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Shen L.,Capital Medical University | Jia J.,Capital Medical University | Jia J.,Beijing Institute for Brain Disorders | Jia J.,Beijing Key Laboratory of Geriatric Cognitive Disorders | Jia J.,Neurodegenerative Laboratory of Ministry of Education of the Peoples Republic of China
Neuroscience Bulletin | Year: 2016

Genome-wide association studies (GWASs) have revealed a plethora of putative susceptibility genes for Alzheimer’s disease (AD). With the sole exception of the APOE gene, these AD susceptibility genes have not been unequivocally validated in independent studies. No single novel functional risk genetic variant has been identified. In this review, we evaluate recent GWASs of AD, and discuss their significance, limitations, and challenges in the investigation of the genetic spectrum of AD. © 2016 Shanghai Institutes for Biological Sciences, CAS and Springer Science+Business Media Singapore

Li H.,Capital Medical University | Jia J.,Capital Medical University | Jia J.,Beijing Institute for Brain Disorders | Jia J.,Beijing Key Laboratory of Geriatric Cognitive Disorders | And 2 more authors.
Journal of Alzheimer's Disease | Year: 2016

Background: Chinese nationwide norms of the Mini-Mental State Examination (MMSE) have not been established despite its wide use. Objective: To obtain norms for the MMSE based on age, gender, education, and rural or urban residences and to determine the optimal cut-off points of the MMSE in elderly Chinese. Methods: A cross-sectional study was conducted in Chinese community residents aged 65 years or over selected by cluster random sampling. The MMSE was administered to 9,629 subjects (7,110 cognitively normal, 2,024 with mild cognitive impairment, and 495 with dementia). The demographic influences on MMSE scores were investigated and the norms were established considering those factors. Receiver operating characteristic (ROC) analysis was used to determine the optimal cut-off points. Results: Years of education (standardized β=0.399), rural residence (standardized β=-0.261), age (standardized β=-0.198), and being female (standardized β=-0.101) had significant effects on MMSE scores (p<0.001). Accordingly, we presented the demographic-stratified normative data for the MMSE. The optimal cut-off points for dementia screening were 16/17 for illiterate (sensitivity 87.6 and specificity 80.8), 19/20 for individuals with 1-6 years of education (sensitivity 93.6 and specificity 92.7), and 23/24 for individuals with 7 or more years of education (sensitivity 94.3 and specificity 94.3). Conclusion: We provide the age-, gender-, education-, and residence-specific reference norms for the MMSE derived from an investigation of a large-scale, multicenter, nationwide representative Chinese elderly population. It could be of great improvement for the use of the MMSE in dementia screening in Chinese elderly population. © 2016 - IOS Press and the authors. All rights reserved.

Xing Y.,Capital Medical University | Tang Y.,Capital Medical University | Jia J.,Capital Medical University | Jia J.,Beijing Institute for Brain Disorders | And 2 more authors.
Behavioural Neurology | Year: 2015

Sex differences in neuropsychiatric symptoms of Alzheimer's disease (AD) have been demonstrated in previous studies, and apolipoprotein E (ApoE) ε4 status influences psychiatric manifestations of AD. However, whether ApoE ε4 status modifies the sex differences in neuropsychiatric symptoms of AD is still unclear. In this study, sex differences in neuropsychiatric abnormalities were stratified and analyzed by ApoE ε4 status in mild AD and moderate to severe AD separately. The Clinical Dementia Rating (CDR) scale and the Neuropsychiatric Inventory (NPI) were used to assess dementia severity and neuropsychiatric symptoms. No sex differences were found in mild AD. In moderate to severe AD, among ε4 positive individuals, disinhibition was significantly more prevalent (8.0% in men versus 43.2% in women, p=0.003) and severer p=0.003 in female patients. The frequency (16.0% in men versus 51.4% in women, p=0.005) and score p=0.004 of irritability were of borderline significance after strict Bonferroni correction. In conclusion, this study supported the modifying effect of ApoE ε4 status on sex differences in neuropsychiatric symptoms of AD, and this modifying effect was pronounced in moderate to severe stage of AD. The interaction between gender and ApoE ε4 status should be considered in studies on neuropsychiatric symptoms of AD. © 2015 Yi Xing et al.

Xie Y.,Capital Medical University | Cui Z.,Beijing Normal University | Zhang Z.,Mudanjiang Medical College | Sun Y.,Capital Medical University | And 8 more authors.
Journal of Alzheimer's Disease | Year: 2015

Identifying amnestic mild cognitive impairment (aMCI) is of great clinical importance because aMCI is a putative prodromal stage of Alzheimer's disease. The present study aimed to explore the feasibility of accurately identifying aMCI with a magnetic resonance imaging (MRI) biomarker.We integrated measures of both gray matter (GM) abnormalities derived from structural MRI and white matter (WM) alterations acquired from diffusion tensor imaging at the voxel level across the entire brain. In particular, multi-modal brain features, including GM volume, WM fractional anisotropy, and mean diffusivity, were extracted from a relatively large sample of 64 Han Chinese aMCI patients and 64 matched controls. Then, support vector machine classifiers for GM volume, FA, and MD were fused to distinguish the aMCI patients from the controls. The fused classifier was evaluated with the leave-one-out and the 10-fold cross-validations, and the classifier had an accuracy of 83.59% and an area under the curve of 0.862. The most discriminative regions of GM were mainly located in the medial temporal lobe, temporal lobe, precuneus, cingulate gyrus, parietal lobe, and frontal lobe, whereas the most discriminative regions of WM were mainly located in the corpus callosum, cingulum, corona radiata, frontal lobe, and parietal lobe. Our findings suggest that aMCI is characterized by a distributed pattern of GM abnormalities and WM alterations that represent discriminative power and reflect relevant pathological changes in the brain, and these changes further highlight the advantage of multi-modal feature integration for identifying aMCI. © 2015 - IOS Press and the authors. All rights reserved.

Peng M.,Capital Medical University | Peng M.,Beijing Institute for Brain Disorders | Peng M.,Beijing Key Laboratory of Geriatric Cognitive Disorders | Peng M.,Key Neurodegenerative Laboratory of Ministry of Education of the Peoples Republic of China | And 7 more authors.
Neuroscience Letters | Year: 2015

Gelsolin (GSN) levels and matrix metalloproteinase 3 (MMP3) activity have been found to be altered in the plasma in patients with Alzheimer disease (AD). The aim of this study was to determine whether a combination of these proteins with clinical data is specific and sensitive enough for AD diagnosis. In 113 non-demented controls and 113 patients with probable AD, the plasma GSN levels were determined using the enzyme-linked immunosorbent assay (ELISA), and the plasma MMP3 activity was determined using casein zymography. Logistic regression and receiver operating characteristic (ROC) curve analysis were used to determine the diagnostic accuracy of these proteins combined with clinical data. Compared with the controls, the AD patients had significantly lower GSN levels and significantly higher MMP3 activity. Moreover, both the GSN level and MMP3 activity were significantly correlated with the MMSE scores. In AD patients, the GSN level was negatively correlated with MMP3 activity. ROC curve analysis showed that the specificity and sensitivity were 77% and 75.2%, respectively, for the combination of the following candidate biomarkers: GSN level/the total amount of Aβ42 and Aβ40, plasma MMP3 activity and clinical data. With its relatively high sensitivity and specificity, this combined biomarker panel may have potential for the screening of AD patients. © 2015 Elsevier Ireland Ltd.

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