Red cell distribution width, anemia and their associations with white matter integrity among middle-aged urban adults

Anemia (blood hemoglobin [Hb] <13 g/dL among males; <12 g/dL among females) and elevated red cell distribution width (RDW) are potential risk factors for reduced brain white matter integrity (WMI), reflected by lower fractional anisotropy or increased mean diffusivity. Cross-sectional data with exposure-outcome lag time was used, whereby hematological exposures (RDW and Hb) and covariates were compiled from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study with available visit 1 (v₁; 2004-2009) and/or v₂ (2009-2013) data; while diffusion tensor magnetic resonance imaging (dMRI) outcome data were collected at HANDLS SCAN visit (v_scan: 2011-2015, n = 214, mean follow-up from v₁ ±SD: 5.6 ± 1.8 year). Multivariable-adjusted linear regression analyses were conducted, overall, stratifying by sex, and further restricting to the nonanemic for RDW exposures in part of the analyses. Among males, RDW_(v1) was linked with lower global mean fractional anisotropy (standardized effect size b = -0.30, p= 0.003, q < 0.05; basic model), an association only slightly attenuated with further covariate adjustment. Anemia was not a risk factor for poor WMI, independently of RDW. Ultimately, pending further longitudinal evidence, initial RDW appears to be associated with poorer WMI among males.