Cuibai Wei

The prevalence of dementia in urban and rural areas of China

The Chinese population has been aging rapidly and the countrys economy has experienced exponential growth during the past three decades. The goal of this study was to estimate the changes in the prevalence of dementia, Alzheimers disease (AD), and vascular dementia (VaD) among elderly Chinese individuals and to analyze differences between urban and rural areas.

The prevalence of mild cognitive impairment and its etiological subtypes in elderly Chinese

Epidemiologic studies on mild cognitive impairment (MCI) are limited in China.

The effects of DL-3-n-butylphthalide in patients with vascular cognitive impairment without dementia caused by subcortical ischemic small vessel disease: A multicentre, randomized, double-blind, placebo-controlled trial

Vascular cognitive impairment without dementia is very common among the aged and tends to progress to dementia, but there have been no proper large‐scale intervention trials dedicated to it. Vascular cognitive impairment without dementia caused by subcortical ischemic small vessel disease (hereinafter, subcortical Vascular cognitive impairment without dementia) represents a relatively homogeneous disease process and is a suitable target for therapeutic trials investigating Vascular cognitive impairment without dementia. Preclinical trials showed that dl‐3‐n‐butylphthalide (NBP) is effective for cognitive impairment of vascular origin.

Association between polymorphisms in the apolipoprotein D gene and sporadic Alzheimer's disease

Apolipoprotein D (apoD) is a lipoprotein-associated glycoprotein that is increased in the hippocampus and cerebrospinal fluid of patients with Alzheimers disease (AD), which implies that apoD might be involved in the pathogenesis of AD. We used polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing techniques to screen all exons (1-5) and the flanking exon-intron boundaries of the apoD gene (APOD). Thirty subjects [15 sporadic AD (SAD) patients and 15 controls] were randomly selected and tested for APOD variations by direct sequencing. Two APOD polymorphisms (rs5952T/C and rs1568566C/T) were detected. We further investigated APOD polymorphisms in 256 SAD patients and 294 healthy subjects from a North Chinese population to investigate whether they affect the risk of SAD. Logistic analysis revealed that both rs5952 C and rs1568566 T alleles increase the risk of SAD [rs5952, adjusted odds ratio (OR) 1.817, 95% confidence interval (CI) 1.237-2.669, P = 0.002; rs1568566, adjusted OR 1.563, 95% CI 1.060-2.306, P = 0.024). The rs5952T-rs1568566C haplotype showed lower risk of SAD (OR 0.421, 95% CI 0.305-0.583, P = 0.000). Case-control analysis revealed that the rs5952T-rs1568566C haplotype could serve as a novel defendant factor against SAD. APOD polymorphisms might play an important role in modifying SAD risk in some way.

Stage-Specific Gender Differences in Cognitive and Neuropsychiatric Manifestations of Vascular Dementia

Studies on gender differences in the clinical manifestations of vascular dementia (VaD) are still lacking. In the present study, gender comparisons of cognitive and neuropsychiatric profiles were conducted separately for mild and moderate-to-severe VaD in a total of 467 patients with VaD. There were no significant gender differences in cognitive manifestations, except that females performed better on immediate verbal recall than males in mild stage. Women were more likely to exhibit delusions (15.5% vs 7.4%), hallucinations (9.5% vs 3.4%), and depression (43.1% vs 27.3%) in mild stage. The predominance of male patients was observed in apathy at moderate-to-severe stage (50.5% vs 34.8%). To conclude, gender differences existed in neuropsychiatric symptoms of VaD and were especially pronounced in mild stage. Delusions, hallucinations, and depression were more prevalent in females in mild VaD, with the male predominance only in apathy in the later stage.

Exploration of 16 candidate genes identifies the association of IDE with Alzheimer's disease in Han Chinese

Alzheimers disease (AD) has a complex pattern of inheritance and many genes have recently been reported to contribute to the disease susceptibility. We selected 106 SNPs within 16 candidate genes and performed a multistage association study using 4 sample sets consisting of 731 AD patients and 738 control subjects to identify genetic factors for AD in Han Chinese. A single nucleotide polymorphism (SNP) in the insulin degrading enzyme gene (IDE), rs3781239, showed a significant association with AD. The C allele increased the risk of AD 1.72-fold than the G allele (odds ratio [OR] = 1.72, 95% confidence interval [CI] = 1.17-2.53, p = 0.006) and CC carriers had a 4.89-fold higher risk for AD than that of the carriers with CG and GG genotypes (odds ratio = 4.89, 95% CI = 1.85-12.91, p = 0.001). Moreover, the CC genotype was significantly associated with earlier age at onset (p = 0.001, hazard ratio [HR] = 2.09, 95% CI = 1.38-3.18). Our data suggest that the polymorphism of IDE is associated with susceptibility to Alzheimers disease in Han Chinese.

Elevated plasma angiogenesis factors in Alzheimer's disease.

Evidence has shown that aberrant angiogenesis is an integral part of Alzheimers disease (AD). Angiogenesis is a complex process requiring successive activation of a rather large series of factors. The aim of this study was to determine which angiogenesis molecule(s) abnormalities were changed in plasma of AD subjects and whether plasma levels of angiogenesis factors were associated with cognitive function and risk of AD. Discovery-phase antibody arrays were used to detect plasma concentrations of 55 angiogenesis-related factors. Enzyme-linked immunosorbent assays (ELISAs) in a large cohort were further performed to identify the association of plasma angiogenesis factors with AD. We found that plasma angiogenin (ANG) and tissue inhibitor of matrix metalloproteinase-4 (TIMP-4) levels were higher in patients with AD than those in normal subjects. Significantly higher ANG and TIMP-4 were observed in the severe AD group relative to the mild AD. There were different levels of plasma ANG and TIMP-4 compared with vascular dementia and other dementias. Age or gender had no major effects on levels of these proteins. Plasma ANG and TIMP-4 levels tended to be higher in ApoE ε4 carriers compared with non-carriers, but not significantly. A multiple regression analysis after adjusting for covariates revealed correlations between plasma ANG and TIMP-4 and the MMSE and CDR. Higher plasma ANG and TIMP-4 levels were associated with significant AD risk. These results demonstrate that plasma ANG and TIMP-4 may reflect the severity of cognitive function impairment, and higher levels were associated with risk of AD.

Rationale and Design of a Multicenter, Phase 2 Clinical Trial to Investigate the Efficacy of Traditional Chinese Medicine SaiLuoTong in Vascular Dementia

BACKGROUND Vascular dementia (VaD) is the second most prevalent type of dementia among the aged, for whom limited pharmacologic options are available so far. SaiLuoTong capsule is a modern traditional Chinese medicine formula, which has been demonstrated to improve cognition of VaD by the reports of animal experiments and preliminary clinical trial. However, evaluation of this therapy in randomized multicenter trials is needed. In this article, we present the rationale and design of the SaiLuoTong in Vascular Dementia Study. METHODS This phase 2 clinical trial of SaiLuoTong among patients with mild-to-moderate VaD is a 26-week, multicenter, randomized, double-blind, placebo-controlled study with a subsequent 26-week, open-label extension. After a 4-week placebo run-in period, participants are centrally randomized (1:1:1) to 3 groups: group A receives SaiLuoTong 360 mg per day for 52 weeks; group B receives SaiLuoTong 240 mg per day for 52 weeks; group C (the control group) are further randomly assigned to 2 groups in a 1:1 ratio and receives placebo during the double-blind phase, then SaiLuoTong 360 mg per day or SaiLuoTong 240 mg per day during the extension phase. The primary outcome measures include the VaD assessment scale cognitive subscale and the Alzheimer Disease Cooperative Study-clinical global impression of change. Safety measures include body weight, vital signs, electrocardiography, laboratory tests, and records of adverse events. Assuming an attrition rate of 20%, at least 372 patients are required to obtain a statistical power of 80%. RESULTS The first patient was enrolled into the study in April 2012 and the completion of the study is expected in September 2014. CONCLUSIONS The rigorous methodology of the study will hopefully move forward the scientific evaluation of traditional Chinese medicine in treatment of VaD. The results of the present study will provide high-quality evidence on the effect of SaiLuoTong in patients with VaD and has the potential to establish a novel therapeutic approach for this disorder.

Efficacy and Safety of Donepezil in Chinese Patients with Severe Alzheimer’s Disease: A Randomized Controlled Trial

BACKGROUND Donepezil has been used worldwide for the treatment of severe Alzheimers disease (AD). Whether it is also appropriate for severe AD in Chinese patients remains unknown. OBJECTIVE To determine whether donepezil is effective and tolerable for Chinese patients with severe AD. METHODS The present study was a 24-week, multicenter, double-blind, randomized, placebo-controlled, parallel-group study conducted at 38 investigational hospitals in China. Patients with severe AD were enrolled in this trial. Patients were randomly assigned in a 1:1 ratio to receive either donepezil or placebo (5 mg for 6 weeks and10 mg for the remaining 18 weeks). The efficacy for donepezil were evaluated by the SIB, the Clinicians Interview-Based Impression of Change-Plus caregiver input (CIBIC-plus) and the MMSE. Safety parameters were monitored throughout. RESULTS A total of 313 patients included the donepezil (n = 157) and the placebo groups (n = 156). Donepezil group improved more in SIB scores (least squares [LS] mean difference: 4.8, 95% CI 1.56 to 8.08, p = 0.004) and CIBIC-plus scores (drug-placebo difference: -0.4, 95% CI -0.66 to 0.03, p = 0.04) than placebo groups at Week 24. The MMSE scores between drug and placebo groups did not differ significantly. Twenty-nine patients with serious adverse events (SAEs) were reported in donepezil (n = 11) and placebo groups (n = 18) (p = 0.08). Most SAEs were not considered drug-related. CONCLUSION Donepezil for 24 weeks was more effective than placebo and showed good safety and tolerability in Chinese patients with severe AD. This study supports utility of the drug in severe stages of AD in the Chinese population.

The cost of Alzheimer's disease in China and re-estimation of costs worldwide

The socioeconomic costs of Alzheimers disease (AD) in China and its impact on global economic burden remain uncertain.