EEG coherence in Alzheimer's disease

Abstract

EEG coherence can be used to evaluate the functionality of cortical connections and to get information about the synchronization of the regional cortical activity. We studied EEG coherence in patients affected by clinically probable Alzheimer's disease (AD) in order to quantify the modifications in the cortico-cortical or cortico-subcortical connections. The EEGs were recorded in 10 AD patients (with mild or moderate degrees of dementia) and in 10 normal age-matched subjects, at rest and eye-closed, from 16 electrodes with linked-ears reference. Spectral parameters and coherence were calculated by a multichannel autoregressive model using 50 artifact-free epochs, 1 s duration each. Alpha coherence was significantly decreased in 6 patients, the decrease being more accentuated in the area near the electrode taken into account; a significant delta coherence increase was found in a few patients between frontal and posterior regions. The AD group showed a significant decrease of alpha band coherence, in particular in temporo-parieto-occipital areas, more evident in patients with a more severe cognitive impairment. These abnormalities could reflect two different pathophysiological changes: the alpha coherence decrease could be related to alterations in cortico-cortical connections, whereas the delta coherence increase could be related to the lack of influence of subcortical cholinergic structures on cortical electrical activity.

Introduction

Slowing of the electroencephalogram (EEG) is a frequent finding in patients with Alzheimer's disease (AD) and its occurrence is related to the stage of the disease (Coben et al., 1985). An increase of slow bands can be found in over 90% of patients with moderate or severe AD (Soininen and Riekkinen, 1992). In the early stages of the disease, changes are more subtle, as a considerable number of patients may have a normal EEG (Penttila et al., 1985). Spectral analysis of the EEG has greatly contributed to a better definition of the modifications of the EEG in the early stages of the disease: these changes consist in a slowing of the peak of the alpha band and in an increase of the power of the theta band (Coben et al., 1983; Soininen and Riekkinen, 1992). Delta band power increases and alpha band power decreases only in more advanced stages; in slightly demented patients alpha activity can be even higher than in control groups (Dierks et al., 1991). All these EEG changes are not specific to AD, and have been reported also in vascular dementia.

Modifications of spectral parameters have been found to be related to the decrease in metabolic activity assessed by PET (Comi et al., 1992; Szelies et al., 1992).

EEG coherence can be defined as the normalized cross-power spectrum per frequency of two signals recorded simultaneously at different sites of the scalp. It is a measure of the synchronization between the two signals and may be interpreted as an expression of their functional interaction (Sklar et al., 1972; Shaw et al., 1978). EEG coherence decreases with the distance between recording electrodes in normal subjects. Thatcher et al. (1986)proposed a two-compartmental model of EEG coherence in order to separate the contributions of long and short cortico-cortical associative fibers. Excluding volume conductor contribution, coherence between near electrodes is particularly influenced by short connections, as the axonal density per unit volume of cortex is approximately 10–100 times higher for short-axoned stellate and Martinotti cells than for long-axoned pyramidal cells (Braitenberg, 1978). On the contrary, the coherence between distant electrodes is mainly due to long axon connections. The influence of subcortical nuclei, particularly of thalamic nuclei, on both local and long-distance coherence, seems also to be relevant. Leuchter et al. (1992), using bipolar recordings, found an alpha coherence decrease in AD patients; they interpreted changes as related to the impairment of the cortico-cortical connections, particularly of the long fibers that connect temporo-parieto-occipital areas to frontal ones. These findings could be consistent with neuropathological evidence that associative areas lose afferent and efferent connections in parallel with the damage and the death of pyramidal neurons (Pearson et al., 1985).

We studied EEG coherence in a group of probable AD patients in the early phases of the disease. The aims of the study are to define if there are changes of EEG coherence in AD, to evaluate whether short-distance or long-distance coherence is more affected and the possible diagnostic value of coherence analysis in AD.