AbstractBackgroundChronic peripheral inflammation is associated with cognitive decline and increased risk of dementia. Easily measured circulating blood cell parameters, including the neutrophil to lymphocyte ratio (NLR), red cell distribution width (RDW), and mean platelet volume (MPV), reflect peripheral inflammation. We sought to investigate the cross‐sectional association between these measures and neuropsychological (NP) test performance in the Framingham Heart Study (FHS) Offspring, Third‐generation, and Omni cohorts.MethodWe identified FHS participants who attended an exam that included a complete blood cell count sample and underwent NP testing within five years of blood draw. Linear mixed effect models were used to investigate the association between the blood cell parameters (NLR, RDW, MPV) and individual NP test scores adjusting for age, sex, education, cohort, time between blood draw and NP testing, prevalent cardiovascular disease, APOE‐ε4 genotype, and C‐reactive protein, and accounting for familial correlation using a random effect. We additionally tested for interactions between age (≥ 60 years vs. < 60 years) and blood cell parameters on NP scores and associations were reported separately by age group when significant (P for interaction ≤ 0.01).ResultAmong the 3531 participants (mean age 60.3 years, range 25 to 97 years, 47% male), 80% had at least some college and 22% were APOE‐ε4 carriers. We observed significant association between higher NLR and poorer NP performance on visual reproductions – delayed recall, Trails B ‐ Trails A, and Hooper visual organization test, that assess visual memory, executive function, and visuospatial abilities respectively (Table). There was also a significant association between higher RDW and poorer performance on digit symbol test assessing executive function. We observed different effects for the two age groups for the association between RDW and a metric of executive function (i.e., Trails B ‐ Trails A), where higher RDW correlated with decreased cognitive performance in participants aged ≥ 60 years (n=1865).ConclusionChronic peripheral inflammation as measured by NLR and RDW associates with lower cognitive function in FHS participants ≥ 60 years. In younger individuals, chronic peripheral inflammation may have a smaller effect on cognitive function.
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