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. 2018 Dec 6;12(12):CD010284.
doi: 10.1002/14651858.CD010284.pub2.

Traditional Chinese herbal medicine for vascular dementia

Edwin Sy Chan  1 , Dianne T Bautista, Yanan Zhu, Yong You, Jian Ting Long, Wenyun Li, Christopher Chen
Affiliations

Traditional Chinese herbal medicine for vascular dementia

Edwin Sy Chan et al. Cochrane Database Syst Rev. .

Abstract

Background: Traditional Chinese herbal medicine (TCHM) is widely used for treating vascular dementia (VaD) in China. Recent studies of a number of TCHMs have demonstrated in vitro biological activity and therapeutic effects in animals, but the published clinical evidence has not been systematically appraised.

Objectives: To evaluate the efficacy and safety of TCHMs listed in either the Chinese Pharmacopoeia (CP) or the Chinese National Essential Drug List (NEDL) that are used to treat VaD. A secondary aim was to identify promising TCHMs for further clinical research.

Search methods: We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group's Specialised Register (on 14 March 2018) and also several Chinese biomedical databases: the Chinese Biological Medicine Database (January 1979 to May 2015), Wanfang database (January 1998 to May 2015), Chongqing VIP Information Co. Ltd or Weipu (January 1998 to May 2015) and the Chinese National Knowledge Infrastructure (January 1979 to May 2015).

Selection criteria: We included randomised controlled trials (RCTs) of TCHMs compared to placebo, to Western medicine (WM) or to routine therapy for VaD risk factors. Eligible participants were men and women aged 18 years and above, diagnosed with VaD by any of the following four criteria: (1) Diagnostic and Statistical Manual of Mental Disorders (DSM) versions III, III-R, IV, IV-TR; (2) National Institute of Neurological Disorders and Stroke (NINDS-AIREN); (3) International Classification of Diseases 9 or 10; (4) the Hachinski or the Modified Hachinski Ischaemic Score. We required the use of an imaging technique to differentiate VaD from other dementias. We excluded (1) trials with participants diagnosed with mixed dementia or those that did not use an imaging technique to ascertain VaD; (2) trials of NEDL-listed Gingko biloba or Huperzine A as experimental interventions, to avoid duplication of existing Cochrane Reviews; (3) trials using acupuncture alone as the experimental intervention; (4) trials using another CP- or NEDL-listed TCHM (except for Huperzine A and Gingko which are popular in Western practice) as the control intervention; and (5) trials using purely non-pharmacological interventions as the control intervention unless explicitly described as 'routine therapy for VaD risk factors'.

Data collection and analysis: We assessed the risks of bias using the Cochrane 'Risk of bias' tool and adapted the Outcome Reporting Bias in Trials (ORBIT) classification system for outcome reporting bias. We assessed TCHM effects on five clinically important outcomes: cognition, global performance, safety, activities of daily living and behaviour and summarised the effects using mean differences for continuous outcomes and risk ratios or risk differences for binary outcomes. We stratified the studies into those that estimated the TCHM versus 'no treatment' effect and those that estimated the TCHM versus the WM effect, with further stratification by the specific TCHM tested or by one of the four modes of action. We pooled using a random-effects model. Due to substantial clinical and design heterogeneity, we did not estimate an 'overall TCHM effect'.

Main results: We only found studies (47 studies, 3581 participants) for 18 of the 29 eligible TCHMs as defined by our inclusion criteria. All were superiority trials conducted in China between 1997 and 2013, with most employing a two-arm parallel design with sample sizes ranging from 26 to 240 and a median treatment duration of 12 weeks (range: 2 to 24 weeks).We found that reporting and trial methodology were generally poor; in particular, there was a lack of information on randomisation, an absence of blinding of participants and outcome assessors and incomplete reporting of adverse events (AEs). None of the 30 trials published from 2007 onwards adopted the CONSORT recommendations for reporting RCTs of herbal interventions.We found seven TCHMs which each had potentially large benefits in studies estimating the TCHM versus 'no treatment' effect and in studies estimating the TCHM versus the WM effect. Two TCHMs (NaoXinTong and TongXinLuo) were common to both groups. Three of these TCHMs - Nao XinTong, NaoMaiTai and TongXinLuo - had the strongest evidence to justify further research. Two TCHMs (NaoMaiTai and TongXinLuo) had a 5% or more increased risk of AEs compared to the 'no Treatment' control, but the quality of this evidence was poor.

Authors' conclusions: We found moderate- to very low-quality evidence of benefit and harm of TCHMs for VaD. Methodological inadequacies need to be addressed by better conducted and reported trials. We identified NaoMaiTai, NaoXinTong and TongXinLuo as warranting special research priority.

PubMed Disclaimer

Conflict of interest statement

Edwin SY Chan: None known Dianne T Bautista: None known Yanan Zhu: None known Yong You: None known Jian Ting Long: None known Wenyun Li: None known Christopher Chen: None known

Figures

1
1
Study flow diagram.
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1 TCHM versus 'no treatment' (Subgroup: specific TCHM and comparators), Outcome 1 Cognition‐MMSE.
1.2
1.2. Analysis
Comparison 1 TCHM versus 'no treatment' (Subgroup: specific TCHM and comparators), Outcome 2 Cognition‐HDS.
1.3
1.3. Analysis
Comparison 1 TCHM versus 'no treatment' (Subgroup: specific TCHM and comparators), Outcome 3 Cognition‐ADAS‐Cog.
1.4
1.4. Analysis
Comparison 1 TCHM versus 'no treatment' (Subgroup: specific TCHM and comparators), Outcome 4 Global performance.
1.5
1.5. Analysis
Comparison 1 TCHM versus 'no treatment' (Subgroup: specific TCHM and comparators), Outcome 5 AEs.
1.6
1.6. Analysis
Comparison 1 TCHM versus 'no treatment' (Subgroup: specific TCHM and comparators), Outcome 6 Activities of Daily Living.
2.1
2.1. Analysis
Comparison 2 TCHM versus 'no treatment' (Subgroup: TCHM primary mode of action), Outcome 1 Cognition ‐ MMSE.
2.2
2.2. Analysis
Comparison 2 TCHM versus 'no treatment' (Subgroup: TCHM primary mode of action), Outcome 2 Cognition ‐ HDS.
2.3
2.3. Analysis
Comparison 2 TCHM versus 'no treatment' (Subgroup: TCHM primary mode of action), Outcome 3 Cognition ‐ ADAS‐Cog.
2.4
2.4. Analysis
Comparison 2 TCHM versus 'no treatment' (Subgroup: TCHM primary mode of action), Outcome 4 Global performance.
2.5
2.5. Analysis
Comparison 2 TCHM versus 'no treatment' (Subgroup: TCHM primary mode of action), Outcome 5 AEs.
2.6
2.6. Analysis
Comparison 2 TCHM versus 'no treatment' (Subgroup: TCHM primary mode of action), Outcome 6 Activities of Daily Living.
3.1
3.1. Analysis
Comparison 3 TCHM versus WM (Subgroup: common TCHMs), Outcome 1 Cognition‐MMSE.
3.2
3.2. Analysis
Comparison 3 TCHM versus WM (Subgroup: common TCHMs), Outcome 2 Cognition‐HDS.
3.3
3.3. Analysis
Comparison 3 TCHM versus WM (Subgroup: common TCHMs), Outcome 3 Cognition‐ADAS‐Cog.
3.4
3.4. Analysis
Comparison 3 TCHM versus WM (Subgroup: common TCHMs), Outcome 4 Global performance.
3.5
3.5. Analysis
Comparison 3 TCHM versus WM (Subgroup: common TCHMs), Outcome 5 AEs.
3.6
3.6. Analysis
Comparison 3 TCHM versus WM (Subgroup: common TCHMs), Outcome 6 Activities of Daily Living.
3.7
3.7. Analysis
Comparison 3 TCHM versus WM (Subgroup: common TCHMs), Outcome 7 Behaviour.
4.1
4.1. Analysis
Comparison 4 TCHM versus WM (Subgroup: TCHM primary mode of action), Outcome 1 Cognition ‐ MMSE.
4.2
4.2. Analysis
Comparison 4 TCHM versus WM (Subgroup: TCHM primary mode of action), Outcome 2 Cognition ‐ HDS.
4.3
4.3. Analysis
Comparison 4 TCHM versus WM (Subgroup: TCHM primary mode of action), Outcome 3 Cognition ‐ ADAS‐Cog.
4.4
4.4. Analysis
Comparison 4 TCHM versus WM (Subgroup: TCHM primary mode of action), Outcome 4 Global performance.
4.5
4.5. Analysis
Comparison 4 TCHM versus WM (Subgroup: TCHM primary mode of action), Outcome 5 AEs.
4.6
4.6. Analysis
Comparison 4 TCHM versus WM (Subgroup: TCHM primary mode of action), Outcome 6 Activities of Daily Living.
4.7
4.7. Analysis
Comparison 4 TCHM versus WM (Subgroup: TCHM primary mode of action), Outcome 7 Behaviour.
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References

References to studies included in this review

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Mayu 2013 {published data only}
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Wanglinglin 2005 {published data only}
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Wengyinghong 2011 {published data only}
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Wuhongbin 2007 {published data only}
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Xujingqiang 2007 {published data only}
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Xuke 2011 {published data only}
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Yanyongxing 2007 {published data only}
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Yaoxinsheng 2011 {published data only}
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Yudecai 2008 {published data only}
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Zhangjianping 2006 {published data only}
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Zhangjinsheng 2003 {published data only}
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Zhangtao 2000 {published data only}
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Zhangyoutai 2012 {published data only}
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Zhangyujin 2002 {published data only}
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Zhengtaolin 2013 {published data only}
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Zhoulongshou 2013 {published data only}
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Zhouqiang 2003 {published data only}
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Zhouwei 2009 {published data only}
    1. Zhou W, Wu YB, Xu XR. Clinical observation on NaoXinTong capsule for the treatment of vascular dementia [脑心通胶囊治疗血管性痴呆患者临床观察]. Shandong Medical Journal 2009;49(8):99‐100.
Zhufengmei 2003 {published data only}
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References to studies excluded from this review

Caijing 2003 {published data only}
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    1. Deng PR, Su YJ. Clinical observation of ZhuYuTongMai capsule for the treatment of multi‐infarct dementia [逐瘀通脉胶囊治疗多梗死性痴呆的临床观察]. Guide of China Medicine 2011;9(7):131‐2.
Duguiyou 2003 {published data only}
    1. Du GY, Zhu XC, Zhao JJ, Wang J, Tian JZ, Liu XF, et al. Clinical observation of TianZhi granule for the treatment of senile vascular dementia [天智颗粒治疗老年血管性痴呆临床观察]. China Journal of Chinese Materia Medica 2003;28(1):73‐7. - PubMed
Fengjiong 2010 {published data only}
    1. Feng J, Zang M. Clinical study on LiuWeiDiHuangWan for the treatment of mild and moderate vascular cognitive impairment [六味地黄丸治疗轻中度血管性认知障碍的临床研究]. Clinical Journal of Traditional Chinese Medicine April 2010;22(2):131‐2.
Gaoqi 2007 {published data only}
    1. Gao Q. Clinical study of ShuMaiYiNao capsule for the treatment of 58 cases of vascular dementia [疏脉益脑胶囊治疗血管性痴呆58例临床研究]. Journal of Gansu College of TCM 2007;24(5):14‐6.
Gongxuhai 2004 {published data only}
    1. Gong XH, Yang FM, He XH, Li XS, Zhang JH, Yu RL, et al. The efficacy of ShenQiFuZheng injection for vascular dementia [参芪扶正注射液治疗血管性痴呆的疗效观察]. Chinese Journal for Clinicians 2004;32(6):37‐8.
Guolei 2009 {published data only}
    1. Guo L, Feng HS. Efficacy of TianZhi Granule combined with Nunodipine in the treatment of vascular dementia [天智颗粒联合尼莫地平治疗老年血管性痴呆的临床疗效观察]. Medical Information August 2009;22(8):4‐6.
Guoqiang 2015 {published data only}
    1. Guo Q, Cao WZ, Zhao H, Zhu YX, Yang DD, Zhong S, et al. Effect of Sancaijiangtang on plasma nitric oxide and endothelin‐1 levels in patients with type 2 diabetes mellitus and vascular dementia: a single‐blind randomized controlled trial. Journal of Traditional Chinese Medicine 2015;35(4):375‐80. - PubMed
Guozhisheng 2009 {published data only}
    1. Guo ZS, Jin J, Jia JX. Clinical observation of DanHong injection for the treatment of 42 cases of vascular dementia [丹红注射液治疗气滞血瘀型血管性痴呆42例疗效观察]. Chinese Journal of Practical Nervous Diseases 2009;12(1):59‐61.
Hejinbo 2012 {published data only}
    1. He JB, Jin J. Clinical research of ShenXiong glucose injection treating vascular dementia and influence on AVP [参芎葡萄糖注射液治疗血管性痴呆的疗效及对AVP的影响]. Chinese Journal of Experimental Traditional Medical Formulae 2012;18(21):306‐10.
Hejun 2006 {published data only}
    1. He J, Cai YY, Wang HW, Zang DJ, Tan XM. Danshen injection with cerebrolysin for vascular dementia [丹参联合脑神经生长素对血管性痴呆病人智能状况的改善]. Chinese Journal of Integrative Medicine on Cardio‐/Cerebrovascular Disease February 2006;4(2):104‐5.
Hejun 2010 {published data only}
    1. He J, Zang DJ, Zhai J. DanHong injection and Vinpocetine injection improve intelligence of vascular dementia patients in clinic [丹红注射液联合长春西汀对于老年血管性痴呆患者智能康复的临床研究]. Journal of Chengdu University of TCM 2010;33(1):32‐4.
Houderen 2009 {published data only}
    1. Hou DR, Chen K, Wang Y, Tian Y, Wan S, Tang JC, et al. Efficacy and mechanism of Butylphthalide for the treatment of vascular dementia [丁苯酞治疗血管性痴呆的疗效和作用机制]. Journal of Southern Medical University 2009;29(3):574‐5,8.
Huangliwu 2006 {published data only}
    1. Huang LW, Yuan JF, Wu Y, Mai LS, Pan HZ. Mongolian milkvetch root injection for improving the cognitive disorder of chronic cerebral ischaemic patients [黄芪注射液改善慢性脑缺血患者认知功能障碍的效应]. Chinese Journal of Clinical Rehabilitation 2006;10(43):34‐6.
Jiajianping 2014 {published and unpublished data}
    1. Jia Jianping (study leader). Phase 2 clinical trial of SaiLuoTong capsule for vascular dementia：A 26‐week, multicentre, randomized, double‐blind, placebo‐controlled trial with a 26‐week open‐label extension. www.chictr.org/en/proj/show.aspx?proj=6441 (first received 7 May 2014). [Trial registration: ChiCTR‐TRC‐14004613]
Jiajianping 2016 {published data only}
    1. Jia JP, Wei CB, Liang JH, Zhou AH, Zuo XM, Song HQ, et al. The effects of DL‐3‐n‐butylphthalide in patients with vascular cognitive impairment without dementia caused by subcortical ischaemic small vessel disease: A multicentre, randomized, double‐blind, placebo‐controlled trial. Alzheimer's & Dementia 2016;12(2):89‐99. - PubMed
Jianghaipeng 2010 {published data only}
    1. Jiang HP, Kuang SX. Early efficacy observation of NaoTong capsule for the treatment of vascular dementia [脑通胶囊治疗血管性痴呆早期疗效观察]. Journal of Emergency in Traditional Chinese Medicine 2010;19(10):1669‐70,78.
Liguolin2013 {published data only}
    1. Li GL. Clinical study on FuFangDanShen injection combined with HuangQi injection for the treatment of vascular dementia [复方丹参注射液与黄芪注射液联合治疗血管性痴呆临床研究]. Nei Mongol Journal of Traditional Chinese Medicine 2013;32(19):33‐4.
Lihong2013 {published data only}
    1. Li H. Clinical study on FuFangDanShen injection combined with HuangQi injection for the treatment of vascular dementia [复方丹参注射液联合黄芪注射液治疗血管性痴呆临床研究]. China Health Industry 2013;10(5):67.
Lishilin 2011 {published data only}
    1. Li SL. Clinical observation of TianZhi granule for the treatment of 62 cases of vascular dementia [天智颗粒治疗血管性痴呆62例临床观察]. Chinese Journal of Practical Nervous Diseases 2011;14(13):35‐7.
Liuguirong 2009 {published data only}
    1. Liu GR. Efficacy observation on TianZhi granule for the treatment of mild and moderate vascular dementia [天智颗粒治疗轻度及中度血管性痴呆疗效观察]. Chinese Community Doctors 2009;19:119.
Liuq 2016 {published data only}
    1. Liu Q, Wang X‐J, Zhang Z‐C, Xue R, Li P, Li B. Neuroprotection against vascular dementia after acupuncture combined with donepezil hydrochloride: P300 event related potential. Neural Regeneration Research 2016;11(3):460‐4. - PMC - PubMed
Liuwei 2009 {published data only}
    1. Liu W. Clinical observation of Butylphthalide for the treatment of vascular dementia [丁苯酞治疗血管性痴呆临床观察]. Clinical Focus 2009;24(17):1533‐4.
Liuxifei 2007 {published data only}
    1. Liu XF, Du J, Cai J, Liu XF, Wang LL, Xu GL, et al. Clinical observation of KangXin capsule for the treatment of vascular dementia [康欣胶囊治疗老年肾虚血瘀型血管性痴呆的临床观察]. Journal of Nanjing TCM University 2007;23(3):148‐51.
Liweiwei 2013 {published data only}
    1. Li WW, Wang MC, Yu PP, Wang Y. Observation on clinical effects of Oxiracetam capsule and SanQiTongShu capsule in treating vascular dementia [奥拉西坦联合三七通舒治疗血管性痴呆的临床疗效观察]. Western Journal of Traditional Chinese Medicine 2013;26(2):81‐3.
Liying 2009 {published data only}
    1. Li Y, Du XH, Zhao XW. Clinical efficacy of ShuXueTong injection for vascular dementia [疏血通注射液治疗血管性痴呆的临床观察]. China Pharmacy 2009;20(33):2620‐1.
Liyuehua 2011 {published data only}
    1. Li YH. Clinical observation of PeiYuanTongNao capsule for the treatment of vascular dementia [培元通脑胶囊治疗老年血管性痴呆的临床观察]. Seek Medical And Ask The Medicine 2011;9(6):143,110.
Majingmei 2006 {published data only}
    1. Ma JM. The efficacy of ShenMai injection for patients with vascular dementia [参麦注射液治疗血管性痴呆的疗效观察]. Chinese Journal of Practical Nervous Diseases 2006;9(1):89.
NCT02641886 {unpublished data only}
    1. Zhang YL. The study of Jian Pi Yi Shen Hua Tan granules in cognitive impairment after acute cerebral infarction. clinicaltrials.gov/show/NCT02641886 (first received 30 December 2015). [NCT02641886]
NCT02693795 {unpublished data only}
    1. Mao S. Baduanjin exercise prevents post‐myocardial infarction left ventricular remodeling (BE‐PREMIER Trial). clinicaltrials.gov/show/NCT02693795 (first received 29 February 2016). [NCT02693795] - PubMed
NCT02728180 {unpublished data only}
    1. Gao Y. Xingnaojing for Moderate‐to‐severe Acute Ischaemic Stroke (XMAS). clinicaltrials.gov/show/NCT02728180 (first received 5 April 2016). [NCT02728180]
NCT02802072 {unpublished data only}
    1. Meng Ji. Enterprise stent implantation in the treatment of carotid artery stenosis with ischaemic stroke. clinicaltrials.gov/show/NCT02802072 (first received 16 June 2016). [NCT02802072]
Qinfusheng 2009 {published data only}
    1. Qin FS, Liu XM. Clinical observation on DanHong injection for the treatment of 68 cases of vascular dementia [丹红注射液治疗血管性痴呆68例临床观察]. Chinese Journal of Modern Drug Application 2009;3(11):141‐2.
Shidehai 2011 {published data only}
    1. Shi DH, Zhang HT, Zhao MY, He L, Sun Q, Tan JW, et al. Clinical research of DanHong injection combined with piracetam on vascular dementia [丹红注射液联合吡拉西坦治疗血管性痴呆临床研究]. Clinical Journal of Medical Officers 2011;39(1):43‐5.
Shiguangxia 2014 {published data only}
    1. Shi GX, Liu CZ, Guan W, Wang ZK, Wang L, Xiao C. Effects of acupuncture on Chinese medicine syndromes of vascular dementia. Chinese Journal of Integrative Medicine 2014;20(9):661‐6. - PubMed
Shihaiting 2011 {published data only}
    1. Shi HT. Efficacy observation on TianZhi granule for the treatment of vascular dementia [天智颗粒治疗血管性痴呆疗效观察]. Chinese Journal of Integrative Medicine on Cardio‐/Cerebrovascular Disease 2011;9(8):955‐6.
Sunmeibo 2005 {published data only}
    1. Sun MB, Chen XZ. Effect of tetramethylpyrazine in improving cognitive function and content of arginine vasopressin in plasma and cerebrospinal fluid of patients with vascular dementia [川芎嗪对血管性痴呆患者认知功能及血浆和脑脊液中精氨酸加压素含量的提高效应]. Chinese Journal of Clinical Rehabilitation 2005;9(24):194‐6.
Taogenyu 2004 {published data only}
    1. Tao GY. Clinical research on treatment of vascular dementia with Brain‐refreshing Pill [醒脑丸治疗血管性痴呆临床研究]. Journal of Shaanxi College of Traditional Chinese Medicine 2004;27(1):5‐7.
Wangdongming 2003 {published data only}
    1. Wang DM, Li AM, Yuan YG, Wang L, Yi RB, Lin YJ, et al. Study of effect of treatment of vascular dementia on event related potential by Tzepao Sanpien pills [三鞭丸治疗血管性痴呆对事件相关电位影响的研究]. Journal of Chinese Clinical Medicine 2003;4(7):30‐1.
Wangguang 2006 {published data only}
    1. Wang G. Clinical study of YangXueQingNao granule and needing in treating vascular dementia [养血清脑颗粒配合针刺治疗血管性痴呆的临床研究]. Hebei Medicine 2006;12(2):131‐3.
Wanglixin 1999 {published data only}
    1. Wang LX, Liu GH, Yan RP, Zheng XL, Li LH. The treatment of XingNaoJing injection for 39 patients with vascular dementia [醒脑静治疗血管性痴呆39例临床分析]. Chinese Journal of Information on Traditional Chinese Medicine 1999;6(5):54‐5.
Wanglixin 2000 {published data only}
    1. Wang LX, Li LH, Liu GH, Ma ZJ, Ma YQ. Effect of XingNaoJing injection and hyperbaric oxygen on intelligence and apolipoprotein in treating vascular dementia [醒脑静注射液联合高压氧对血管性痴呆患者智能和载脂蛋白的影响]. Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2000;7(3):158‐60.
Wangsongzhen 2002 {published data only}
    1. Wang SZ, Zhang YJ. XingNaoJing injection for 31 patients with dementia [醒脑静注射液治疗痴呆症31 例]. TCM Research 2002;15(6):32.
Wangyankuo 2010 {published data only}
    1. Wang YK, Sun LP, Zhang M. Butylphthalide soft capsules joint donepezil treatment of vascular dementia in clinical efficacy [丁苯酞软胶囊联合多奈哌齐治疗血管性痴呆临床疗效观察]. Journal of Brain and Nervous Diseases 2010;18(5):387‐90.
Wanjifeng 2012 {published data only}
    1. Wan JF, Lu Y, Xu YY, Liu CC, Chang SJ, Zhou WD. Clinical effect of LeMai granule combined with Oxiracetam on treatment of vascular dementia [乐脉颗粒联合奥拉西坦治疗血管性痴呆疗效观察]. Chinese Journal of General Practice 2012;10(1):31,82.
Weichunhua 2013 {published data only}
    1. Wei CH. Clinical observation on TianZhi granule for the treatment of vascular dementia [天智颗粒治疗血管性痴呆的临床观察]. Chinese Journal of Practical Nervous Diseases 2013;16(16):83‐4.
Wutianchen 2012 {published data only}
    1. Wu TC, Xu RQ. Clinical observation on HuanShaoDan for the treatment of 32 patients with vascular dementia [还少丹加减治疗血管性痴呆32例临床观察]. Hunan Journal of Traditional Chinese Medicine 2012;28(5):43‐4.
Xieyongyong 1996 {published data only}
    1. Xie YY. FuFangDanShen injection for the treatment of 15 cases of vascular dementia [复方丹参注射液治疗血管性痴呆15例]. Zhejiang Journal of Traditional Chinese Medicine 1997;4:156.
Xudongmei 2009 {published data only}
    1. Xu DM, Zhang YL, Ma XQ. Clinical efficacy observation on YangXueQingNao granule for the treatment of 60 cases of vascular dementia [养血清脑颗粒治疗血管性痴呆60例疗效观察]. Chinese Journal of Practical Nervous Diseases 2009;12(19):64.
Xuhaibo 2007 {published data only}
    1. Xu HB, Chen H. Clinical observation of TongXinLuo capsule for vascular dementia [通心络胶囊联合氢麦角碱治疗血管性痴呆效果观察]. Medical Journal of Communications 2007;21(4):390‐1.
Yangxiaoli 2011 {published data only}
    1. Yang XL. Butylphthalide soft capsules and nimodipine treatment of vascular dementia after stroke effect assessment (Master Degree Thesis) [丁苯酞软胶囊与尼莫地平治疗卒中后血管性痴呆的疗效评价]. HeBei Medical University 2008.
Yinjunxiang 2000 {published data only}
    1. Yin JX, Tian JZ, Yang CZ, Liu H. A single‐blind controlled study of Jian Nao An( JNA) treatment of the syndrome of deficiency of the kidney and phlegm turbidness of vascular dementia [健脑安治疗血管性痴呆肾虚痰浊证的单盲对照研究]. Chinese Journal of Natural Medicine 2000;2(4):212‐5.
Yufangchen 1999 {published data only}
    1. Yu FC, Yu MQ, Song JC. The efficacy of HuaTuoZaiZao pill for age‐related dementia [华佗再造丸治疗老年期痴呆205例疗效观察]. Journal of Chinese Medicinal Materials 1999;22(5):269‐70.
Zhangchunyan 2009 {published data only}
    1. Zhang CY, Li YP, Li MX, Wang RL. Efficacy observation on TianMaSu for the treatment of vascular dementia [天麻素治疗血管性痴呆疗效观察]. Journal of Emergency in Traditional Chinese Medicine 2009;18(8):1220‐1.
Zhangdaodong 1999 {published data only}
    1. Zhang DD, Yang YQ. MaiLuoNing injection for 64 patients with vascular dementia [脉络宁注射液治疗脑血管性痴呆64例]. Journal of PLA Junior College of Medicine 1999;27(2):110‐2.
Zhangfeng 2011 {published data only}
    1. Zhang F, He L, Zhu C, Zhu QF. HuanShaoDan for the treatment of 60 cases of vascular dementia [还少丹加减治疗血管性痴呆60例]. GuangMing Chinese Medicine 2011;26(8):1591‐2.
Zhangxuehong 2013 {published data only}
    1. Zhang XH. Efficacy observation on Butylphthalide soft capsule combined with Donepezil for the treatment of vascular dementia [丁苯酞软胶囊联合多奈哌齐治疗血管性痴呆疗效观察]. Chinese Journal of Practical Nervous Diseases 2013;16(3):70‐1.
Zhangyunling 2016 {unpublished data only}
    1. Zhang YL. An fMRI Study of the Efficacy and Safety of Jianpi Yishen Huatan Granules for Cognitive Impairment After Acute Cerebral Infarction. clinicaltrials.gov 2016; Vol. ClinicalTrials.gov Identifier: NCT02752867.
Zhangzhipeng2014 {published data only}
    1. Zhang ZP, Gao JF, Dong SX, Zhang RK, Wang YL, Li HS. Clinical observation on YangXueQingNao granule for the treatment of vascular dementia [养血清脑颗粒治疗血管性痴呆临床观察]. Clinical Journal of Clinical Rational Drug Use 2014;7(11A):48‐9.
Zhaoyan 2010 {published data only}
    1. Zhao Y. Clinical observation of DanHong injection treatment of vascular dementia [丹红注射液治疗血管性痴呆的临床观察]. Journal of China Traditional Chinese Medicine Information 2010;2(10):113.
Zhaoyiming 1994 {published data only}
    1. Zhao YM, Wu XS. Observation of MaiLuoNing for 36 patients with vascular dementia [脉络宁治疗血管性痴呆36例疗效观察]. Journal of Zheijiang College of TCM 1994;18(6):19‐20.
Zhaoyun 2010 {published data only}
    1. Zhao Y, Li ZX. HuanShaoDan for the treatment of 80 cases of vascular dementia [还少丹治疗肝肾亏虚型血管性痴呆80例]. Henan Traditional Chinese Medicine 2010;30(4):380‐1.
Zhuaihua 2005 {published data only}
    1. Zhu AH, Tian JZ, Zhong J, Shi J. A clinical study on a randomized, double‐blind control of Tianzhi granules in treatment of the senile vascular dementia [天智颗粒治疗老年人血管性痴呆的随机双盲临床对照研究]. Chinese Journal of Gerontology 2005;12:1435‐8.
Zhuanghuikui 2007 {published data only}
    1. Zhuang HK, Chi YL, Gao HF. Clinical study of HuaZhuoQingNao decoction for vascular dementia [化浊清脑合剂治疗血管性痴呆临床研究]. Journal of Shandong University of TCM 2007;31(1):28‐30.
Zhuning 2011 {published data only}
    1. Zhu N, Zhu HS, Liu HY. Effect of Tianzhi granule combined oxiracetam on mild or moderate vascular dementia [天智颗粒联合奥拉西坦治疗轻中度血管性痴呆临床观察]. Chinese Journal of Practical Nervous Diseases 2011;14(17):29‐31.

References to ongoing studies

NCT01761227 {unpublished data only}
    1. Jinzhou Tian. Efficacy and safety of Fufangdanshen tablets in mild to moderate vascular dementia. ClinicalTrials.gov/show/ NCT01761227 (first received 4 January 2013). [NCT01761227 ]

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