To evaluate national trends and demographic disparities in mortality associated with sepsis and neurodegenerative diseases among U.S. adults from 1999 to 2023.

Sepsis, a life-threatening consequence of infection, remains a leading cause of death despite advances in care. Neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis, are increasingly prevalent with population aging. Understanding parallel mortality trends between these conditions is critical to inform integrated prevention and care strategies.

We conducted a retrospective, population-based analysis using CDC WONDER mortality data for adults aged ≥25 years. Sepsis deaths were identified using ICD-10 code A41 and neurodegenerative diseases using codes G00–G98. Age-adjusted mortality rates (AAMRs) per 100,000 population were calculated, and Joinpoint regression was applied to assess annual percent changes (APCs) with p<0.05 considered significant.

Between 1999 and 2023, 344,749 deaths were attributed to sepsis and neurodegenerative diseases. The AAMR increased from 5.5 to 7.6 per 100,000 (average annual percent change [AAPC] 1.4%). Males consistently exhibited higher mortality than females, though both rose significantly (males: 1.47%; females: 1.29%). The most significant increase occurred among adults aged 25–34 years (AAPC: 3.45%), while rates stabilized in those ≥85 years. Non-Hispanic Black individuals had the highest AAMRs, and the Western U.S. showed the steepest regional increase (AAPC: 3.18%).

Mortality linked to sepsis and neurodegenerative diseases has risen over two decades, with persistent disparities by age, sex, race, and geography. These concurrent trends underscore shared biological and social determinants, highlighting the need for equity-centered, multidisciplinary strategies addressing both acute and chronic disease burdens in aging populations.