Background: Noninvasive and effective biomarkers for early detection of amnestic mild cognitive impairment (aMCI) before measurable changes in behavioral performance remain scarce. Cognitive event-related potentials (ERPs) measure synchronized synaptic neural activity associated with a cognitive event. Loss of synapses is a hallmark of the neuropathology of early Alzheimer’s disease (AD). In the present study, we tested the hypothesis that ERP responses during working memory retrieval discriminate aMCI from cognitively normal controls (NC) matched in age and education.

Methods: Eighteen NC, 17 subjects with aMCI, and 13 subjects with AD performed a delayed match-to-sample task specially designed not only to be easy enough for impaired participants to complete but also to generate comparable performance between subjects with NC and those with aMCI. Scalp electroencephalography, memory accuracy, and reaction times were measured.

Results: Whereas memory performance separated the AD group from the others, the performance of NC and subjects with aMCI was similar. In contrast, left frontal cognitive ERP patterns differentiated subjects with aMCI from NC. Enhanced P3 responses at left frontal sites were associated with nonmatching relative to matching stimuli during working memory tasks in patients with aMCI and AD, but not in NC. The accuracy of discriminating aMCI from NC was 85% by using left frontal match/nonmatch effect combined with nonmatch reaction time.

Conclusions: The left frontal cognitive ERP indicator holds promise as a sensitive, simple, affordable, and noninvasive biomarker for detection of early cognitive impairment.

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Published in Alzheimer's Research & Therapy, v. 9, 3, p. 1-10.

© The Author(s). 2017

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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JL was supported by the National Science Foundation of China (grants 31671157, 31470998, 31271108), the Chinese Academy of Sciences and State Administration of Foreign Experts Affairs (CAS/SAFEA) International Partnership Program for Creative Research Team (Y2CX131003), and the China Abroad Scholarship Fund. The research project was sponsored in part by the Laboratory Directed Research and Development program of ORNL, UT-Battelle LLC, for the U.S. Department of Energy under contract number DE-AC05-00OR22725; the U.S. National Institutes of Health (grants P30AG028383, T32 AG 242-18, UL1RR033173, UL1TR000117, TL1TR00015, P50AG05144, and AG000986); and a pilot grant from the University of Kentucky Department of Behavioral Science.