0.64.Conclusions: We have identified a composite cognitive test score representing multiple cognitive domains that has improved power compared with the most sensitive single test item to track preclinical AD decline and evaluate preclinical AD treatments. We are confirming the power of the composite in independent cohorts and with other analytical approaches, which may result in refinements, have designated it as the primary endpoint in the Alzheimer's Prevention Initiative's preclinical treatment trials for individuals at high imminent risk for developing symptoms due to late-onset AD. (C) 2014 The Alzheimer's Association. All rights reserved.