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. 2022;87(3):1291-1305.
doi: 10.3233/JAD-215533.

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

Yuan Fang  1 , Margaret F Doyle  2 , Michael L Alosco  3   4 , Jesse Mez  3   4   5 , Claudia L Satizabal  4   6 , Wei Qiao Qiu  3   7   8 , Kathryn L Lunetta  1 , Joanne M Murabito  5   9
Affiliations

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

Yuan Fang et al. J Alzheimers Dis. 2022.

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.

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Conflict of interest statement

CONFLICT OF INTEREST

The authors have no conflict of interest to report.

Figures

Figure 1.
Figure 1.
Study sample for the NP testing outcomes and the brain MRI measures outcomes. The blood draw sample was collected from the Offspring cohort examination 9, the Omni cohort examination 4 (2011 – 2014) and the Gen 3 cohort and Omni 2 cohort examination 2 (2008 – 2011). NP testing batteries were included if they were within five years and were the closest to the examination dates, with a range of time from 2006 to 2017. Brain MRI scans were also included if they were collected within five years and were the closest to the examination dates; date range for the MRI data are between 2006 and 2018. Participants with missing APOE genotype information and prevalent stroke at the examination were excluded. Additionally, for the MRI study, participants were excluded if a 3T or unknown strength scanner was used to obtain the imaging. NP = neuropsychological; MRI = magnetic resonance imaging.
Figure 2.
Figure 2.
Effect estimates (color) and unadjusted p-values (numbers) for the cross-sectional associations of CBC phenotypes with Neuropsychological testing scores. Each color block shows the estimated effect per standard deviation unit for each pair of associations investigated in the primary study adjusting for the covariates from Model 1. P-values are shown for associations where p ≤ 0.01. When the age interaction term is significant, the effect estimates for the total sample are hidden, and the p-values for associations in the age subgroups are also included. CBC = complet blood count; CI = confidence interval; NLR = Neutrophil-to-lymphocyte ratio; RDW = red cell distribution width; MPV = mean platelet volume; LMD = Logical Memory – delayed recall; PASD = Paired Association learning – delayed recall; VRD = Visual Reproduction – delayed recall; TRAILSBA = Trails Making test B – Trails Making test A; SIM = Similarities subtest; DS = Digit Symbol coding test; HVOT = Hooper Visual Organization Test; BNT30 = 30 – item Boston Naming Test.
Figure 3.
Figure 3.
Effect estimates(color) and unadjusted p-values (numbers) for the cross-sectional association of CBC phenotypes with brain MRI measures. Each color block shows the estimated effect per standard deviation unit for each pair of associations investigated in the primary study, adjusting for the covariates from Model 1. P-values are shown for associations where p ≤ 0.01). The age interaction was not significant for any test. CBC = complete blood count; CI = confidence interval; NLR = Neutrophil-to-lymphocyte ratio; RDW = red cell distribution width; MPV = mean platelet volume; TCBV = total cerebral brain volume; TCV = total intracranial volume; HPV = hippocampal volume; WMH = white matter hyperintensity; CGV = cerebrum gray matter volume; FGV = frontal gray matter volume; OGV = occipital gray matter volume; PGV = parietal gray matter volume; TGV = temporal gray matter volume; MRI = magnetic resonance imaging.
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