Trends in Alzheimer Disease and Chronic Kidney Disease–Associated Mortality in the United States, 1999–2020: A Multiple-Cause Analysis of CDC WONDER Data

Introduction: Alzheimer’s disease (AD) and chronic kidney disease (CKD) are major global health burdens with rising prevalence and significant mortality. Increasing evidence highlights a bidirectional “kidney–brain axis,” where renal dysfunction accelerates cognitive decline, while AD-related systemic inflammation and vascular injury contribute to kidney impairment. However, mortality trends associated with the co-occurrence of AD and CKD in the United States remain poorly characterized. We aimed to examine temporal trends, demographic disparities, and geographic variations in AD- and CKD-related mortality from 1999 to 2020. Methods: We conducted a retrospective analysis using the CDC WONDER Multiple Cause of Death database to identify deaths among adults (≥ 25 years) in which both AD (ICD-10 code G30) and CKD (ICD-10 code N18) were listed as causes. Crude mortality rates (CMRs) and age-adjusted mortality rates (AAMRs) per 100,000 population were calculated. Temporal patterns were evaluated using Joinpoint regression to determine annual percentage changes (APCs). Subgroup analyses were performed by sex, race/ethnicity, age, urbanization level, and U.S. state. Results: From 1999 to 2020, a total of 48,770 deaths were attributed to AD and CKD. The AAMR rose more than fivefold, from 0.35 in 1999 to 1.80 in 2020 (average annual percent change [AAPC]: 5.97; 95% CI: 4.31–8.39; p < 0.000001). Males had consistently higher mortality rates than females (AAMR: 1.13 vs 0.94), though females experienced a steeper rise. Non-Hispanic Black individuals exhibited the highest overall AAMR (1.36), while non-Hispanic Whites showed the sharpest increase over time. Mortality was slightly higher in non-metropolitan areas (1.17) compared to metropolitan ones (0.98), with both showing significant upward trends. The burden was greatest among those ≥ 85 years. State-level disparities were marked, with the highest AAMR in North Dakota (1.94) and the lowest in Nevada (0.37). Conclusions: Mortality associated with AD and CKD has risen significantly in the U.S. over the past two decades, with disproportionate impacts among older adults, males, non-Hispanic Black individuals, and rural residents. These findings underscore the need for targeted public health strategies, early detection, and integrated management of these intersecting conditions to mitigate future mortality.