Clinical trials of anti-dementia drugs and biological markers

1626年，日本文献首次记载了一种名为“神云丹土”的日本草药。KUT由13种不同的草药组成，长期以来一直用于治疗各种神经精神问题，包括抑郁症和失眠。最近，Yabe等人。研究表明，KUT在培养的大鼠脑细胞中增加了胆碱乙酰转移酶（ChAT）和NGF的蛋白质和mRNA水平。此外，同一研究小组还报道，KUT改善了基底前脑损伤大鼠和老年大鼠被动回避测试的平均潜伏期。KUT显著提高老龄大鼠的存活率，增加chat阳性神经元数量。在这里，我们报告了为期12个月的开放式临床试验，KUT和雌激素，维生素e和非甾体抗炎药的组合旨在减缓AD的进展。20例AD患者（MMSE评分：18.6【±±】5.8）接受原始KUT草药提取物治疗，7例AD患者（MMSE评分：21.3【±±】2.8）接受联合治疗。与未接受任何药物治疗的32例AD对照患者（MMSE评分：20.8【正负】5.6）相比，对照组（1.4分）和联合组（1.5分）的认知衰退率为4.1分。值得注意的是，在KUT治疗后，CSF-ChAT水平显著（p=0.005, n=6）降低。3个月时疗效最明显。我们的研究结果表明，传统的日本草药可能为阿尔茨海默病提供新的干预策略。

A Japanese herbal medicine "Kami-Untan-To (KUT)" was first described in Japanese literature in 1626. KUT is composed of 13 different herbs, and has been used for a long time in the treatment of a variety of neuropsychiatric problems including depression and insomnia. Recently, Yabe et al. Have demonstrated that KUT increased both choline acetyltransferase (ChAT) and NGF at the protein and mRNA levels in cultured rat brain cells. Moreover, the same research group has reported that KUT improved mean latency on passive avoidance test in both basal forebrain lesioned and aged rats. KUT significantly improved the survival rate, and increased the number of ChAT-positive neurons in aged rats. Here, we report 12 months open clinical trials of KUT and a combination of estrogen, vitamin-E and NSAID to aim at slowing down the progression of AD. Twenty AD patients (MMSE score : 18.6【minus-plus】5.8) were receiving extracts from original KUT herbs, and 7 AD patients (MMSE score : 21.3【minus-plus】2.8) were placed on the combination therapy. Rate of cognitive decline as measured by group (1.4 point) and the combination group (1.5 point) as compared to 4.1 point in 32 control AD patient (MMSE score : 20.8【minus-plus】5.6) who received no medicines tested in the therapies for AD. Notably, CSF-ChAT levels were significantly (p=0.005, n=6) reduced following the KUT therapy. The efficacy of the KUT was most obvious at 3-month point. Our results suggest that traditional Japanese herbal medicines may serve a new intervention strategy for AD.