Association of 1H-MR Spectroscopy and Cerebrospinal Fluid Biomarkers in Alzheimer's Disease: Diverging Behavior at Three Different Brain Regions

Background: In Alzheimer's disease (AD), levels of N-acetylaspartate (NAA) is diminished and choline (Cho) and myo-inositol (mI) are increased. In cerebrospinal fluid (CSF), tau and phosphoylated tau (p-tau181P) is increased and amyloid-β(1-42) (Aβ42) decreased.

Objectives: 1) To compare metabolites of different 1H-MRS voxels and assess its utility to differentiate AD from controls and to examine the relationship to cognition and to CSF markers.

Methods: 17 healthy controls and 19 AD subjects were studied using 1H-MRS. In the AD cases, additional CSF analysis was obtained.

Results: Relative to controls, AD subjects had reduced NAA/Creatine (Cr) levels in hippocampus (42.3% to 26.0%, p < 0.001), posterior cingulate gyrus (10.4% to 0.2%, p = 0.04), and parietal lobe (14.9% to 3.8%, p = 0.002). Further differences of Cho/Cr and mI/Cr in the hippocampus (Cho/Cr: p = 0.04; mI/Cr: p = 0.015) and posterior cingulate (Cho/Cr: p = 0.001; mI/Cr: p = 0.001) were observed. NAA/Cr of the hippocampus yielded the highest sensitivity (94.1%) and specificity (92.3%) to differentiate AD from controls. NAA/Cr was associated with general cognition (hippocampus: R = 0.68, p < 0.001; parietal lobe: R = 0.57, p = 0.001; posterior cingulate: R = 0.50, p = 0.003). Higher hippocampal NAA/Cr was related to higher CSF Aβ42, while lower parietal NAA/Cr was associated with a higher CSF total tau (t-tau) and p-tau181P. Posterior cingulate mI/Cr was related to CSF t-tau and NAA/mI.

Conclusion: 1H-MRS is an appropriate measure in AD. Measurement at different regions presumably reflects different pathological changes.