Abstract Background Cognitive impairment is common among patients undergoing hemodialysis and worsens their quality of life and survival. The programmed cell death 1 (PD-1) pathway—comprising the receptor PD-1 and its ligand programmed cell death ligand 1 (PD-L1)—was initially recognized as a mechanism of tumor immune evasion that was also involved in chronic inflammation and immune aging. However, its role in cognitive impairment remains poorly understood. Methods In this cross-sectional study, patients aged ≥65 years undergoing hemodialysis were recruited from 7 centers. Global cognitive function was assessed by the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE). Serum soluble PD-1 (sPD-1) and soluble PD-L1 (sPD-L1) were measured by enzyme-linked immunosorbent assay. Multivariable logistic regression was used to adjust for age, sex, dialysis vintage, C-reactive protein, and other confounders. Results Median age of the 384 patients was 74 years (interquartile range, 70–80), 67.5% were male, 61.2% scored below the MoCA score cutoff of 26, and 10.2% scored below the MMSE score cutoff of 24. Higher sPD-1 levels were associated with cognitive impairment as defined by both assessment tools; moreover, higher sPD-L1 levels were associated with MoCA-defined impairment (odds ratio, 2.53; 95% confidence interval, 1.26–5.06, P = .009). The association between sPD-1 and MMSE-defined impairment was stronger in patients without cancer history. Conclusion These findings highlight the potential role of the PD-1 pathway in risk stratification and future interventions in cognitive impairment in patients undergoing hemodialysis.
Kato et al. (Fri,) studied this question.