Bredesen Dale E
Mary S. Easton Center for Alzheimer's Disease Research, Department of Neurology, University of California, Los Angeles, CA 90095. Buck Institute for Research on Aging, Novato, CA 94945.
Aging (Albany NY). 2014 Sep;6(9):707-17. doi: 10.18632/aging.100690.
This report describes a novel, comprehensive, and personalized therapeutic program that is based on the underlying pathogenesis of Alzheimer's disease, and which involves multiple modalities designed to achieve metabolic enhancement for neurodegeneration (MEND). The first 10 patients who have utilized this program include patients with memory loss associated with Alzheimer's disease (AD), amnestic mild cognitive impairment (aMCI), or subjective cognitive impairment (SCI). Nine of the 10 displayed subjective or objective improvement in cognition beginning within 3-6 months, with the one failure being a patient with very late stage AD. Six of the patients had had to discontinue working or were struggling with their jobs at the time of presentation, and all were able to return to work or continue working with improved performance. Improvements have been sustained, and at this time the longest patient follow-up is two and one-half years from initial treatment, with sustained and marked improvement. These results suggest that a larger, more extensive trial of this therapeutic program is warranted. The results also suggest that, at least early in the course, cognitive decline may be driven in large part by metabolic processes. Furthermore, given the failure of monotherapeutics in AD to date, the results raise the possibility that such a therapeutic system may be useful as a platform on which drugs that would fail as monotherapeutics may succeed as key components of a therapeutic system.
本报告描述了一种新颖、全面且个性化的治疗方案，该方案基于阿尔茨海默病的潜在发病机制，涉及多种旨在实现神经退行性变代谢增强（MEND）的治疗方式。首批使用该方案的10名患者包括患有与阿尔茨海默病（AD）相关的记忆丧失、遗忘型轻度认知障碍（aMCI）或主观认知障碍（SCI）的患者。10名患者中有9名在3至6个月内开始出现主观或客观的认知改善，唯一未改善的是一名晚期AD患者。其中6名患者在就诊时不得不停止工作或在工作中遇到困难，而所有患者都能够恢复工作或继续工作，且工作表现有所改善。这些改善一直持续，目前患者从初始治疗开始的最长随访时间为两年半，且持续显著改善。这些结果表明有必要对该治疗方案进行更大规模、更广泛的试验。结果还表明，至少在病程早期，认知衰退可能在很大程度上由代谢过程驱动。此外，鉴于迄今为止AD单一疗法的失败，这些结果增加了这样一种可能性，即这种治疗系统可能作为一个平台有用，在该平台上作为单一疗法会失败的药物作为治疗系统的关键组成部分可能会成功。
