Xiumei Zuo

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.

Montreal Cognitive Assessment in Detecting Cognitive Impairment in Chinese Elderly Individuals: A Population-Based Study

The Montreal Cognitive Assessment (MoCA) has been proved brief and sensitive to screen for mild cognitive impairment (MCI) and early dementia in some developed countries or areas. However, little MoCA data are available from mainland China. In this study, the MoCA was applied to 8411 Chinese community dwellers aged 65 or older (6283 = cognitively normal [CN], 1687 = MCI, and 441 = dementia). The MoCA norms were established considering significant influential factors. The optimal cutoff points were 13/14 for illiterate individuals, 19/20 for individuals with 1 to 6 years of education, and 24/25 for individuals with 7 or more years of education. With the optimal cutoffs, the sensitivity of the MoCA was 83.8% for all cognitive impairments, 80.5% for MCI and 96.9% for dementia, and the specificity for identifying CN was 82.5%. These indicate that with optimal cutoffs, the MoCA is valid to screen for cognitive impairment in elderly Chinese living in communities.

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.

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.

APOE Effects on Default Mode Network in Chinese Cognitive Normal Elderly: Relationship with Clinical Cognitive Performance

Background Functional connectivity in default mode network (DMN) may be changed in Alzheimer’s disease (AD) patients and related risk populations, such as amnestic mild cognitive impairment (aMCI) patients and APOE ε4 carriers. Exploring DMN changes and related behavioral performance of APOE ε4 population might provide valuable evidence for better understanding the development of AD. Methods Subjects were enrolled from a population-based cohort established in a multi-center study in China. Forty-nine cognitive normal individuals were enrolled after standardized cognitive evaluations, MRI examination and APOE genotyping. Regions of interest (ROI)-based functional connectivity analyses were performed, and voxel-based analyses were used to validate these findings. The correlation between DMN functional connectivity and behavioral performance was further evaluated between APOE ε4ε3 and ε3ε3 carriers. Results Comparing to ε3ε3 carriers, functional connectivity between left parahippocampal gyrus and right superior frontal cortex (LPHC-R.Sup.F), left parahippocampal gyrus and medial prefrontal cortex (ventral) (LPHC-vMPFC) were significantly increased in ε4ε3 carriers, while connectivity between cerebellar tonsils and retrosplenial was decreased. LPHC-R.Sup.F connectivity was positively correlated with the changes of delay recall from baseline to follow-up (r = 0.768, p = 0.009), while LPHC-vMPFC connectivity had a positive correlation with MMSE at baseline (r = 0.356, p = 0.018), and a negative correlation with long-delayed recognition at follow-up (r = -0.677, p = 0.031). Significantly increased functional connectivity in vMPFC was confirmed in voxel-based analyses by taking LPHC as seed region. Conclusion APOE ε4 carriers present both increased and decreased functional connectivity in DMN, which is correlated with clinical cognitive performances. DMN changes might be an early sign for cognitive decline.

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.

The relationship between ADAM17 promoter polymorphisms and sporadic Alzheimer's disease in a Northern Chinese Han population.

The deposition of amyloid beta peptides (Abeta) in the brain is crucial in the pathogenesis of Alzheimers disease (AD). A disintegrin and metalloproteinase (ADAM) 17 cleaves the amyloid precursor protein (APP) within the Abeta sequence and, therefore, precludes the formation of neurotoxic Abeta. To explore the correlation between the ADAM17 promoter and sporadic AD (SAD), a case-control study was conducted in a Northern Chinese Han population. The ADAM17 gene promoter region was screened, resulting in five known and one novel single nucleotide polymorphisms (SNP): -1672C/T (rs11689958), -1638T/G (rs1524668), -1437T/C (rs11684747), -1333C/T (rs12474969), -172T/C (rs12692386) and -154C/A. Using direct sequencing, genotypes were determined in 403 patients who had SAD and 323 control participants. No association was observed between these polymorphisms and SAD. These data indicated that, in a Northern Chinese Han population, SNP in the ADAM17 promoter do not influence the risk of SAD.

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.