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.

Measurement of Brain Metabolites by 1H Magnetic Resonance Spectroscopy in Patients with Schizophrenia: A Systematic Review and Meta-Analysis

“…Extensive evidence confirms that NAA levels are lower than normal in patients with tumor or stroke (Zimmerman and Wang 1997;Taylor et al, 1998), but recent evidence shows that NAA is also reduced in traumatic brain injury (Ariza et al, 2004), multiple sclerosis (Gadea et al, 2004;Tartaglia et al, 2004), epilepsy (Bernasconi et al, 2003;Vermathen et al, 2003), vascular dementia , Alzheimer disease (Dixon et al, 2002;Valenzuela and Sachdev, 2001), Huntington disease (Sanchez-Pernaute et al, 1999), spinocerebellar ataxia (Guerrini et al, 2004), perinatal asphyxia (Pavlakis et al, 1999), transposition of the great arteries (Miller et al, 2004), mood disorder (Cecil et al, 2003), gliomatosis cerebri (Galanaud et al, 2003), focal cortical dysplasia (Vuori et al, 2004), and radiation necrosis …”

Impact of cerebrospinal fluid contamination on brain metabolites evaluation with 1H‐MR spectroscopy: A single voxel study of the cerebellar vermis in patients with degenerative ataxias

“…Many different CSF content estimation methods, based on segmentation (14) and on differences in T 2 relaxation time between CSF and brain tissue water (15)(16)(17) were developed to correct brain metabolite quantities for the variable amount of the CSF in the VOI of 1 H-MRS. Our segmentation method proved reproducible results and as expected showed consistently lower VF values in patients with cerebellar ataxias as compared to healthy controls. While internal standards can be used to measure metabolite concentrations (18,19), in our study, we adopted the external phantom method because it does not need any a priori statement regarding creatine (20) or water tissue concentration (21,22).…”

Longitudinal 1H MRS changes in mild cognitive impairment and Alzheimer's disease

“…We previously showed that Cho/Cr and mI/Cr levels are also elevated in a paralimbic cortical region, the posterior cingulate gyri in aMCI [20]. Although serial MRS studies did not identify any longitudinal change in Cho, mI,, Cho/Cr or mI/Cr, levels in people with AD [1,10,18], Cho/Cr levels decreased with cholinergic agonist treatment in AD with respect to the placebo [44]. To our knowledge, no serial 1 H MRS study has been published in aMCI.…”

“…The responsiveness of NAA to improved neuron "health" suggests similar measures of NAA as a potential surrogate for therapeutic efficacy in aMCI and AD. There are few longitudinal 1 H MRS studies in AD that have measured the longitudinal change in NAA levels [1,10,17]. One 1 H MRS imaging study showed that NAA declines in the cortical grey matter of people with AD with respect to normal [1], and another single voxel 1 H MRS study showed that the decline in NAA/Cr correlates with the decline in Mini-Mental state examination (MMSE) scores in the medial temporal lobe [17].…”