Association of CSF Biomarkers With Hippocampal-Dependent Memory in Preclinical Alzheimer Disease. (9th March 2021)

• Record Type: Journal Article
• Authors: Trelle, Alexandra N.; Carr, Valerie A.; Wilson, Edward N.; Swarovski, Michelle S.; Hunt, Madison P.; Toueg, Tyler N.; Tran, Tammy T.; Channappa, Divya; Corso, Nicole K.; Thieu, Monica K.; Jayakumar, Manasi; Nadiadwala, Ayesha; Guo, Wanjia; Tanner, Natalie J.; Bernstein, Jeffrey D.; Litovsky, Celia P.; Guerin, Scott A.; Khazenzon, Anna M.; Harrison, Marc B.; Rutt, Brian K.; Deutsch, Gayle K.; Chin, Frederick T.; Davidzon, Guido A.; Hall, Jacob N.; Sha, Sharon J.; Fredericks, Carolyn A.; Andreasson, Katrin I.; Kerchner, Geoffrey A.; Wagner, Anthony D.; Mormino, Elizabeth C.
• Is Part Of: Neurology. Volume 96:Number 10(2021)
• Publication Date: 2021-03-09
• Subjects: Neurology -- Periodicals; Neurology -- Periodicals; Neurologie -- Périodiques; 616.8
• DOI: 10.1212/WNL.0000000000011477
• Languages: English
• ISSNs: 0028-3878

Abstract

Abstract : Objective: 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)42 /Aβ40 and phosopho-tau181 (p-tau181 ) in cognitively unimpaired older adults (CU). Methods: 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 Aβ42, Aβ40, and p-tau181 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. Results: Age and lower Aβ42 /Aβ40 were independently associated with elevated p-tau181 . Age, Aβ42 /Aβ40, and p-tau181 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 Aβ42 /Aβ40 on memory. Relationships between CSF proteins and delayed recall were similar but nonsignificant. CSF Aβ42 was not significantly associated with p-tau181 or memory. Conclusions: 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.