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Sequential Therapy Based on Evolvement of Patterns: A New Model for Treatment of Alzheimer’s Disease

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Abstract

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.

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Authors and Affiliations

  1. BUCM Neurology Centre at Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China

    Jin-zhou Tian, Jing Shi, Jing-nian Ni, Ming-qing Wei & Xue-kai Zhang

  2. Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China

    Ke-ji Chen

  3. Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, 100700, China

    Yong-yan Wang

Authors
  1. Jin-zhou Tian
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  2. Jing Shi
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  3. Jing-nian Ni
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Corresponding author

Correspondence to Jin-zhou Tian.

Additional information

Supported by the National Natural Science Foundation of China (Nos. 81473518, 81573824, 81503625), Changjiang Scholar Program of Ministry of Education of the People’s Republic of China (No. IRT0810), Ministry of Education of the People’s Republic of China (No. B08006), Beijing Science and Technology Commission (No. Z141107002515019), and Beijing Health and Family Planning Commission (No. SF2014-1-4191)

Conflict of interest

The authors have no conflict of interests to declare.

Author Contributions

Tian JZ, Chen KJ and Wang YY are responsible for the overall framework design of this paper. Tian JZ, Shi J and Chen KJ are responsible for the design and evaluation of the clinical trials mentioned in the third part of this paper. Ni JN, Wei MQ and Zhang XK completed the systematic reviews, tables and figures in supplementary appendixes. Tian JZ and Zhang XK wrote the paper. Final manuscript was reviewed by all authors.

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Tian, Jz., Shi, J., Ni, Jn. et al. Sequential Therapy Based on Evolvement of Patterns: A New Model for Treatment of Alzheimer’s Disease. Chin. J. Integr. Med. 25, 565–573 (2019). https://doi.org/10.1007/s11655-019-3066-y

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  • DOI: https://doi.org/10.1007/s11655-019-3066-y

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