GABA in the anterior cingulate cortex mediates the association of white matter hyperintensities with executive...

White matter hyperintensities (WMH) and gamma-aminobutyric acid (GABA) are associated with executive function. Multiple studies suggested cortical alterations mediate WMH-related cognitive decline. The aim of this study was to investigate the crucial role of cortical GABA in the WMH patients. In the 87 WMH patients (46 mild and 41 moderate to severe) examined in this study, GABA levels in the anterior cingulate cortex (ACC) and posterior cingulate cortex (PCC) assessed by the Meshcher-Garwood point resolved spectroscopy (MEGA-PRESS) sequence, WMH volume and executive function were compared between the two groups. Partial correlation and mediation analyses were carried out to examine the GABA levels in mediating the association between WMH volume and executive function. Patients with moderate to severe WMH had lower GABA+/Cr in the ACC (p = 0.034) and worse executive function (p = 0.004) than mild WMH patients. In all WMH cases, the GABA+/Cr levels in the ACC mediated the negative correlation between WMH and executive function (ab: effect = -0.020, BootSE = 0.010, 95% CI: -0.042 to -0.004). This finding suggested GABA+/Cr levels in the ACC might serve as a protective factor or potential target for preventing the occurrence and progression of executive function decline in WMH people.