Brain-wide slowing of spontaneous alpha rhythms in mild cognitive impairment

Pilar Garcés,Alberto Fernández,Fernando Maestú,Sara Aurtenetxe,Alberto Marcos,Raul Vicente,Jose Ángel Pineda-Pardo,Maria Emiliana De Andrés,Michael Wibral,Miguel Yus,Maria Eugenia López,Miguel Sancho

doi:10.3389/fnagi.2013.00100

Abstract

The neurophysiological changes associated with Alzheimer's Disease (AD) and Mild Cognitive Impairment (MCI) include an increase in low frequency activity, as measured with electroencephalography or magnetoencephalography (MEG). A relevant property of spectral measures is the alpha peak, which corresponds to the dominant alpha rhythm. Here we studied the spatial distribution of MEG resting state alpha peak frequency and amplitude values in a sample of 27 MCI patients and 24 age-matched healthy controls. Power spectra were reconstructed in source space with linearly constrained minimum variance beamformer. Then, 88 Regions of Interest (ROIs) were defined and an alpha peak per ROI and subject was identified. Statistical analyses were performed at every ROI, accounting for age, sex and educational level. Peak frequency was significantly decreased (p < 0.05) in MCIs in many posterior ROIs. The average peak frequency over all ROIs was 9.68 ± 0.71 Hz for controls and 9.05 ± 0.90 Hz for MCIs and the average normalized amplitude was (2.57 ± 0.59)·10−2 for controls and (2.70 ± 0.49)·10−2 for MCIs. Age and gender were also found to play a role in the alpha peak, since its frequency was higher in females than in males in posterior ROIs and correlated negatively with age in frontal ROIs. Furthermore, we examined the dependence of peak parameters with hippocampal volume, which is a commonly used marker of early structural AD-related damage. Peak frequency was positively correlated with hippocampal volume in many posterior ROIs. Overall, these findings indicate a pathological alpha slowing in MCI.

Highlights

Mild Cognitive Impairment (MCI) is often considered a prodromal stage of Alzheimer’s Disease (AD). This is due to the fact that some studies have found that around 10–15% of MCI patients annually progress to AD while it only occurs at a 1–4% rate for the healthy aged population (Petersen, 2001; Petersen and Negash, 2008)
In the present study we investigated the spatial distribution of resting state alpha peak frequency and amplitude over the whole brain for MCI patients and age-matched healthy controls
The peak was harder to find in anterior areas of the brain, since for around 10–15% of the subjects the criteria for robustness introduced before were not fulfilled in frontal Regions of Interest (ROIs)

Summary

Introduction

Mild Cognitive Impairment (MCI) is often considered a prodromal stage of Alzheimer’s Disease (AD). This is due to the fact that some studies have found that around 10–15% of MCI patients annually progress to AD while it only occurs at a 1–4% rate for the healthy aged population (Petersen, 2001; Petersen and Negash, 2008). Electroencephalographic (EEG) and magnetoencephalographic (MEG) studies have shown a slowing of the oscillatory rhythms in AD (Berendse et al, 2000; Huang et al, 2000). MCI patients exhibit a reduced mean frequency score in MEG power spectra (Fernández et al, 2006), indicating that the AD-related oscillatory slowing may have its onset in the predementia stage. It has been reported that changes in the high alpha/low alpha ratio or in the theta/gamma ratio are associated with the cognitive status, conversion to AD, hippocampal and amygdalar atrophy or gray matter changes (Moretti et al, 2009a, 2011, 2012)

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