Bone Turnover Markers Associated with Cognitive Dysfunction in Patients Undergoing Hemodialysis: A Cross-Sectional Study

Abstract

Cognitive impairment is common in patients undergoing hemodialysis; however, evidence linking routinely measured bone turnover markers to cognition remains limited. In this exploratory cross-sectional study, we aimed to evaluate whether bone-specific alkaline phosphatase (BAP), total alkaline phosphatase (ALP), and tartrate-resistant acid phosphatase 5b (TRACP-5b) are related to global cognitive function in older patients undergoing hemodialysis. Adults aged ≥65 yr receiving maintenance hemodialysis were enrolled at seven centers in Tokyo and Chiba, Japan (November 2021-November 2022). Global cognition was assessed using the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE). Multivariable linear regression with robust standard errors and facility fixed effects was used to examine associations with MoCA scores across sequentially adjusted models. Because of a ceiling effect, MMSE was analyzed using logistic regression with MMSE ≤23 as the outcome (unadjusted and age−/sex-adjusted). For statistical analyses, bone turnover markers were natural log-transformed. Among 380 participants (median age 74 yr; 67.6% male), higher BAP was consistently associated with lower MoCA scores (fully adjusted β −1.03; 95% confidence interval [CI] -1.90 to −0.16). Total ALP showed inverse associations in less-adjusted models; however, these associations attenuated after full adjustment (β − .88; 95% CI -1.89 to 0.14). TRACP-5b was not clearly associated with MoCA scores. Higher BAP and total ALP were associated with higher odds of MMSE-defined cognitive dysfunction, whereas TRACP-5b was not. These findings suggest a potential association between bone formation-related markers and cognitive performance in older patients undergoing hemodialysis. Prospective and mechanistic studies are warranted to clarify causality and clinical utility.