Alzheimer's disease-like features in resting state EEG/fMRI of cognitively intact and healthy middle-aged <i>APOE</i> / <i>PICALM</i> risk carriers

BackgroundGenetic susceptibility is a primary factor contributing to etiology of late-onset Alzheimer's disease (LOAD). The exact mechanisms and timeline through which <i>APOE</i>/<i>PICALM</i> influence brain functions and contribute to LOAD remain unidentified. This includes their effects on individuals prior to the development of the disease.ObjectiveTo investigate the effects of <i>APOE</i> and <i>PICALM</i> risk genes on brain health and function in non-demented individuals. This study aims to differentiate the combined risk effects of both genes from the risk associated solely with <i>APOE</i>, and to examine how <i>PICALM</i> alleles influence the risk linked to <i>APOE</i>.Methods<i>APOE</i>/<i>PICALM</i> alleles were assessed to determine the genetic risk of LOAD in 79 healthy, middle-aged participants who underwent electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) recordings. The resting-state signal was analyzed to estimate relative spectral power, complexity (Higuchi's algorithm), and connectivity (coherence in EEG and independent component analysis-based connectivity in fMRI).ResultsThe main findings indicated that individuals at risk for LOAD exhibited reduced signal complexity and the so-called "slowing of EEG" which are well-known EEG markers of Alzheimer's disease. Additionally, these individuals showed altered functional connectivity in fMRI (within attention-related areas).ConclusionsRisk alleles of <i>APOE/PICALM</i> may affect brain integrity and function prior to the clinical onset of the disease.