An in vivo study of phosphorus and glucose metabolism in Alzheimer's disease using magnetic resonance spectroscopy and PET.
OBJECTIVE
To study phosphorus and glucose metabolism in whole-brain slices of otherwise healthy patients with dementia of the Alzheimer type (DAT) and healthy controls.


METHODS
We used proton nuclear magnetic resonance imaging phosphorus spectroscopy and positron emission tomography to study in vivo brain phosphorus and glucose metabolism.


METHODS
Whole-brain slice phosphorus metabolism was studied in nine drug free patients with mild to moderately severe dementia of the Alzheimer type (DAT) and in eight age- and sex-matched healthy controls. Mean ages (+/- SD) of the patients and controls were 60 +/- 10 years and 64 +/- 16 years, respectively. Positron emission tomography was used to study cerebral glucose metabolism in seven of the patients with DAT and seven of the healthy controls.


RESULTS
Patients with DAT had significant brain glucose hypometabolism compared with controls, but there was no significant group difference in any phosphorus metabolite concentration or ratio in the same volume of brain tissue. Also, within patients with DAT there was no correlation between any phosphorus metabolite concentration or ratio and either severity of dementia or glucose metabolism.


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, or abnormal coupling between oxidation and phosphorylation. Normal or near-normal levels of phosphorus metabolites are maintained in mild, moderate, and severe DAT. Therefore, altered high-energy phosphate levels are not a consequence of reduced glucose metabolism in DAT, and do not play a major role in the pathophysiology of the disorder, at least in whole-brain sections.
Murphy
D G
DG
Laboratory of Neurosciences, National Institute on Aging, Bethesda, Md.
Bottomley
P A
PA
Salerno
J A
JA
DeCarli
C
C
Mentis
M J
MJ
Grady
C L
CL
Teichberg
D
D
Giacometti
K R
KR
Rosenberg
J M
JM
Hardy
C J
CJ
D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D010758:Phosphorus / Q000378:metabolism*; D012720:Severity of Illness Index; D014055:Tomography, Emission-Computed
D010758:Phosphorus; D005947:Glucose