Alterations of cerebral metabolism in probable Alzheimer's disease: a preliminary study

Previous in vitro and in vivo 31P MRS studies of Alzheimer's disease patients have revealed alterations in membrane phospholipid metabolism and PET studies have shown alterations in glucose and oxidative metabolism. This study of probable Alzheimer's disease patients demonstrates severity dependent alterations in measures of both high-energy phosphate and membrane phospholipid metabolism. Mildly demented Alzheimer's patients compared to the controls, have increases in the levels of phosphomonoesters, decreases in the levels of phosphocreatine and probably adenosine diphosphate, and an increased oxidative metabolic rate. As the dementia worsens, the levels of phosphocreatine and adenosine diphosphate increase, the levels of phosphomonoesters decrease, and the oxidative metabolic rate decreases. The phosphomonoester findings replicate previous findings and provide a new dimension to the molecular pathology of Alzheimer's disease, implicating basic defects in membrane metabolism. The changes in oxidative metabolic rate suggest the AD brain is under energetic stress. The changes in energy metabolites with increasing dementia could be a consequence of nerve terminal degeneration and are consistent with previous PET findings. 31P MRS provides new diagnostic and metabolic insights into this disease and would be a noninvasive method to follow the progression of the disease and the metabolic response to therapeutic interventions.