Longitudinal Whole-Brain N-Acetylaspartate Concentration in Healthy Adults

BACKGROUND AND PURPOSE: Although NAA is often used as a marker of neural integrity and health in different neurologic disorders, the temporal behavior of WBNAA is not well characterized. Our goal therefore was to establish its normal variations in a cohort of healthy adults over typical clinical trial periods.

MATERIALS AND METHODS: Baseline amount of brain NAA, Q_NAA, was obtained with nonlocalizing proton MR spectroscopy from 9 subjects (7 women, 2 men; 31.2 ± 5.6 years old). Q_NAA was converted into absolute millimole amount by using phantom-replacement. The WBNAA concentration was derived by dividing Q_NAA with the brain parenchyma volume, V_B, segmented from MR imaging. Temporal variations were determined with 4 annual scans of each participant.

RESULTS: The distribution of WBNAA levels was not different among time points with respect to the mean, 12.1 ± 1.5 mmol/L (P > .6), nor was its intrasubject change (coefficient of variation = 8.6%) significant between any 2 scans (P > .5). There was a small (0.2 mL) but significant (P = .05) annual V_B decline.

CONCLUSIONS: WBNAA is stable over a 3-year period in healthy adults. It qualifies therefore as a biomarker for global neuronal loss and dysfunction in diffuse neurologic disorders that may be well worth considering as a secondary outcome measure candidate for clinical trials.