Abnormalities of Glucose Metabolism in Alzheimer's Disease

In normoglycemic patients with either incipient early-onset or incipient late-onset dementia of the Alzheimer type, the predominant disturbance consisted of a significant reduction in cerebral glucose utilization. Alterations in cerebral blood flow and oxygen consumption first occurred in late-onset dementia types. In advanced late-onset dementia, these parameters had decreased most severely. The calculated ATP production rate from glucose indicated a drastic loss of energy in all patients studied. As not all oxygen consumed by the brain was used for glucose oxidation, oxidation of substrates other than glucose (endogenous amino acids and free fatty acids) is assumed to minimize the energy loss from glucose. The possibility that the abnormalities in oxidative and energy metabolism in dementias of the Alzheimer's type are due to metabolic abnormalities in glycolytic glucose breakdown and pyruvate oxidation, rather than to an uncoupling of oxidative phosphorylation, is discussed.