BUCM Neurology Centre at Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China.
Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China.
Chin J Integr Med. 2019 Aug;25(8):565-573. doi: 10.1007/s11655-019-3066-y. Epub 2019 May 7.
In order to solve the problem of long-term (>9 months) efficacy in the treatment of Alzheimer's disease (AD) by conventional therapy (CT), a staged and multiply-targeted sequential therapy based on the evolvement of patterns (STEP) was developed. Its main innovations include: (1) the time order of evolution of patterns defined by Chinese medicine (CM) in AD was found, that is, "the orderly pattern evolution starting from Shen (Kidney) deficiency, progressing to phlegm, stasis and fire, and worsening to severe toxin as well as functional collapse"; (2) the cascade hypothesis of Shen deficiency in AD and its sequential therapy based on Shen-reinforcing was proposed, that is, "reinforcing Shen in the early stage and throughout the whole process, resolving phlegm, activating blood and purging fire in the middle stage, detoxifying and replenishing vitality to stop the collapse in the advanced stage", and through meta-analysis, clinical drug use was optimized, thus the leap from "inferential selection" to "evidence-based selection" was realized; (3) the STEP regimen combined with CT maintained cognitive and behavioral stability in AD patients for at least 12 months, with cognitive enhancement and behavioral synergy after 9 months, and cognitive benefit was superior to CT at 9, 12, 15, 18, 21, and 24 months, respectively. The 2-year cognitive improvement rate was increased by 25.64% (P=0.020) and the cognitive deterioration rate was decreased by 48.71% (P=0.000). Among them, the cognitive and functional benefits of Shen-reinforcing therapy for very early AD (350 cases) for 1 year were better than the placebo (P<0.001), and the dementia conversion rate was reduced by 8.85% (P=0.002). The behavioral symptomatic relief of patients with vascular dementia received fire-purging therapy (540 cases) was superior to those received CT (P=0.016). These data suggested that the STEP regimen has synergistic effects on CTs at least in terms of cognitive benefit, and the earlier the use, the greater the benefit will have. Therefore, the STEP regimen should be considered as one of the clinical options, particularly for the dearth of effective pharmaceutical or immunological interventions that are currently available for AD.
为了解决传统疗法（CT）治疗阿尔茨海默病（AD）长期（>9 个月）疗效的问题，开发了一种基于模式演变的分阶段和多靶点序贯治疗（STEP）。其主要创新点包括：（1）发现了中医（CM）定义的 AD 模式演变的时间顺序，即“从肾虚开始，有序模式演变，进展为痰、瘀、火，加重为严重毒素以及功能衰竭”；（2）提出了 AD 肾虚级联假说及其基于补肾的序贯治疗，即“早期和全程补肾，中期化痰、活血、泻火，晚期解毒、补气止衰”，并通过荟萃分析优化临床用药，实现了从“推理选择”到“证据选择”的飞跃；（3）STEP 方案联合 CT 可使 AD 患者认知和行为稳定至少 12 个月，9 个月后认知增强和行为协同，9、12、15、18、21 和 24 个月时认知获益优于 CT，2 年认知改善率提高 25.64%（P=0.020），认知恶化率降低 48.71%（P=0.000）。其中，补肾治疗非常早期 AD（350 例）1 年的认知和功能获益优于安慰剂（P<0.001），痴呆转化率降低 8.85%（P=0.002）。接受泻火治疗的血管性痴呆患者（540 例）的行为症状缓解优于 CT（P=0.016）。这些数据表明，STEP 方案至少在认知获益方面对 CT 具有协同作用，且越早使用获益越大。因此，STEP 方案应被视为临床选择之一，特别是对于目前 AD 缺乏有效药物或免疫干预措施的情况。
