Andrew Aschenbrenner, PhD, 4488 Forest Park Ave, STE 301, St. Louis, MO, 63108,
J Prev Alzheimers Dis. 2024;11(6):1696-1702. doi: 10.14283/jpad.2024.130.
A decline in episodic memory is one of the earliest cognitive characteristics of Alzheimer disease and memory tests are heavily featured in cognitive composite endpoints that are used to demonstrate treatment efficacy. Assessments of episodic memory can take many forms including free recall, associate learning, and paragraph or story recall. Plasma biomarkers of Alzheimer disease are now widely available and will likely form the backbone of cohort enrichment strategies for future clinical trials. Thus, it is critical to evaluate which episodic memory measures are most sensitive to plasma markers of Alzheimer disease pathology.
To compare the associations of common episodic memory tests with plasma biomarkers of Alzheimer disease.
Longitudinal cohort study.
Academic medical center in the midwestern United States.
A total of 161 cognitively normal older adults with at least one plasma biomarker assessment and two or more annual clinical and cognitive assessments which included up to three different tests of episodic memory.
Episodic memory performance using free recall, paired associates recall or paragraph recall. Plasma Aβ42, Aβ40, ptau217, and neurofilament light chain were measured.
Free recall on the Free and Cued Selective Reminding Test with Immediate Recall (FCSRT + IR) was substantially more sensitive to longitudinal cognitive change associated with abnormal baseline plasma Aβ42/Aβ40 and ptau217 compared to other measures of episodic memory. A cognitive composite that included only free recall showed larger decline associated with baseline Aβ42/Aβ40 when compared to those that included paragraph recall. Differences in decline across composites were minimal when considering baseline ptau217 or NfL.
Episodic memory is a critical domain to assess in preclinical Alzheimer disease. Methods of assessing memory are not equal and longitudinal change in free recall substantially outperformed both paired associates and paragraph recall. Clinical trial results will depend critically on the episodic memory test(s) that are chosen for a composite endpoint and free recall from the FCSRT + IR is an optimal memory measure to include rather than paired associates or paragraph recall.
情景记忆的衰退是阿尔茨海默病最早出现的认知特征之一，而记忆测试则是用于证明治疗效果的认知综合终点的重要特征。情景记忆评估可以采用多种形式，包括自由回忆、联想学习以及段落或故事回忆。阿尔茨海默病的血浆生物标志物现在已经广泛应用，并且可能成为未来临床试验中队列富集策略的基础。因此，评估哪些情景记忆测量最能反映阿尔茨海默病病理的血浆标志物至关重要。
比较常见的情景记忆测试与阿尔茨海默病的血浆生物标志物的相关性。
纵向队列研究。
美国中西部的一所学术医疗中心。
共有 161 名认知正常的老年人，他们至少进行了一次血浆生物标志物评估，并且进行了两次或更多次年度临床和认知评估，其中包括多达三种不同的情景记忆测试。
使用自由回忆、成对联想回忆或段落回忆评估情景记忆表现。测量血浆 Aβ42、Aβ40、ptau217 和神经丝轻链。
与基线血浆 Aβ42/Aβ40 和 ptau217 相关的纵向认知变化相比，自由和线索选择性回忆测试的即时回忆（FCSRT + IR）中的自由回忆对其他情景记忆测量更敏感。与包括段落回忆的认知综合指标相比，仅包括自由回忆的认知综合指标与基线 Aβ42/Aβ40 相关的下降更大。当考虑基线 ptau217 或 NfL 时，复合指标之间的下降差异很小。
情景记忆是评估临床前阿尔茨海默病的关键领域。评估记忆的方法并不相同，自由回忆的纵向变化明显优于成对联想和段落回忆。临床试验结果将取决于用于综合终点的情景记忆测试，而 FCSRT + IR 的自由回忆是最佳的记忆测量方法，而不是成对联想或段落回忆。
