To evaluate the energy metabolic status of Alzheimer's disease, we examined the cerebral arteriovenous differences of glucose, oxygen, lactate, pyruvate, ketone bodies, and free fatty acids and N-isopropyl-p-(123I) iodoamphetamine (IMP) single-photon emission computed tomography in 5 patients with Alzheimer's disease (4 male and 1 female patients; mean age of 64.80 +/- 8.47 years). Compared with 5 age matched normal control subjects (4 males and 1 female; mean age of 63.20 +/- 10.76 years), the patients showed significantly decreased regional cerebral blood flow only in the parietotemporal region. The global cerebral glucose metabolic rate (CMRGlu) had significantly low value, whereas the global cerebral oxygen metabolic rate (CMRO2) was not changed. The metabolic ratio (CMRO2/CMRGlu) was significantly elevated to 9.73 in the patients with Alzheimer's disease, compared with 5.50 in the normal controls. The cerebral metabolic rates of ketone bodies and free fatty acids were unchanged. The cerebral pyruvate output was significantly decreased. The cerebral lactate output became negative, but the decrease did not reach statistical significance. We concluded that the markedly elevated metabolic ratio suggests an altered energy metabolism in Alzheimer's disease.