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Research Paper|Volume 16, Issue 5|pp 4282—4298

GABA in the anterior cingulate cortex mediates the association of white matter hyperintensities with executive function: a magnetic resonance spectroscopy study

Xiaona Fu1,2, Peng Sun3, Xinli Zhang1,2, Dongyong Zhu1,2, Qian Qin1,2, Jue Lu1,2, Jing Wang1,2
  • 1Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
  • 2Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430030, China
  • 3Clinical and Technical Support, Philips Healthcare, Beijing 100600, China
* Equal contribution and co-first authorship
Received: October 13, 2023Accepted: January 24, 2024Published: March 1, 2024
https://doi.org/10.18632/aging.205585

Copyright: © 2024 Fu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

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.