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

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.

Pharmacogenetics of Atremorine-Induced Neuroprotection and Dopamine Response in Parkinsonʼs Disease

“…8). This effect is more evident in APOE-3 carriers than in APOE-4 carriers (data not shown), similar to what is currently observed in patients with Alzheimerʼs disease [28,29].…”

Global EEG coherence as a marker for cognition in older adults at risk for dementia

“…Results on changes in delta spectral coherence have been controversial: while some studies reported an attenuated delta spectral coherence in patients with AD compared to controls (e.g., Knott et al, 2000), others found an increase in delta spectral coherence in individuals with AD (Babiloni et al, 2009). Studies on coherence in mild cognitive impairment (MCI), as possible prodromal stage of AD, suggested that changes might already occur in this at-risk stage for dementia (e.g., Michels et al, 2017). Besides group comparisons, positive correlative associations have been reported between spectral coherence and cognitive performance, especially in the Mini-Mental State Examination (MMSE; Folstein, Folstein, & McHugh, 1975), in subjects with AD as well as with MCI (e.g., Brunovsky, Matousek, Edman, Cervena, & Krajca, 2003;Dunkin, Osato, & Leuchter, 1995;Jelic et al, 1996; for controversial results see Babiloni et al, 2009;Knott et al, 2000, and for missing associations see Jiang, 2005;Leuchter et al, 1992).…”

Alpha Power and Functional Connectivity in Cognitive Decline: A Systematic Review and Meta-Analysis

“…Three additional studies found lower alpha power in people with AD than in people with MCI (Huang et al [72], n = 38 AD, 31 MCI, 24 OA; Smailovic et al [73], n = 197 AD, 230 MCI; Jelic et al [75], n = 18 AD, 19 aMCI, 16 OA). Though decreases were also reported for global measures [70,72,73] and for all areas of the scalp, they were most often found in posterior (temporal, parietal, and occipital) areas [43,58,72,75,77].…”

“…In four studies, alpha power in the full band was lower in people with MCI than in cognitively healthy older adults (OA; Michels et al [43], n = 17 aMCI, 17 OA; Musaeus et al [58], n = 117 AD, 117 MCI, 138 OA; Bonanni et al [70], n = 50 AD, 14 AD-MCI, 50 OA; Roh et al [77], n = 41 AD, 38 aMCI, 39 OA), and in two of these, alpha power decreased with increasing impairment (Musaeus et al [58], n = 117 AD, 117 MCI, 138 OA; Roh et al [77], n = 41 AD, 38 aMCI, 39 OA). Three additional studies found lower alpha power in people with AD than in people with MCI (Huang et al [72], n = 38 AD, 31 MCI, 24 OA; Smailovic et al [73], n = 197 AD, 230 MCI; Jelic et al [75], n = 18 AD, 19 aMCI, 16 OA).…”

“…Lastly, lower power and synchronization of alpha oscillations have consistently been associated with neurodegenerative dementias, especially AD [29,[37][38][39]. These decreases were found to correlate with lower cognitive scores [40,41], higher atrophy of the hippocampus [42] and higher amyloid burden [43], as well as with genetic susceptibility for AD [44,45]. Though alpha activity in other neurodegenerative dementias is less well-researched, there is evidence of lower alpha power in people with dementia due to Lewy body disorders [46][47][48][49].…”