Abstract
BACKGROUND: Knee osteoarthritis (KOA) is common in older adults and may relate to cognitive decline. We explore whether changes in specific brain areas and body inflammation levels help explain this connection, focusing on the hippocampus-a memory-critical brain region. METHODS: We studied 36 older adults with KOA over time. Using brain scans, we measured volumes of hippocampal subregions (especially the fimbria). Blood tests tracked six inflammation markers, including brain-derived neurotrophic factor (BDNF), interferon-gamma (IFN-γ), programmed death 1(PD-1), recombinant cannabinoid receptor 1 (CNR1), recombinant cannabinoid receptor 2 (CNR2), and T cell immunoglobulin domain and mucin domain 3 (TIM3). Memory was tested using the Wechsler Memory Scale - Chinese Revision (WMS-CR), while global cognition used the Montreal Cognitive Assessment (MoCA). Relationships between knee pain, brain structure, inflammation, and cognition were analyzed statistically. RESULTS: Here, we show that shrinking fimbria volume predicts cognitive decline in those developing dementia. We identify a robust correlation between fimbria volume and cognitive performance. Higher IFN-γ levels are protective against cognitive decline. Critically, fimbria volume serves as a mediator in the relationship between pain, TIM3/IFN-γ levels, and cognitive scores. CONCLUSIONS: Fimbria serves as a key pathway through which KOA may drive cognitive impairment, while IFN-γ could help protect memory. Monitoring these hippocampal changes and inflammation levels might help identify at-risk patients early.