Nathanael R. Fillmore
Publications / 2026
paper
Alzheimer's & Dementia2026doi:10.1002/alz.71335

Neutrophil inflammation metrics are associated with the risk of future dementia in large data from NYU Langone Hospitals and the Veterans Health Administration.

Tianshe He, Rebecca A. Betensky, Ricardo S. Osorio, Kaitlin Swinnerton, Chunlei Zheng, Tovia Jacobs, Alok Vedvyas, Karyn Marsh, Joshua Chodosh, Ula Y. Hwang, Natalia Sifnugel, Omonigho M. Bubu, Thomas Wisniewski, Mary Brophy, Nhan V. Do, Nathanael R. Fillmore‡, Jaime Ramos-Cejudo‡

‡ Equal senior authorship

Summary

Higher neutrophil-to-lymphocyte ratios are associated with an increased risk of developing Alzheimer's disease and related dementias across diverse patient populations. These findings suggest that systemic inflammation may serve as a significant indicator of future neurodegenerative decline.

Key result

Higher neutrophil-to-lymphocyte ratio was independently associated with an increased risk of incident Alzheimer disease and related dementias in both the NYU cohort (hazard ratio 1.07, 95% CI 1.02-1.15) and the Veterans Health Administration cohort (hazard ratio 1.21, 95% CI 1.10-1.34).

Abstract

INTRODUCTION: Neutrophil-to-lymphocyte ratio (NLR), a marker of systemic inflammation, has been linked to dementia risk, but prior studies were limited by small sample sizes. METHODS: We assessed the association between baseline NLR and incident Alzheimer's disease (AD) and Alzeimer's disease and related dementias (AD/ADRD) using electronic health records from New York University (NYU) (n = 284,530) and the Veterans Health Administration [VA] (n = 85,836) Hospitals from 2011 to 2023. AD/ADRD diagnoses were identified via International Classification of Diseases (ICD) codes ≥6 months post-baseline. Cox models and cumulative incidence functions (CIFs) adjusted for demographic and clinical variables, with death as a competing risk. RESULTS: Higher NLR was associated significantly with increased AD/ADRD risk in both cohorts (NYU hazard ratio [HR] = 1.07, 95% confidence interval [CI] 1.02-1.15; VA HR = 1.21, 95% CI 1.10-1.34). Spline analysis further confirmed a continuous dose-response relationship, and subgroup analyses showed higher risk among female and Hispanic patients. DISCUSSION: Elevated NLR is independently associated with higher AD/ADRD risk across diverse populations, highlighting the role of systemic inflammation and neutrophil-mediated pathways in neurodegeneration.