Longitudinal MRI identifies associations between cognitive decline, inflammatory markers, and hippocampal subregion volumes in individuals with knee osteoarthritis
Bibliographic record
Abstract
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. 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. 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. 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. 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. Wang, Cai, Li et al. examine how knee osteoarthritis (KOA) drives cognitive decline through hippocampal fimbria shrinkage and peripheral inflammation. Fimbria volume mediates pain-related memory loss while elevated interferon-gamma protects against dementia, enabling early risk detection.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".