Abstract Purpose: Growing evidence links living in rural or socioeconomically disadvantaged areas with worse outcomes in cancer patients. Our previous work indicated that growing up in a rural area and experiencing food insecurity in childhood are associated with more severe activity and mood-related interference from symptoms in the primary brain tumor (PBT) population. This study investigates the association of current neighborhood deprivation and population density with activity- and mood-related interference in a cross-sectional cohort of 555 patients with a PBT enrolled in a natural history study (NCT03251989). Methods: National Area Deprivation Index (ADI) and population density were dichotomized into more (>40) and less (<40) disadvantaged and urbanized (>1,000 persons/sq mi) and non-urbanized (<1,000 persons/sq mi). Activity- and mood-related interference was stratified into none/mild (0-1) and moderate/severe (2-10). Logistic regression was used to test univariate and multivariate associations of moderate/severe activity- and mood-related interference with demographic and clinical variables. Bonferroni-Holm was implemented to adjust for multiple comparisons (p < 0.001) in univariate analyses. We used backwards elimination multivariate analyses to fit the final model. Variables were included modeling when univariate p <0.10. Results: The sample included more males (57%), median age 49 (range 18-85), living in more disadvantage neighborhoods (25%), and primarily in urbanized areas (61%). The majority (74%) had high grade tumors, most commonly glioblastoma (39%), with 49% with tumor recurrence, and 21% on active treatment. Univariate analysis showed neither ADI nor population density was significantly associated with activity-related interference (ADI OR=1.35, 95% CI [0.85, 2.13]; population density OR=1.20, 95% CI [0.80, 1.79]) or mood-related interference (ADI OR=0.85, 95% CI [0.52, 1.38]; population density OR=1.19, 95% CI [0.78, 1.81]). In the multivariate analyses tumor diagnosis (OR=0.92 CI [0.53, 1.58]) growing up in a non-urbanized area (OR=1.56 CI [1.02, 2.40]), not having enough to eat when growing up (OR=2.50 CI [1.13, 5.54], and number of surgeries (OR=1.50 CI [1.00, 2.23]) remained associated with moderate/severe activity-related interference with ADI, and similar results were found in the population density model. Tumor recurrence (OR=1.77 CI [1.17, 2.66]) and comorbidities (OR=0.53 CI [0.33, 0.85]) were associated with moderate/severe mood-related interference with ADI and similar results were found in the population density model. Conclusions: Although activity- and mood-related interference were not associated with current ADI or population density, activity-related interference was significantly related to early life social variables including growing up in a rural area and not having enough to eat growing up. This study may be foundational for future study directions exploring other social deprivation factors early life or current that contributes to more interference in the PBT population. Citation Format: Tara S. Davis, Bennett A. McIver, Kimberly Reinhart, Elizabeth Vera, Vivian A. Guedes, Macy L. Stockdill, Orieta Celiku, Terri S. Armstrong, Michelle L. Wright. Further evaluation of social determinants of health including association of neighborhood disadvantage and population density with severity of activity- and mood- related interference in primary brain tumor patients [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B140.