Department of Psychiatry, Columbia University, New York, NY, USA.
Taub Institute, Columbia University, New York, NY, USA.
J Alzheimers Dis. 2020;75(4):1391-1403. doi: 10.3233/JAD-191265.
There are currently no disease-targeted treatments for cognitive or behavioral symptoms in patients with behavioral variant frontotemporal dementia (bvFTD).
To determine the effect of tolcapone, a specific inhibitor of Catechol-O-Methyltransferase (COMT), in patients with bvFTD.
In this randomized, double-blind, placebo-controlled, cross-over study at two study sites, we examined the effect of tolcapone on 28 adult outpatients with bvFTD. The primary outcome was reaction time on the N-back cognitive test. As an imaging outcome, we examined differences in the resting blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) signal intensity between subjects on placebo versus tolcapone performing the N-back test. Secondary outcomes included measures of cognitive performance and behavioral disturbance using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Neuropsychiatric Inventory-Questionnaire (NPI-Q), and Clinical Global Impressions scale (CGI).
Tolcapone was well tolerated and no patients dropped out. The most frequent treatment-related adverse event during tolcapone treatment was elevated liver enzymes (21%). There were no significant differences between tolcapone treatment and placebo in the primary or imaging outcomes. However, there were significant differences between RBANS total scores (p < 0.01), NPI-Q total scores (p = 0.04), and CGI total scores (p = 0.035) between treatment conditions which were driven by differences between baseline and tolcapone conditions. Further, there was a trend toward significance between tolcapone and placebo on the CGI (p = 0.078).
Further study of COMT inhibition and related approaches with longer duration of treatment and larger sample sizes in frontotemporal lobar degeneration-spectrum disorders may be warranted.
目前，对于行为变异额颞叶痴呆（bvFTD）患者的认知或行为症状，尚无针对疾病的治疗方法。
确定托卡朋（一种儿茶酚-O-甲基转移酶（COMT）的特异性抑制剂）对 bvFTD 患者的疗效。
在两个研究地点进行的这项随机、双盲、安慰剂对照、交叉研究中，我们检查了托卡朋对 28 名患有 bvFTD 的成年门诊患者的影响。主要结果是 N-back 认知测试的反应时间。作为一种影像学结果，我们检查了在 N-back 测试中，安慰剂与托卡朋组之间静息血氧水平依赖（BOLD）功能磁共振成像（fMRI）信号强度的差异。次要结果包括使用重复性成套神经心理状态评估量表（RBANS）、神经精神问卷-问卷（NPI-Q）和临床总体印象量表（CGI）评估认知表现和行为障碍的措施。
托卡朋耐受性良好，没有患者退出。托卡朋治疗期间最常见的与治疗相关的不良事件是肝酶升高（21%）。在主要或影像学结果方面，托卡朋治疗与安慰剂治疗之间没有显著差异。然而，在 RBANS 总分（p<0.01）、NPI-Q 总分（p=0.04）和 CGI 总分（p=0.035）之间存在显著差异，这些差异是由治疗条件下的基线与托卡朋条件之间的差异驱动的。此外，CGI 方面托卡朋与安慰剂之间存在显著趋势（p=0.078）。
可能需要在额颞叶变性谱障碍中进行更长时间的治疗和更大样本量的 COMT 抑制和相关方法的进一步研究。
