Open-label study of the short-term effects of memantine on FDG-PET in frontotemporal dementia.
Open-label study of the short-term effects of memantine on FDG-PET in frontotemporal dementia.
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DOI：
10.2147/ndt.s22635
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发表时间：
2011
影响因子：
3.2
通讯作者：
Pollock BG
中科院分区：
文献类型：
--
作者：
Chow TW;Graff-Guerrero A;Verhoeff NP;Binns MA;Tang-Wai DF;Freedman M;Masellis M;Black SE;Wilson AA;Houle S;Pollock BG
美金刚已显示出对阿尔茨海默病（AD）中的皮质代谢的影响，并且作用机制可能不是AD单独特异性的。我们假设，额颞叶痴呆的参与者服用美金刚胺会增加额叶区、颞叶区或显着网络中心的皮质代谢活动。在这项固定剂量、开放标签的初步研究中，从三级FTD诊所招募了16名患有行为或语言变异性额颞叶痴呆综合征（FTD）的受试者，并接受盐酸美金刚10 mg每日两次治疗。主要终点是治疗7-8周后皮质代谢活性的增强。次要终点是情绪和行为障碍、额叶执行功能和运动障碍的测量。对7例行为变异型FTD患者、8例语义性痴呆患者和1例进行性非流利性失语患者的正电子发射断层扫描（PET）数据进行体素参数图像分析，这些患者的平均年龄为64.3岁，平均病程为4.25年，基线平均总箱临床痴呆评分为6.59，显示双侧岛叶和左侧眶额皮质[18 F]-氟脱氧葡萄糖（FDG）标准化代谢活性增加（P < 0.01）。FDG-PET的增加与行为清单的变化无关。事后分析表明，语义性痴呆参与者推动了这一发现。这项开放标签临床PET研究表明，美金刚可诱导FTD显着网络中代谢的增加。需要进行安慰剂对照的随访研究。
Memantine has shown effects on cortical metabolism in Alzheimer’s disease (AD), and the mechanism of action may not be specific to AD alone. We hypothesized that participants with frontotemporal dementia taking memantine would show an increased cortical metabolic activity in frontal regions, temporal regions, or in salience network hubs. Sixteen participants with behavioral or language variant frontotemporal dementia syndromes (FTD) were recruited from tertiary FTD clinics and treated with memantine hydrochloride 10 mg twice daily in this fixed-dose, open-label pilot study. The primary endpoint was enhancement of cortical metabolic activity after 7–8 weeks of treatment. Secondary endpoints were measures of mood and behavior disturbance, frontal executive function, and motor disturbance. Voxel-wise parametric image analysis of positron emission tomography (PET) data from seven behavioral variant FTD patients, eight semantic dementia patients, and one progressive nonfluent aphasia patient, of mean age 64.3 years, mean duration of illness 4.25 years, and baseline mean sum of boxes Clinical Dementia Rating score 6.59, revealed an increase in [18F]-fluorodeoxyglucose (FDG) normalized metabolic activity in bilateral insulae and the left orbitofrontal cortex (P < 0.01). The increase on FDG-PET did not correlate with changes on behavioral inventories. Post hoc analysis indicated that semantic dementia participants drove this finding. This open-label clinical PET study suggests that memantine induces an increase in metabolism in the salience network in FTD. A placebo-controlled follow-up study is warranted.