Anemia-associated smaller brain volume and sex differences: a cross-sectional study of magnetic resonance imaging in brain health checkups

Introduction: Anemia is a risk factor for dementia development. However, few studies have examined the relationship between brain volume and anemia. This study aimed to analyze the association between anemia and brain volume using magnetic resonance imaging data from brain health checkups. Method: Participants underwent brain health checkups between January 2015 and March 2022. Blood samples were collected to measure hemoglobin concentrations and mean corpuscular volumes. The modified Mini-Mental State Examination (MMSE) was used to evaluate cognitive function. Magnetic resonance images were analyzed using voxel-based Morphometry to evaluate the overall patterns of brain volume. After extracting the principal components (PCs) from PC analysis, we investigated their association with MMSE scores and anemia. Results: This study included 1,029 participants and identified principal components, representing smaller volume in the frontal lobe (PC1), and smaller volume in the limbic system to the temporal lobe (PC2). A higher PC2 score was significantly associated with a lower MMSE score. Male participants with anemia had smaller bilateral PC1 volumes and left hippocampal volumes, and female participants with anemia had smaller bilateral PC2 volumes and hippocampus volumes. Discussion: PC2 may represent the extent of disease affecting limbic system volume, such as Alzheimer’s disease. Our results suggest that anemia may be associated with smaller volumes in the limbic system, especially in women. Further studies are required to determine which type of anemia is more strongly correlated with smaller brain volumes.