Mingqing Wei

The utility of the Hopkins Verbal Learning Test (Chinese version) for screening dementia and mild cognitive impairment in a Chinese population

BackgroundThe Hopkins Verbal Learning Test (HVLT) has been validated for detecting dementia in English-speaking populations. However, no studies have examined the Chinese version of the HVLT scale, and appropriate cut-off scores for dementia in the Chinese population remain unclear.Methods631 subjects aged 60 and over were recruited at a memory clinic at Dongzhimen Hospital in Beijing. Of these, 249 were classified as exhibiting normal cognition (NC), 134 were diagnosed with mild cognitive impairment (MCI), 97 were diagnosed with Alzheimer’s disease (AD), 14 met the diagnosis for vascular dementia (VaD), and 50 were diagnosed with other types of dementia, including mixed dementia. The discriminative capacity of the HVLT total learning score, recognition score and total score were calculated to determine their sensitivity and specificity for detecting MCI, AD and other dementias, and various cut-off scores.ResultsHVLT scores were affected by age, education and sex. The HVLT total learning score exhibited an optimal balance between sensitivity and specificity using a cut-off score of 15.5 for distinguishing AD and other types of dementia from NC using the ROC curve, with sensitivity of 94.7% for distinguishing AD and all types of dementia, and specificity of 92.5% for detecting AD and 93.4% for detecting all types of dementias. We stratified the AD and MCI groups by age, and calculated the validity in each age group. In the 50–64 years age group, when the cutoff score was 18.5, the sensitivity of 0.955 and specificity of 0.921 were obtained for discriminating the NC and AD groups, and in the 65–80 years group, and optimal sensitivity and specificity values (0.948 and 0.925, respectively) were obtained with a cutoff score of 14.5.When the cutoff score was 21.5 in HVLT total recall, an optimal balance was obtained between sensitivity and specificity (69.1% and 70.7%, respectively) in distinguishing MCI from NC.ConclusionA cut-off score of 15.5 in the HVLT total learning score led to high discriminative capacity between the dementia and NC groups. This suggests that the HVLT total learning score can provide a useful tool for discriminating dementia, but not MCI, from NC in clinical and epidemiological practice.

A combination extract of ginseng, epimedium, polygala, and tuber curcumae increases synaptophysin expression in APPV717I transgenic mice

BackgroundThe density of presynaptic markers of synaptic communication and plasticity, especially synaptophysin (SYP), is significantly correlated with cognitive decline and the progression of Alzheimer’s disease (AD), indicating that synaptic protection is an important therapeutic strategy for AD. This study aims to investigate the synaptic protective effects of a combination of several active components extracted from the Chinese herbs ginseng, epimedium, polygala and tuber curcumae (GEPT), in the brains of APPV717I transgenic mice.MethodsThree-month-old APPV717I mice were arbitrarily divided into 10 groups (n = 12 per group): APP groups receiving vehicle treatment for four or eight months (model groups), three dose groups of GEPT-treated mice for each treatment period, and donepezil-treated mice for each treatment period. Three-month-old C57BL/6 J mice (n = 12) were also given vehicle for four or eight months (control groups). Vehicle, donepezil or GEPT were intragastrically administered. Immunohistochemistry (IHC) and Western blot analysis were used to assess protein expression in the hippocampal CA1 region and ratios of SYP to β-actin levels in hippocampal tissue homogenate, respectively.ResultsBoth IHC and Western blot revealed a decrease in SYP levels in the CA1 region of 7- and 11-month-old APPV717I transgenic mice compared with the control groups, whereas SYP levels were increased in donepezil- and GEPT-treated transgenic mice compared with the APP group. There was a significant difference in the levels of SYP detected by IHC between the GEPT high-dose group and the APP group after 4 months of treatment, and there were significant differences between all three GEPT groups and the APP group after 8 months of treatment. Western blotting showed that the SYP protein–β-actin ratio was decreased in APP mice, while donepezil- and GEPT-treated transgenic mice showed increased trends in the SYP protein–β-actin ratios.ConclusionGEPT increases SYP expression and protects synapses before and after the formation of amyloid plaques in the brains of APPV717I transgenic mice.

Screening mild cognitive impairment by delayed story recall and instrumental activities of daily living.

Dementia has been a major public health problem, and mild cognitive impairment (MCI) has been recognized as an object of secondary prevention especially for Alzheimer’s disease. The pooled prevalence of MCI for the elderly population was 12.7% in China (Nie et al., 2011). Amnestic MCI is the main type, approximately 80% of which converted to dementia in a 6-year follow-up (Petersen, 2004). The previous study found delayed story recall (DSR) was a useful tool for differentiating MCI from normal cognition (NC), but not so good for differentiating MCI with dementia (Shi et al., 2014). In addition to memory impairment, recent studies confirmed instrumental activities of daily living (IADL) were also affected in patients with MCI. The aim of this study was to investigate the diagnostic validity of combining DSR and IADL for detecting MCI.

A combination extract of Renshen (Panax Ginseng), Yinyanghuo (Herba Epimedii Brevicornus), Yuanzhi (Radix Palygalae) and Jianghuang (Rhizoma Curcumae Longae) decreases glycogen synthase kinase 3β expression in brain cortex of APPV717I transgenic mice

OBJECTIVE To investigate the neuroprotective mechanism of combination extract of Renshen (Panax Ginseng), Yinyanghuo (Herba Epimedii Brevicornus), Yuanzhi (Radix Palygalae) and Jianghuang (Rhizoma Curcumae Longae) (GEPT) in treating Alzheimers disease on the target of glycogen synthase kinase 3beta (GSK-3beta). METHODS Three-month-old APPV7171 transgenic mice were randomly divided into ten groups (n = 12 per group) and intragastrically administrated vehicle or medicines: APP group was given 0.5% CMC, donepezil group was given donepezil (APP + D group) (0.92 mg/kg(-1) x day(-1)), and GEPT groups were given small dose of GEPT (APP+Gs group) (0.075 g/ kg(-1) x day(-1)), medium dose (APP+Gm group) (0.15 g/ kg(-1) day(-1)), and large dose (APP+GI group) (0.30 g/ kg(-1) x day(-1)) for 4 or 8 months, respectively. Three-month-old C57BL/6J mice as vehicle controls (n=12) were given 0.5% CMC for 4 or 8 months as well. The GSK-3beta expression in the cortex of 7- and 11-month-old APPV7171 transgenic mice with and without GEPT or donepezil treatment and normal C57BL/6J mice were measured via Western blotting and Immunohistochemistry. RESULTS Immunohistochemistry analysis showed significant increase of GSK-3beta in the cerebral cortex of 7-month-old APP group (compare to control group P = 0.003), while the GSK-3beta expression of donepezil or GEPT group were all significantly decreased (Donepezil vs APP: P = 0.041; GI vs APP: P = 0.049; Gm vs APP: P = 0.029; Gh vs APP: P = 0.036). Western blot analysis showed similar results. The densitometric measures of GSK-3beta in APP mice increased significantly as compared with the control group (P = 0.008). And the GSK-3beta expression in donepezil and GEPT groups were all decreased. There was significant difference between Gh group or donepezil group and the control group (P = 0.05). Similar findings were shown in the 11-month-old mice in each group, except for greater decrease of GSK-3beta in the GEPT group. CONCLUSION GEPT can effectively decrease the level of GSK-3beta expression in the brain cortex of APPV7171 transgenic mice, and such effect is more significant in 11-month-old mice. This partially explains the neuroprotecting mechanism of GEPT in preventing and treating of AD.

Diagnostic Accuracy of the Chinese Version of the Trail-Making Test for Screening Cognitive Impairment

The Trail‐Making Test (TMT), which is commonly used to measure executive function, consists of two components (TMT‐A and TMTB). There is a lack of normative TMT data for Chinese elderly adults. This study aimed to evaluate the validity of the TMT in screening for cognitive impairment.

The scale of delayed story recall: A brief screening tool for amnestic mild cognitive impairment in Chinese elderly

was to validate the HVLT Chinese version and develop proper cut-off point in detecting mild cognitive impairment (MCI) or Alzheimer’s disease (AD) from population with normal cognition (NC).Methods:A t otal of 631 subjects aged 60 and over were recruited in a Memory Clinic at Dongzhimen Hospital in Beijing. Of them, 249 subjects were considered as NC, 134 were considered as MCI, 97 subjects were considered as AD, 1 4 subjects met the diagnosis of vascular dementia (VaD), 50 subjects were considered as other dementia including mixed dementia. Discriminative capacity of the HVLT total recall, recognition score and total scores were calculated by the sensitivity and specificity of these tests for detecting MCI or AD and other dementia for various cut scores. Results: The score of the HVLT was impacted by age, education and sex. The HVLT total recall showed an optimal balance between sensitivity and specificity using a cut-off score of 15.5 for detecting AD or other dementia from NC using the ROC curve, with the same sensitivity 94.7% for detecting AD and other dementia, and specificity 92.5% for AD, 93.4% for other dementia. When the cutoff score was 21.5 in the HVLT total recall, an optimal balance were obtained between the sensitivity (69.1%) and specificity (70.7%) in detecting MCI from NC. The HVLT were highly correlated to the Mini-mental state examination (MMSE) (r 1⁄4 0.856,P 1⁄4 0.000). Conclusions: The cut-off score 15.5 of the HVLT total recall score was showed a good discriminative capacity between dementia and normal controls. This data suggests that the HVLT total recall score can be used as brief tool in discriminating well dementia but not MCI from NC in clinical and epidemiological practice.

Efficacy and safety of SQJZ herbal mixtures on nonmotor symptoms in Parkinson disease patients: Protocol for a randomized, double-blind, placebo-controlled trial

Background: As a multisystemic neurodegenerative disorder, Parkinson disease (PD) has a broad spectrum of symptoms including motor and nonmotor symptoms (NMS). As shown in studies, NMS can also impact patients quality of life, and many of them often go untreated. Chinese herbal medicines with multiconstituent may alleviate NMS in PD patients. This research is carried out to assess the efficacy and safety of a Chinese herbal formula for NMS, with its Chinese name acronym of SQJZ. Methods/design: It will be a multicenter, randomized, double-blind, placebo-controlled trial. Idiopathic PD with a Hoehn and Yahr scale score ⩽4, aged 18 to 80 years, will be involved. About 240 patients will be randomly assigned to either SQJZ or placebo in a 2:1 ratio. There is a 2-week run-in period before the randomization, and the follow-up will be 24 weeks, including 12-week treatment period, with visit once every 4 weeks and 12-week washout follow-up. All participants are asked to maintain the regular medication schedule. SQJZ formula will consist of Chinese herbs with effects for insomnia, constipation, anxiety, and so on. The primary outcome will be measured using NMS scale, and secondary outcomes will include unified PD rating scale, PD sleep scale, the Parkinson fatigue scale, the constipation severity instrument, and PD Questionnaire-39. The primary efficacy analysis will be based on the intention-to-treat method, and mixed-model repeated-measures analyses will be used. Discussion: The findings from this research might provide evidence of the efficacy and safety of SQJZ Chinese herbal formula for treating NMS in PD patients. The results will sustain the broader use of SQJZ formula in PD.

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

ObjectiveTo 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.MethodsSixty 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).ResultsIn 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.ConclusionGAPT 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.

The utility of Hopkins verbal learning test (Chinese version) for screening dementia and mild cognitive impairment in a Chinese population

Background: The Hopkins Verbal Learning Test (HVLT) has been validated for detecting dementia in English-speaking populations. However, no studies have examined the Chinese version of the HVLT scale, and appropriate cut-off scores for dementia in the Chinese population remain unclear. Methods: 631 subjects aged 60 and over were recruited at a memory clinic at Dongzhimen Hospital in Beijing. Of these, 249 were classified as exhibiting normal cognition (NC), 134 were diagnosed with mild cognitive impairment (MCI), 97 were diagnosed with Alzheimer’s disease (AD), 14 met the diagnosis for vascular dementia (VaD), and 50 were diagnosed with other types of dementia, including mixed dementia. The discriminative capacity of the HVLT total learning score, recognition score and total score were calculated to determine their sensitivity and specificity for detecting MCI, AD and other dementias, and various cut-off scores. Results: HVLT scores were affected by age, education and sex. The HVLT total learning score exhibited an optimal balance between sensitivity and specificity using a cut-off score of 15.5 for distinguishing AD and other types of dementia from NC using the ROC curve, with sensitivity of 94.7% for distinguishing AD and all types of dementia, and specificity of 92.5% for detecting AD and 93.4% for detecting all types of dementias. We stratified the AD and MCI groups by age, and calculated the validity in each age group. In the 50–64 years age group, when the cutoff score was 18.5, the sensitivity of 0.955 and specificity of 0.921 were obtained for discriminating the NC and AD groups, and in the 65–80 years group, and optimal sensitivity and specificity values (0.948 and 0.925, respectively) were obtained with a cutoff score of 14.5. When the cutoff score was 21.5 in HVLT total recall, an optimal balance was obtained between sensitivity and specificity (69.1% and 70.7%, respectively) in distinguishing MCI from NC. Conclusion: A cut-off score of 15.5 in the HVLT total learning score led to high discriminative capacity between the dementia and NC groups. This suggests that the HVLT total learning score can provide a useful tool for discriminating dementia, but not MCI, from NC in clinical and epidemiological practice.

A NEW AGE-BASED CUTOFF OF VISUAL RATING SCALES IN MRI: IMPROVING THE DIAGNOSTIC ACCURACY OF AD IN A CHINESE POPULATION

Background: We investigated the diagnostic accuracy of various white matter hyperintensities(WMH) indexes and DTI measures for diagnosing Alzheimer’s dementia(AD) and compared their impacts on global cognition according to the diagnosis of cognitive status. Methods:Sociodemographic data, neuropsychological tests, 3 Tesla brain MRIs including DTI of 388 subjects(149 cognitive normal(CN), 106 mild cognitive impairment(MCI), 133 AD) were used. The WMHs were segmented automatically using automated monospectral segmentation method forWMHs using FLAIR MRIs. The WMH indexes using Fazekas classification, modified Fazekas classification, 3-dimensional smoothness index, texture index, and combined WMH indexed were examined. Fractional anisotropy, mean diffusivity, axial diffusivity, radial diffusivity of each white matter tract based on JHU ICBM-DTI-81 White-Matter Labels atlas were calculated as DTI measures. Discriminant analysis for classifying CN, MCI, and AD and Receiver Operating Characteristic(ROC) Curve analysis for diagnosing AD were performed. Stepwise linear regression analysis was performed to examine the impacts of WMH indexes and DTI measures on Mini-Mental State Examination(MMSE) score according to the diagnosis. Results: 50.4% for Fazekas classification, 54.0% for modified Fazekas, 60.3% for smoothness index, 59.2% for texture index, 63.5% for combined WMH index, 96.1% for DTI measures, and 96.6% for DTI+WMH index were correctly classified by discriminant analysis. AUCs for diagnosing Alzheimer’s dementia were 0.740 for combinedWMH index, and 1.000 for DTImeasures. Texture indexes based on T1(CN), texture indexes based on FLAIR(MCI) and only DTI measures(AD) were included for stepwise linear regression model with highest R squared value for MMSE score. Conclusions: DTI measures showed superiority for classifying CN/MCI/AD and diagnosing AD than any WMH indexes. However, in CN and MCI groups, the texture index better explained the global cognitive function than the DTI measures. A replication of the results is needed through an independent sample, and the relationship between WHMs, DTI measures, and cognitive function needs to be clarified through longitudinal studies. Funding: This research was supported by Basic Science Research Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Education(2015R1D1A1A01059251) and grant from the Korean Health Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (grant no. HI09C1379).