Abstract
BACKGROUND: Zinc deficiency is prevalent among older adults and individuals with dementia; however, its prognostic significance in this population remains unclear. We investigated the association between zinc deficiency and clinical outcomes in patients with dementia. METHODS: This retrospective matched cohort study used data from the TriNetX Research Network. Adult patients with dementia diagnosed between January 2010 and December 2024 were categorized according to their first recorded serum zinc measurement as zinc-deficient (<70 μg/dL) or normal (70-120 μg/dL). The date of the first qualifying zinc measurement served as the index date. The primary outcome was 1-year all-cause mortality. Secondary outcomes included sepsis, intensive care unit admission, urinary tract infection, pneumonia, acute kidney injury, and elevated C-reactive protein levels. Sensitivity, subgroup, and dose-response analyses were performed. RESULTS: After matching, 1,241 patients remained in each cohort. Zinc deficiency was significantly associated with higher 1-year mortality (10.1% vs. 6.8%; hazard ratio [HR] 1.54; p = 0.002). Increased risks were also observed for sepsis (HR 1.76; p = 0.001), intensive care unit admission (HR 1.67; p = 0.004), urinary tract infection (HR 1.47; p < 0.001), and elevated C-reactive protein levels (HR 1.49; p = 0.002). These associations were attenuated during extended follow-up (1-3 years) and were no longer statistically significant. Dose-response analysis revealed that severe zinc deficiency (<50 μg/dL) conferred a greater mortality risk (HR 1.85; p = 0.002) and nearly three-fold higher sepsis risk (HR 2.92; p < 0.001). Sensitivity analyses confirmed the robustness of the findings. CONCLUSION: In this observational study, zinc deficiency was associated with increased 1-year mortality and infection-related complications in patients with dementia, with evidence of a dose-response relationship. However, these findings do not establish causation. Future prospective studies are warranted to determine whether zinc supplementation can improve the clinical outcomes of zinc-deficient patients with dementia.