A cognitive electrophysiological signature differentiates amnestic mild cognitive impairment from normal aging

Juan Li, Lucas S. Broster, Gregory A. Jicha, Nancy B. Munro, Frederick A. Schmitt, Erin Abner, Richard Kryscio, Charles D. Smith, Yang Jiang

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


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.

Original languageEnglish
Article number3
JournalAlzheimer's Research and Therapy
Issue number1
StatePublished - Jan 19 2017

Bibliographical note

Funding Information:
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.

Publisher Copyright:
© 2017 The Author(s).


  • Alzheimer's disease
  • Amnestic mild cognitive impairment
  • Early detection
  • Event-related potentials
  • Working memory

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cognitive Neuroscience


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