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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.