No abstract

The relationship between regional brain myelination and aging has been the subject of intense study, with magnetic resonance imaging (MRI) perhaps the most effective modality for elucidating this. However, most of these studies have used nonspecific methods to probe myelin content, including diffusion tensor imaging, magnetization transfer ratio, and relaxation times. In the current study, we used the BMC-mcDESPOT analysis, a direct and specific method for imaging of myelin water fraction (MWF), a surrogate of myelin content. We investigated age-related differences in MWF in several brain regions in a large cohort of cognitively unimpaired participants, spanning a wide age range. Our results indicate a quadratic, inverted U-shape, relationship between MWF and age in all brain regions investigated, suggesting that myelination continues until middle age followed by decreases at older ages. We also observed that these agerelated differences vary across different brain regions, as expected. Our results provide evidence for nonlinear associations between age and myelin in a large sample of well characterized adults, using a direct myelin content imaging method.

BackgroundMyelin loss and cerebral blood flow (CBF) decline are central features of several neurodegenerative diseases. Myelin maintenance through oligodendrocyte metabolism is an energy-demanding process, so that myelin homeostasis is particularly sensitive to hypoxia, hypoperfusion or ischaemia. However, in spite of its central importance, little is known about the association between blood supply and myelin integrity.ObjectiveTo assess associations between cortical and subcortical CBF, and subcortical myelin content, in critical brain white matter regions.Materials and methodsMRI was performed on a cohort of 67 cognitively unimpaired adults. Using advanced MRI methodology, we measured whole-brain longitudinal and transverse relaxation rates (R1 and R2), sensitive but non-specific markers of myelin content, and myelin water fraction (MWF), a direct surrogate of myelin content, as well as regional CBF, from each of these participants.ResultsAll quantitative relaxometry metrics were positively associated with CBF in all brain regions evaluated. These associations between MWF or R1 and CBF, and, to a lesser extent, between R2 and CBF, were statistically significant in most brain regions examined, indicating that lower regional cortical or subcortical CBF corresponds to a decrease in local subcortical myelin content. Finally, all relaxometry metrics exhibited a quadratic, inverted U-shaped, association with age; this is attributed to the development of myelination from young to middle age, followed by progressive loss of myelin in later years.ConclusionsIn this first study examining the association between local blood supply and myelin integrity, we found that myelin content declines with CBF across a wide age range of cognitively normal subjects.