Abstract
The present study characterized associations among brain metabolite levels, applying bivariate and multivariate (i.e., factor analysis) statistical methods to total creatine (tCr)-referenced estimates of the major Point RESolved Spectroscopy (PRESS) proton MR spectroscopy ((1) H-MRS) metabolites (i.e., total NAA/tCr, total choline/tCr, myo-inositol/tCr, glutamate + glutamine/tCr) acquired at 3 T from medial parietal lobe in a large (n = 299), well-characterized international cohort of healthy volunteers. Results supported the hypothesis that (1) H-MRS-measured metabolite estimates are moderately intercorrelated (M(r) = 0.42, SD(r) = 0.11, ps < 0.001), with more than one-half (i.e., 57%) of the total variability in metabolite estimates explained by a single common factor. Older age was significantly associated with lower levels of the identified common metabolite variance (CMV) factor (β = -0.09, p = 0.048), despite not being associated with levels of any individual metabolite. Holding CMV factor levels constant, females had significantly lower levels of total choline (i.e., unique metabolite variance; β = -0.19, p < 0.001), mirroring significant bivariate correlations between sex and total choline reported previously. Supplementary analysis of water-referenced metabolite estimates (i.e., including tCr/water) demonstrated lower, although still substantial, intercorrelations among metabolites, with 37% of total metabolite variance explained by a single common factor. If replicated, these results would suggest that applied (1) H-MRS researchers shift their analytical framework from examining bivariate associations between individual metabolites and specialty-dependent (e.g., clinical, research) variables of interest (e.g., using t-tests) to examining multivariable (i.e., covariate) associations between multiple metabolites and specialty-dependent variables of interest (e.g., using multiple regression).