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Effect of Memantine on Brain Metabolic Activity and Perfusion in Drug-naïve Moderate Alzheimer’s Disease Patients

Author(s): Tomo Iwamoto, Kumiko Utsumi, Seiju Kobayashi, Shuichi Yasumura, Shigeki Hatakeyama, Ayako Hayashi,Chiaki Kawanishi

Objective: Memantine is a noncompetitive N-methyl-D-aspartate receptor (NMDAR)ant  agoni st that im proves or stabilizes cognitive impairment in moderate to severeAlzheimer’s disease (AD). However, the effects of memantine on regional brain metabolic activity and perfusion are not fully known. To clarify these effects, we investigated the efficacyof memantine monotherapy using multimodal neuroimaging in drug-naïve patients withmoderate AD.

Methods: This was a prospective open-labeled study of patients with drug- naïve  modera  teAD  ( Mini-Mental State Examination scores of 14-19) before and after 12 weeks of treatmentwith memantine, conducted between April 2015 and December 2016. Imaging was performedusing 18F-fluorodeoxyglucose-positron emission tomography (18F-FDG-PET) and 99mTcethylcysteinate dimer-single photon emission computed tomography (99mTc-ECD-SPECT),to assess brain metabolic activity and perfusion, respectively. The imaging data, registered toa probabilistic anatomical atlas, were evaluated by voxel-based analysis.

Results: A total of 20 patients were enrolled and 17 patients’ datasets were a nalyzed. T  heaver age Mini-Mental State Examination was 16.6 (1.8) at baseline and 16.9 (4.1) posttreatment.The average Neuropsychiatric Inventory score was 2.8 (7.6) at baseline and 3.9(9.2) post-treatment. Brain regions with increased metabolic activity following memantinetreatment in previously drug-naïve AD patients included a wide range of cerebral cortexes,
particularly the right inferior pari etal lobule, right supramarginal gyrus, right angular gyru s,and right paracentral lobule (p < 0.01, paired t-test). Only small regions had increased brainperfusion (p < 0.01, paired t-test).

Conclusion: We believe this is the first stu dy focusing on brain metabolic activity and perfusioni   n  the same drug-naïve moderate AD patients before and after memantine treatment. Therewere inconsistencies between the regions with increased metabolic activity and perfusionafter memantine treatment in drug-naïve AD patients, suggesting that brain metabolism mayincrease without a concurrent increase in blood perfusion. This study may help elucidate themechanism of action of memantine.



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