Effect of Memantine Treatment on Regional Cortical Metabolism in Alzheimer's Disease
Effect of Memantine Treatment on Regional Cortical Metabolism in Alzheimer's Disease
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DOI：
10.1097/jgp.0b013e3181ca3a4e
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发表时间：
2010-07-01
影响因子：
7.2
通讯作者：
Mandelkern, Mark A.
中科院分区：
文献类型：
--
作者：
Sultzer, David L.;Melrose, Rebecca J.;Mandelkern, Mark A.
目的：阿尔茨海默病（AD）药物治疗反应中涉及的皮质系统知之甚少。临床前研究已经证明了美金刚对神经受体和细胞生理学的影响，尽管治疗对体内皮质活性的影响尚不清楚。设计：（18）开放标签美金刚治疗前后的F-氟脱氧葡萄糖正电子发射断层扫描（PET）成像和临床评估。参与者/设置：17例门诊患者可能AD稳定胆碱酯酶抑制剂药物。干预：美金刚胺高达10毫克，每天两次，持续10周。测量值：皮质代谢活动变化的基于体素的分析; Mattis痴呆评定量表（DRS）和神经行为评定量表（NRS）。结果：平均年龄为81岁，平均简易精神状态检查评分为19.4。与基线相比，10周美金刚治疗后，双侧两个皮质区域的代谢活性显著升高：颞下回（BA 20）和角回/缘上回（BA 39，40）。DRS评分的变化与皮质代谢的变化之间没有显著关系，尽管NRS评分的变化与右顶叶和颞叶皮质的代谢变化程度相关。结论：AD患者接受美金刚治疗10周后，双侧顶叶下部和颞叶皮质的代谢活性增加。PET成像可以揭示药物对神经活动的功能影响，并可能有助于确定药物治疗中涉及的关键机制。(Am J Geriatr Psychiatry 2010; 18：606-614）
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: (18)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. (Am J Geriatr Psychiatry 2010; 18: 606-614)