Decreased GABA levels of the anterior and posterior cingulate cortex are associated with executive dysfunction in mild cognitive impairment

Xiaona Fu; Mengting Qin; Xiaoming Liu; Lan Cheng; Lan Zhang; Xinli Zhang; Yu Lei; Qidong Zhou; Peng Sun; Liangjie Lin; Ying Su; Jing Wang

doi:10.3389/fnins.2023.1220122

Decreased GABA levels of the anterior and posterior cingulate cortex are associated with executive dysfunction in mild cognitive impairment

Front Neurosci. 2023 Aug 11:17:1220122. doi: 10.3389/fnins.2023.1220122. eCollection 2023.

Authors

Xiaona Fu^{1

2}, Mengting Qin³, Xiaoming Liu^{1

2}, Lan Cheng^{1

2}, Lan Zhang^{1

2}, Xinli Zhang^{1

2}, Yu Lei^{1

2}, Qidong Zhou³, Peng Sun⁴, Liangjie Lin⁴, Ying Su³, Jing Wang^{1

2}

Affiliations

¹ Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
² Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China.
³ Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
⁴ Clinical & Technical Solutions, Philips Healthcare, Beijing, China.

Abstract

Background and purpose: Executive function impairment, a slight but noticeable cognitive deficit in mild cognitive impairment (MCI) patients, is influenced by gamma-aminobutyric acid (GABA) levels. Reduced cognitive function is accompanied by thinning of the cerebral cortex, which has higher GABA levels than white matter. However, the relationships among GABA levels, cortical thickness, and executive function in MCI patients have not yet been elucidated. We investigated the relationships among GABA levels, cortical thickness, and executive function in MCI patients.

Methods: In this study, a total of 36 MCI patients and 36 sex-, age-, and education-matched healthy controls (HC) were recruited. But 33 MCI patients and 35 HC were included because of head motion or poor data quality for three MCI patients and one HC. The levels of gamma-aminobutyric acid plus relative to creatine (GABA+/Cr) and glutamate-glutamine relative to creatine (Glx/Cr) in the anterior cingulate cortex (ACC) and posterior cingulate cortex (PCC) were measured using the Meshcher-Garwood point resolved spectroscopy (MEGA-PRESS) sequence. Metabolite ratios, cortical thickness, and executive function and their interrelationships were determined in the MCI and HC groups.

Results: Patients with MCI showed lower GABA+/Cr levels in the ACC and PCC. Combined levels of GABA+ and Glx in the ACC and GABA+ in the PCC showed good diagnostic efficacy for MCI (AUC: 0.82). But no differences in cortical thickness were found between the two groups. In the MCI group, lower GABA+/Cr level was correlated to worse performance on the digit span test backward, and the shape trail test-B. The cortical thickness was not associated with GABA+ levels and executive function in patients.

Conclusion: These results implied that decreased GABA levels in the ACC and PCC had a critical role in the early diagnosis of impaired executive function of MCI. Therefore, GABA in the ACC and PCC could be a potential diagnostic marker of the executive function decline of MCI.

Keywords: GABA; MEGA-PRESS; anterior cingulate cortex; executive function; mild cognitive impairment; posterior cingulate cortex.