Vitamin D deficiency and dementia risk in patients with chronic kidney disease

Patients with chronic kidney disease (CKD) face elevated dementia risk, and vitamin D deficiency (VDD) has emerged as a potential contributor to cognitive decline. This study investigated the association between VDD and dementia development in patients with CKD using real-world data. We conducted a retrospective cohort study using the TriNetX database, analyzing patients with CKD aged ≥50 years from January 2010 to December 2022. Patients were stratified by serum 25-hydroxyvitamin D levels as follows: VDD group (<20 ng/mL) vs control group (≥30 ng/mL). The primary outcome was new-onset dementia occurring 1 to 10 years post-index, with the risk of Alzheimer's disease (AD) as a secondary outcome. During the 10-year follow-up, patients with VDD were associated with a significantly higher dementia risk (hazard ratios [HR] 1.45, 95% confidence intervals [CIs]: 1.37-1.54, P < .001). The association emerged early, with a 5-year HR of 1.52 (1.41-1.64, P < .001). The risk of AD was similarly elevated (10-year HR 1.37, 95% CI: 1.21-1.56, P < .001). Dose-response analysis revealed an increased risk even with mild insufficiency (20-30 ng/mL), while severe deficiency (<10 ng/mL) showed the highest risk. Subgroup analysis identified hypertension as a significant effect modifier, with VDD conferring an elevated risk in hypertensive patients (HR 1.43, 95% CI: 1.35-1.52) but not normotensive individuals. VDD was significantly associated with increased risks of dementia and AD in patients with CKD, following a clear dose-response pattern. The association is particularly pronounced among hypertensive patients, suggesting that VDD represents a potentially modifiable risk factor warranting clinical attention in CKD management.