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

Article type: Research Article

Authors: Fang, Yuan^{a; *} | Doyle, Margaret F.^b | Alosco, Michael L.^{c; d} | Mez, Jesse^{c; d; e} | Satizabal, Claudia L.^{d; f} | Qiu, Wei Qiao^{c; g; h} | Lunetta, Kathryn L.^a | Murabito, Joanne M.^{e; i}

Affiliations: [a] Boston University School of Public Health, Department of Biostatistics, Boston, MA, USA | [b] University of Vermont, Larner College of Medicine, Department of Pathology and Laboratory Medicine, Burlington, VT, USA | [c] Boston University School of Medicine, Boston University Alzheimer’s Disease Research Center and CTE Center, Boston, MA, USA | [d] Boston University School of Medicine, Department of Neurology, Boston, MA, USA | [e] Framingham Heart Study, National Heart, Lung, and Blood Institute and Boston University School of Medicine, Framingham, MA, USA | [f] University of Texas Health Science Center at San Antonio, Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases, San Antonio, TX, USA | [g] Boston University School of Medicine, Department of Psychiatry, Boston, MA, USA | [h] Boston University School of Medicine, Department of Pharmacology & Experimental Therapeutics, Boston, MA, USA | [i] Boston University School of Medicine, Department of Medicine, Section of General Internal Medicine, Boston, MA, USA

Correspondence: [*] Correspondence to: Yuan Fang, PhD, Boston University School of Public Health, Department of Biostatistics, 801 Massachusetts Ave, 3rd floor, Boston, MA 02118, USA. Tel.: +1 617 358 2476; E-mail: [email protected].

Abstract: 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.

Keywords: Biomarkers, cognitive aging, complete blood count, inflammation

DOI: 10.3233/JAD-215533

Journal: Journal of Alzheimer's Disease, vol. 87, no. 3, pp. 1291-1305, 2022