Abstract:
Alzheimer’s disease (AD) is a chronic degenerative brain disorder with an insidious, gradual onset and a progressive course, culminating in the loss of functional connectivity (FC) and atrophy within the brain. Amnestic Mild Cognitive Impairment (aMCI), the prodromal stage of AD is characterised by impairments in episodic memory, and delayed recall of visual and auditory information. Changes in resting-state (rs) FC are observable across visual and auditory networks when comparing aMCI populations with cognitively normal groups. Graph theory, an emerging mathematical tool provides a means to measure and visualise the connectivity between nodes or regions within the brain. Graph theoretical analysis of regions within functional neural networks allows us to determine the degree of connectivity or 'betweenness' between nodes, the ratio of connections or 'clustering' between a node and its neighbours, and the path length and degree of centrality between a node and all other nodes within a graph. There is a limited amount of research applying graph theoretical analysis to assess resting-state FC between cognitively normal (HC) and aMCI populations, as most studies involve taskbased fMRI, or AD populations. Here, we assess the relationship between rsFC and graph theoretical metrics, and their correlations with neuropsychological test results across an aMCI group and a healthy control (HC) group. We applied graph theoretical metrics to 116 ROIs across the connectome, assessing betweenness (BC), clustering coefficient (CC), and degree of centrality (DoC) at global and individual nodal levels. This study cohort comprised 22 participants, who fell into two clinical groups: HC (n = 11), and aMCI (n = 11). Our results revealed decreased rsFC in aMCI compared to HC, specifically with lower level in performance across all neuropsychological tests for the aMCI group, and a negative correlation between the decrease in test scores and BC, CC and DoC for aMCI individuals. The cognitive processes measured through these behavioural tests demonstrate a relationship between decreased performance in delayed visual and verbal memory tasks and functional connectivity. The combination of graph theoretical analysis, with structural functional magnetic resonance imaging (fMRI) and neuropsychological testing may provide us with the ability to identify areas of strength and weakness for rehabilitation, and longitudinal observation of global and nodal alterations to functional connectivity associated with aMCI.
