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Basic Science and Pathogenesis.
Mark He1, Sean R Jacobson2, Rebecca A Betensky3
1New York University (NYU) Grossman School of Medicine, New York City, NY, USA.
Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 25, 2025
Summary
Higher neutrophil to lymphocyte ratio (NLR), a marker of inflammation, is linked to increased risk of Alzheimer's disease and related dementias (AD/ADRD). This finding, based on a large electronic health record study, highlights the importance of peripheral inflammation in AD/ADRD development.
Area of Science:
- Neuroscience
- Immunology
- Gerontology
Background:
- Neutrophils are implicated in Alzheimer's disease (AD) pathology.
- The neutrophil-to-lymphocyte ratio (NLR) indicates neutrophil-mediated inflammation and is linked to dementia risk.
- Previous studies on NLR and dementia risk used small cohorts.
Purpose of the Study:
- To investigate the generalizability of the association between NLR and dementia risk in a large population.
- To utilize electronic health records (EHR) data for a comprehensive analysis.
Main Methods:
- Analysis of EHR data from 287,985 patients (2011-2023).
- Utilized cause-specific Cox regression to assess the association between NLR and AD/ADRD incidence.
- Adjusted for demographic and clinical confounders, with death as a censoring event.
- Employed cumulative incidence function (CIF) curves for risk assessment over time.
Main Results:
- A positive and independent association was found between log-transformed NLR and the risk of AD/ADRD (HR = 1.160).
- Significant increasing relationships were observed between NLR and AD/ADRD risk.
- Subgroup analyses confirmed significant associations, notably higher risk among Hispanic patients.
Conclusions:
- Elevated NLR is associated with a greater risk of future AD/ADRD.
- These findings underscore the role of peripheral inflammation in AD pathology.
- Further research is needed to elucidate the mechanisms linking neutrophil biology to AD.
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