Objectives: 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.
Design: F-fluorodeoxyglucose positron emission tomography (PET) imaging and clinical assessment before and after open-label memantine treatment.
Participants/setting: Seventeen outpatients with probable AD on stable cholinesterase inhibitor medication.
Intervention: Memantine up to 10 mg twice daily for 10 weeks.
Measurements: 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.
Conclusion: 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.