Neural network disruptions between default mode network and salience network in mild cognitive impairment with neuropsychiatric symptoms.

Abstract

Background: Neuropsychiatric symptoms (NPS) in mild cognitive impairment (MCI) are associated with accelerated Alzheimer's disease (AD) progression. Identifying multimodal brain imaging patterns associated with NPS in MCI may help understand pathophysiology correlates AD.

Methods: This cross-sectional resting-state functional magnetic resonance imaging study included 376 participants: 130 MCI with neuropsychiatric symptoms (MCI+NPS), 154 MCI without neuropsychiatric symptoms (MCI-NPS), 92 cognitively normal (CN). NPS were assessed by the Neuropsychiatric Inventory Questionnaire (NPI-Q). Functional connectivity between default mode network (DMN) and salience network (SN) was compared among MCI+NPS, MCI-NPS and CN. Then, the morphometric measurements of abnormal node in default mode and salience networks was explored. Furthermore, correlation analysis was performed to investigate the relationship between NPS and functional and structural alterations in DMN and SN in MCI.

Results: In the MCI+NPS group, the most frequently endorsed NPS was anxiety (46.2 %), the less prevalent NPS was euphoria/elation (1.44 %). Compared with the MCI-NPS group, there was abnormal FC between medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC) (P < 0.05) in the MCI+NPS group, which was significantly associated with total NPI-Q score (r = 0.244, p = 0.000), affective symptoms (r = 0.212, p = 0.000), and hyperactivity symptoms (r = 0.196 p = 0.000). The mPFC area of MCI-NPS group was smaller than that of CN group (p < 0.05), and the area of mPFC was significantly associated with hyperactivity symptoms in MCI group.

Conclusions: Dysfunction of DMN and SN may partly contribute to the NPS in MCI patients, especially affective symptoms and hyperactivity symptoms. Our results complement the evidence linking NPS with Alzheimer's disease biomarkers.