The interplay between orthopedic events and dementia is complicated. A recent Japanese study by Matsumoto et al. revealed that individuals with early-onset dementia faced an increased likelihood of experiencing osteoporotic fractures compared to those without cognitive impairments. 1 As for the reverse direction of orthopedic events-dementia association, integrated evidence showed that osteoarthritis patients were at higher risk of developing dementia and cognitive impairments. 2 However, whether orthopedic surgical interventions, such as joint arthroplasty, influence the onset of dementia remains controversial. Cognitive dysfunction among individuals who underwent total joint arthroplasty was evaluated in recent studies. 3,4 A US study reported that individuals who had undergone total joint replacement demonstrate no significant disparity in the degree of cognitive decline compared to controls. 4 Nonetheless, the existing body of literature predominantly comprises small-scale investigations; largescale real-world studies investigating whether patients undergoing joint replacement surgery are susceptible to dementia based on the US population are lacking. Therefore, we performed an analysis in the TriNetX research network to evaluate the risk of new-onset dementia following total knee replacement (TKR) surgery among patients with osteoarthritis.We utilized subsets of the TriNetX network, including the US collaborative network, the Global Collaborative Network, and the EMEA collaborative network. The US network comprises 64 institutions in the United States, covering data from over 18 million patients, and has been widely utilized in epidemiological studies. 5,6 The Global network includes 119 institutions across 19 countries, with data from over 120 million patients. The EMEA network consists of 25 institutions across nine European countries, with data from over 14 million patients. The TriNetX database undergoes monthly updates, ensuring up-to-date information. Participants diagnosed with osteoarthritis between January 1, 2005, and December 31, 2018, with more than two visit records were included. The TKR group comprised osteoarthritis patients with a TKR record. Propensity score matching in a 1:1 ratio (adjusted for covariates such as age, sex, race, socioeconomic status, comorbidities, medications, laboratory data, medical utilization status, and substance use) was done to determine controls. Exclusion criteriaThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.