Neurodegenerative disorders including Alzheimer, Parkinson, Huntington, motor neuron disease, and other degenerative nervous system conditions are rising globally with aging populations. Despite their growing impact, population-level mortality patterns and disparities across demographic and regional strata remain understudied. Defining these trends can help target prevention, improve care delivery, and inform health policy.

We conducted a population-based analysis using the CDC WONDER Multiple Cause-of-Death (MCOD) database. Deaths were identified using ICD-10 codes G20, G10, G30, G31, and G12.2. Age-adjusted mortality rates (AAMRs) were standardized to the 2000 U.S. population and stratified by sex, race/ethnicity, region, urbanization, and place of death. Temporal trends were analyzed using Joinpoint regression to estimate annual percent change (APC) and average annual percent change (AAPC).

Between 1999 and 2023, 4,589,315 deaths were attributed to neurodegenerative disorders (AAMR: 53.0). Mortality increased steadily (AAPC: 1.75). Females had higher AAMRs than males (49.4 vs. 47.3). Non-Hispanic Whites had the highest AAMR (75.6), while Asian/Pacific Islanders had the lowest (40.3). The South showed the highest regional AAMR (77.2) and steepest growth (AAPC: 2.16). Rural mortality exceeded urban (74.0 vs. 70.8), with both increasing over time. Most deaths occurred in long-term care facilities (2.2 million), followed by home and hospice settings, which rose markedly in recent years.

Neurodegenerative disease mortality has increased significantly over two decades, with marked demographic and geographic disparities. Higher mortality among females, non-Hispanic Whites, rural residents, and those in the South highlights the need for targeted interventions, equitable care access, and enhanced surveillance to address this growing public health burden.