Vascular mild cognitive impairment,Medicine, Chinese traditional,Syndrome,Latent tree analysis," /> Vascular mild cognitive impairment,Medicine, Chinese traditional,Syndrome,Latent tree analysis,"/> Identification and classification of traditional Chinese medicine syndrome types among senior patients with vascular mild cognitive impairment using latent tree analysis
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Journal of Integrative Medicine ›› 2017, Vol. 15 ›› Issue (3): 186-200.doi: 10.1016/S2095-4964(17)60335-2

Special Issue: Traditional Chinese Medicine

• Research Article • Previous Articles     Next Articles

Identification and classification of traditional Chinese medicine syndrome types among senior patients with vascular mild cognitive impairment using latent tree analysis

Chen Fua, Nevin Lianwen Zhangb, Bao-xin Chena, Zhou Rong Chenb, Xiang Lan Jina, Rong-juan Guoa, Zhi-gang Chena, Yun-ling Zhanga   

  1. a Department of Neurology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing 100078,China
    b Department of Computer Science and Engineering, The Hong Kong University of Science and Technology,Hong Kong, China
  • Received:2016-08-30 Accepted:2016-11-07 Online:2017-05-15 Published:2017-05-15
  • Contact: Yun-ling Zhang, MD, Professor; E-mail:
  • Supported by:
    Research on this article was supported by the Hong Kong Research Grants Council under grant NO. 16202515 and 16212516, Guangzhou HKUST Fok Ying Tung Research Institute, China Ministry of Science and Technology TCM Special Research Projects Program under grant No. 200807011, No. 201007002 and No. 201407001-8, Beijing Science and Technology Program under grant No. Z111107056811040, Beijing New Medical Discipline Development Program under grant No. XK100270569, and Project of Beijing University of Chinese Medicine under grant No. 2011-CXTD-23.


To treat patients with vascular mild cognitive impairment (VMCI) using traditional Chinese medicine (TCM), it is necessary to classify the patients into TCM syndrome types and to apply different treatments to different types. In this paper, we investigate how to properly carry out the classification for patients with VMCI aged 50 or above using a novel data-driven method known as latent tree analysis (LTA).


A cross-sectional survey on VMCI was carried out in several regions in Northern China between February 2008 and February 2012 which resulted in a data set that involves 803 patients and 93 symptoms. LTA was performed on the data to reveal symptom co-occurrence patterns, and the patients were partitioned into clusters in multiple ways based on the patterns. The patient clusters were matched up with syndrome types, and population statistics of the clusters are used to quantify the syndrome types and to establish classification rules.


Eight syndrome types are identified: Qi deficiency, Qi stagnation, Blood deficiency, Blood stasis, Phlegm-dampness, Fire-heat, Yang deficiency, and Yin deficiency. The prevalence and symptom occurrence characteristics of each syndrome type are determined. Quantitative classification rules are established for determining whether a patient belongs to each of the syndrome types.


A solution for the TCM syndrome classification problem for patients with VMCI and aged 50 or above is established based on the LTA of unlabeled symptom survey data. The results can be used as a reference in clinic practice to improve the quality of syndrome differentiation and to reduce diagnosis variances across physicians. They can also be used for patient selection in research projects aimed at finding biomarkers for the syndrome types and in randomized control trials aimed at determining the efficacy of TCM treatments of VMCI.

Key words: Vascular mild cognitive impairment, Medicine, Chinese traditional, Syndrome, Latent tree analysis

1 Lim A, Tsuang D, Kukull W, Nochlin D, Leverenz J, McCormick W, Bowen J, Teri L, Thompson J, Peskind ER, Raskind M, Larson EB. Clinico-neuropathological correlation of Alzheimer’s disease in a community-based case series.J Am Geriatr Soc. 1999; 47(5): 564-569.
2 Knopman DS, Parisi JE, Boeve BF, Cha RH, Apaydin H, Salviati A, Edland SD, Rocca WA.Vascular dementia in a population-based autopsy study. Arch Neurol.2003; 60(4): 569-575.
3 Barker WW, Luis CA, Kashuba A, Luis M, Harwood DG, Loewenstein D, Waters C, Jimison P, Shepherd E, Sevush S, Graff-Radford N, Newland D, Todd M, Miller B, Gold M, Heilman K, Doty L, Goodman I, Robinson B, Pearl G, Dickson D, Duara R.Relative frequencies of Alzheimer disease, Lewy body, vascular and frontotemporal dementia and hippocampal sclerosis in the state of Florida brain bank.Alzheimer Dis Assoc Disord. 2002; 16(4): 203-212.
4 Neuropathology Group, Medical Research Council Cognitive Function and Aging Study. Pathological correlates of late-onset dementia in a multicentre, community-based population in England and Wales. Neuropathology group of the Medical Research Council Cognitive Function and Ageing Study (MRC CFAS).Lancet. 2001; 357(9251): 169-175.
5 White L, Petrovitch H, Hardman J, Nelson J, Davis DG, Ross GW, Masaki K, Launer L, Markesbery WR.Cerebrovascular pathology and dementia in autopsied Honolulu-Asia Aging Study participants. Ann N Y Acad Sci.2002; 977: 9-23.
6 Fernando MS Ince PG; MRC Cognitive Function and Ageing Neuropathology Study Group. Vascular pathologies and cognition in a population-based cohort of elderly people.J Neurol Sci. 2004; 226(1-2): 13-17.
7 Hachinski V, Iadecola C, Petersen RC, Breteler MM, Nyenhuis DL, Black SE, Powers WJ, DeCarli C, Merino JG, Kalaria RN, Vinters HV, Holtzman DM, Rosenberg GA, Wallin A, Dichgans M, Marler JR, Leblanc GG. National Institute of Neurological Disorders and Stroke- Canadian stroke network vascular cognitive impairment harmonization standards.Stoke. 2006; 37(9): 2220-2241.
8 Pantoni L, Poggesi A, Inzitari D.Cognitive decline and dementia related to cerebrovascular diseases: some evidence and concepts. Cerebrovascular Dis.2009; 27(Suppl 1): 191-196.
9 Gorelick PB, Scuteri A, Black SE, Decarli C, Greenberg SM, Iadecola C, Launer LJ, Laurent S, Lopez OL, Nyenhuis D, Petersen RC, Schneider JA, Tzourio C, Arnett DK, Bennett DA, Chui HC, Higashida RT, Lindquist R, Nilsson PM, Roman GC, Sellke FW, Seshadri S; American Heart Association Stroke Council, Council on Epidemiology and Prevention, Council on Cardiovascular Nursing, Council on Cardiovascular Radiology and Intervention, Council on Cardiovascular Surgery and Anesthesia. Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the American Heart Association/American Stroke Association.Stroke. 2011; 42(9): 2672-2713.
10 Stephan BC, Matthews FE, Khaw KT, Dufouil C, Brayne C.Beyond mild cognitive impairment: vascular cognitive impairment, no dementia (VCIND). Alzheimers Res Ther.2009; 1(1): 4.
11 Wentzel C, Rockwood K, MacKnight C, Hachinski V, Hogan DB, Feldman H, Østbye T, Wolfson C, Gauthier S, Verreault R, McDowell I. Progression of impairment in patients with vascular cognitive impairment without dementia.Neurology. 2001; 57(4): 714-716.
12 Han HY, Yin H, Zhou YL, Zhang G, Wu YH, Xing W, Sun F, Jin XY, Xu HZ.Investigation on the changes of dependent signal on the amplitude of low frequency fluctuations at blood oxygen level in brain after acupuncture Neiguan (PC 6). Zhongguo Zhen Jiu, 2009; 29(8): 647-651.Chinese with abstract in English.
13 Zhu XT, Feng TJ, Zheng L, Qiu L, Zhang Y, Zhang ZJ.Influences of acupuncture with effects of awakening consciousness and improving intelligence in group acupoints on brain resting state function. Beijing Zhong Yi Yao Da Xue Xue Bao.2011; 34(3), 181-184. Chinese with abstract in English.
14 Cao HJ, Wang YY, Chang D, Zhou L, Liu JP.Acupuncture for vascular mild cognitive impairment: a systematic review of randomized controlled trials.Acupunct Med. 2013; 31(4): 368-374.
15 Han YH, Liu LD, Wang L. Effects of the Qingnaoyizhi grain on leukoaraiosis mild cognitive impairment and investigation on its mechanism of actions. Zhongguo Yi Yuan Yao Xue Za Zhi.2014; 34(18): 1582-1585. Chinese with abstract in English.
16 Zhang YL, Gao F, Chen ZG, Guo RJ, Hou XB, Jin XL, Chen BX, He TT, Zheng S.Effect of TCM comprehensive intervention on the mild cognitive impairment caused by leukoaraiosis. Zhong Yi Zha Zhi.2010; 51(9): 793-796. Chinese with abstract in English.
17 Zhang QH, Zhang YL, Shi YR, Jin XL, Dai Z. Primary exploration of etiology, pathogenesis and syndromes in vascular cognitive impairment no dementia. Tianjin Zhong Yi Yao.2005; 22(1): 49-52. Chinese.
18 Zhang NL, Fu C, Liu TF, Chen BX, Poon KM, Chen PX, Zhang LY.A data-driven approach to syndrome type identification and classification in traditional Chinese medicine.J Integer Med. 2017; 15(2) 110-123.
19 Li Y, Aggen S, Shi S, Gao J, Li Y, Tao M, Zhang K, Wang X, Gao C, Yang L, Liu Y, Li K, Shi J, Wang G, Liu L, Zhang J, Du B, Jiang G, Shen J, Zhang Z, Liang W, Sun J, Hu J, Liu T, Wang X, Miao G, Meng H, Li Y, Hu C, Li Y, Huang G, Li G, Ha B, Deng H, Mei Q, Zhong H, Gao S, Sang H, Zhang Y, Fang X, Yu F, Yang D, Liu T, Chen Y, Hong X, Wu W, Chen G, Cai M, Song Y, Pan J, Dong J, Pan R, Zhang W, Shen Z, Liu Z, Gu D, Wang X, Liu X, Zhang Q, Flint J, Kendler KS.Subtypes of major depression: latent class analysis in depressed Han Chinese women. Psychol Med. 2014; 44(15): 3275-3288.
20 Rindskopf D.The use of latent class analysis in medical diagnosis. New York: Joint Statistical Meetings. 2002-08.
21 21 Zhang NL, Poon LKM, Liu TF, Liu H, Chen PX, Chen ZR. Lantern software. [2015-08-30]. . Lantern software. [2015-08-30]. faculty/lzhang/tcm/.
22 Chen T, Zhang NL, Liu TF, Poon KM, Wang Y.Modelbased multidimensional clustering of categorical data.Artif Intell. 2011; 176(1): 2246-2269.
23 Ji SL, Cheng ZZ.Diagnostics of traditional Chinese medicine. Beijing: People’s Medical Publishing House. 2002.
24 Zhao GQ. Perplexity and outlet of TCM syndrome essence’s study. Yi Xue Yu Zhe Xue.1999; 20: 47-50. Chinese.
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