Abstract

Deficits in executive functioning have been reported in the early stages of Alzheimer’s disease (AD) and in mild cognitive impairment (MCI); however, the neural underpinnings of these deficits remain unclear. It has been proposed that AD can be characterized as a disconnection syndrome, where functional connectivity between brain regions is compromised. Therefore, it may be hypothesized that altered functional connectivity may be related to executive functioning in MCI and AD. The research presented in this dissertation examined group differences for MCI and AD patients relative to controls for EEG coherence within a fronto-parietal network measured at rest (Study 1), during a Go/No-go inhibitory control task (Study 2), and during an N-back working memory task (Study 3). The relationships between coherence and measures of cognition and brain integrity (cortical thickness and PiB retention) were also explored.

Results indicated that AD patients, but not MCI patients, had reduced resting coherence between cross-hemisphere parietal regions versus normal controls, and that MCI patients who later converted to dementia had higher resting fronto-parietal coherence versus MCI patients who remained stable. Furthermore, both AD and MCI patients showed altered coherence during task performance. During both tasks, AD patients showed reduced coherence and less of a task-related increase in coherence versus controls (for cross-hemisphere electrode pairs during the Go/No-go task and for cross-hemisphere and fronto-parietal pairs during the N-back task). In contrast, in comparison to controls, MCI patients had higher fronto-parietal coherence during the Go/No-go task and a larger task-related increase in fronto-parietal coherence for both tasks, but less of a task-related increase in cross-hemisphere frontal coherence for both tasks. Correlational analyses showed different relationships between EEG coherence and cognition and brain integrity across groups, with some evidence of a potential compensatory mechanism for higher coherence in controls and MCI patients in some conditions.

These results demonstrate that functional connectivity within a fronto-parietal network is altered in AD patients and MCI patients during the performance of executive tasks. In AD patients, coherence is decreased, whereas MCI patients show a potential compensatory increase in fronto-parietal coherence. The implications of these findings and directions for future research are discussed.