Association between serum free hemoglobin level and cerebral white matter hyperintensity volume in older adults

The association between serum free hemoglobin (sfHb) level and white matter hyperintensity (WMH) volume is controversial. This study is to examine this association considering nonlinearity, sex dimorphism, and WMH type. We enrolled 704 older adults among the participants of the Korean Longitudinal Study on Cognitive Aging and Dementia and visitors to the Dementia Clinic of Seoul National University Bundang Hospital. We measured sfHb level in the venous blood and WMH volume (V_WMH) using fluid-attenuated inversion recovery magnetic resonance images. The association between sfHb level and periventricular V_WMH was linear in men (linear regression; β =  - 0.18, p = 0.006) and U-shaped in women (restricted cubic spline; F = 6.82, p < 0.001). sfHb level was not associated with deep V_WMH in either sex. These findings were also observed in participants without anemia. To conclude, sfHb level is associated with periventricular V_WMH in older adults of both sexes. Maintaining an optimal sfHb level may contribute to the prevention of WMH.