EEG/ERP evidence of possible hyperexcitability in older adults with elevated beta-amyloid

Background: Although growing evidence links beta-amyloid (A beta) and neuronal hyperexcitability in preclinical mouse models of Alzheimer's disease (AD), a similar association in humans is yet to be established. The first aim of the study was to determine the association between elevated AP (A beta+) and cognitive processes measured by the P3 event-related potential (ERP) in cognitively normal (CN) older adults. The second aim was to compare the eventrelated power between CNA beta+ and CNA beta-. Methods: Seventeen CNA beta+ participants (age: 73 +/- 5, 11 females, Montreal Cognitive Assessment [MoCA] score 26 +/- 2) and 17 CNA beta- participants group-matched for age, sex, and MOCA completed a working memory task (n-back with n = 0, 1 , 2) test while wearing a 256-channel electro-encephalography net. P3 peak amplitude and latency of the target, nontarget and task difference effect (nontarget-target), and event-related power in the delta, theta, alpha, and beta bands, extracted from Fz, Cz, and Pz, were compared between groups using linear mixed models. P3 amplitude of the task difference effect at Fz and event-related power in the delta band were considered main outcomes. Correlations of mean AP standard uptake value ratios (SUVR) using positron emission tomography with P3 amplitude and latency of the task difference effect were analyzed using Pearson Correlation Coefficient r. Results: The P3 peak amplitude of the task difference effect at Fz was lower in the CNA beta+ group (P = 0.048). Similarly, power was lower in the delta band for nontargets at Fz in the CNA beta+ participants (P = 0.04). The CNA beta+ participants also demonstrated higher theta and alpha power in channels at Cz and Pz, but no changes in P3 ERR. Strong correlations were found between the mean AP SUVR and the latency of the 1-back (r= - 0.69; P= 0.003) and 2-back (r= - 0.69; P = 0.004) of the task difference effect at channel Fz in the CNA beta+ group. Conclusions: Our data suggest that the elevated amyloid in cognitively normal older adults is associated with neuronal hyperexcitability. The decreased P3 task difference likely reflects early impairments in working memory processes. Further research is warranted to determine the validity of ERP in predicting clinical, neurobiological, and functional manifestations of AD.