Cognitive Impairment: A Novel Risk Factor for Rapid Kidney Function Decline and Incident CKD in Middle-Aged Adults.

Abstract

Background: Emerging evidence suggests that better cognition is associated with a lower risk of chronic kidney disease (CKD). However, whether early-onset cognitive impairment (CI) at baseline is linked to rapid estimated glomerular filtration rate (eGFR) decline or incident CKD remains unclear.

Methods: We conducted a prospective cohort study of 5,761 World Trade Center (WTC) responders (mean age: 53.8 ± 7.9 years) without CKD at baseline, followed for a mean of 4.2 ± 1.9 years. CI was defined as a Montreal Cognitive Assessment (MoCA) score ≤23, with a subgroup analysis for baseline dementia (MoCA ≤18). Primary outcomes included annual eGFR change and rapid eGFR decline (< -5 mL/min/1.73 m2 per year). The secondary outcome was incident CKD (eGFR <60 mL/min/1.73 m2 or diagnosis code). Multivariable Cox proportional hazards models and linear regressions were used for binary and continuous outcomes, respectively. Sensitivity analyses included looking at the effect of baseline mild cognitive impairment (MCI) (MoCA score 19-23), propensity matching for demographics, baseline age <60 years, removal of baseline post-traumatic stress disorder (PTSD)/ depression or baseline head trauma/stroke/cardiovascular disease and after exclusion of those who died during follow-up.

Results: At baseline, 1,446 (25%) individuals had CI, while 89 (2%) had dementia. The mean baseline eGFR was 91.1 mL/min/1.73 m2, with an overall decline of -1.2 mL/min/1.73 m2 per year. Rapid eGFR decline occurred in 550 (10%) individuals. After adjusting for age, sex, race/ethnicity, comorbidities, WTC exposure, screened PTSD, and baseline eGFR, CI and dementia were significantly associated with rapid eGFR decline (adjusted hazard ratio [aHR]: 1.63 and 2.42, respectively; both p < 0.001) and faster annual eGFR decline. Findings were consistent across all sensitivity analyses. Additionally, 248 (4%) individuals developed incident CKD. Both baseline CI (aHR: 1.72, p < 0.001) and dementia (aHR: 2.77, p = 0.010) were significantly associated with incident CKD.

Conclusions: Among middle-aged individuals without CKD, early-onset cognitive impairment was independently associated with rapid eGFR decline and incident CKD. These findings warrant validation in other cohorts.