EEG and ERP biosignatures of mild cognitive impairment for longitudinal monitoring of early cognitive decline in Alzheimer’s disease

Cognitive decline in Alzheimer's disease is associated with electroencephalographic (EEG) biosignatures even at early stages of mild cognitive impairment (MCI). The aim of this work is to provide a unified measure of cognitive decline by aggregating biosignatures from multiple EEG modalities and to evaluate repeatability of the composite measure at an individual level. These modalities included resting state EEG (eyes-closed) and two event-related potential (ERP) tasks on visual memory and attention. We compared individuals with MCI (n = 38) to age-matched healthy controls HC (n = 44). In resting state EEG, the MCI group exhibited higher power in Theta (3-7Hz) and lower power in Beta (13-20Hz) frequency bands. In both ERP tasks, the MCI group exhibited reduced ERP late positive potential (LPP), delayed ERP early component latency, slower reaction time, and decreased response accuracy. Cluster-based permutation analysis revealed significant clusters of difference between the MCI and HC groups in the frequency-channel and time-channel spaces. Cluster-based measures and performance measures (12 biosignatures in total) were selected as predictors of MCI. We trained a support vector machine (SVM) classifier achieving AUC = 0.89, accuracy = 77% in cross-validation using all data. Split-data validation resulted in (AUC = 0.87, accuracy = 76%) and (AUC = 0.75, accuracy = 70%) on testing data at baseline and follow-up visits, respectively. Classification scores at baseline and follow-up visits were correlated (r = 0.72, p<0.001, ICC = 0.84), supporting test-retest reliability of EEG biosignature. These results support the utility of EEG/ERP for prognostic testing, repeated assessments, and tracking potential treatment outcomes in the limited duration of clinical trials.