Hemoglobin, Anemia, and Cognitive Function: The Atherosclerosis Risk in Communities Study

Background. Our objective was to characterize the relationship of low and high hemoglobin concentrations and normocytic, microcytic, and macrocytic anemia with cross-sectional cognition and change in cognition over a median of 6 years. Methods. Cross-sectional and prospective analyses of 13,133 participants (mean age 57 years, 56% women, 24% black, 10% anemia) in the Atherosclerosis Risk in Communities (ARIC) study (baseline 1990-1992) were carried out. Anemia was defined as hemoglobin concentrations lower than 13g/dl for men and lower than 12g/dl for women and was subclassified as normocytic (mean corpuscular volume [MCV] 80-100 fL), microcytic (MCV < 80 fL), and macrocytic (MCV > 100 fL). Cognition was assessed by delayed word recall test (DWRT), digit symbol substitution test (DSST), word fluency test (WFT), and global Z-score at Visit 2 (1990-1992) and Visit 4 (1996-1998). Adjusted linear regression models and splines were used. Results. Cross-sectionally, anemia overall was associated with lower cognitive test scores on DSST and global Z-score among men and women (all p <. 05), but not on DWRT or WFT. Anemia subtypes were associated similarly with cognition, with strongest associations for the DSST and global Z-score. Additionally, elevated hemoglobin level was associated with nonsignificantly worse cognition in cross-sectional analyses, suggesting a nonlinear association of hemoglobin with cognition. In contrast, anemia overall and anemia subtypes were not associated with cognition in prospective analyses (all p >. 05). Conclusions. There was a cross-sectional, but not prospective, nonlinear association between hemoglobin concentrations and cognitive function, although only associations of low levels of hemoglobin (anemia) were statistically significant. Subtypes of anemia had similar magnitudes of associations with cognition.