Changes of Functional and Directed Resting-State Connectivity Are Associated with Neuronal Oscillations, ApoE Genotype and Amyloid Deposition in Mild Cognitive Impairment.

Lars Michels,Anton F Gietl,Michael Siniatchkin,Paul G Unschuld,Abdul R Anwar,Spyros Kollias,Florian Riese,Muthuraman Muthuraman,Sandra E Leh,Christoph Hock

doi:10.3389/fnagi.2017.00304

Abstract

The assessment of effects associated with cognitive impairment using electroencephalography (EEG) power mapping allows the visualization of frequency-band specific local changes in oscillatory activity. In contrast, measures of coherence and dynamic source synchronization allow for the study of functional and effective connectivity, respectively. Yet, these measures have rarely been assessed in parallel in the context of mild cognitive impairment (MCI) and furthermore it has not been examined if they are related to risk factors of Alzheimer’s disease (AD) such as amyloid deposition and apolipoprotein ε4 (ApoE) allele occurrence. Here, we investigated functional and directed connectivities with Renormalized Partial Directed Coherence (RPDC) in 17 healthy controls (HC) and 17 participants with MCI. Participants underwent ApoE-genotyping and Pittsburgh compound B positron emission tomography (PiB-PET) to assess amyloid deposition. We observed lower spectral source power in MCI in the alpha and beta bands. Coherence was stronger in HC than MCI across different neuronal sources in the delta, theta, alpha, beta and gamma bands. The directed coherence analysis indicated lower information flow between fronto-temporal (including the hippocampus) sources and unidirectional connectivity in MCI. In MCI, alpha and beta RPDC showed an inverse correlation to age and gender; global amyloid deposition was inversely correlated to alpha coherence, RPDC and beta and gamma coherence. Furthermore, the ApoE status was negatively correlated to alpha coherence and RPDC, beta RPDC and gamma coherence. A classification analysis of cognitive state revealed the highest accuracy using EEG power, coherence and RPDC as input. For this small but statistically robust (Bayesian power analyses) sample, our results suggest that resting EEG related functional and directed connectivities are sensitive to the cognitive state and are linked to ApoE and amyloid burden.

Highlights

Mild cognitive impairment (MCI) is a syndrome, identified by formal testing, which is characterized by single or multiple cognitive complaints (Albert et al, 2011)
Tests from the Consortium to Establish a Registry for Alzheimer’s disease (AD) (CERAD)-plus battery (Morris et al, 1988, 1989) were applied including tests on verbal and non-verbal memory
CERAD recall scores were lower for MCI than healthy controls (HC) (Table 1)

Summary

Introduction

Mild cognitive impairment (MCI) is a syndrome, identified by formal testing, which is characterized by single or multiple cognitive complaints (Albert et al, 2011). The occurrence of MCI is accompanied on the neuronal level by structural and functional alterations, such as gray matter atrophy (Convit et al, 1997; Jack et al, 1999), reduced cerebral blood flow (Hirao et al, 2005; Chen et al, 2011), or altered neuronal oscillations. The latter is seen as abnormalities of power density at specific frequency bands in quantitative electroencephalography (qEEG; Huang et al, 2000; Jelic et al, 2000; Hatz et al, 2013). Other EEG studies showed a loss of long-range EEG synchronicity between fronto-parietal and fronto-temporal electrode pairs in MCI and AD patients (Dauwels et al, 2009, 2010)

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