Association between neutrophil to lymphocyte ratio and Alzheimer’s Disease in large biobank cohorts

Abstract

AbstractBackgroundNeutrophil to lymphocyte ratio (NLR) is used as a marker for systematic inflammation and innate immune system activation; NLR has been associated with Alzheimer’s disease (AD) in previous literature, but mostly in relatively small case control studies. The goal of this study is to investigate the association between AD and NLR in two large biobanks, the UK Biobank and the United States based All of Us.MethodAD was defined using inpatient ICD10/9 codes and death certificates (UK Biobank) or inpatient ICD10/9 codes and Systematized Nomenclature of Medicine (All of Us). Cox proportional hazards models were used to estimate hazard ratios (HR) adjusting for age, sex, race, and recruitment center (UK Biobank). Because the UK Biobank had extensive covariate data available, we also estimated HRs further adjusting for hypertension, hypercholesterolemia, education, body mass index, and smoking.ResultWith complete covariate data, 233,173 UK Biobank (mean age = 58; 56% female; 2,049 incident AD cases) and 68,382 All of Us (mean age = 59; 65% female; 239 incident AD cases) participants were included. In the UK Biobank, every 1 standard deviation (SD) increase in NLR was associated with a 3% increase in AD risk (HR = 1.03, 95% CI = 1.01‐1.05, p‐value = 0.001) and this relationship was robust to lifestyle and clinical factor adjustment. NLR per 1 SD increase was not associated with AD (HR = 1.03, 95% CI = 0.81‐1.17, p‐value = 0.755) in All of Us.ConclusionNLR was associated with AD in UK Biobank but not in All of Us, however, we note that power is lower in All of Us due to fewer AD cases. We plan to repeat this analysis as more cases accrue in All of Us and explore the neutrophil‐associated Duffy null variant for potential modification of this AD/NLR association. These findings provide further evidence for the association between NLR and AD as well as the possible role of systemic inflammation in AD pathology.