Association of cerebral blood flow with myelin content in cognitively unimpaired adults

BACKGROUND: Myelin 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. OBJECTIVE: To assess associations between cortical and subcortical CBF, and subcortical myelin content, in critical brain white matter regions. MATERIALS AND METHODS: MRI was performed on a cohort of 67 cognitively unimpaired adults. Using advanced MRI methodology, we measured whole-brain longitudinal and transverse relaxation rates (R(1) and R(2)), 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. RESULTS: All quantitative relaxometry metrics were positively associated with CBF in all brain regions evaluated. These associations between MWF or R(1) and CBF, and, to a lesser extent, between R(2) 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. CONCLUSIONS: In 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.