학술논문
Association of CSF Biomarkers with Hippocampal-dependent Memory in Preclinical Alzheimer Disease
Document Type
Academic Journal
Author
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
Source
Neurology. Jan 06, 2021
Subject
Language
English
ISSN
0028-3878
Abstract
OBJECTIVE:: To determine if memory tasks with demonstrated sensitivity to hippocampal function can detect variance related to preclinical Alzheimer’s disease (AD) biomarkers, we examined associations between performance in three memory tasks and CSF Aβ42/Aβ40 and 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 yrs; 94 female) completed a lumbar puncture and memory assessments. CSF Aβ42, Aβ40, and phosopho-tau181 (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 between 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 a) poorer associative memory and b) 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 non-significant. 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 cognitively unimpaired older adults with preclinical AD pathology.