Effect of memantine treatment on regional cortical metabolism in Alzheimer's disease.
OBJECTIVE
Cortical systems involved in the response to medication treatment for Alzheimer's disease (AD) are poorly understood. Preclinical studies have demonstrated the effect of memantine on neuroreceptors and cell physiology, although the impact of treatment on cortical activity in vivo is not known.


METHODS
F-fluorodeoxyglucose positron emission tomography (PET) imaging and clinical assessment before and after open-label memantine treatment.


METHODS
Seventeen outpatients with probable AD on stable cholinesterase inhibitor medication.


METHODS
Memantine up to 10 mg twice daily for 10 weeks.


METHODS
Voxel-based analyses of change in cortical metabolic activity; Mattis Dementia Rating Scale (DRS), and Neurobehavioral Rating Scale (NRS).


RESULTS
: Mean age was 81 years; mean Mini-Mental State Examination score was 19.4. Compared with baseline, metabolic activity was significantly higher after 10 weeks memantine treatment in two cortical regions bilaterally: the inferior temporal gyrus (BA 20) and the angular gyrus/supramarginal gyrus (BA 39, 40). There was no significant relationship between change in DRS score and change in cortical metabolism, although change in NRS score was associated with the extent of metabolic change in the right parietal and temporal cortex.


CONCLUSIONS
Metabolic activity in bilateral inferior parietal and temporal cortex increases during 10 weeks of memantine treatment in patients with AD. PET imaging can reveal functional effects of medications on neural activity and may help to define critical mechanisms involved in drug treatment.
Sultzer
David L
DL
Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, UCLA, CA, USA. dsultzer@ucla.edu
Melrose
Rebecca J
RJ
Harwood
Dylan G
DG
Campa
Olivia
O
Mandelkern
Mark A
MA
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy*; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism*; D015259:Dopamine Agents / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008559:Memantine / Q000627:therapeutic use*; D009483:Neuropsychological Tests; D010296:Parietal Lobe / Q000187:drug effects / Q000378:metabolism; D049268:Positron-Emission Tomography; D011446:Prospective Studies; D013702:Temporal Lobe / Q000187:drug effects / Q000378:metabolism
D015259:Dopamine Agents; D008559:Memantine