Brain Amyloid-β Peptide Is Associated with Pain Intensity and Cognitive Dysfunction in Osteoarthritic Patients

Considerable studies have demonstrated that osteoarthritis (OA) is a risk factor for dementia. The precise mechanisms underlying the association between OA and increased risk for cognitive dysfunction, however, remain unclear. This study aimed at exploring the associations between pro-inflammatory cytokines/chemokines, biomarkers of Alzheimer's disease (AD), pain intensity, and cognitive decline in knee joint OA patients. A total of 50 patients (26 in OA group and 24 in non-OA control group) were enrolled in this prospective, observational study. The visual analogue scale (VAS) score for pain intensity and Cognitive Abilities Screening Instrument (CASI) score for cognitive functions were examined in both groups. The plasma and cerebrospinal fluid (CSF) levels of pro-inflammatory molecules (IL-1β, IL-6, TNF-α, fractalkine, BDNF, MCP-1, and TGF-β), as well as biomarkers of AD (Aβ 40, Aβ 42, total-tau, and phospho-tau), were measured by multiplex immunoassay. Correlations among plasma or CSF biomarkers and questionnaire scores were assessed using Pearson's correlation coefficient and simple linear regressions. There were more patients in the OA group whose CASI cutoff percentiles were <P5 or at P5 than in the control group. VAS pain scores were negatively correlated with cognitive domains, including total score, short term memory, attention, mental manipulation, abstract thinking, and judgment, of the CASI score. VAS scores were positively correlated with fractalkine, Aβ 40, and Aβ 42 in CSF of OA patients. The CSF levels of Aβ 40 and Aβ 42 in OA patients were negatively correlated with attention and abstract scores in CASI. The findings of this study suggest that knee OA is associated with poor cognitive performance, and this association is particularly pronounced in OA patients with chronic pain. Higher levels of brain AD biomarkers, such as Aβ 40 and Aβ 42, may partially mediate this relationship.