Abstract
BACKGROUND: Persistent pain is a prominent symptom of knee osteoarthritis (KOA) and has been associated with cognitive decline in individuals with KOA. The amygdala, a complex structure consisting of nine subnuclei, and programmed cell death protein-1 (PD-1) levels play crucial roles in pain regulation and cognitive processing. This study aims to investigate the relationships among amygdala subregion volumes, cognitive function, and PD-1 levels to elucidate the underlying mechanism of cognitive decline in KOA. METHODS: In this cross-sectional study, we recruited 36 patients with KOA and 25 age/gender-matched healthy controls for neuropsychological tests, structural magnetic resonance imaging scanning, and measurement of serum PD-1 levels. We used the atlas provided by FreeSurfer software to automatically segment the amygdala subnuclei. Subsequently, we compared the volumes of amygdala subregions between groups and explored their correlation with clinical scores and PD-1 levels. RESULTS: Compared to healthy controls, individuals with KOA exhibited significantly lower scores on global cognition tasks, such as long-delay free recall, short-delay free recall, and immediate recall tasks. Moreover, they displayed decreased volumes in lateral nucleus basal nucleus paralaminar nucleus while showing increased volumes in accessory basal nucleus, central nucleus, medial nucleus, and cortical nucleus. Within the KOA group specifically, paralaminar volume was negatively correlated with immediate recall scores; pain scores were negatively correlated with global cognition; basal volume was negatively correlated with PD-1 levels. CONCLUSION: Our findings highlight those alterations in amygdala subregion volumes along with changes in serum PD-1 levels may contribute to observe cognitive decline among individuals suffering from KOA.