Evaluation of Renal Impairment in Patients with Diabetic Kidney Disease by Integrated Chinese and Western Medicine.

OBJECTIVE: To investigate the factors related to renal impairment in patients with diabetic kidney disease (DKD) from the perspective of integrated Chinese and Western medicine. METHODS: Totally 492 patients with DKD in 8 Chinese hospitals from October 2017 to July 2019 were included. According to Kidney Disease Improving Global Outcomes (KDIGO) staging guidelines, patients were divided into a chronic kidney disease (CKD) 1-3 group and a CKD 4-5 group. Clinical data were collected, and logistic regression was used to analyze the factors related to different CKD stages in DKD patients. RESULTS: Demographically, male was a factor related to increased CKD staging in patients with DKD (OR=3.100, P=0.002). In clinical characteristics, course of diabetes >60 months (OR=3.562, P=0.010), anemia (OR=4.176, P<0.001), hyperuricemia (OR=3.352, P<0.001), massive albuminuria (OR=4.058, P=0.002), atherosclerosis (OR=2.153, P=0.007) and blood deficiency syndrome (OR=1.945, P=0.020) were factors related to increased CKD staging in patients with DKD. CONCLUSIONS: Male, course of diabetes >60 months, anemia, hyperuricemia, massive proteinuria, atherosclerosis, and blood deficiency syndrome might indicate more severe degree of renal function damage in patients with DKD. (Registration No. NCT03865914).

The Correlation Between Olfactory Test and Hippocampal Volume in Alzheimer's Disease and Mild Cognitive Impairment Patients: A Meta-Analysis.

Background: Previous studies have reported that olfactory identification deficits may be the earliest clinical features of Alzheimer's disease (AD). However, the association between odor identification and hippocampal atrophy remains unclear. Objective: This meta-analysis quantified the correlation between odor identification test scores and hippocampal volume in AD. Method: A search of the PUBMED, EMBASE, and WEB OF SCIENCE databases was conducted from January 2003 to June 2020 on studies with reported correlation coefficients between olfactory identification score and hippocampal volume in patients with amnestic AD or mild cognitive impairment (MCI). The quality of the studies was assessed using the Newcastle-Ottawa quality assessment scale (NOS). Pooled r-values were combined and computed in R studio. Results: Seven of 627 original studies on AD/MCI using an olfactory identification test (n = 902) were included. A positive correlation was found between hippocampal volume and olfactory test scores (r = 0.3392, 95% CI: 0.2335-0.4370). Moderator analysis showed that AD and MCI patients were more profoundly correlated than normal controls (AD: r = 0.3959, 95% CI: 0.2605-0.5160; MCI: r = 0.3691, 95% CI: 0.1841-0.5288; NC: r = 0.1305, 95% CI: -0.0447-0.2980). Age difference and patient type were the main sources of heterogeneity in this analysis. Conclusion: The correlation appears to be more predominant in the cognitive disorder group (including MCI and AD) than in the non-cognitive disorder group. Age is an independent factor that affects the severity of the correlation during disease progression. The mildness of the correlation suggests that olfactory tests may be more accurate when combined with other non-invasive examinations for early detection. Systematic Review Registration: https://inplasy.com/, identifier INPLASY202140088.

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

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.

Effect of GAPT extract on expression of tau protein and its phosphorylation related enzymes in hippocampal neurons of APPV717I transgenic mice.

OBJECTIVE: To investigate the effect of GAPT, an extract mixture from Radix Ginseng, Rhizoma Acor tatarinowii, Radix Polygalae and Radix Curcuma (containing ingredient of turmeric), etc. on expression of tau protein and its phosphorylation related enzyme in hippocampal neurons of APPV717I transgenic mice. METHODS: Sixty three-month-old APPV717I transgenic mice were randomly divided into model group, donepezil group [0.92 mg/(kg•d)], the low, medium and high dosage of GAPT groups [0.075, 0.15, 0.30 g/(kg•d), 12 in each group], and 12 three-month-old C57BL/6J mice were set as a normal control group, treatments were administered orally once a day respectively, and both the normal group and model group were given 0.5% sodium carboxymethyl cellulose solution. Immunohistochemistry (IHC) and Western blot analysis were used to detect the expression of total tau protein (Tau-5), cyclin-dependent kinase 5 (CDK5) and protein phosphatase 2A (PP2A) in hippocampal neurons of experimental mice after 8-month drug administration (11 months old). RESULTS: In the model group, the expression of Tau-5 and CDK5 were increased, whereas the expression of PP2A was decreased in hippocampal neurons, which were signifificantly different compared with that in the normal group (all P<0.01). IHC test indicated the number and area of either Tau-5 or CDK5 positive cells were decreased with a dose-depended way in GAPT groups, and an increase of PP2A. Compared with the model group, the changes were signifificant in GAPT groups (P<0.05 or P<0.01). Similar results were shown by Western blot. CONCLUSION: GAPT could attenuate abnormal hyperphosphorylation of tau protein in hippocampal neurons of APPV717I transgenic mice via inhibiting the expression of CDK5 and activating the expression of PP2A.

Curcumin ameliorates insulin signalling pathway in brain of Alzheimer's disease transgenic mice.

Deficits in glucose, impaired insulin signalling and brain insulin resistance are common in the pathogenesis of Alzheimer's disease (AD); therefore, some scholars even called AD type 3 diabetes mellitus. Curcumin can reduce the amyloid pathology in AD. Moreover, it is a well-known fact that curcumin has anti-oxidant and anti-inflammatory properties. However, whether or not curcumin could regulate the insulin signal transduction pathway in AD remains unclear. In this study, we used APPswe/PS1dE9 double transgenic mice as the AD model to investigate the mechanisms and the effects of curcumin on AD. Immunohistochemical (IHC) staining and a western blot analysis were used to test the major proteins in the insulin signal transduction pathway. After the administration of curcumin for 6 months, the results showed that the expression of an insulin receptor (InR) and insulin receptor substrate (IRS)-1 decreased in the hippocampal CA1 area of the APPswe/PS1dE9 double transgenic mice, while the expression of phosphatidylinositol-3 kinase (PI3K), phosphorylated PI3K (p-PI3K), serine-threonine kinase (AKT) and phosphorylated AKT (p-AKT) increased. Among the curcumin groups, the medium-dose group was the most effective one. Thus, we believe that curcumin may be a potential therapeutic agent that can regulate the critical molecules in brain insulin signalling pathways. Furthermore, curcumin could be adopted as one of the AD treatments to improve a patient's learning and memory ability.

[Treatment of vascular dementia by Chinese herbal medicine: a systematic review of randomized controlled trials of clinical studies].

OBJECTIVE: Chinese herbal medicine has been extensively used in the treatment of vascular dementia (VaD), but lacked systematic review on its efficacy and safety. So we conducted a systematic review to assess the efficacy and safety of Chinese herbal medicine in treating VaD. METHODS: CNKI, CBM, PubMed, and Wiley Online Library were retrieved for randomized trials (RCTs) on Chinese herbal medicine treating VaD patients. Randomized parallel control trials by taking Chinese herbal medicine as one treatment method and placebos/cholinesterase inhibitors/Memantine hydrochloride as the control were included. Quality rating and data extraction were performed. RevMan5.2.0 Software was used for meta-analysis. Standardized mean difference (SMD) at 95% confidence interval (CI) was used to indicate effect indicators of results. RESULTS: Seven RCTs met the inclusive criteria. Totally 677 VaD patients were randomly assigned to the treatment group and the control group. Descriptive analyses were performed in inclusive trials. The cognitive function was assessed in all trials. Results showed Mini-Mental state examination (MMSE) score was better in the Chinese herbal medicine group than in the placebo group, but with no significant difference when compared with the donepezil group (P > 0.05). Adverse reactions were mainly manifested as gastrointestinal symptoms such as abdominal pain in the Chinese herbal medicine group. But they occurred more in the donepezil group than in the Chinese herbal medicine group. CONCLUSIONS: The methodological quality of included trials was poor with less samples. Results of different trials were lack of consistency. Present evidence is not sufficient to prove or disapprove the role of Chinese herbal medicine in improving clinical symptoms and outcome indicators of VaD patients. Their clinical efficacy and safety need to be supported by more higher quality RCTs.

[Treatment of refractory depression patients of yin deficiency inner heat syndrome by jieyu granule combined paroxetine: an efficacy observation].

OBJECTIVE: To explore the efficacy of jieyu granule (JG) combined Paroxetine in treating refractory depression (RD) patients of yin deficiency inner heat syndrome (YDIHS). METHODS: Seventy RD patients of YDIHS were randomly assigned to the experimental group (JG combined Paroxetine) and the control group (Chinese medical placebo combined Paroxetine), 35 cases in each group. Hamilt Depression Rating Scale and Hamilton Anxiety Scale were used before treatment, and at the weekend of the 2nd, 4th, and 8th week, respectively. RESULTS: In the experimental group, 32 patients completed the trial and 3 patients dropped out. In the control group, 33 patients completed the trial and 2 patients dropped out. At the end of the 8th week of the treatment, the total score of Hamilt Depression Rating Scale was (14.75 +/- 7.85) in the experimental group, lower than that of the control group (19. 06 +/- 8. 31, P <0.05). At the end of the 2nd, 4th, and 8th week of the treatment, the score of Hamilton Anxiety Scale was 17.03 +/- 4.25, 14.50 +/- 5. 13, and 11.03 +/- 4.88, respectively in the experimental group, lower than that of the control group at each corresponding time point (19. 60 +/-3. 96, 17. 12 +/- 4.14, 14.64 +/- 4.47, P <0.05, P <0.01). CONCLUSION: The efficacy of JG combined Paroxetine for treating RD patients of YDIHS was superior to that of using Paroxetine alone.

[Case constitution and medication intention of bipolar disordered outpatients at two grade IIIa hospitals in Beijing].

OBJECTIVE: To acquire the case constitution of bipolar disordered (BPD) in mood disordered (MD) outpatients at two local Beijing hospitals to understand the case constitution and medication intention of clinical psychiatrists in terms of differentiation and treatment of BPD. METHODS: All psychiatrists at Anding Hospital and neurological physicians at Xuanwu Hospital were surveyed by self-rated questionnaires and the analysis focused on the composition of proportions of BPD cases out of MD patients. The items included estimated ratio of BPD cases, doctors' intention of drug prescription and clinical therapeutic regimen for treatment of BPD. RESULTS: (1) BPD ratio in MD outpatients of two hospitals were 41.79% and 12.24% respectively; (2) Doctor's ratio who estimated BPD ratio in MD cases < 40% were 60% and 100% respectively; (3) 100% psychiatrists at Beijing Anding Hospital and 72.22% neurological physicians at Beijing Xuanwu Hospital prescribed antidepressant to BPD cases; (4) Doctor's ratio who adopted therapeutic schedule of 'antidepressant + mood stabilizer' or 'antidepressant + mood stabilizer + antipsychotic' agents for BPD were 100% and 66.67% respectively. CONCLUSION: Regardless of mental specialized hospital or general hospital, the physicians should pay great attention to the differentiation of BPD and the rationality of drug prescription.

[Assessment of the results of syndrome in clinical trials of dementia treated by Chinese herbal medicine].

Chinese medical syndrome efficacy, as a second efficacy indicator, has been widely used in clinical trials of treating dementia by Chinese herbal medicine. The syndrome assessment tool is a key point in assessing the efficacy of Chinese medical syndrome. The syndrome assessment tool for dementia used nowadays needs to be optimized in content, reliability, and validity. In this paper, the authors reviewed some problems correlated with the design of Chinese medical assessment questionnaire on the basis of Chinese medical theories by combining the common requirements for questionnaire development.

Effects of Chinese medicine for promoting blood circulation and removing blood stasis in treating patients with mild to moderate vascular dementia: a randomized, double-blind and parallel-controlled trial.

BACKGROUND: Vascular dementia (VaD) is the second common subtype of dementia after Alzheimer's disease. However, there is still a lack of medication that demonstrates clinically relevant symptomatic improvement. Static blood obstructing the brain is the main Chinese medicine syndrome of VaD. OBJECTIVE: To evaluate the effects of Chinese medicine for promoting blood circulation and removing blood stasis in patients with mild to moderate VaD. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: In this 12-week randomized, double-blind, parallel-controlled trial, a total of 48 patients with mild to moderate VaD were enrolled between March 2009 and December 2010. All the patients entered a two-week placebo run-in period followed by a 12-week treatment with Chinese medicine for promoting blood circulation and removing blood stasis (n=24) or placebo (n=24), respectively. The placebo tablets have the identical taste and appearance as the Chinese medicine tablets. MAIN OUTCOME MEASURES: The primary outcome measure was the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog); the secondary outcome measures included the Activities of Daily Living (ADL) and the Mini-Mental State Examination (MMSE). RESULTS: The Chinese medicine group showed a slight deterioration of 0.25 points and the placebo group showed a deterioration of 2.35 points from baseline by the ADAS-cog, and there was a significant difference between the two groups (P=0.027). The ADL and the MMSE showed no significant difference from baseline in both groups. Adverse events were rare in both groups. CONCLUSION: The Chinese medicine for promoting blood circulation and removing blood stasis may improve cognition and it is safe and well tolerated.

Recognition of dementia in ancient China.

A search of previous records in the literatures was done to summarize the opinions for dementia in ancient China. The earliest description of dementia was traced in the Yellow emperor's internal classic, a book written 2000 years ago. Hua Tuo (AD 140-208) in Han Dynasty first denominated "dementia" in the book, Hua Tuo Shen Yi Mi Zhuan. The pathogenesis of dementia could be generalized as the insufficiency of Qi, a flowing energy; the stagnation of phlegm, a harmful liquid substance in the body; and the blood stasis, which were also regarded as therapeutic targets. Therefore, we can conclude that dementia has been recognized and investigated in traditional Chinese medicine, which is definitely before the industrial civilization era.

Effects of Chinese medicine for tonifying the kidney and resolving phlegm and blood stasis in treating patients with amnestic mild cognitive impairment: a randomized, double-blind and parallel-controlled trial.

BACKGROUND: It is important to detect and prevent Alzheimer disease (AD) at its early stage. Constituting the early stage sign of AD, amnestic mild cognitive impairment (aMCI) has drawn much attention. Studies have shown that donepezil could reduce the AD assessment scale-cognitive subscale (ADAS-Cog) score in MCI patients and improve the patient's attention and speed of response; however, it also has many side effects. Therefore, the authors aim to explore the effects of Chinese herbal medicine for treating aMCI. OBJECTIVE: To explore the clinical efficacy and safety of Chinese medicine for tonifying the kidney, and resolving phlegm and blood stasis in the treatment of aMCI. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: This clinical trial used randomized, double-blind, double-dummy and parallel-controlled design. According to the randomized, double-blind principle, some aMCI patients were randomly divided into Chinese medicine group and donepezil group. Other patients who did not receive any treatment were enrolled as the control. Patients in the Chinese medicine group received oral administration of Chinese medicine, 1 bag/dose, two doses per day, while patients in the donepezil group received donepezil hydrochloride, 5mg/day. Twelve weeks were allocated as the trial period. MAIN OUTCOME MEASURES: After 12 weeks, the Chinese medicine group patients, the donepezil group patients and those patients who did not receive any treatment were accessed using the scores of ADAS-Cog and mini-mental status examination (MMSE). RESULTS: The ADAS-Cog and MMSE scores of the Chinese medicine group and the donepezil group were both improved from baseline (P=0.001, P=0.000), but the non-treatment group showed no change from baseline (P=0.151, P=0.125); furthermore, there was no significant difference between the Chinese medicine group and the donepezil group. The attention function of the Chinese medicine group was better than baseline (P=0.015), but no change was seen in the donepezil group (P=0.085) at the 12th week. Safety data showed that the occurrence of insomnia, nausea and diarrhea was greater in the donepezil group than in the Chinese medicine group (P=0.002, P=0.005, P=0.000), and both treatments had no influence in participants' vital signs and laboratory examination results. CONCLUSION: Both Chinese medicine and donepezil can improve global cognition in patients with aMCI after 12 weeks of treatment. Chinese medicine can also improve attention function and some clinical symptoms in patients with aMCI. Furthermore, Chinese medicine is safe for aMCI patients. Further study is necessary to explore the long-term effect of Chinese medicine for aMCI.

[Correlation between cognitive functions and syndromes of traditional Chinese medicine in vascular cognitive impairment].

OBJECTIVE: To investigate the correlation between cognitive function and the Chinese medicine syndrome characteristics of vascular cognitive impairment (VCI). METHODS: A total of 774 subjects (age from 41 to 87 years old) from Beijing of China accepted neuropsychological assessments and differentiation of Chinese medicine syndromes. The mini-mental state examination (MMSE) and clinic dementia rating (CDR) were used to access the global cognitive function; the Hachinski ischemia scale (HIS) and the Hamilton depression scale (HAMD) were used for differential diagnosis; the ability of daily living (ADL) scale was used to assess the ability of daily living; the clock drawing test was used to access the executive function; the investigation of syndrome manifestations and the syndrome differentiation scale of vascular dementia (SDSVD) were used for diagnosis of syndrome manifestations. According to the diagnostic criteria of vascular cognitive impairment, subjects were subgrouped as normal cognition (NC) group and VCI group, and then the correlation between the cognitive functions and Chinese medicine syndromes was analyzed. RESULTS: The correlation between cognitive scales and Chinese medical syndrome: in the VCI group, the syndrome of phlegm turbid blocking upper orifices showed negative correlation with the scores of MMSE and CDT (r=-0.525, r=-0.321, P=0.000, P=0.001), and the ADL demonstrated positive correlation to the syndrome (r=0.424, P=0.000). The correlation between cognitive function and Chinese medical syndrome: the phlegm turbid blocking upper orifices was closely correlated with the total orientation, time orientation and place orientation (r=-0.451, r=-0.448, r=-0.392, P=0.001, P=0.000, P=0.004); instant word recall and delayed word recall were closely correlated with the syndrome of phlegm turbid blocking upper orifices (r=-0.355, r=-0.225, P=0.000, P=0.021); calculation/attention, language function and executive function had negative correlation to the syndrome of phlegm turbid blocking upper orifices (r=-0.379, r=-0.448, r=-0.321, P=0.000, P=0.000, P=0.013). The scores of orientation, calculation/attention, delayed word recall and language function in the patients with phlegm turbid blocking upper orifices were significantly lower than the patients with non-phlegm turbid blocking upper orifices (P<0.05). CONCLUSION: The syndrome of phlegm turbid blocking upper orifices is significantly correlated to the scores of MMSE and ADL, indicating that the phlegm turbid blocking upper orifices is related to the cognitive function and ability of daily living in the VCI patients. Treatment of the phlegm is important in the cognitive impairment in VCI patients.

Effects of Chinese herbal medicine Yinsiwei compound on spatial learning and memory ability and the ultrastructure of hippocampal neurons in a rat model of sporadic Alzheimer disease.

OBJECTIVE: To study the effects of Chinese herbal medicine Yinsiwei compound (YSW) on spatial learning and memory ability in rats with sporadic Alzheimer disease (SAD) and the ultrastructural basis of the hippocampal neurons. METHODS: A rat model of SAD was established by intracerebroventricular injection of streptozotocin. The rats were divided into six groups: sham-operation group, model group, donepezil control group, and YSW low, medium and high dose groups. Drug interventions were started on the 21st day after modeling and each treatment group was given the corresponding drugs by gavage for two months. Meanwhile, the model group and the sham-operation group were given the same volume of distilled water by gavage once a day for two months. The Morris water maze was adopted to test spatial learning and memory ability of the rats. The place navigation test and the spatial probe test were conducted. The escape latency, total swimming distance and swimming time in the target quadrant of the rats were recorded. Also, the hippocampus tissues of rats were taken out and the ultrastructure of hippocampus neurons were observed by an electron microscope. RESULTS: In the place navigation test, compared with the model group, the mean escape latency and the total swimming distance of the donepezil group and the YSW low, medium and high dose groups were significantly shortened (P<0.05 or P<0.01). In the space probe test, the swimming time of each treatment group in the target quadrant was significantly longer than that of the model group (P<0.05 or P<0.01). For most of the test period, the donepezil group had no significant change compared with the YSW low, medium and high dose groups, respectively. The ultrastructure of the hippocampus neurons under the electron microscope also confirmed the efficacy of the drug treatment. CONCLUSION: Chinese herbal medicine YSW compound can improve spatial learning and memory impairment of rats with SAD. The ultrastructural basis may be that it can protect the microtubule structures of hippocampal neurons and prevent nerve axons from being damaged.

Correlation between cognitive functions and syndromes of traditional Chinese medicine in amnestic mild cognitive impairment.

OBJECTIVE: To explore the correlation between the cognitive functions and syndromes of traditional Chinese medicine (TCM) in amnestic mild cognitive impairment (aMCI), and to provide evidence for clinical syndrome differentiation treatment. METHODS: Six hundred subjects from Dongzhimen Hospital and seven communities in Beijing, aged between 40 and 85 years, accepted neuropsychological assessments, imaging and biochemical examinations, and syndrome differentiation, from whom 159 aMCI patients, 213 normal control (NC) subjects and 171 Alzheimer's dementia (AD) patients were screened out. Correlation between the cognitive functions and TCM syndromes in aMCI patients was analyzed. RESULTS: Mini-Mental State Examination (MMSE) score in aMCI patients was closely correlated with kidney essence vacuity and deficiency of blood and qi (r = -0.11, r = -0.11; P = 0.003, P = 0.015). Delayed Word Recall (DWR) score was correlated with kidney essence vacuity (r = -0.20, P = 0.020). Instant Story Recall (ISR) and Delayed Story Recall (DSR) scores were respectively correlated with turbid phlegm blocking upper orifices (r = -0.11, r = -0.27; P = 0.021, P = 0.000). Language function was correlated with kidney essence vacuity and deficiency of blood and qi (r = -0.11, r = -0.13; P = 0.042, P = 0.007). Attention/calculation was also closely correlated with kidney essence vacuity and deficiency of blood and qi (r = -0.10, r = -0.21; P = 0.039, P = 0.010). Attention score of aMCI patients was correlated with excess of heat toxin syndrome (r = -0.29, P = 0.026). CONCLUSION: The memory decline of aMCI is correlated with kidney essence vacuity and turbid phlegm blocking upper orifices. Furthermore, turbid phlegm blocking upper orifices is correlated with episodic memory decline, which is closely related to AD. The aMCI patients with phlegm have the risk to progress into AD. Although other cognitive functions of aMCI remain relatively intact, the patients' language function, attention/calculation and the whole cognitive function may be worsen as the aggravation of kidney essence vacuity, deficiency of blood and qi, phlegm and heat toxin, and may eventually lead to multiple cognitive domains impairment, even dementia.

[Guiding principles of clinical research on mild cognitive impairment (protocol)].

Mild cognitive impairment (MCI), as a nosological entity referring to elderly people with MCI but without dementia, was proposed as a warning signal of dementia occurrence and a novel therapeutic target. MCI clinical criteria and diagnostic procedure from the MCI Working Group of the European Alzheimer's Disease Consortium (EADC) may better reflect the heterogeneity of MCI syndrome. Beijing United Study Group on MCI funded by the Capital Foundation of Medical Developments (CFMD) proposed the guiding principles of clinical research on MCI. The diagnostic methods include clinical, neuropsychological, functional, neuroimaging and genetic measures. The diagnostic procedure includes three stages. Firstly, MCI syndrome must be defined, which should correspond to: (1) cognitive complaints coming from the patients or their families; (2) reporting of a relative decline in cognitive functioning during the past year by the patient or informant; (3) cognitive disorders evidenced by clinical evaluation; (4) activities of daily living preserved and complex instrumental functions either intact or minimally impaired; and (5) absence of dementia. Secondly, subtypes of MCI have to be recognized as amnestic MCI (aMCI), single non-memory MCI (snmMCI) and multiple-domains MCI (mdMCI). Finally, the subtype causes could be identified commonly as Alzheimer disease (AD), vascular dementia (VaD), and other degenerative diseases such as frontal-temporal dementia (FTD), Lewy body disease (LBD), semantic dementia (SM), as well as trauma, infection, toxicity and nutrition deficiency. The recommended special tests include serum vitamin B12 and folic acid, plasma insulin, insulin-degrading enzyme, Abeta40, Abeta42, inflammatory factors. Computed tomography (or preferentially magnetic resonance imaging, when available) is mandatory. As measurable therapeutic outcomes, the primary outcome should be the probability of progression to dementia, the secondary outcomes should be cognition and function, and the supplement outcome should be the syndrome defined by traditional Chinese medicine. And for APOE epsilon4 carrier, influence of the carrier status on progression rate to dementia and the effect of treatment should be evaluated.

[An explanation on "guiding principles of clinical research on mild cognitive impairment (protocol)"].

In order to provide the "guiding principles of clinical research on mild cognitive impairment (MCI) (protocol)" edited by Beijing United Study Group on MCI of the Capital Foundation of Medical Developments (CFMD) with evidence support, clinical criteria, subtypes, inclusion and exclusion of MCI, and use of rating scales were reviewed. The authors suggested that MCI clinical criteria and new diagnosis procedure from the MCI Working Group of the European Alzheimer's disease Consortium (EADC) may better reflect the heterogeneity of MCI syndrome. Diagnostic rating scales including Clinical Dementia Rating (CDR), Global Deterioration Scale (GDS), Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and Instrumental Activities of Daily Living (IADL) are very useful in definition of MCI but can not replace its clinical criteria. Absence of major repercussions on daily life in patients with MCI was emphasized, but the patients may have minimal impairment in complex IADL. According to their previous research, the authors concluded that highly recommendable neuropsychological scales with cut-off scores in the screening of MCI cases should include Mini-Mental State Examination (MMSE), logistic memory test such as Delayed Story Recall (DSR), executive function test such as Clock Draw Test (CDT), language test such as Verbal Category Fluency Test (VCFT), etc. And finally, the detection of biological and neuroimaging changes, including atrophy in hippocampus or medial temporal lobe in patients with MCI, was introduced.

[Clinical study on a randomized, double-blind control of Shenwu gelatin capsule in treatment of mild cognitive impairment].

OBJECTIVE: To evaluate the effectiveness of Shenwu gelatin capsule (compound Chinese ginseng and fleeceflower root etc) in the treatment on senile mild cognitive impairment. METHOD: 166 patients meeting criteria for mild cognitive impairment were selected from patients in Dongzhimen Hospital and were randomly assigned into a treatment group (n = 83 cases), given 5 capsules of Shenwu gelatin capsule, and a positive control group (n = 83 cases) , given 2 capsules of aniracetam with 3 placebo capsules. All subjects took this medication 3 times a day for 3 months, double-blind and double-moulding control were used in this study. At a baseline and end (three months later), all subjects were assessed using a battery consisting of MMSE and clinical memory scale (CMS). RESULT: Both Shenwu gelatin capsule and aniracetam can remarkably increase the score of memory quotient (MQ), P < 0. 01. They have the similarly effectiveness, there are no statistical difference between the two groups in effectiveness of increasing memory scores. CONCLUSION: Shenwu gelatin capsule has certain effects on mild cognitive impairment.

[Research of kingsbrain on improving the learning and memory ability of MCAO rats].

OBJECTIVE: To explore the influence of Kingsbrain (GETO) on the learning memory impairment of rats with cerebral ischemia. METHOD: Rats with cerebral ischemia were administered GETO orally once a day for one month. The ability of spatial-learning memory of rats was evaluated by Morris Water Maze (MWM). Duxil was used as a positive control. RESULT: the results of place navigation of MWM showed that at the 3rd time of swimming training, the escape latency of rats of the GETO group, Duxil group and Sham group were shorter than that of model group. The escape latency were (54.1 +/- 43.94), (55.9 +/- 43.49), (50.4 +/- 34.99) and (85.4 +/- 42.8) s, respectively; but there was no significantly difference. After the 6th time of swimming training, the escape latency of rats of the GETO group (37.8 +/- 38.69) s, the Duxil group (37.4 +/- 38.03) s and the sham group (26.9 +/- 21.63) s were significantly shorter than that of model rats (77.5 +/- 47.59) s, P < 0.05, respectively. Comparison of the swimming distance among groups were similar to the escape latency among groups. In the test of spatial probe, results of the ratio of the swimming time of platform quadrant (tP) vs the total swimming time (tT) and the ratio of the swimming distance of platform quadrant (dP) vs the total swimming distance (dT) indicated that the ratios of the GETO group (0.347 +/- 0.0662, 0.344 +/-0.055 1), the Duxil group (0.345 +/- 0.0984, 0.34 +/- 0.0934) and the sham group (0.35 +/- 0.0662, 0.349 +/- 0.0589) were significantly higher than those of the Model group (0.261 +/- 0.0689, 0.274 +/- 0.0544), P < 0.05, respectively. CONCLUSION: GETO can significantly improve the spatial learning and memory ability of rats with cerebral ischemia, which provides the pharmacodynamics evidence for its clinical application of improveing the learning and memory ability in poststroke patients.

[Effect of GETO on expression of protein in postsynaptic dense zone of Alzheimer's disease model rats].

OBJECTIVE: To observe the effect of GETO on expression of PSD-95 and Shank-1 protein in postsynaptic dense zone in Alzheimer disease (AD) model rats. METHODS: The AD model rats were established by beta-amyloid protein (Abeta(1-42)) injection into hippocampus CA1 zone. They were assigned into the model group, the donepezil treated group and the GETO treated group, besides, a normal group was set for control. Four weeks after modeling, Morris water maze test was applied to determine the learning and memory function of the AD rats, the number of PSD-95 and Shank-1 protein positive neuron as well as the optical density (OD) in post-synaptic dense zone of hippocampus CA1 area were determined by using immuno-histochemical stain and computerized graphic analysis techniques. RESULTS: Morris water maze test showed that the mean escape latent period (MELP) of the model rats obviously prolonged than that of the normal rats, and the times of traversing flat roof obviously decreased (P < 0.01), while in the model rats after being treated by GETO, the two parameters were significantly shortened and increased respectively (P < 0.01), reaching the level insignificantly different to those in the donepezil group and the normal group. Immunohistochemical test showed that the number of positive stained neuron of PSD-95 and Shank-1 in hippocampus CA1 zone in the model group was significantly different to those in the normal group (P < 0.01), while in the GETO group those indexes were insignificantly different to those in the donepezil group and the normal group (P > 0.05), but showed a significant difference when compared with those in the model group (P < 0.05). CONCLUSION: GETO can obviously improve the function of learning and memory of AD rats induced by Abeta(1-42), and the mechanism may be associated with its actions in improving expressions of PSD-95 and Shank-1 protein in hippocampus CA1 zone, and recovering the structure and function of synapse and enhancing its plasticity.