Abstract
Currently established and employed biomarkers of Alzheimer's disease (AD) predominantly mirror AD-associated molecular and structural brain changes. While they are necessary for identifying disease-specific neuropathology, they lack a clear and robust relationship with the clinical presentation of dementia; they can be altered in healthy individuals, while they often inadequately mirror the degree of cognitive and functional deficits in affected subjects. There is growing evidence that synaptic loss and dysfunction are early events during the trajectory of AD pathogenesis that best correlate with the clinical symptoms, suggesting measures of brain functional deficits as candidate early markers of AD. Resting-state electroencephalography (EEG) is a widely available and noninvasive diagnostic method that provides direct insight into brain synaptic activity in real time. Quantitative EEG (qEEG) analysis additionally provides information on physiologically meaningful frequency components, dynamic alterations and topography of EEG signal generators, i.e. neuronal signaling. Numerous studies have shown that qEEG measures can detect disruptions in activity, topographical distribution and synchronization of neuronal (synaptic) activity such as generalized EEG slowing, reduced global synchronization and anteriorization of neuronal generators of fast-frequency resting-state EEG activity in patients along the AD continuum. Moreover, qEEG measures appear to correlate well with surrogate markers of AD neuropathology and discriminate between different types of dementia, making them promising low-cost and noninvasive markers of AD. Future large-scale longitudinal clinical studies are needed to elucidate the diagnostic and prognostic potential of qEEG measures as early functional markers of AD on an individual subject level.