ALTERATIONS OF CEREBRAL METABOLISM IN PROBABLE ALZHEIMERS-DISEASE - APRELIMINARY-STUDY

Previous in vitro and in vivo P-31 MRS studies of Alzheimer's disease patients have revealed alterations in membrane phospholipid metabolism and PET studies have shown alterations in glucose and oxidative metab olism. This study of probable Alzheimer's disease patients demonstrate s severity dependent alterations in measures of both high-energy phosp hate and membrane phospholipid metabolism. Mildly demented Alzheimer's patients compared to the controls, have increases in the levels of ph osphomonoesters, decreases in the levels of phosphocreatine and probab ly adenosine diphosphate, and an increased oxidative metabolic rate. A s the dementia worsens, the levels of phosphocreatine and adenosine di phosphate increase, the levels of phosphomonoesters decrease, and the oxidative metabolic rate decreases. The phosphomonoester findings repl icate previous findings and provide a new dimension to the molecular p athology of Alzheimer's a disease, implicating basic defects in membra ne metabolism. The changes in oxidative metabolic rate suggest the AD brain is under energetic stress. The changes in energy metabolites wit h increasing dementia could be a consequence of nerve terminal degener ation and are consistent with previous PET findings. P-31 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.