Apolipoprotein E and alpha brain rhythms in mild cognitive impairment: A multicentric Electroencephalogram study

Abstract

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 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. Neurol 2006;59:323-334 Mild cognitive impairment (MCI) is characterized by selective memory impairment insufficient to meet criteria for a diagnosis of dementia. Ann1-3 This condition is considered as a prodromic stage of Alzheimer's disease (AD), 4 -6 because a high rate of progression to AD has been clearly shown. 3,7,8 Annual conversion rate to AD is 0.2 to 3.9% in normal aging (with no MCI symptoms) and 6 to 25% in MCI subjects. 3,9 At the end of 6 years of observation, approximately 80% of MCI subjects develop AD.10 Taken together, these data suggest the hypothesis that in most (yet not all) of cases, MCI is a transition state on a linear progression toward AD. According to such a hypothesis, early identification of MCI patients might be clinically crucial. 11,12 In mild AD, electroencephalographic (EEG) rhythms differ from normal elderly (Nold) and vascular dementia subjects, AD patients being characterized by higher delta (0 -3Hz) and lower parietooccipital alpha (8 -12Hz).13-17 Similarly, MCI subjects have shown increase of theta (4 -7Hz) power 18 -20 as well as decrease of alpha power, 15,18 -22 when compared with Nold subjects. These EEG parameters have presented an intermediate magnitude in MCI with respect to Nold and dementia patients. 15,23,24 Despite the converging evidence of abnormal cortical rhythms in MCI and AD, EEG analysis alone is unable to predict conversion of MCI to dementia. It is reasonable that additional biological parameters are needed for this purpose. In this regard, several studies have shown a strict relationship between apolipoproFrom the

Healthy and Pathological Brain Aging: From the Perspective of Oscillations, Functional Connectivity, and Signal Complexity

“…Recent evidence suggests that genetic factors of pathological aging like clusterin ( CLU ) gene polymorphisms and the apolipoprotein E ε4 ( APOE4 ) mutation may affect upper alpha absolute power in nondemented elderly individuals [27], or reduce the amplitude of the posterior-dominant alpha rhythm in early AD [28, 29]. Taken together, these alpha frequency findings suggest that the genotype is associated with age-related preclinical dysregulation of hippocampal function and contributes to AD pathophysiology.…”

MEG spectral analysis in subtypes of mild cognitive impairment

“…Delta power is usually believed to increase only in more severe stages of the disease (Jeong 2004). However, several studies also reported an increase in delta power in MCI patients when compared with healthy aged controls (see, for example, Babiloni et al 2006aBabiloni et al , b, 2010Rossini et al 2008). Moreover, Fernandez et al (2006c) demonstrated than MCI patients with elevated delta activity in posterior parietal regions had a significantly elevated risk of conversion to AD.…”

Abnormalities of Cortical Neural Synchronization Mechanisms in Subjects with Mild Cognitive Impairment due to Alzheimer’s and Parkinson’s Diseases: An EEG Study

“…The procedure is reported in the following. Firstly, we selected the standard fixed frequency bands in line with previous field studies of our research group [14,[32][33][34][35], namely delta (2-4 Hz), theta (4-8 Hz), alpha1 (8.5-10 Hz), alpha2 (10.5-13 Hz), beta1 (13.5-20 Hz), beta2 (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30), and gamma (30-40 Hz). Secondly, eLORETA solutions using the following fixed frequency bands were computed.…”

“…LORETA estimation unveiled a positive correlation between activities in the posterior cortical regional sources of low-frequency alpha rhythms (8-10.5 Hz) and the global cognitive status in Nold, ADMCI, and ADD subjects as a whole group; in contrast, that correlation was negative for occipital cortical sources of the delta rhythms [14,[32][33][34]. Compared to the groups of Nold and ADD subjects, the PPD group exhibited a higher activity in the central delta and posterior theta sources, besides a lower activity in the posterior beta sources [35].…”