Relationship between the Presence of the ApoE ε4 Allele and EEG Complexity along the Alzheimer's Disease Continuum

Alzheimer's disease (AD) is the most prevalent cause of dementia, being considered a major health problem, especially in developed countries. Late-onset AD is the most common form of the disease, with symptoms appearing after 65 years old. Genetic determinants of AD risk are vastly unknown, though,epsilon 4 allele of theApoEgene has been reported as the strongest genetic risk factor for AD. The objective of this study was to analyze the relationship between brain complexity and the presence ofApoE epsilon 4 alleles along the AD continuum. For this purpose, resting-state electroencephalography (EEG) activity was analyzed by computing Lempel-Ziv complexity (LZC) from 46 healthy control subjects, 49 mild cognitive impairment subjects, 45 mild AD patients, 44 moderate AD patients and 33 severe AD patients, subdivided byApoEstatus. Subjects with one or moreApoE epsilon 4 alleles were included in the carriers subgroups, whereas theApoE epsilon 4 non-carriers subgroups were formed by subjects without any epsilon 4 allele. Our results showed that AD continuum is characterized by a progressive complexity loss. No differences were observed between ADApoE epsilon 4 carriers and non-carriers. However, brain activity from healthy subjects withApoE epsilon 4 allele (carriers subgroup) is more complex than from non-carriers, mainly in left temporal, frontal and posterior regions (p-values < 0.05, FDR-corrected Mann-WhitneyU-test). These results suggest that the presence ofApoE epsilon 4 allele could modify the EEG complexity patterns in different brain regions, as the temporal lobes. These alterations might be related to anatomical changes associated to neurodegeneration, increasing the risk of suffering dementia due to AD before its clinical onset. This interesting finding might help to advance in the development of new tools for early AD diagnosis.