AUTHOR=Ramos-Cejudo Jaime , Johnson Andrew D. , Beiser Alexa , Seshadri Sudha , Salinas Joel , Berger Jeffrey S. , Fillmore Nathanael R. , Do Nhan , Zheng Chunlei , Kovbasyuk Zanetta , Ardekani Babak A. , Bubu Omonigho M. , Parekh Ankit , Convit Antonio , Betensky Rebecca A. , Wisniewski Thomas M. , Osorio Ricardo S.
TITLE=The Neutrophil to Lymphocyte Ratio Is Associated With the Risk of Subsequent Dementia in the Framingham Heart Study
JOURNAL=Frontiers in Aging Neuroscience
VOLUME=13
YEAR=2021
URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2021.773984
DOI=10.3389/fnagi.2021.773984
ISSN=1663-4365
ABSTRACT=Objective: Active neutrophils are important contributors to Alzheimer’s disease (AD) pathology through the formation of capillary stalls that compromise cerebral blood flow (CBF) and through aberrant neutrophil signaling that advances disease progression. The neutrophil to lymphocyte ratio (NLR) is a proxy of neutrophil-mediated inflammation, and higher NLR is found in persons diagnosed with clinical AD. The objective of this study was to investigate whether increased NLR in older adults is independently associated with the risk of subsequent dementia.
Methods: We examined associations of baseline NLR with incident dementia risk in the community-based Framingham Heart Study (FHS) longitudinal cohorts. The association between NLR and risk of dementia was evaluated using the cumulative incidence function (CIF) and inverse probability-weighted Cox proportional cause-specific hazards regression models, with adjustment for age, sex, body mass index (BMI), systolic and diastolic blood pressure, diabetes, current smoking status, low-density lipoprotein (LDH), high-density lipoprotein (LDL), total cholesterol, triglycerides, and history of cardiovascular disease (CVD). Random forest survival models were used to evaluate the relative predictive value of the model covariates on dementia risk.
Results: The final study sample included 1,648 participants with FHS (average age, 69 years; 56% women). During follow-up (median, 5.9 years), we observed 51 cases of incident dementia, of which 41 were AD cases. Results from weighted models suggested that the NLR was independently associated with incident dementia, and it was preceded in predictive value only by age, history of CVD, and blood pressure at baseline.
Conclusion: Our study shows that individuals with higher NLR are at a greater risk of subsequent dementia during a 5.9-year follow-up period. Further evaluating the role of neutrophil-mediated inflammation in AD progression may be warranted.