BACKGROUND: Osteoarthritis is associated with a higher risk of developing dementia, though the underlying biological mechanisms have remained unclear. Recent studies suggest that blood phosphorylated tau proteins, particularly Tau-PT217, are sensitive biomarkers capable of detecting cognitive decline in its early stages, making it useful for early diagnosis of Alzheimer's disease and other forms of cognitive impairment. METHODS: In this study, we investigated the plasma phosphorylated tau protein levels (Tau-PT217 and Tau-PT181), hippocampus functional connectivity, and cognitive function in people with knee osteoarthritis compared to age and gender matched pain-free controls. RESULTS: We found that knee osteoarthritis was associated with increased plasma levels of Tau-PT217 (but not Tau-PT181), and that the Tau-PT217 is also correlated with reduced hippocampal functional connectivity with middle cingulate cortex. Our findings suggest a potential biological correlation between knee osteoarthritis and an elevated risk of dementia, contributing valuable insights that may guide the formulation of early intervention and preventative strategies to mitigate dementia in individuals with knee osteoarthritis.