Diminished glucose transport and phosphorylation in Alzheimer's disease determined by dynamic FDG-PET.
Using dynamic [18F]fluorodeoxyglucose (FDG) and PET, kinetic rate constants that describe influx (K1) and efflux (k2) of FDG as well as phosphorylation (k3) and dephosphorylation (k4) were determined in patients with probable Alzheimer's disease and similarly aged normal controls.


METHODS
The regional cerebral metabolic rate for glucose (CMRglu) was calculated from individually fitted rate constants in frontal, temporal, parietal and occipital cerebral cortex, caudate nucleus, putamen, thalamus and cerebellar cortex. Dynamic PET scans were obtained in normal controls (n = 10, mean age = 67) and Alzheimer's disease patients (n = 8, mean age = 67) for 60 min following injection of 10 mCi of FDG.


RESULTS
The Alzheimer's disease group was characterized by decreases of the CMRglu ranging from 13.3% in the frontal to 40.9% in the parietal cortex, which achieved significance in all regions except the thalamus. K1 was significantly reduced in the parietal (p < 0.01) and temporal cortices (p < 0.05). Significant declines in k3 were found in the parietal (p < 0.005), temporal and occipital cortex, and in the putamen and cerebellum (p < 0.05). The rate constants k2 and k4 were unchanged in the Alzheimer's disease group.


CONCLUSIONS
These data suggest that hypometabolism in Alzheimer's disease is related to reduced glucose phosphorylation activity as well as diminished glucose transport, particularly in the most metabolically affected areas of the brain, the parietal and temporal cortex.
Piert
M
M
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, USA.
Koeppe
R A
RA
Giordani
B
B
Berent
S
S
Kuhl
D E
DE
D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000378:metabolism; D001693:Biological Transport, Active; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D016022:Case-Control Studies; D003847:Deoxyglucose / Q000031:analogs & derivatives*; D005260:Female; D005462:Fluorine Radioisotopes; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism*; D006593:Hexokinase / Q000378:metabolism; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008962:Models, Theoretical; D010766:Phosphorylation; D014055:Tomography, Emission-Computed
D005462:Fluorine Radioisotopes; D019788:Fluorodeoxyglucose F18; D003847:Deoxyglucose; D006593:Hexokinase; D005947:Glucose