Cholesterol and its subfractions play a role in the development of atherosclerosis. Cerebral CO2 reactivity reflects the compensatory capacity of cerebral arterioles. The authors investigated the relationship between total cholesterol, high-density lipoprotein (HDL), their ratio, and cerebral CO2 reactivity in 826 participants from the Rotterdam Study. Cerebral CO2 reactivity increased significantly with increasing levels of HDL and decreased significantly with an increasing total cholesterol/HDL ratio. This suggests that blood lipids may also affect smaller cerebral blood vessels.