Cross-Sectional Association Between Blood Cell Phenotypes, Cognitive Function, and Brain Imaging Measures in the Community-Based Framingham Heart Study

Background: Peripheral inflammation is associated with increased risk for dementia. Neutrophil to lymphocyte ratio (NLR), red cell distribution width (RDW), and mean platelet volume (MPV), are easily measured circulating blood cell phenotypes reflecting chronic peripheral inflammation, but their association with dementia status is unclear. Objective: We sought to investigate the cross-sectional association of these inflammatory measures with neuropsychological (NP) test performance, and brain magnetic resonance imaging (MRI) measures in the Framingham Heart Study (FHS) Offspring, Third-generation, and Omni cohorts. Methods: We identified FHS participants who attended an exam that included a complete blood cell count (CBC) and underwent NP testing (n = 3,396) or brain MRI (n = 2,770) within five years of blood draw. We investigated the association between NLR, RDW, and MPV and NP test performance and structural MRI-derived volumetric measurements using linear mixed effect models accounting for family relationships and adjusting for potential confounders. Results: Participants were on average 60 years old, 53% female, and about 80% attended some college. Higher NLR was significantly associated with poorer performance on visual memory, and visuospatial abilities, as well as with larger white matter hyperintensity volume. We also observed associations for higher RDW with poorer executive function and smaller total cerebral brain volume. Conclusion: Chronic peripheral inflammation as measured by NLR and RDW was associated with worse cognitive function, reduced brain volume, and greater microvascular disease in FHS participants. If confirmed in other samples, CBC may provide informative and cost-effective biomarkers of abnormal brain aging in the community.