Magnetic Resonance Spectroscopy in Alzheimer’s Disease: Systematic Review and Meta-Analysis

Article type: Research Article

Authors: Wang, Hui^a | Tan, Lan^{a; b; c; *} | Wang, Hui-Fu^b | Liu, Ying^a | Yin, Rui-Hua^b | Wang, Wen-Ying^b | Chang, Xiao-Long^b | Jiang, Teng^d | Yu, Jin-Tai^{b; c; d; e; *}

Affiliations: [a] Department of Neurology, Qingdao Municipal Hospital, Dalian Medical University, China | [b] Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, China | [c] Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, China | [d] Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China | [e] Memory and Aging Center, Deparment of Neurology, University of California, San Francisco, USA

Correspondence: [*] Correspondence to: Lan Tan, MD, PhD, Department ofNeurology, Qingdao Municipal Hospital, School of Medicine,Qingdao University, No.5 Donghai Middle Road, Qingdao, Shandong Province 266071, China. E-mail: [email protected]

Correspondence: [*] Correspondence to:Jin-Tai Yu, MD, PhD, Deparment of Neurology, University of California, San Francisco, 675 Nelson Rising Lane, Suite 190, Box 1207, San Francisco, CA 94158, USA. E-mails: [email protected] or E-mail: [email protected]

Abstract: Background: The application of non-invasive proton magnetic resonance spectroscopy (1H-MRS) could potentially identify changes in cerebral metabolites in the patients with Alzheimer’s disease (AD). However, whether these metabolites can serve as biomarkers for the diagnosis of AD remains unclear. Objective: Using meta-analysis, we aimed to investigate the patterns of cerebral metabolite changes in several cerebral regions that are strongly associated with cognitive decline in AD patients. Methods: Using Hedges’ g effect size, a systematic search was performed in PubMed, Cochrane Library, Ovid, Embase, and EBSCO, and 38 studies were integrated into the final meta-analysis. Results: According to the observational studies, N-acetyl aspartate (NAA) in AD patients was significantly reduced in the posterior cingulate (PC) (effect size (ES) =−0.924, p <  0.005) and bilateral hippocampus (left hippocampus: ES =−1.329, p <  0.005; right hippocampus: ES =−1.287, p <  0.005). NAA/Cr (creatine) ratio decreased markedly in the PC (ES =−1.052, p <  0.005). Simultaneously, significant elevated myo-inositol (mI)/Cr ratio was found not only in the PC but also in the parietal gray matter. For lack of sufficient data, we failed to elucidate the efficacy of pharmacological interventions with the metabolites changes. Conclusion: The available data indicates that NAA, mI, and the NAA/Cr ratio might be potential biomarkers of brain dysfunction in AD subjects. Choline (Cho)/Cr and mI/NAA changes might also contribute toward the diagnostic process. Thus, large, well-designed studies correlated with cerebral metabolism are needed to better estimate the cerebral extent of alterations in brain metabolite levels in AD patients.

Keywords: Alzheimer’s disease, choline, creatine, glutamate and glutamine, magnetic resonance spectroscopy, meta-analysis, myo-inositol, N-acetyl aspartate

DOI: 10.3233/JAD-143225

Journal: Journal of Alzheimer's Disease, vol. 46, no. 4, pp. 1049-1070, 2015