Functional connectome and neuropsychiatric symptom clusters of Alzheimer's disease

Background: Neuropsychiatric symptoms (NPSs) are important aspects of Alzheimer's disease (AD). Investigation of the effect of functional network abnormalities on clustered NPSs may uncover loci of altered connectivity for more targeted pharmacological and behavioral interventions in AD. The study aimed to investigate functional connectivity in AD and the clustered NPSs, as assessed by the Neuropsychiatric Inventory (NPI). Methods: In one hundred and fifty-nine patients with mild dementia stage of AD, graph metrics measuring functional connectivity at global network- and local network-level were assessed by closeness-centrality, betweenness-centrality, average-path-length, local-efficiency, and clustering-coefficient, respectively. The relationship between the NPI composite score and functional connectivity was assessed. Results: In AD, an increase in behavioral composite score was associated with changes in functional connectivity at local network-level, and regions displayed the changes was left lingual gyrus, left sub-genual ACC nodes, and left supra-genual ACC nodes (P < 0.05). An increase in affective composite score was associated with changes in functional connectivity at global network-level, and regions displayed the change was right caudate (P = 0.014). An increase in psychotic composite score was associated with changes in functional connectivity at global network-level, and regions displayed the change was left precuneus and right dorsolateral superior frontal gyrus (P < 0.05). Limitations: Cognitively normal elderly subjects and longitudinal follow-up will be needed to see the evolution of NPS clusters and pathological changes in the functional connectivity at global or local network-level. Conclusions: Different NPS clusters corresponded to distinct changes in functional connectivity at global and local network-level.