Supplementary Material for: Subsets of a Large Cognitive Battery Better Power Clinical Trials on Early Stage Alzheimer's Disease

<b><i>Background/Aims:</i></b> Cognitive batteries routinely used by the Alzheimer's disease (AD) research community may contain items that are uninformative for tracking disease progression to power clinical trials on early stage AD. We aim to identify the subsets of the most informative items from an existing cognitive battery to better power clinical trials on early AD. <b><i>Methods:</i></b> Longitudinal change in item scores from the battery was associated with the onset of mild cognitive impairment (MCI) in 1,513 elderly individuals. Items whose longitudinal changes were correlated with the onset of MCI were selected as informative for tracking the early cognitive progression. <b><i>Results:</i></b> 226 items in the battery were annually assessed over a follow-up of up to 13 years. Changes of item scores over time from 187 items were significantly correlated with the onset of MCI. For clinical trials on preclinical AD and on MCI, informative items permit smaller or similar sample sizes as compared to the entire battery, whereas uninformative items require much larger sample sizes. <b><i>Conclusions:</i></b> Longitudinal changes in item scores from about 17% of items in the cognitive battery are uninformative for tracking early disease progression. Clinical trials on early AD can be better powered using informative items rather than the entire battery.

<b><i>背景与目标：</i></b> 阿尔茨海默病（Alzheimer's disease, AD）研究领域常规使用的认知成套测试工具，可能包含无法用于追踪疾病进展、以助力早期阿尔茨海默病临床试验的条目。本研究旨在从现有认知成套测试中筛选出最具信息价值的条目子集，以更好地为早期阿尔茨海默病临床试验提供统计效力支撑。<b><i>研究方法：</i></b> 本研究对1513名老年个体展开纵向追踪，分析该成套测试中各条目得分的纵向变化与轻度认知障碍（mild cognitive impairment, MCI）发病的关联。将纵向变化与MCI发病显著相关的条目筛选为可用于追踪早期认知进展的有效条目。<b><i>研究结果：</i></b> 该成套测试共包含226个条目，在最长达13年的随访周期内每年接受评估。其中187个条目的得分随时间的纵向变化与MCI发病呈显著相关。针对临床前阿尔茨海默病与轻度认知障碍的临床试验而言，使用有效条目组所需的样本量相较于使用全套条目组更小或相当；而无效条目组则需要显著更大的样本量。<b><i>研究结论：</i></b> 本研究所用认知成套测试中约17%的条目，其得分的纵向变化无法有效追踪早期疾病进展。采用有效条目组开展早期阿尔茨海默病临床试验，可获得优于使用全套条目组的统计效力。