Clinical trials of anti-dementia drugs and biological markers

1626年，日本文献中首次描述了日本草药“Kami-Untan-To（KUT）”。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等人已经证明KUT在培养的大鼠脑细胞中在蛋白质和mRNA水平上增加胆碱乙酰转移酶（ChAT）和NGF。此外，同一研究小组还报道了KUT改善基底前脑损伤和老年大鼠被动回避测试的平均潜伏期。KUT能显著提高老龄大鼠的存活率，增加ChAT阳性神经元的数量。在这里，我们报告了12个月的开放临床试验，KUT和雌激素，维生素E和NSAID的组合，旨在减缓AD的进展。20名AD患者（MMSE评分：18.6[-+]5.8）接受原始KUT草药提取物，7名AD患者（MMSE评分：21.3[-+]2.8）接受联合治疗。按组（1.4分）和联合用药组（1.5分）测量的认知下降率与32例对照AD患者（MMSE评分：20.8[-+]5.6）的4.1分相比，后者未接受AD治疗中的试验药物。值得注意的是，CSF-ChAT水平在KUT治疗后显著降低（p=0.005，n=6）。KUT的疗效在3个月时最明显。我们的研究结果表明，传统的日本草药可能为AD的新的干预策略。

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.