Associations of serum uric acid, renal function, and intermittent hypoxemia with post-stroke cognitive impairment and physical frailty in older adults with ischemic stroke: a retrospective cross-sectional study

Abstract Background Post-stroke cognitive impairment (PSCI) is common in older adults with ischemic stroke. The association between serum uric acid (SUA) and cognition remains uncertain and may depend on renal function and sleep-related hypoxemia. We examined associations of SUA with renal function, sleep-disordered breathing, cognition, and physical frailty. Methods This single-center retrospective cross-sectional study included 500 patients aged ≥ 60 years hospitalized between January 2023 and January 2026. Clinical data, laboratory measures, overnight polysomnography, and geriatric assessments were collected. PSCI was defined as an education-adjusted Montreal Cognitive Assessment score < 26, and physical frailty was assessed using the Fried phenotype. SUA was analyzed per 1-standard-deviation (SD) increase and by sex-specific tertiles. Multivariable linear and logistic regression, progressively adjusted cognitive models including estimated glomerular filtration rate (eGFR) and oxygen desaturation index (ODI), restricted cubic splines, and frailty sensitivity analyses were used. Results Among 500 participants, 230 (46.0%) had PSCI. Each 1-SD increase in SUA was associated with lower eGFR (β=-5.78 mL/min/1.73 m²; 95% CI, -6.60 to -4.97) and higher ODI (β = 4.50 events/h; 95% CI, 3.69 to 5.31). In the fully adjusted cognitive model, higher SUA remained associated with a lower MoCA score (β=-0.43; 95% CI, -0.63 to -0.24) and higher odds of PSCI (OR = 1.75; 95% CI, 1.26 to 2.43), although estimates were attenuated after adjustment for eGFR and ODI. Compared with the lowest SUA tertile, the highest tertile was associated with a lower MoCA score (β=-0.86; 95% CI, -1.25 to -0.46) and higher odds of PSCI (OR = 2.41; 95% CI, 1.22 to 4.76). Spline analyses showed significant overall associations with both cognitive outcomes (both P < 0.001) but no significant nonlinearity (MoCA, P = 0.073; PSCI, P = 0.157). Higher SUA and ODI and lower eGFR and minimum SpO₂ were also associated with physical frailty. Conclusions Higher SUA was associated with poorer renal function, greater sleep-related hypoxemia, poorer cognition, and physical frailty in older adults with ischemic stroke. Attenuation of the SUA-cognition associations after adjustment for eGFR and ODI suggests shared variation rather than established mediation. Multicenter prospective studies are needed to clarify temporal relationships and clinical utility.