Objective: Relationships between the apolipoprotein E 4 allele and electroencephalographic (EEG) rhythmicity have been demonstrated in Alzheimer's disease (AD) patients but not in the preclinical stage prodromic to it, namely, mild cognitive impairment (MCI). The present multicentric EEG study tested the hypothesis that presence of 4 affects sources of resting EEG rhythms in both MCI and AD subjects. Methods: We enrolled 89 MCI subjects (34.8% with 4) and 103 AD patients (50.4% with 4). Resting

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... eyes-closed EEG data were recorded for all subjects. EEG rhythms of interest were delta (2-4Hz), theta (4 -8Hz), alpha 1 (8 -10.5Hz), alpha 2 (10.5-13Hz), beta 1 (13-20Hz), and beta 2 (20 -30Hz). EEG cortical sources were estimated by low-resolution brain electromagnetic tomography. Results: Results showed that amplitude of alpha 1 and 2 sources in occipital, temporal, and limbic areas was lower in subjects carrying the 4 allele than in those not carrying the 4 allele (p < 0.01). This was true for both MCI and AD. For the first time to our knowledge, a relationship was shown between ApoE genotype and global neurophysiological phenotype (ie, cortical alpha rhythmicity) in a preclinical AD condition, MCI, in addition to clinically manifest AD. Interpretation: Such a demonstration motivates future genotype-EEG phenotype studies for the early prediction of AD conversion in individual MCI subjects.