Inflammation affects dynamic functional network connectivity pattern changes via plasma NFL in cognitive impairment patients.

Abstract

Plasma neurofilament light chain (NFL) is a biomarker of inflammation and neurodegenerative diseases such as Alzheimer's disease (AD). However, the underlying neural mechanisms by which NFL affects cognitive function remain unclear. In this study, we investigated the effects of inflammation on cognitive integrity in patients with cognitive impairment through the functional interaction of plasma NFL with large-scale brain networks. This study included 29 cognitively normal, 55 LowNFL patients, and 55 HighNFL patients. Group independent component analysis (ICA) was applied to the resting-state fMRI data, and 40 independent components (IC) were extracted for the whole brain. Next, the dynamic functional network connectivity (dFNC) of each subject was estimated using the sliding-window method and k-means clustering, and five dynamic functional states were identified. Finally, we applied mediation analysis to investigate the relationship between plasma NFL and dFNC indicators and cognitive scales. The present study explored the dynamics of whole-brain FNC in controls and LowNFL and HighNFL patients and highlighted the temporal properties of dFNC states in relation to psychological scales. A potential mechanism for the association between dFNC indicators and NFL levels in cognitively impaired patients. Our findings suggested the decreased ability of information processing and communication in the HighNFL group, which helps us to understand their abnormal cognitive functions clinically. Characteristic changes in the inflammation-coupled dynamic brain network may provide alternative biomarkers for the assessment of disease severity in cognitive impairment patients.