Resting-state beta-band oscillatory dysfunction bridges Alzheimer’s pathology and memory impairment

Abstract Background Resting-state electroencephalography (rs-EEG) is a promising non-invasive biomarker of Alzheimer’s disease (AD), yet its role in linking molecular pathology to cognitive impairment remains unclear. We investigated whether rs-EEG spectral activity is associated with amyloid-β and tau pathology and how these measures relate to cognition. Methods Thirty-six biomarker-confirmed participants with amyloid-positive Alzheimer’s disease-related mild cognitive impairment (AD-MCI) and 38 cognitively normal older adults underwent rs-EEG assessment. Patients with AD-MCI additionally received amyloid-β and tau positron emission tomography (PET). Power spectral density across frequency bands was compared between groups. Partial correlation analyses examined associations among PET biomarkers, rs-EEG activity, and cognitive performance measured by the Cognitive Abilities Screening Instrument (CASI). Regression-based mediation analyses were performed with adjustment for age, sex, education, and APOE ε4 status. Results Compared with controls, patients with AD-MCI showed increased delta/theta power and reduced beta power. Greater amyloid burden was associated with lower beta-band activity across multiple regions, whereas higher tau burden was associated with reduced beta activity and regionally increased delta and theta activity. Poorer memory performance was associated with reduced beta activity and increased theta activity. Amyloid burden showed no robust direct association with memory performance; however, it was indirectly associated with memory through beta-band activity. In contrast, tau burden was directly associated with poorer memory, and no significant mediation effects through beta activity were observed. Conclusions Beta-band activity may represent a systems-level correlate linking AD pathology and cognition, with amyloid-β showing indirect associations via network dynamics and tau demonstrating more direct relationships with memory impairment.