Study On Neuropsychology And Syndrome Manifestations Of TCM In Patients With Vascular Cognitive Impairment

Background1. Neuropsychological characteristics of vascular cognitive impairment(VCI)Most previous studies indicate that the main feature of cognitive impairment of VaD (Which is one of the subtypes of VCI) is executive dysfunction and with less memory impairment. The impairment pattern of VaD is considered as "patchy damage". The main feature of cognitive impairment of Vscular Cognitive impairment No Dementia (VCIND)(which is anthor subtype of VCI) is also executive dysfunction and with less or no memory impairment. But recent study proposes a different view that VaD shows comprehensive cognitive impairment, rather than "patchy damage", and executive dysfunctions is as common as memory dysfunctions in VCIND.2. Neuropsychological characteristics of Subcortical Ischemic Vascular disease(SIVD)SIVD is the one of the subtypes of VCI, which are relatively homogeneous, and have similar pathogenesis. SIVD is caused by small vessel disease, characterized by a wide range of white matter damage and multiple lacunar infarcts in deep gray matter and white matter structure. At present, many studies have shown that SIVD closely relate to cognitive decline, most of studies indicated that white matter lesions destroyes the frontal-subcortical pathway, resulting in executive dysfunction.3. The selection of early screening scales for VCIThe concept of VCI was proposed to emphasize the importance of early detection of the patients with cognitive impairment, so early screening is very important.The Mini-Mental State Examination (MMSE) is the most widely used cognitive assessment scale in the world, which was designed for AD patients, and may be not suitable for screening VCI patients. The National Institute of Neurological Disorders and Stroke in Canada Stroke Network recommended a simple and practical cognitive assessment scale-The Montreal Cognitive Assessment(MoCA). MoCA was previously used in screening and diagnosis MCI patients, There have been a widely accepted cutoff point(<26 points) for screening MCI and AD, but few studies was conducted to explore the best cutoff point for screening VCI.4. Study on TCM syndromes of VCIVCI is Caused by a variety of factors, it has complex pathogenesis, and diverse TCM syndromes. Objective research on TCM syndrome can help to accurately differentiate VCI syndromes, understand the nature of the disease, explore the law of onset and development of the disease, and it has great significance in improving clinical efficacy of Chinese medicine. Internal medicine branch of Institute of Traditional Chinese Medicine anti-aging Commission established the criteria of diagnosis, syndrome differentiation, determination of the efficacy of vascular dementia. The TCM syndrome manifestations of VaD was divided into 7 types:kidney essence vacuity, turbid phlegm blocking upper orifices, blood stasis obstructing brain collaterals, hyperactivity of liver yang due to yin deficiency, excess of heat toxin, deficiency of blood and qi, viscera stagnation and turbid left. This proposition of diagnostic criteria for VaD laies foundation for further study on TCM syndrome types and distribution, the evolution of VaD, and contributes to standardize the syndrome differentiation of VaD.5. Study on the correspondence of TCM prescription and syndrome differention of VCI (A clinical research on Cistanchis glycosides capsule treating vascular dementia (with TCM syndrome of sea of marrow insufficient) (one of the subtypes of VCI))The conclusion of early cross-sectional study of TCM syndromes of this study is"kidney essence vacuity is a major pathogenesis of post-stroke VCI". In order to verify the correctness of the conclusion, we conduct a syndrome application study, treating VaD(one of the subtypes of VCI) patients with Cistanchis Glycosides Capsule(which has the efficacy of increasing kidney essence, keeping brain health and improving intelligence), observing whether this medicine can play a role in improving the cognitive function, ability of daily life, behavior and TCM syndromes in VaD patients, and evaluating its clinical efficacy. Object1.To preliminary conclude the neuropsychological characteristics of post-stroke VCI (mainly VaD and VCIND subtypes).2. To explore the characteristics of neuropsychological and TCM syndromes of subcortical ischemic vascular disease.3. To evaluate the reliability and validity of the Montreal Cognitive Assessment (MoCA), and to explore the optimal cutoff point of MoCA applied in detecting VCI and VaD patients from post-stroke patients;4. To preliminary conclude the characteristics of TCM syndromes of VCI, and to explore the TCM pathogenesis of cognitive impairment of VCI.5. According to the conclusion of early cross-sectional study of TCM syndromes of this study--"kidney essence vacuity is a major pathogenesis of post-stroke VCI", In order to verify the correctness of the conclusion, we conduct a syndrome application study, treating VaD(one of the subtypes of VCI) patients with Cistanchis Glycosides Capsule(which has the efficacy of increasing kidney essence, keeping brain health and improving intelligence).observing the efficacy of this medicine.Methods1. Cross-sectional survey of neuropsychology and TCM syndromes of VCI.We conducted a Cross-sectional study to survey post-stroke patients which had been admited in Guangdong Provincial Hospital in 2005-2009, and set normal elderly as control. Contents of this survey include:(1) comprehensive neuropsychological tests (involving five cognitive domains); (2) integrated cognitive function assessment (MMSE, MoCA) (3)TCM Syndrome (Syndrome Differentiation Scale of Vascular Dementia (SDSVD)); Test steps:Post-stroke patients were diagnosed as "Cognitive impairment" and "cognitively normal" according to the results of comprehensive neuropsychological tests, Who were diagosed as "Cognitive impairment" were futher diagnosed as VaD or VCIND by several senior neurologist. All the post-stroke patients were divided into three groups:PSCN group, VCIND group, VaD group, with the NC group as control.The diagnosis mentioned above was used as the relatively gold standard, we evaluate the sensitivity, specificity of MoCA in detecting VCI from post-stroke patients, and ROC curves was constructed to determine the optimal cut-off point. We also compared VCI patients with normal controls to summary the features of neuropsychology and TCM syndrome of VCI.2. Study on the correspondence of TCM prescription and syndrome differention of VCI(A clinical research on Cistanchis glycosides capsule treating vascular dementia (with TCM syndrome of sea of marrow insufficient) (one of the subtypes of VCI))We conducted a opened phaseⅣclinical trials with single group, VaD (with TCM syndrome of sea of marrow insufficient) patients was recruited and treated with Cistanchis glycosides capsules (2 capsules,3 times/day, oral) 12 weeks, they were examined by the Alzheimer's Disease Assessment Scale-Cognitive part(ADAS-Cog), mini-mental state examination (MMSE), ability of daily life(ADL), Blessed Behavior Scale (BBS), TCM symptom scale before and after treatment, and evaluated the safety of this medicine. Scores of these assessement before and after treatment were compared to determine the efficacy, and summarizes the security of this drug in treating vascular dementia.Results1. General information(1)A total of 318 post-stroke patients and 60 normal elderly people were recruited in this study. Of which 127 cases of post-stroke patients and 35 normal elderly people have completely data. The subjects with completely data were diagnosed as three groups, VaD group (n=55), VCIND group (n=46), PSCN group (n=26), and NC group (n=35).(2)There were significantly differences in sex, age and education level among the four groups of subjects. There were no significantly differences in personal history such as smoking, drinking, and no significantly differences in stroke course, type of stroke, hypertension, diabetes, hyperlipidemia, coronary heart disease, atrial fibrillation and other disease history among the post-stroke subjects(P>0.05).2. Neuropsychological characteristics of VCI(1) VaD group have higher impairment rate in every cognitive domains, and often coexists three to four cognitive domains impaired (76.4%). The cognitive domain with highest impairment rate is executive functions in VCIND group, followed by memory and attention impairments, visual spatial skills and language impairment rates are lower, VCIND group often coexists 2 to 3 cognitive domain impaired (67.4%).(2)VaD group and VCIND group have similar impairment rate and degree in the cognitive domains of attention, they have similar impairment rate in the cognitive domains of executive function, but VCIND group have lower impairment degree than VaD group. VCIND group have lower impairment rate and degree in the cognitive domains of memory, spatial skills and language than VaD group.3. The cognitive profile of SIVD and the relationship between SIVD and TCM syndrome.(1) There are 50 patients meet the diagnostic criteria of SIVD in this study, 23 patients meet the diagnostic criteria of LS,15 patients with other types of subcortical ischemic damage.(2)Multiple linear regression analysis was used to explore which types of subcortical ischemic damage could influence cognitive function, the results reveales that all the three types of subcortical ischemic damage could influence MoCA scores. And only SIVD could influence MMSE scores and the short form IQ scores.(3) Results of logistic regression analysis showed that all the three types of subcortical ischemic damage tend to cause memory impairment compared with NC group, and SIVD tends to cause executive dysfunction compared with NC group, visual spatial and language impairment. Both LS and SIVD tend to cause attention impairment compared with NC group.(4) Results of Logistic regression analysis showed that all the three types of subcortical ischemic damage tend to cause the TCM syndrome of kidney essence vacuity compared with NC group. Both LS and SIVD tend to cause the TCM syndrome of hyperactivity of liver yang due to yin deficiency, viscera stagnation and turbid left, deficiency of blood and qi compared with NC group. 4. A study on reliability and validity of MOCA of Chinese Hong Kong Cantonese version and determination of the optimal cut-off point of MoCA in detecting VCI from the post-stroke patients.(1) Internal consistency evaluation was conducted for Chinese Hong Kong Cantonese version of MoCA, Cronbach'sα=0.813. Principal component/factor analysis was used to evalute construct validity, the results suggesting that MoCA has good validity.(2)The ability of the two cognitive assessment scales(MoCA and MMSE)in differentiating VCI and cognitive normal patients in post-stroke patients. The results showed that when the cut-off point of MoCA was<=23, it had the highest Youden index(0.82). When the cut-off point of MMSE was<=27, it had highest Youden index(0.76).The results of the comparision of the AUC of the two cognitive assessment scales in differentiating VCI and cognitive normal patients in post-stroke patients showed:MoCA(0.956±0.0177)>MMSE(0.920±0.0233), Z=2.339, P=0.019. That results indicated that MoCA is superior to MMSE in differentiating VCI and cognitive normal patients in post-stroke patients.(3)The ability of the two cognitive assessment scales(MoCA and MMSE)in differentiating Vad and no VaD patients in post-stroke patients. The results showed that when the cut-off point of MoCA was<=19, it has the highest Youden index (0.75). When the cut-off point of MMSE was<=24, it had highest Youden index (0.78). The results of the comparision of the AUC of the two cognitive assessment scales in differentiating Vad and no VaD patients in post-stroke patients showed:there was no significant differences in MoCA (0.945±0.0194) and MMSE (0.931±0.0248), Z=1.453, P=0.146. That results indicateed that MoCA and MMSE had the similar ability in differentiating Vad and no VaD patients in post-stroke patients.5. The characteristics of TCM Syndrome of VCI and the relationship between TCM Syndrome and neuropsychology of VCI(1)Results of logistic regression analysis showed that VaD group tended to cause TCM syndrome of kidney essence vacuity, turbid phlegm blocking upper orifices, hyperactivity of liver yang due to yin deficiency, deficiency of blood and qi, viscera stagnation and turbid left compared with NC group. VCIND group tended to cause TCM syndrome of kidney essence vacuity compared with NC group.(2)Multiple linear regression analysis was used to explore the relationship between TCM syndrome and scores of comprehensive cognitive function scales (MoCA, MMSE, short form IQ).MMSE scores was influenced by the TCM syndromes of turbid phlegm blocking upper orifices, deficiency of blood and qi, kidney essence vacuity. MoCA and short form IQ scores were only influenced by the TCM syndrome of kidney essence vacuity.(3)Logistic regression analysis was used to explore the relationship between TCM syndrome and cognitive domains impairment, the results showed that there was no significant relationship between executive dysfunction and TCM syndrome, language dysfunction and TCM syndrome. Memory, attention and visual spatial impairment were all influenced by TCM syndrome of kidney essence vacuity. Visual spatial impairment was also influenced by TCM syndrome of deficiency of blood and qi. Patients with TCM syndrome of kidney essence vacuity has more numbers of impaired cognitive domains compared with the patients without TCM syndrome of kidney essence vacuity.(4)Logistic regression analysis was used to explore the relationship between whether the post-stroke patients progressed to VCI and TCM syndrome.The results showed that TCM syndrome of kidney essence vacuity was the only influential syndromes.6. Study on the correspondence of TCM prescription and syndrome differention of VCI (A clinical research on Cistanchis glycosides capsule treating vascular dementia (with TCM syndrome of sea of marrow insufficient) (one of the subtypes of VCI))(1)The scores of ADAS-Cog, MMSE, TCM syndrome, BBS and ADL Before and after treatment were analyzed by PPA and ITT analysis, the results showed that after 12 weeks'treatment by Cistanchis Glycosides capsule, VaD(with TCM syndrome of sea of marrow insufficient) patients have improved scores on all of the mentioned scales above.(2)Cistanchis glycosides capsules has good security in treating vascular dementia(with TCM syndrome of sea of marrow insufficient).Conclusion1. VaD has a comprehensive cognitive impairment rather than "patchy damage". The main feature of cognitive impairment of VCIND is executive dysfunction, and memory impairment is also prominent in VCIND.2. SIVD relates to the overall cognitive decline. SIVD and LS compared with normal control tend to have TCM syndromes of kidney essence vacuity, hyperactivity of liver yang due to yin deficiency, deficiency of blood and qi, viscera stagnation and turbid left.3. MoCA has good reliability and validity. MoCA is superior to MMSE in differentiating VCI and cognitive normal patients in post-stroke patients. They have the similar ability in differentiating Vad and no VaD patients in post-stroke patients.4. TCM syndromes of kidney essence vacuity maybe the major pathogenesis of the post-stroke VCI.5. Cistanchis glycosides capsule can effectively improve the VaD (one of the subtypes of VCI)patients with cognitive ability, ability of daily life, behavior, and TCM syndrome scores, verified the correctness of the conclusion that kidney essence vacuity is a major pathogenesis of post-stroke VCI.