Aging alters regional multichemical profile of the human brain: an in vivo 1H-MRS study of young versus middle-aged subjects

Age-related differences in the multichemical proton magnetic resonance spectroscopy (1H-MRS) profile of the human brain have been reported for several age groups, and most consistently for ages from neonates to 16-year-olds. Our recent 1H-MRS study demonstrated a significant age-related increase of total chemical concentration (relative to creatine) in the prefrontal and sensorimotor cortices within young adulthood (19-31-year-olds). In the present study we test the hypothesis that the level of brain chemicals in the same cortices, which show increased chemical levels during normal development, are reduced with normal aging after young adulthood. The multichemical 1H-MRS profile of the brain was compared between 19 young and 16 middle-aged normal subjects across multiple brain regions for all chemicals of 1H-MRS spectra. Chemical concentrations were measured relative to creatine. Over all age groups the total relative chemical concentration was highest in the prefrontal cortex. Middle-aged subjects demonstrated a significant decrease of total relative chemical concentration in the dorsolateral prefrontal (F = 54.8, p < 10(-7), ANOVA), orbital frontal (F = 3.7, p < 0.05) and sensorimotor (F = 15.1, p < 0.0001) cortices, as compared with younger age. Other brain regions showed no age-dependent differences. The results indicate that normal aging alters multichemical 1H-MRS profile of the human brain and that these changes are region-specific, with the largest changes occuring in the dorsolateral prefrontal cortex. These findings provide evidence that the processes of neuronal maturation of the human brain, and neurotransmitters and other chemical changes as the marker of these neuronal changes are almost finished by young adulthood and then reduced during normal aging toward middle age period of life. The present data also support the notion of heterochronic regressive changes of the aging human brain, where the multichemical brain regional profile seems to inversely recapitulate cortical chemical maturation within normal development.