Maturation and degeneration of the human brainstem across the adult lifespan.

Brainstem tissue microstructural properties change across the adult lifespan. However, studies elucidating the biological processes that govern brainstem maturation and degeneration in-vivo are lacking. In the present work, conducted on a large cohort of 140 cognitively unimpaired subjects spanning a wide age range of 21 to 94 years, we implemented a multi-parameter approach to characterize the sex- and age differences. In addition, we examined regional correlations between myelin water fraction (MWF), a direct measure of myelin content, and diffusion tensor imaging indices, and transverse and longitudinal relaxation rates to evaluate whether these metrics provide information complementary to MWF. We observed region-dependent differences in myelin content and axonal density with age and found that both exhibit an inverted U-shape association with age in several brainstem substructures. We emphasize that the microstructural differences captured by our distinct MRI metrics, along with their weak associations with MWF, strongly indicate the potential of using these outcome measures in a multi-parametric approach. Furthermore, our results support the gain-predicts-loss hypothesis of tissue maturation and degeneration in the brainstem. Indeed, our results indicate that myelination follows a temporally symmetric time course across the adult life span, while axons appear to degenerate significantly more rapidly than they mature.

Association of central arterial stiffness with hippocampal blood flow and N-acetyl aspartate concentration in hypertensive adult Dahl salt sensitive rats.

BACKGROUND: Central arterial stiffness (CAS) is associated with elevated arterial blood pressure (BP) and is likely associated with stiffening of cerebral artery walls, with attendant cerebral hypoperfusion, neuronal density loss and cognitive decline. Dahl salt-sensitive (Dahl-S) rats exhibit age-associated hypertension and memory loss, even on a normal salt intake. METHOD: We sought to explore whether central arterial pulse wave velocity (PWV), a marker of CAS, is associated with hippocampal cerebral blood flow (CBF) and neuronal density in hypertensive Dahl-S rats. We measured systolic BP (by tail-cuff plethysmography), aortic PWV (by echocardiography) and CBF and N-acetyl aspartate (NAA) (by magnetic resonance imaging) in 6 month-old male Dahl-S rats (n = 12). RESULTS: Greater PWV was significantly associated with lower CBF and lower NAA concentration in the hippocampus, supporting a role of CAS in cerebrovascular dysfunction and decline in cognitive performance with aging. CONCLUSION: These findings implicate increased CAS in cerebral hypoperfusion and loss of neuronal density and function in the Dahl-S model of age-associated cardiovascular dysfunction.