Associations of cognitive decline, peripheral inflammatory factors and hippocampal subregions volume in knee osteoarthritis - a longitudinal MRI study

Abstract Knee osteoarthritis (KOA) patients often suffer from cognitive decline. This study aims to investigate the relationship between cognitive decline, hippocampal subregions, and serum inflammatory cytokines levels in KOA. Their correlation and mediating effects were analyzed. Cognitive function declined at follow-up, and the decline was more pronounced in the AD8>1 group. The fimbria volume decreased in the AD8>1 group, while increased in the AD8≤1 group. The fimbria volume was correlated with cognitive performance in both group. Brain-derived neurotrophic factor (BDNF) levels were negatively correlated with the Montreal Cognitive Assessment_Language (MoCA_Language) subscore change in the AD8≤1 group and Recombinant Cannabinoid Receptor 2 (CNR2) levels were negatively correlated with the Wechsler Memory Scale – Chinese Revision_1-100 (WMS-CR_1-100) subscore change in the AD8>1 group. In addition, the serum Interferon-gamma (IFN-γ) level was a protective factor against cognitive decline and the fimbria volume played a mediating role between pain, T cell immunoglobulin domain and mucin domain 3 (TIM3) /IFN-γ levels, and the WMS-CR_1-100 subscore. Our results suggested that the fimbria was an important mediator of cognitive decline in KOA, and CNR1, CNR2, and BDNF were strongly associated with cognitive decline while IFN-γ levels may be a protective factor against cognitive progression in KOA. Clinical trial registration number: ChiCTR-IOR-16009308