Effect of memantine on CBF and CMRO2 in patients with early Parkinson's disease.
OBJECTIVE
Parkinson's disease (PD) may be associated with increased energy metabolism in overactive regions of the basal ganglia. Therefore, we hypothesized that treatment with the N-methyl-d-aspartate receptor (NMDAR) antagonist memantine would decrease regional cerebral blood flow (rCBF) and oxygen metabolism in the basal ganglia of patients with early-stage PD.


METHODS
Quantitative positron emission tomography (PET) recordings were obtained with 15O]water and 15O]oxygen in 10 patients, scanned first in a baseline condition, and again 6 weeks after treatment with a daily dose of 20 mg memantine. Dynamic PET data were analyzed using volume of interest and voxel-based approaches.


RESULTS
The treatment evoked rCBF decreases in basal ganglia, and in several frontal cortical areas. The regional cerebral metabolic rate of oxygen (rCMRO2) did not decrease in any of the a priori defined regions, and consequently the oxygen extraction fraction was increased in these regions. Two peaks of significantly decreased rCMRO2 were detected near the frontal poles in both hemispheres, using a posteriori voxel-based analysis.


CONCLUSIONS
Although we did not find the predicted decrease in basal ganglia oxygen consumption, our data suggest that treatment with memantine actively modulates neuronal activity and/or hemodynamic response in basal ganglia of PD patients. This finding may be relevant to the putative neuroprotective properties of NMDAR antagonists.
Borghammer
P
P
PET Center, Aarhus University Hospital, Aarhus, Denmark. per@pet.auh.dk
Vafaee
M
M
Ostergaard
K
K
Rodell
A
A
Bailey
C
C
Cumming
P
P
D000368:Aged; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008559:Memantine / Q000627:therapeutic use*; D008875:Middle Aged; D010100:Oxygen / Q000378:metabolism*; D010104:Oxygen Radioisotopes / Q000378:metabolism; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods
D000978:Antiparkinson Agents; D010104:Oxygen Radioisotopes; D010100:Oxygen; D008559:Memantine