Positron emission tomography–guided magnetic resonance spectroscopy in Alzheimer disease

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Abstract
Objective: To determine whether the level of metabolites in magnetic resonance spectroscopy (MRS) is a representative marker of underlying pathological changes identified in positron emission tomographic (PET) images in Alzheimer disease (AD).Methods: We performed PET‐guided MRS in cases of probable AD, mild cognitive impairment (MCI), and healthy controls (HC). All participants were imaged by 11C‐Pittsburgh compound B (11C‐PiB) and 18F‐fluorodeoxyglucose (18F‐FDG) PET followed by 3T MRS. PET images were assessed both visually and using standardized uptake value ratios (SUVRs). MRS voxels were placed in regions with maximum abnormality on amyloid (Aβ+) and FDG (hypometabolic) areas on PET scans. Corresponding normal areas were selected in controls. The ratios of total N‐acetyl (tNA) group, myoinositol (mI), choline, and glutamate + glutamine over creatine (Cr) were compared between these regions.Results: Aβ + regions had significantly higher (p = 0.02) mI/Cr and lower tNA/Cr (p = 0.02), whereas in hypometabolic areas only tNA/Cr was reduced (p = 0.003). Multiple regression analysis adjusting for sex, age, and education showed mI/Cr was only associated with 11C‐PiB SUVR (p < 0.0001). tNA/Cr, however, was associated with both PiB (p = 0.0003) and 18F‐FDG SUVR (p = 0.006). The level of mI/Cr was not significantly different between MCI and AD (p = 0.28), but tNA/Cr showed significant decline from HC to MCI to AD (p = 0.001, p = 0.04).Interpretation: mI/Cr has significant temporal and spatial associations with Aβ and could potentially be considered as a disease state biomarker. tNA is an indicator of early neurodegenerative changes and might have a role as disease stage biomarker and also as a valuable surrogate marker for treatment response. Ann Neurol 2018;83:771–778
Funding Information
  • National Institute for Health Research Cambridge Biomedical Research Centre

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