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. 2025 Sep 26;5(1):400.
doi: 10.1038/s43856-025-01104-1.

Longitudinal MRI identifies associations between cognitive decline, inflammatory markers, and hippocampal subregion volumes in individuals with knee osteoarthritis

Yajun Wang #  1   2 , Guiyan Cai #  3   4 , Ming Li #  5 , Ruilin Chen  3 , Peiling Zeng  3 , Baoru Zhao  3 , Jing Tao  6   7   8   9 , Jiao Liu  10   11
Affiliations

Longitudinal MRI identifies associations between cognitive decline, inflammatory markers, and hippocampal subregion volumes in individuals with knee osteoarthritis

Yajun Wang et al. Commun Med (Lond). .

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.

Plain language summary

Knee osteoarthritis (KOA) occurs when the protective cartilage at the end of the bones wears down, and can result in inflammation of the joint. In addition to pain and stiffness, arthritis can also affect memory in older adults. We studied 36 people with KOA over 5 years and found that a part of the brain known to be involved in memory shrank. The volume of this brain area impacted the amount of knee pain experienced, levels of blood-based markers of inflammation, and extent of memory loss. Our results suggest that monitoring blood-based markers and imaging the brain could enable dementia, a condition in which people have memory issues, to be identified earlier in people with KOA.

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Conflict of interest statement

Competing interests: The authors declare no competing interests.

References

    1. Long, H. et al. Prevalence trends of site-specific osteoarthritis from 1990 to 2019: findings from the global burden of disease study 2019. Arthritis Rheumatol. 74, 1172–1183 (2022). - PubMed - PMC - DOI
    1. Safiri, S. et al. Global, regional and national burden of osteoarthritis 1990-2017: a systematic analysis of the Global Burden of Disease Study 2017. Ann. Rheum. Dis. 79, 819–828 (2020). - PubMed - DOI
    1. Yuan, H. et al. Contribution of pain to subsequent cognitive decline or dementia: A systematic review and meta-analysis of cohort studies. Int. J. Nurs. Stud. 138, 104409 (2023). - PubMed - DOI
    1. Bell, T., Franz, C. E. & Kremen, W. S. Persistence of pain and cognitive impairment in older adults. J. Am. Geriatr. Soc. 70, 449–458 (2022). - PubMed - DOI
    1. Gagliese, L., Gauthier, L. R., Narain, N. & Freedman, T. Pain, aging and dementia: towards a biopsychosocial model. Prog. Neuropsychopharmacol. Biol. Psychiatry 87, 207–215 (2018). - PubMed - DOI