Alzheimer's disease-like features in resting state EEG/fMRI of cognitively intact and healthy middle-aged APOE/PICALM 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 APOE/PICALM 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 APOE and PICALM 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 APOE, and to examine how PICALM alleles influence the risk linked to APOE.MethodsAPOE/PICALM 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 APOE/PICALM may affect brain integrity and function prior to the clinical onset of the disease.