Neutrophils, a type of white blood cell circulating in the bloodstream, act as some of the body’s first responders to infection and inflammation. When the immune system is activated, their numbers can rise quickly, altering the balance between neutrophils and other immune cells.
Doctors can measure this balance using a standard lab value called the neutrophil to lymphocyte ratio (NLR). This number is routinely calculated from a complete blood count, a common test used to detect infections and assess immune health.
New research from NYU Langone Health suggests that this simple measurement may do more than reflect current illness. It could also help identify people at higher risk of developing Alzheimer’s disease and related dementias, even before any symptoms appear. The study examined NLR data from nearly 400,000 patients across two large healthcare systems.
Large Study Links Immune Cells to Dementia Risk
“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, a data scientist in the Department of Psychiatry at NYU Grossman School of Medicine. “Neutrophil elevation is happening before any evidence of cognitive decline, which makes a compelling case for studying whether neutrophils are actively contributing to disease progression.”
Dr. He and co-senior author Jaime Ramos-Cejudo, PhD, an assistant professor in the Departments of Psychiatry and Neurology at NYU Grossman School of Medicine, are both affiliated with the VA Boston Healthcare System’s Cooperative Studies Program.
Published online April 3 in Alzheimer’s & Dementia, the research included data from about 285,000 patients treated at four NYU Langone hospitals and roughly 85,000 individuals from the Veteran’s Health Administration.
To ensure accuracy, the team used each patient’s earliest qualifying NLR measurement. These readings had to fall within the study period, be taken when patients were at least 55 years old, and occur before any diagnosis of Alzheimer’s or dementia. The researchers then tracked whether those individuals went on to develop dementia during the study timeframe.
Elevated NLR Linked to Short and Long Term Risk
Across both groups, higher NLR levels were consistently associated with an increased likelihood of developing Alzheimer’s or other forms of dementia. This relationship held true for both near-term and long-term risk. Researchers defined “high” NLR based on the median value, meaning half of the participants had higher readings and half had lower ones.
The analysis also revealed differences among subgroups. Hispanic patients showed a stronger association between elevated NLR and dementia risk, though it remains unclear whether this reflects genetic influences or social factors such as differences in access to care. Women in both healthcare systems also had a higher risk linked to elevated NLR.
Why This Blood Marker Matters
According to Dr. Ramos-Cejudo, the findings are important for two main reasons. On its own, a high NLR is unlikely to serve as a definitive predictor of dementia. However, when combined with other known risk factors, it could help identify individuals who may benefit from closer monitoring, additional testing, or early interventions before cognitive symptoms emerge.
The results also support growing evidence that neutrophils may play a more active role in the disease process itself.
Could Immune Cells Drive Alzheimer’s Progression
Neutrophils are essential for fighting infections and aiding tissue repair, but they can also contribute to damage under certain conditions. In Alzheimer’s and other dementias, this damage may occur in blood vessels and brain tissue. Signs of neutrophil-driven inflammation have been observed in the brains of Alzheimer’s patients, and animal studies suggest these cells can accelerate disease progression.
Aging may further complicate the picture. As the body’s ability to clear out old neutrophils changes over time, disruptions in this process could lead to increased tissue damage.
Even so, researchers caution that a direct cause-and-effect relationship has not yet been confirmed. One challenge is that neutrophils have a very short lifespan and must be studied using fresh blood samples, unlike other cell types that can be stored for later analysis.
Ongoing Research Into Diagnosis and Treatment
Dr. Ramos-Cejudo and his colleagues at the Vascular and Immune Dysfunction in Aging and Alzheimer’s Disease (VIDA) lab are continuing to investigate whether neutrophils actively contribute to cognitive decline. Their work combines measures of neutrophil activity with advanced brain imaging (such as PET and diffusion MRI) and cognitive assessments in patients.
“These and future studies will show whether neutrophils are just a marker of Alzheimer’s disease or are actively causing dementia progression — in which case, they could make a compelling therapeutic target,” said Dr. Ramos-Cejudo. “In the meantime, we hope the neutrophil to lymphocyte ratio can contribute to gateway diagnostic tools for people at risk of developing Alzheimer’s and dementia, so they can get more in-depth testing and interventions long before they experience cognitive decline.”
Funding and Research Team
The study was supported by National Institutes of Health grants R01AG092953, R01AG070821, R01AG079282, P30AG066512, K23AG068534, R01AG082278, and RF1AG083975. Additional funding came from the National Alzheimer’s Coordinating Center, the VA Boston Healthcare System’s Cooperative Studies Program, Alzheimer’s Association grant AARG-21-848397, and BrightFocus Foundation grant A2022033S.
Other NYU researchers involved in the study were Rebecca A. Betensky, PhD; Ricardo S. Osorio, MD; Tovia Jacobs; Alok Vedvyas, MS, MSJ; Karyn Marsh, PhD; Joshua Chodosh, MD; Ula Y. Hwang, MD, MPH; Natalia Sifnugel, MPH; Omonigho M. Bubu, MD, PhD, MPH; and Thomas Wisniewski, MD.
Additional co-investigators included Chunlei Zheng, PhD; Kaitlin Swinnerton, MIDS; Mary Brophy, MD; and Nhan V. Do, MD, from the VA Boston Healthcare System’s Cooperative Studies Program (MAVERIC). Nathaniel Fillmore, PhD, at Harvard Medical School, also served as co-senior author.
