To evaluate the energy metabolism in Alzheimer's disease (AD), the cerebral arteriovenous differences of oxygen, glucose, lactate, pyruvate, ketone bodies and free fatty acids, and regional cerebral blood flow (rCBF) were examined in 7 patients with Alzheimer's disease (AD). The ratio of oxygen and glucose molar utilization was significantly elevated to 9.86 in AD, compared with 5.63 for 7 age matched controls. Single-photon emission computed tomography revealed that the patients had significantly decreased rCBF only in the parietotemporal region. The glucose extraction fraction and global cerebral metabolic rate of glucose were significantly decreased, whereas the global cerebral metabolic rate of oxygen was slightly decreased. However, the elevated oxygen/glucose utilization ratio is not due to the oxygenation of ketone bodies or free fatty acids, because the cerebral metabolic rates of these substrates did not alter. We concluded that the marked elevated value of the oxygen/glucose utilization ratio suggests an altered energy metabolism in AD.