Baoru Zhao,1,* Xiaowen Lian,2,* Peiling Zeng,1,* Yajun Wang,1 Guiyan Cai,1 Ruilin Chen,1 Jiao Liu,1,3– 6 Lidian Chen1,4– 6 

1College of Rehabilitation Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, People’s Republic of China; 2Affiliated Rehabilitation Hospital, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, People’s Republic of China; 3School of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 4National-Local Joint Engineering Research Center of Rehabilitation Medicine Technology, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, People’s Republic of China; 5Traditional Chinese Medicine Rehabilitation Research Center of State Administration of Traditional Chinese Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, People’s Republic of China; 6National-Local Laboratory of Orthopedics & Traumatology of Traditional Chinese Medicine and Rehabilitation (Fujian University of Traditional Chinese Medicine), Ministry of Education, Fuzhou, Fujian, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Jiao Liu; Lidian Chen, College of Rehabilitation Medicine, Fujian University of Traditional Chinese Medicine, 1 Qiuyang Road, Minhou Shangjie, Fuzhou, Fujian, 350122, People’s Republic of China, Email liujiao0415@outlook.com; cld@fjtcm.edu.cn

Purpose: Knee osteoarthritis (KOA) has been linked to increased cognitive decline risk, but the specific mechanisms underlying this phenomenon remain unclear. Research suggests neuroimaging changes and chronic low-grade inflammation may play key roles as common pathways linking osteoarthritis (OA) to cognitive decline.
Patients and Methods: This cross-sectional study recruited 36 individuals diagnosed with KOA and 25 healthy controls (HCs). Cognition was assessed using the Montreal Cognitive Assessment (MoCA) and the Digit Cancellation Test (DCT). The gray matter volume of 12 hippocampal subfields and the serum TIM-3 levels were also measured.
Results: KOA patients had significantly lower MoCA scores (P < 0.01) and fewer correct responses on the DCT (P < 0.01). They also exhibited a larger volume of the right hippocampal tail (FDR-corrected P = 0.010) and a smaller volume of the right hippocampal fissure (FDR-corrected P = 0.036). Correlation analysis revealed that the volume of the right hippocampal tail was associated with the number of correct responses on the DCT (r = − 0.356, P = 0.049). Additionally, a smaller volume of the left hippocampal fissure was linked to higher serum TIM-3 levels (r = − 0.404, P = 0.030) in KOA patients.
Conclusion: The hippocampal tail and hippocampal fissure exhibited reduced volume in KOA patients, and these changes were associated with alterations in attention and serum TIM-3 levels, respectively. These findings suggest a potential link between KOA and cognitive decline through inflammation and neuroscience, offering a theoretical basis for further study. Meanwhile, serum TIM-3 and right hippocampal fissure/tail volume might be potential biomarkers for detecting cognitive decline in KOA patients. Further studies are necessary for the investigation of this possibility.

Keywords: cognitive decline, knee osteoarthritis, hippocampal subfields, TIM-3