Abstract
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.
Highlights
Alzheimer’s disease (AD) is a progressive neurodegenerative disease leading to a disruption of normal brain oscillations (Coben et al, 1985; Jeong, 2004; Musaeus et al, 2018a)
We investigated the differences in gamma/theta cross-frequency coupling (CFC) between AD, mild cognitive impairment (MCI), and healthy controls (HC) and the differences in patients with pMCI compared to patients with sMCI
In AD, we found that cerebrospinal fluid (CSF) amyloid was significantly lower than in both MCI (p-value = 0.015) and HC (p-value < 0.001) and that it was significantly lower in MCI compared to HC (p-value 0.022)
Summary
Alzheimer’s disease (AD) is a progressive neurodegenerative disease leading to a disruption of normal brain oscillations (Coben et al, 1985; Jeong, 2004; Musaeus et al, 2018a). The most commonly studied coupling is between the amplitude in the gamma band and the phase in the theta range (gamma/theta) This has been associated with activity in the hippocampus and performance in memory tasks in rodents (Tort et al, 2009; Canolty and Knight, 2010; Lisman and Jensen, 2013) and has been shown to be vital for working memory in humans (Axmacher et al, 2010). We investigated the differences in gamma/theta CFC between AD, MCI, and HC and the differences in patients with pMCI compared to patients with sMCI. We investigated the association between gamma/theta CFC and both cognitive function and cerebrospinal fluid (CSF) markers in AD
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