Functional and effective EEG connectivity patterns in Alzheimer's disease and mild cognitive impairment: A systematic review

Elizabeth R. Paitel ¹ Christian B. D. Otteman ² Mary C. Polking ² Henry J. Licht ² Kristy A. Nielson ^1*

• ¹ Psychology, Marquette University, Milwaukee, WI, United States
• ² Marquette University, Milwaukee, Wisconsin, United States

Background: Alzheimer’s disease (AD) might be best conceptualized as a disconnection syndrome, such that symptoms may be largely attributable to disrupted communication between brain regions, rather than to deterioration within discrete systems. EEG is uniquely capable of directly and non-invasively measuring neural activity with precise temporal resolution; connectivity quantifies the relationships between such signals in different brain regions. EEG research on connectivity in AD and mild cognitive impairment (MCI), often considered a prodromal phase of AD, has produced mixed results and has yet to be synthesized for comprehensive review. Thus, we performed a systematic review of EEG connectivity in MCI and AD participants compared with cognitively healthy older adult controls. Methods: We searched PsycINFO, PubMed, and Web of Science for peer-reviewed studies in English on EEG, connectivity, and MCI/AD relative to controls. Of 1,344 initial matches, 124 articles were ultimately included in the systematic review. Results: The included studies primarily analyzed coherence, phase-locked, and graph theory metrics. The influence of factors such as demographics, design, and approach was integrated and discussed. An overarching pattern emerged of lower connectivity in both MCI and AD compared to healthy controls, which was most prominent in the alpha band, and most consistent in AD. In the minority of studies reporting greater connectivity, theta band was most commonly implicated in both AD and MCI, followed by alpha. The overall prevalence of alpha effects may indicate its potential to provide insight into nuanced changes associated with AD-related networks, with the caveat that most studies were during the resting state where alpha is the dominant frequency. When greater connectivity was reported in MCI, it was primarily during task engagement, suggesting compensatory resources may be employed. In AD, greater connectivity was most common during rest, suggesting compensatory resources during task engagement may already be exhausted. Conclusions: The review highlighted EEG connectivity as a powerful tool to advance understanding of AD-related changes in brain communication. We address the need for including demographic and methodological details, using source space connectivity, and extending this work to cognitively healthy older adults with AD risk toward advancing early AD detection and intervention.