Neurovascular coupling and cerebrovascular reactivity: physiology, lifespan development, pathophysiology, and clinical relevance

Neurovascular coupling (NVC) and cerebrovascular reactivity (CVR) are two key regulatory mechanisms that maintain adequate cerebral blood flow (CBF) to meet the metabolic demands of the human brain. In this review, we summarize the essential physiological principles needed to understand the distinctions, similarities, and overlaps between these systems, providing a deeper comprehension of cerebral perfusion and its regulation. We further examine their development across the lifespan, including embryogenesis and early life, with a focus on how synaptogenesis, myelination, and synaptic pruning shape NVC, CVR, and CBF. Finally, we discuss the effects of aging, emphasizing cerebrovascular remodeling and its consequences. Various neuropathologies are then explored from the perspective of altered CBF regulation, highlighting numerous correlations between regulatory dysfunction and disease pathogenesis. We also review a range of investigative techniques used to assess NVC and CVR, including (but not limited to) arterial spin labelling, functional magnetic resonance imaging, and transcranial Doppler. This review systematically integrates the developmental trajectories of NVC and CVR across the human lifespan with their pathophysiological alterations and clinical assessment methods. By combining developmental, mechanistic, and clinical perspectives, it provides a comprehensive framework that highlights how age-related changes shape cerebrovascular regulation, with important implications for both research and the interpretation of neurovascular data.