From the Department of Psychology (A.N.T., V.A.C., M.P.H., T.T.T., M.K.T., M.J., W.G., N.J.T., J.D.B., C.P.L., S.A.G., A.M.K., M.B.H., A.D.W.), Stanford University; and Department of Neurology and Neurological Sciences (E.N.W., M.S.S., T.N.T., D.C., N.K.C., A.N., G.K.D., J.N.H., S.J.S., C.A.F., K.I.A., G.A.K., E.C.M.) and Division of Nuclear Medicine & Molecular Imaging Division, Department of Radiology (B.K.R., F.T.C., G.A.D.), Stanford Medical School, CA.
Neurology. 2021 Mar 9;96(10):e1470-e1481. doi: 10.1212/WNL.0000000000011477. Epub 2021 Jan 6.
To determine whether memory tasks with demonstrated sensitivity to hippocampal function can detect variance related to preclinical Alzheimer disease (AD) biomarkers, we examined associations between performance in 3 memory tasks and CSF β-amyloid (Aβ)/Aβ and phosopho-tau (p-tau) in cognitively unimpaired older adults (CU).
CU enrolled in the Stanford Aging and Memory Study (n = 153; age 68.78 ± 5.81 years; 94 female) completed a lumbar puncture and memory assessments. CSF Aβ, Aβ, and p-tau were measured with the automated Lumipulse G system in a single-batch analysis. Episodic memory was assayed using a standardized delayed recall composite, paired associate (word-picture) cued recall, and a mnemonic discrimination task that involves discrimination between studied "target" objects, novel "foil" objects, and perceptually similar "lure" objects. Analyses examined cross-sectional relationships among memory performance, age, and CSF measures, controlling for sex and education.
Age and lower Aβ/Aβ were independently associated with elevated p-tau. Age, Aβ/Aβ, and p-tau were each associated with (1) poorer associative memory and (2) diminished improvement in mnemonic discrimination performance across levels of decreased task difficulty (i.e., target-lure similarity). P-tau mediated the effect of Aβ/Aβ on memory. Relationships between CSF proteins and delayed recall were similar but nonsignificant. CSF Aβ was not significantly associated with p-tau or memory.
Tests designed to tax hippocampal function are sensitive to subtle individual differences in memory among CU and correlate with early AD-associated biomarker changes in CSF. These tests may offer utility for identifying CU with preclinical AD pathology.
为了确定是否具有显示对海马功能敏感性的记忆任务可以检测与临床前阿尔茨海默病（AD）生物标志物相关的变异性，我们研究了认知未受损的老年人（CU）中 3 种记忆任务的表现与 CSFβ-淀粉样蛋白（Aβ）/Aβ和磷酸化 tau（p-tau）之间的相关性。
斯坦福老化和记忆研究（n=153；年龄 68.78±5.81 岁；94 名女性）中的 CU 参与者完成了腰椎穿刺和记忆评估。CSF Aβ、Aβ 和 p-tau 采用自动化 Lumipulse G 系统在单次分析中进行测量。使用标准延迟回忆综合、配对联想（单词-图片）线索回忆以及记忆辨别任务评估情景记忆，该任务涉及对已学习的“目标”对象、新颖的“诱饵”对象和知觉相似的“诱饵”对象进行辨别。分析中，在控制性别和教育程度的情况下，考察了记忆表现、年龄和 CSF 指标之间的横断面关系。
年龄和较低的 Aβ/Aβ 与较高的 p-tau 独立相关。年龄、Aβ/Aβ 和 p-tau 均与（1）联想记忆较差和（2）在降低任务难度（即目标-诱饵相似性）的情况下记忆辨别表现改善幅度减小有关。Aβ/Aβ 对记忆的影响受 p-tau 介导。CSF 蛋白与延迟回忆之间的关系相似但无统计学意义。CSF Aβ 与 p-tau 或记忆无显著相关性。
旨在评估海马功能的测试对 CU 中记忆的微妙个体差异敏感，并与 CSF 中与早期 AD 相关的生物标志物变化相关。这些测试可能有助于识别具有临床前 AD 病理的 CU。
