Abstract Body: Introduction: Hypertension may silently worsen neurodegenerative processes. This study examines hypertension’s role in U.S. neurodegenerative mortality trends from 1999 to 2020 across diverse populations. Hypothesis: Hypertension contributes to neurodegenerative disease mortality, with disparities by sex, race/ethnicity, region, urbanization, and age. Methods: CDC WONDER Multiple Cause of Death data (1999–2020) were analyzed. Deaths from dementia (F03), Parkinson disease (G20), and other neurodegenerative conditions (G30–G31) were assessed as underlying causes. Hypertension (I10–I15) and cerebrovascular disease (I60–I69) were included as contributing causes. AAMRs per 100,000 were calculated. Joinpoint regression estimated APC and AAPC stratified by sex, race/ethnicity, urbanization, census region, and age group. Results: In the U.S., 680,029 neurodegenerative disease-related fatalities occurred between 1999 and 2020. The AAMR climbed from 5.11 in 1999 to 22.74 in 2020. In 1999, the Midwest (5.88), Whites (5.19), rural regions (5.39), and females (5.20) had the highest AAMRs, while the Northeast (3.69), NH Asian/Pacific Islanders (2.11), urban areas (4.85), and males (4.79) had the lowest. In 2020, the highest AAMRs were in the South (26.25), NH Black individuals (25.04), rural areas (25.19), and females (24.54), while the lowest were in the Northeast (16.22), NH Asian/Pacific Islanders (12.11), urban areas (20.45), and males (19.57). The highest AAPC, 7.99% (CI: 6.87–9.12), was observed among Hispanics, and the lowest AAPC, 3.97% (CI: 2.37–5.60), was among American Indians/Alaska Natives. Regionally, the South showed the fastest increase (AAPC: 7.48%; CI: 5.42–9.57), and the West the slowest (AAPC: 6.06%; CI: 4.81–7.32). Rural areas rose faster (AAPC: 6.91%; CI: 5.70–8.13) than urban areas (AAPC: 6.75%; CI: 5.15–8.37). Females had higher growth (AAPC: 6.76%; CI: 5.45–8.08) than males (AAPC: 6.05%; CI: 4.94–7.17). In 1999 and 2020, crude rates were greatest for 85+ individuals (116.59; 584.64) and lowest among ages 55-64 in 1999 (0.33) and 45–54 in 2020 (0.0941) The 85+ group rose the most (AAPC: 7.07%; CI: 5.74–8.42). Conclusion: Despite hypertension treatment breakthroughs, neurodegenerative disease mortality from hypertension continues to climb, especially in minority and rural groups. This expanding public health issue requires targeted hypertension diagnosis, treatment, and neurology care equality methods.