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
- 1 Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- 2 Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430030, China
- 3 Clinical and Technical Support, Philips Healthcare, Beijing 100600, China
Received: October 13, 2023 Accepted: January 24, 2024 Published: March 1, 2024
https://doi.org/10.18632/aging.205585How to Cite
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.
Abbreviations
ACC: anterior cingulate cortex; aMCI: amnestic mild cognitive impairment; AVLT: Auditory verbal learning test; CNS: central nervous system; Cr: creatine; CSF: cerebrospinal fluid; CSVD: cerebral small vessel disease; DBS: Digit span test backward; FDS: Digit span test forward; FLAIR: fluid-attenuated inversion recovery; FOV: field of view; FWHM: full width at half maximum; GABA: gamma-aminobutyric acid; GABA+: GABA plus co-edited macromolecules and homocarnosine; Gln: glutamine; Glu: glutamate; Glx: glutamate-glutamine; GM: gray matter; HAMA: Hamilton Anxiety Rating Scale; HAMD: Hamilton Depression Rating Scale; HCs: healthy controls; 1H-MRS: Proton Magnetic Resonance Spectroscopy; MEGA-PRESS: Meshcher-Garwood point resolved spectroscopy; MoCA-BJ: Beijing version of the Montreal Cognitive Assessment; PCC: posterior cingulate cortex; ROIs: regions of interest; STT: Shape trail test; TE: echo time; TR: repetition time; WM: white matter; WMH: white matter hyperintensities.