Neutrophils, the body's eager first responders to infection, might be leaving a paper trail for future cognitive decline. A new study from NYU Langone Health suggests that a standard lab value, the neutrophil to lymphocyte ratio (NLR), could help identify people at higher risk for Alzheimer's disease and related dementias years before any symptoms appear. The research, published online April 3 in Alzheimer's & Dementia, examined NLR data from nearly 400,000 patients across two large healthcare systems.
"Our study is the first large-scale investigation showing that neutrophil metrics are associated with increased risk of dementia in humans," said study first author Tianshe (Mark) He, PhD. The data, drawn from about 285,000 patients at four NYU Langone hospitals and roughly 85,000 from the Veteran's Health Administration, showed that higher NLR levels were consistently linked to an increased likelihood of developing dementia, with the relationship holding for both near-term and long-term risk.
The analysis revealed some demographic nuances. Hispanic patients showed a stronger association between elevated NLR and dementia risk, and women in both healthcare systems also had a higher risk linked to elevated NLR. According to co-senior author Jaime Ramos-Cejudo, PhD, while a high NLR alone is unlikely to be a definitive predictor, it could be a useful piece of a larger puzzle for identifying individuals who may benefit from closer monitoring.
The findings also add weight to the theory that neutrophils might be more than just passive markers. These cells, essential for fighting infection, may actively contribute to damage in blood vessels and brain tissue in Alzheimer's. However, researchers caution that a direct cause-and-effect relationship has not yet been confirmed, partly because neutrophils have a very short lifespan and are tricky to study.
Dr. Ramos-Cejudo and colleagues at the Vascular and Immune Dysfunction in Aging and Alzheimer's Disease (VIDA) lab are continuing to investigate. Their work combines measures of neutrophil activity with advanced brain imaging and cognitive assessments. The study was supported by multiple National Institutes of Health grants and other funding sources, with a long list of co-investigators from NYU and the VA Boston Healthcare System's Cooperative Studies Program.