Longitudinal quantitative proton magnetic resonance spectroscopy of the hippocampus in Alzheimer's disease

Abstract

Changes in metabolites detected by proton magnetic resonance spectroscopy ((1)H MRS) of the brain have been demonstrated in Alzheimer's disease. Our objectives were, first, longitudinally to measure absolute concentrations of metabolites in both hippocampi, the sites of early Alzheimer's disease, in patients with clinical Alzheimer's disease and controls; secondly, to separate the relative contribution of atrophy and metabolite concentration change to overall signal change; and, thirdly, to determine whether metabolite concentrations in the hippocampus relate to cognitive scores. (1)H MR spectra were acquired from a single voxel (12 x 15 x 25 mm(3) = 4.5 ml) aligned to the long axis of each hippocampus in nine probable or possible Alzheimer's disease subjects diagnosed according to the National Institute of Neurologic and Cognitive Disorders and Stroke (NINCDS) compared with 14 age-matched NINCDS-negative Alzheimer's disease controls. Metabolite concentrations were corrected for the amount of CSF present in the voxel. Hippocampal volumes were measured at the same time. The same protocol was repeated approximately 1 year later. We found that atrophy-corrected hippocampal N-acetylaspartate (NAA) concentration was lower in cognitively impaired subjects compared with controls. This was significant for the left hippocampus (baseline 87% of control, P = 0.013; and at 1 year 76% of control, P = 0.020). Hippocampal volumes also differed significantly between the groups, and decreased significantly over 1 year in the Alzheimer's disease group (12%, P = 0.017). The decrease in [NAA] over 1 year was not significant in either group. Discriminant analysis revealed that the best classification of subjects was by including both left NAA concentration and left hippocampal volume. myo-Inositol signals from these small voxels had poor signal-to-noise and demonstrated no significant changes. We conclude that (1)HMRS-detectable metabolites can be quantified from the hippocampi of cognitively impaired individuals, and that hippocampal [NAA] is significantly reduced in Alzheimer's disease, in excess of atrophy. In our cohort, the differences were more significant for the left hippocampus.