Magnetic resonance spectroscopy reveals abnormalities of glucose metabolism in the Alzheimer's brain

Abstract

Objective: Brain glucose hypometabolism is a prominent feature of Alzheimer's disease (AD), and in this case-control study we used Magnetic Resonance Spectroscopy (MRS) to assess AD-related differences in the posterior cingulate/precuneal ratio of glucose, lactate, and other metabolites.

Methods: J-modulated Point-Resolved Spectroscopy (J-PRESS) and Prior-Knowledge Fitting (ProFit) software was used to measure glucose and other metabolites in the posterior cingulate/precuneus of 25 AD, 27 older controls, and 27 younger control participants. Clinical assessments for AD participants included cognitive performance measures, insulin resistance metrics and CSF biomarkers.

Results: AD participants showed substantially elevated glucose, lactate, and ascorbate levels compared to older (and younger) controls. In addition, the precuneal glucose elevation discriminated well between AD participants and older controls. Myo-inositol correlated with CSF p-Tau_181P, total Tau, and the Clinical Dementia Rating (CDR) sum-of-boxes score within the AD group.

Interpretation: Higher glucose to creatine ratios in the AD brain likely reflect lower glucose utilization. Our findings reveal pronounced metabolic abnormalities in the AD brain and strongly suggest that brain glucose merits further investigation as a candidate AD biomarker.

Figure 1

Segmentation & J‐PRESS Acquisition. (A) Segmented coronal, sagittal, and axial views of a representative younger control participant, showing bilateral precuneus voxel placement in red. Segmentation is displayed with white as white matter, light gray as gray matter, and dark gray as CSF. Figure created in MRIcroGL version 1.150909. (B) ProFit spectral fitting for a representative Alzheimer's disease participant showing labels for location of standard reference metabolite peaks (NAA, Cr, Cho) and mI. (C) ProFit basis sets used for J‐PRESS glucose and mI measurements showing the complex spectral location of these metabolites.

Figure 2

Scatter column graph of select metabolite to creatine ratios. Individual metabolite values are shown as red downward‐facing triangles for the younger control group (CN younger), upward triangles for the older control group (CN Older), and circles for the Alzheimer's disease group (AD). Error bars are unweighted mean ± 95% confidence interval for the metabolite.

Figure 3

Scatterplots of select correlations between myo‐inositol on the y‐axis and CDR sum of boxes, CSF p‐Tau_181P, and Aß₄₂ on the x‐axis. Red circles indicate individual samples for each of the AD participants.

Figure 4

ROC curves for CSF%, glucose, ascorbate, lactate, NAA, and myo‐inositol for discrimination between the AD and older control groups.