Network dysfunction is well established in patients with Alzheimer’s disease (AD) and has been shown to be present early in the disease. This is especially interesting in patients with mild cognitive impairment (MCI) since they are more likely to develop AD. In EEG, one type of network analysis is microstates where the EEG is divided into quasi-stable states and these microstates have been linked to networks found with resting state functional MRI. In the current exploratory study, we therefore wanted to explore the changes in microstates in MCI, and AD compared to healthy controls (HC) and whether microstates were able to separate patients with MCI who progressed (pMCI) and those who remained stable (sMCI). EEGs were recorded at baseline for 17 patients with AD, 27 patients with MCI, and 38 older HC and the patients were followed for 3 years. To investigate whole-brain dynamics we extracted different microstate parameters. We found that patients with MCI, and AD had significantly higher occurrence (
p
-value = 0.028), and coverage (
p
-value = 0.010) for microstate A compared to HC. However, we did not find any significant systematic deviation of the transition probabilities from randomness for any of the groups. No significant differences were found between pMCI and sMCI but the largest difference in duration was found for microstate D. Microstate A has been linked to the temporal lobes in studies combining EEG and fMRI and the temporal lobes are the most affected by AD pathology in the early stages of the disease. This supports our idea that microstate A may be the first affected microstate in early AD. Even though not significant between pMCI and sMCI, Microstate D has previously been shown to be associated with both frontal and parietal areas as measured with fMRI and may correspond to underlying pathological changes in the progression of MCI to AD. However, larger studies are needed to confirm these findings.
In our study, we found that patients with MCI and mild AD have increasing difficulties in dual-tasking compared to healthy elderly. Hence, the dual-tasking paradigm may be a potential complement in the diagnostic assessment in a typical clinical setting.
These findings suggests that relative power in the parietal electrodes in the beta1 band may be a better way to discriminate between pMCI and sMCI at the time of diagnosis than the broad beta band. Similar findings have also been found with resting state fMRI. In addition, we found that anterograde memory was correlated to qEEG parietal beta1 power.
Mild cognitive impairment (MCI) refers to mild objective cognitive deficits and is associated with the later development of Alzheimer’s disease (AD). However, not all patients with MCI convert to AD. EEG spectral power has shown promise as a marker of progression, but brain oscillations in different frequencies are not isolated entities. Coupling between different frequency bands, so-called cross-frequency coupling (CFC), has been associated with memory function and may further contribute to our understanding of what characterizes patients with MCI who progress to AD. In the current study, we wanted to investigate the changes in gamma/theta CFC in patients with AD and MCI compared to HC and in patients with pMCI compared to patients with sMCI. Furthermore, we wanted to investigate the association with cognitive test scores. EEGs were included at baseline for 15 patients with AD, 25 patients with MCI, and 36 older HC, and the participants were followed for up to 3 years. To investigate CFC, we calculated the modulation index (MI), which has been shown to be less affected by noisy data compared to other techniques. We found that patients with pMCI showed a significantly lower global gamma/theta CFC compared to patients with sMCI. In addition, global gamma/theta CFC was significantly correlated with Addenbrooke’s Cognitive Examination (ACE) score (
p
-value = 0.030, rho = 0.527). Although not significant, patients with AD and MCI showed a lower gamma/theta CFC compared to HC. These findings suggest that gamma/theta CFC is important for proper cognitive functioning and that a decrease in gamma/theta CFC in patients with MCI may be a sign of progression. Gamma/theta CFC may therefore serve as a progression marker in MCI, but larger studies are needed to validate these findings.
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