Rising trends in dementia and psychoactive drug-related mortality in the United States, 2000–2023. A retrospective analysis using CDC WONDER

Abstract Background Dementia, termed major neurocognitive disorder in the DSM-5-TR, and substance use disorders (SUD) are major and increasingly overlapping public health concerns in the United States. However, population-level trends examining their combined contribution to mortality remain limited. This study evaluates national mortality trends involving both conditions. Methods We conducted a retrospective analysis of the CDC WONDER Multiple Cause of Death database (2000–2023). Deaths listing both dementia and SUD as underlying or contributing causes were identified using ICD-10 codes. Age-adjusted mortality rates (AAMRs) per 100,000 were calculated using the 2000 U.S. standard population. Trends were analyzed using Joinpoint regression, reporting annual percent change (APC) and average annual percent change (AAPC) with 95% confidence intervals (CIs). Results A total of 283,206 deaths were identified. The overall AAMR increased significantly from 0.58 in 2000 to 7.63 in 2023 (AAPC: 13.29%; 95% CI: 10.42–16.23; p<0.001). Sex-stratified analysis showed higher mortality in males (AAMR: 0.87→9.61) than females (0.41→6.23), although females demonstrated a greater relative increase (AAPC: 14.07% vs 12.55%; both p <0.001). By race, non-Hispanic (NH) White individuals had the highest absolute rates (AAMR: 0.60→8.57), while NH Black individuals exhibited the highest long-term burden (AAPC: 12.69%; p <0.001). Hispanic individuals showed lower rates but consistent increases (AAMR: 0.22→3.33; p <0.001). Age-stratified analysis demonstrated increasing age-adjusted mortality rates among individuals aged 45–64 years (0.14→0.61; p <0.001). Among older adults (≥65 years), mortality rates initially increased substantially (2.79→41.94) through 2020 ( p <0.001), then declined sharply, reaching 0.61 in 2023 ( p <0.001). Regionally, the Midwest had the highest mortality (AAMR: 0.58→10.8; AAPC: 14.38%; p <0.001), while the Northeast had the lowest rates (0.29→4.95; p <0.001). All regions showed significant upward trends ( p <0.001). Urbanization analysis revealed increasing mortality in metropolitan (0.56→3.5) and non-metropolitan areas (0.71→3.8), with stronger growth in non-metropolitan regions (AAPC: 16.72% vs 15.82%; p <0.001). Conclusion Mortality involving both dementia and substance use disorders has increased substantially in the United States over the past two decades, with significant disparities across sex, race, geography, and urbanization. These findings highlight the growing burdens of neurodegenerative disease and substance use, emphasizing the need for integrated public health strategies targeting both conditions.