Elsevier

Neurobiology of Aging

Volume 32, Issue 4, April 2011, Pages 563-571
Neurobiology of Aging

Regular paper
MCI patients’ EEGs show group differences between those who progress and those who do not progress to AD

https://doi.org/10.1016/j.neurobiolaging.2009.04.003Get rights and content

Abstract

The theta/gamma and alpha3/alpha2 ratio were investigated as early markers for prognosticating of progression to dementia. 76 subjects with mild cognitive impairment (MCI) underwent EEG recording, MRI scans and neuropsychological (NPS) tests. After 3 years of follow-up, three subgroups were characterized as converters to Alzheimer's disease (AD, N = 18), converters to non-AD dementia (N = 14) and non-converters (N = 44). The theta/gamma and alpha3/alpha2 ratio, performance on cognitive tests and hippocampal volume, as evaluated at the time of initial MCI diagnosis, were studied in the three groups. As expected, MCI to AD converters had the smallest mean hippocampal volume and poorest performance on verbal learning tests, whereas MCI to non-AD converters had poorest cognitive performance in non-verbal learning tests, abstract thinking, and letter fluency. Increased theta/gamma ratio was associated with conversion to both AD and non-AD dementia; increased alpha3/alpha2 ratio was only associated with conversion to AD.

Theta/gamma and alpha3/alpha2 ratio could be promising prognostic markers in MCI patients. In particular, the increase of high alpha frequency seems to be associated with conversion in AD. EEG markers allow a mean correct percentage of correct classification up to 88.3%. Future prospective studies are needed to evaluate the sensitivity and specificity of these measures for predicting an AD outcome.

Introduction

Mild cognitive impairment (MCI) is a state of the elderly brain intermediate between normal cognition and dementia, being mainly characterized by objective evidence of memory impairment not yet encompassing the definition of dementia (Petersen et al., 1995, Petersen et al., 2001, Petersen and Negash, 2008).

In order to plan optimal therapeutic, organizational and rehabilitative interventions for MCI, a reliable prognostic indicator on the likelihood of progression to dementia would be required (Portet et al., 2006). Along this line, electroencephalogram (EEG) would be an ideal candidate to this issue, since it is a widely diffused, non-invasive and low-cost procedure.

It has been recently evidenced that EEG theta power (3.5–7.5 Hz) is higher in MCI subjects who will convert to Alzheimer's disease (AD) compared with MCI subjects who will not (Prichep et al., 2006). In an independent study of the same year it was showed that delta (temporal), theta (parietal, occipital and temporal), and alpha1 (central, parietal, occipital, temporal and limbic) sources were stronger in MCI converted in AD than in stable subjects and the risk of progression could be calculated on annual basis (Gauthier et al., 2006, Rossini et al., 2006). A recent study showed that converters MCI were differentiated from stable MCI subjects by a reduction of alpha power over posterior leads. Reduction of alpha power and mean frequency were significantly correlated with poorer cognitive performance in psychometric tests (Luckhaus et al., 2008). More recently, individual risk of progression to AD has been identified by using a supervised artificial network EEG analysis (Rossini et al., 2008).

Selective modifications of individual rhythms could be more related to behavioural paradigms such as stimulus onset and motor response (Canolty et al., 2006, Missonnier et al., 2007) as well as to various recording artifacts (Moretti et al., 2003). In contrast, when the ratio between frequencies is considered, the events of interest are features of the ongoing oscillatory activity itself. That is, frequency ratio refers to reciprocal dependence between distinct frequency bands of the ongoing EEG rather than dependence between the EEG and an external/internal events and/or undesired artifacts. For this reason it could be a useful tool in the analysis of rest EEG, together with the single frequency bands power analysis.

A large body of the literature has previously demonstrated that in subjects with cognitive decline is present an increase of theta relative power (Moretti et al., 2007a, Moretti et al., 2007b, Moretti et al., 2009b), a decrease of gamma relative power (Stam et al., 2003, Moretti et al., 2009b) as well as an increase of high alpha as compared to low alpha band (Moretti et al., 2007b). On the whole theta/gamma ratio and alpha3/alpha2 ratio could be considered reliable EEG markers of cognitive decline.

As a working hypothesis, EEG markers like theta/gamma and alpha3/alpha2 power ratio could show different modifications in patients with MCI who convert in AD from patients who will not. In the present study the possibility of two EEG markers of cognitive decline (increase of theta/gamma and increase of alpha3/alpha2 relative power ratio) to predict conversion to AD was investigated in subjects with MCI, also characterized by hippocampal volume measures and neuropsychological (NPS) test scores.

Section snippets

Subjects

For the present study, 76 subjects with MCI were recruited from the memory Clinic of the Scientific Institute for Research and Care (IRCCS) of Alzheimer's and psychiatric diseases ‘Fatebenefratelli’ in Brescia, Italy. All experimental protocols had been approved by the local Ethics Committee. Informed consent was obtained from all participants or their caregivers, according to the Code of Ethics of the World Medical Association (Declaration of Helsinki).

Diagnostic criteria

Patients were taken from a prospective

Results

Table 1 summarizes the ANOVA results of demographic variables (age, education and MMSE score), morphostructural measurements (hippocampal and WMHs volume) and EEG markers (theta/gamma and alpha3/alpha2 ratio). No statistical difference was found in age, education and the WMHs volume. MMSE score and hippocampal volume showed significant statistical difference (F2,73 = 7.31; p < 0.001 and F2,73 = 4.65; p < 0.01, respectively). Duncan post hoc analysis found that both the MMSE score and hippocampal volume

MCI patient, hippocampal volume and NPS tests

MCI subjects who will convert to AD showed the lowest MMSE score and the smallest total hippocampal volume at diagnosis. These findings are in agreement with well-known features of MCI patients at risk for AD (Portet et al., 2006, Dubois et al., 2007). On the whole, stable MCI had the best NPS performances, confirming the reliability of our results. Moreover, MCI-AD patients show a different NPS profile impairment as regards to MCI non-AD converters. Indeed, they were impaired in memory test

Conclusion

Theta/gamma and alpha3/alpha2 ratio could be promising prognostic markers in MCI patients. In particular, the increase of high alpha frequency seems to be associated with conversion in AD. The integration of EEG markers together with other diagnostic tools could allow a better classification of MCI patients.

Conflict of interest

Authors have no conflict of interests.

Acknowledgment

We thank Dr. Carlo Miniussi, for the precious help in the collection of the data used in the present study.

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