A Japanese herbal medicine termed "Kami-Umtan-To (KUT)" was first described in Japanese literature in 1626, KUT consists of 13 different herbs, and it has been used for a long time in the treatment of a variety of neuropsychiatric problems including neurosis and insomnia. Recently, Yabe et al. have demonstrated that KUT increased both choline acetyltransferase (ChAT) and nerve growth factor 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 for brain lesioned and aged rats. KUT significantly improved the survival rate, and increased the number of ChAT-positive neurons in aged rats. Here, we report a 12-month open clinical trial of KUT and combination of estrogen, vitamin E and NSAID to aim at slowing down the progression of Alzheimer's disease (AD). Twenty AD patients (MMSE score: 18.6 +/- 5.8) received extracts from original KUT herbs, and 7AD patients (MMSE score: 21.3 +/- 2.8) were placed on the combination therapy. Rate of cognitive decline as measured by change in MMSE score per year was significantly slower (p = 0.04, ANOVA) in the KUT group (1.4 points) and the combination group (0.4 points) as compared to 4.1 points in 32 control AD patients (MMSE score: 20.8 +/- 5.6) who received no medicines for AD. Any of CSF measures including tau. and A beta 1-42 did not differ significantly after KUT therapy. The efficacy of the KUT therapy was most obvious at 3 months. Our results suggest that traditional Japanese herbal medicine(s) may serve a new interventional strategy for AD.