Disruptions to the mechanisms governing the metabolic supply-and-demand relationship that are integral to brain energy homeostasis can have deleterious consequences on brain health, making it vulnerable to the development of age-related disorders like Alzheimer's disease (AD). Energy supply is dynamically and precisely controlled by mechanisms inherent to the cerebral vasculature, and here, capillary thin-strand pericytes are quickly emerging as key players. A K_ATP channel signalling complex imbues pericytes with the ability to detect subtle changes in local glucose and rapidly couples decreases in this key substrate to robust increases in blood flow. Blocking glucose import into the brain with a glucose transporter-1 blocker (1 µM BAY-876) activates pericyte K_ATP channels to increase brain blood flow in young (2-4 months) mice. Remarkably, this effect is completely lost in older (12-15 months) mice, and even earlier (6-8 months) in mice with familial AD mutations. Our emerging data suggest that a key interaction between membrane cholesterol and K_ATP channels underlies this dysfunction, and disrupting cholesterol in older mice reinstates the ability of pericyte K_ATP channels to sense decreases in local glucose. Perturbations in pericyte membrane cholesterol due to aging or AD may disrupt the delicate macromolecular organization of K_ATP channels, causing a breakdown of energy sensing mechanisms and progressive loss of hemodynamic control by pericytes.