Reduced Hippocampal Glutamate and Posterior Cingulate N-Acetyl Aspartate in Mild Cognitive Impairment and Alzheimer’s Disease Is Associated with Episodic Memory Performance and White Matter Integrity in the Cingulum: A Pilot Study

Article type: Research Article

Authors: Wong, Dickson^a | Atiya, Samir^b | Fogarty, Jennifer^c | Montero-Odasso, Manuel^{c; d; e; f} | Pasternak, Stephen H.^{b; c} | Brymer, Chris^d | Borrie, Michael J.^{c; d} | Bartha, Robert^{a; b; *}

Affiliations: [a] Department of Medical Biophysics, University of Western Ontario, London, ON, Canada | [b] Robarts Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada | [c] Parkwood Institute Research Program, Lawson Health Research Institute, London, ON, Canada | [d] Geriatric Medicine, University of Western Ontario, London, ON, Canada | [e] Gait and Brain Lab, Parkwood Institute, Lawson Health Research Institute, London, ON, Canada | [f] Department of Epidemiology and Biostatistics, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada

Correspondence: [*] Correspondence to: Robert Bartha, Scientist and Director, Imaging Research Laboratories, Robarts Research Institute, The University of Western Ontario, 1151 Richmond St., London, ON N6A 3K7, Canada. Tel.: +1 519 663 5777 /Ex24039; E-mail: [email protected].

Abstract: Identification of biological changes underlying the early symptoms of Alzheimer’s disease (AD) will help to identify and stage individuals prior to symptom onset. The limbic system, which supports episodic memory and is impaired early in AD, is a primary target. In this study, brain metabolism and microstructure evaluated by high field (7 Tesla) proton magnetic resonance spectroscopy (1H-MRS) and diffusion tensor imaging (DTI) were evaluated in the limbic system of eight individuals with mild cognitive impairment (MCI), nine with AD, and sixteen normal elderly controls (NEC). Left hippocampal glutamate and posterior cingulate N-acetyl aspartate concentrations were reduced in MCI and AD compared to NEC. Differences in DTI metrics indicated volume and white matter loss along the cingulum in AD compared to NEC. Metabolic and microstructural changes were associated with episodic memory performance assessed using Craft Story 21 Recall and Benson Complex Figure Copy. The current study suggests that metabolite concentrations measured using 1H-MRS may provide insight into the underlying metabolic and microstructural processes of episodic memory impairment.

Keywords: Alzheimer’s disease, diffusion tensor imaging, diffusion tractography, episodic memory, glutamate, hippocampus, magnetic resonance imaging, magnetic resonance spectroscopy, posterior cingulate cortex

DOI: 10.3233/JAD-190773

Journal: Journal of Alzheimer's Disease, vol. 73, no. 4, pp. 1385-1405, 2020