Early-Onset Cognitive Impairment and Risk of Incident CKD

Background: Chronic kidney disease (CKD) is a well-established risk factor for mild cognitive impairment (MCI) and dementia. In this study, we investigated the reverse association, i.e., if early-onset (age ≤65 years) MCI and dementia are risk factors for incident CKD. Methods: Individuals were sampled from the TriNetX Stony Brook University Network. Individuals were classified as having MCI or dementia if their first recorded ICD code for either disease was recorded between January 2017 and December 2019. Individuals were excluded if they were > 65 years of age, had a history of stroke, head trauma, or neurodegenerative diseases, had end-stage kidney disease (ESKD) diagnosis during the study period, had CKD diagnosis prior to MCI/dementia diagnosis, or had missing serum creatinine values prior to or during the follow-up period. Incident CKD was defined as presence of either ICD-9/10 codes or eGFR < 60 mL/min/1.73 m2 ≥ 3 months. Comorbidities (cardiovascular disease, diabetes mellitus, hyperlipidemia, hypertension, and obesity) and medical non-adherence were obtained via ICD-9/10 codes. Multivariable Poisson regression models with robust standard error variances were used to measure the association between MCI/dementia and incident CKD. Models were adjusted for demographics (age, sex, race, ethnicity), baseline comorbidities, and medical non-adherence. Results: Among 39,515 individuals (mean age: 48.1 ± 12.5 years), 38 (0.1%) were diagnosed with MCI between January 2017 and December 2019. Higher rates of incident CKD were found among those with MCI at baseline compared to those without (21% vs 6%, p = 0.002) and the association remained statistically significant in fully adjusted multivariate models (Risk Ratio (RR): 3.28 [95% CI: 1.76 – 6.11], p = 0.001). Among 35,921 individuals (mean age: 48.1 ± 12.5 years), 48 (0.1%) were diagnosed with dementia. Higher rates of incident CKD were found among those with dementia at baseline compared to those without (25% vs 6%, p < 0.001) and the association remained statistically significant in fully adjusted multivariate models (Risk Ratio (RR): 2.84 [95% CI: 1.64 – 4.92], p < 0.001). Conclusion: Early-onset cognitive impairment is a risk factor for incident CKD, independent of traditional risk factors and medical adherence. Mechanisms underlying this association need to be investigated.