Glutamate-glutamine and GABA in brain of normal aged and patients with cognitive impairment
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To explore the changes of glutamate-glutamine (Glx) and gamma-aminobutyric acid (GABA) in the brain in normal old age and cognitive impairment using magnetic resonance spectroscopy (MRS).
Seventeen normal young controls (NYC), 15 normal elderly controls (NEC), 21 patients with mild cognitive impairment (MCI) and 17 with Alzheimer disease (AD) patients were included in this study. Glx and GABA+ levels in the anterior cingulate cortex (ACC) and right hippocampus (rHP) were measured by using a MEGA-PRESS sequence. Glx/Cr and GABA+/Cr ratios were compared between NYC and NEC and between the three elderly groups using analysis of covariance (ANCOVA); the tissue fractions of voxels were used as covariates. The relationships between metabolite ratios and cognitive performance were analysed using Spearman correlation coefficients.
For NEC and NYC groups, Glx/Cr and GABA+/Cr ratios were lower in NEC in ACC and rHP. For the three elderly groups, Glx/Cr ratio was lower in AD in ACC compared to NEC and MCI; Glx/Cr ratio was lower in AD in rHP compared to NEC. There was no significant decrease for GABA+/Cr ratio.
Glx and GABA levels may decrease simultaneously in normal aged, and Glx level decreased predominantly in AD, and it is helpful in the early diagnosis of AD.
• Glx and GABA levels may decrease simultaneously in normal aged.
• Glx level may decrease predominantly in Alzheimer disease.
• The balance in excitatory–inhibitory systems may be broken in AD.
• Decreased Glx level may be helpful in early diagnosis of AD.
KeywordsMagnetic resonance spectroscopy Aged Mild cognitive impairment Alzheimer disease Neurotransmitters
Anterior cingulate cortex
Mild cognitive impairment
Meshcher–Garwood point resolved spectroscopy
Minimum Mental State Examination
Montreal cognitive assessment
Magnetic resonance spectroscopy
Normal elderly controls
Normal young controls
We would like to acknowledge Dr. Mark A. Brown, Dr. Sinyeob Ahn, Dr. Keith Heberlein and Dr. Panli Zuo from Siemens Healthcare for providing the MEGA-PRESS sequence.
The scientific guarantor of this publication is Hongyan Ni. The authors of this manuscript declare relationships with the following companies: Tianyi Qian is a Siemens Employee. This study has received funding by National Natural Science Foundation of China (Grant No. 30870713), Tianjin Science and Technology Support Projects (Grant Nos. 16JCYBJC25900, 15ZCZDSY00520, and 13JCQNJC14400), and the Tianjin Bureau of Public Health Projects (Grant No.15KG134). No complex statistical methods were necessary for this paper. Institutional review board approval was obtained.
Written informed consent was obtained from all subjects (patients) in this study. Methodology: retrospective, case–control study, performed at one institution.