No Direct Link Found Between Osteoarthritis, Cognitive Decline

Although no causal relationship was found between osteoarthritis (OA) and cognitive decline, depression may play a key role in influencing mental outcomes.¹

The authors of a recent Therapeutic Advances in Musculoskeletal Diseases study explain that several past studies have evaluated the relationship between OA and the risk of dementia and cognitive impairment. However, these studies were prone to bias related to residual confounding factors and reverse causality.

Therefore, further research is needed to address these limitations and better understand the potential link between OA and dementia. The present researchers aimed to investigate causality and associations between OA and cognitive function.

The study was conducted in 2 stages. The first utilized data from the National Health and Nutrition Examination Survey (NHANES) to demonstrate a link between OA and cognitive function through multiple linear logistic regressions and stratified analyses²; NHANES is a national program that collects data on the health and nutrition status of US civilians.

In their analyses, the researchers included adults older than 60 who completed cognitive functioning tests and for whom there was information on OA status.¹ Sample weights were used to ensure the results were generalizable.

A 2-sample Mendelian randomization (MR) design was used in the second stage to assess the causal relationship between OA, knee OA, hip OA, and various subtypes of dementia. MR uses genetic variants as instrumental variables (IVs) to investigate the causal effects of a risk factor on an outcome³; this makes it less prone to confounding issues and capable of establishing causal inferences. Additionally, mediation analyses were performed to explore the impact of depression on cognitive outcomes.¹

The study included 2199 participants, representing a weighted population of about 42.5 million US civilians. The OA group contained 709 patients, and the non-OA group had 1490 patients. Among those with OA, the weighted average age was 69.76 years. A higher proportion of females (65.39%) with significantly higher body mass index was observed in the OA group, and a higher weighted prevalence of depression (9.78%) was observed in those with OA.

No significant differences in total word recall, animal fluency, or Digit Symbol Substitution test scores were observed between the OA and non-OA groups, even with full covariate adjustments. Consequently, the odds of low cognitive performance across all measures were not significantly higher for the OA group.

However, depression was linked to higher odds of low total word recall cognitive performance (OR, 4.74; 95% CI, 1.09-20.63; P = .04), while being female was associated with higher odds of low animal fluency cognitive performance (OR, 1.78; 95% CI, 1.16-2.75; P = .02).

MR revealed no significant causal associations between OA and the risk of dementia (OR, 1.12; 95% CI, 0.96-1.32; P = .16), Alzheimer disease (OR, 0.95; 95% CI, 0.68-1.31; P = .74), or vascular dementia (OR, 1.32; 95% CI, 0.82-2.13; P = .25). However, major depression was found to mediate the pathway between OA and vascular dementia (β, 0.044, 95% CI, −0.391 to 0.479; P < .05).

“…there is no significant association between OA and cognitive decline when adjusting for relevant covariates,” the authors wrote. “However, we observed a higher proportion of individuals with depression within the OA group, highlighting the potential impact of pain and emotional strain on mental health. The MR analysis may further support a causal relationship between OA, depression, and increased risk of dementia.”

The researchers acknowledged their study’s limitations, one being that cognitive decline encompasses various aspects of mental function. Although their study examined specific cognitive performance measures, it may not capture the entire spectrum associated with dementia. Despite their limitations, the researchers suggested areas for further research based on their findings.

“Future studies should aim to confirm the bidirectional causal relationship between these factors [OA, depression, and increased risk of dementia] and explore potential mechanisms underlying this association,” the authors concluded. “…Understanding these relationships can contribute to the development of targeted interventions and strategies for preventing cognitive decline in individuals with OA.”

References

1. Zhao K, Nie L, Zhao J, et al. Association between osteoarthritis and cognitive function: results from the NHANES 2011-2014 and Mendelian randomization study. Ther Adv Musculoskelet Dis. 2025;17:1759720X241304189. doi:10.1177/1759720X241304189

2. National Health and Nutrition Examination Survey. CDC. Accessed January 24, 2025. https://www.cdc.gov/nchs/nhanes/index.html

3. Burgess S, Thompson SG. Mendelian Randomization. Informa; 2021. doi:10.1201/9780429324352

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