AN INVIVO STUDY OF PHOSPHORUS AND GLUCOSE-METABOLISM IN ALZHEIMERS-DISEASE USING MAGNETIC-RESONANCE SPECTROSCOPY AND PET

Objectives: To study phosphorus and glucose metabolism in whole-brain slices of otherwise healthy patients with dementia of the Alzheimer ty pe (DAT) and healthy controls. Design: We used proton nuclear magnetic resonance imaging phosphorus spectroscopy and positron emission tomog raphy to study in vivo brain phosphorus and glucose metabolism. Patien ts: Whole-brain slice phosphorus metabolism was studied in nine drug f ree patients with mild to moderately severe dementia of the Alzheimer type (DAT) and in eight age- and sex-matched healthy controls. Mean ag es (+/-SD) of the patients and controls were 60+/-10 years and 64+/-16 years, respectively. Positron emission tomography was used to study c erebral glucose metabolism in seven of the patients with DAT and seven of the healthy controls. Results: Patients with DAT had significant b rain glucose hypometabolism compared with controls, but there was no s ignificant group difference in any phosphorus metabolite concentration or ratio in the same volume of brain tissue. Also, within patients wi th DAT there was no correlation between any phosphorus metabolite conc entration or ratio and either severity of dementia or glucose metaboli sm. Conclusions: We suggest glucose metabolism is reduced early in DAT (reflecting decreased basal synaptic functioning) and is unrelated to a rate limitation in glucose delivery, abnormal glucose metabolism, o r abnormal coupling between oxidation and phosphorylation. Normal or n ear-normal levels of phosphorus metabolites are maintained in mild, mo derate, and severe DAT. Therefore, altered high-energy phosphate level s are not a consequence of reduced glucose metabolism in DAT, and do n ot play a major role in the pathophysiology of the disorder, at least in whole-brain sections.