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

J Alzheimers Dis. 2020;73(4):1385-1405. doi: 10.3233/JAD-190773.

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 spectroscopy; magnetic resonance imaging; posterior cingulate cortex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / diagnostic imaging*
  • Alzheimer Disease / metabolism*
  • Aspartic Acid / analogs & derivatives*
  • Aspartic Acid / metabolism
  • Cognitive Dysfunction / diagnostic imaging*
  • Cognitive Dysfunction / metabolism*
  • Diffusion Tensor Imaging
  • Female
  • Glutamic Acid / metabolism*
  • Gyrus Cinguli / diagnostic imaging*
  • Gyrus Cinguli / metabolism
  • Hippocampus / metabolism*
  • Humans
  • Limbic System / diagnostic imaging
  • Limbic System / metabolism
  • Magnetic Resonance Spectroscopy
  • Male
  • Memory, Episodic*
  • Mental Status and Dementia Tests
  • Middle Aged
  • Neuropsychological Tests
  • Pilot Projects
  • White Matter / diagnostic imaging*
  • White Matter / metabolism

Substances

  • Aspartic Acid
  • Glutamic Acid
  • N-acetylaspartate

Grants and funding