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Alzheimer′s disease (AD) is an incurable disease in the field of major chronic diseases. Subjective cognitive decline (SCD) is a clinical risk factor for AD. The standardized screening and intervention in individuals with SCD are of great importance in early prevention and treatment of AD. According to the clinical criteria proposed by The characterisation of subjective cognitive decline, which was published online in Lancet Neurology, the article summarized the definition of SCD, the latest perspective of clinical standards in SCD, and the results of AD preclinical SCD research. The purpose of this work was to provide concrete guidance and recommendations for making clinical decisions in diagnosis and scientific research on SCD.
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Objective:To explore the effects of ApoE epsilon4 (ApoE-ε4) alleles on cognitive function and resting-state functional MRI (rs-fMRI) in patients with amnestic mild cognitive impairment(aMCI) based on a prospective cohort study.Methods:An average of 20 months of prospective observations were conducted on 16 ApoE-ε4-carriers and 24 non-carriers of aMCI. Neuropsychological assessments and rs-fMRI data were collected at both baseline and follow-up. All participants were assessed by a battery of neuropsychological tests and underwent rs-fMRI. Two core regions of the default mode network (DMN), the left posterior cingulate cortex (PCC) and the medial prefrontal cortex (mPFC), were selected as seeds to calculate the functional connectivity. Two-way repeated measures analysis of variance was used to assess the effects of ApoE genotype(ε4-carriers, nonε4-carriers), interval and the interaction between these two factors for functional connectivity extracted from changed region found by t-test.Conversion rates of dementia were compared between ApoE-ε4-carriers and nonε4-carriers at follow-up using Chi-square test. For the comparison of functional connectivity and clinical data between ApoE-ε4-carriers and nonsε4-carriers in baseline and follow-up, the normal distribution test was carried out first. If the normal distribution was fitted, the two-sample t test was used, otherwise, the Mann-Whitney rank sum test was used. Finally, the general linear model was used to assess the relationships between alterations in functional connectivity and in neuropsychological assessments as well as the interaction effect. Results:(1)Significant decline in memory domains were found in ApoE-ε4-carriers as compared to non-carriers at both baseline and follow-up. The ApoE-ε4-carriers (14/16) presented a higher conversation rate than non-carriers(13/24, χ 2=4.862, P=0.027) at follow-up. (2)Functional imaging analysis revealed that ApoE-ε4-carriers exhibited significantly higher functional connectivity between the left PCC and the left angular (ApoE-ε4-carriers: 0.23±0.11, non-carriers: -0.03±0.13, t=4.800, cluster size: 1 944 mm 3, P=0.004), and between the left mPFC and the left angular (ApoE-ε4-carriers: 0.33±0.21, non-carriers: 0.08±0.18, t=5.040, cluster size:1 836 mm 3, P=0.006) as compared to non-carriers at follow-up. We detected significant effect for the interaction interval by ApoE-ε4 on functional connectivity between the left angular and the left PCC ( F=10.833, P=0.002)as well as the left mPFC ( F=7.280, P=0.010). (3)The alteration of functional connectivity value between the left mPFC and the left angular in ApoE-ε4-carriers was positively correlated with the changes ofimmediate memory ( r=0.692, P=0.018). The correlation was not statistically significant in ApoE-ε4-noncarriers ( r=-0.198, P=0.417) and the integration effect was significant ( F=8.632, P=0.006). Conclusions:The ApoE-ε4 actually accelerates the deterioration of cognitive function in aMCI patients and carriers presented relatively reserved functional connectivity between the left angular and other core regions within DMN, which indicated the disruption of functional connectivity may be one of the underline mechanisms of ApoE-ε4 during AD process.
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Objective@#To explore the effects of ApoE epsilon4 (ApoE-ε4) alleles on cognitive function and resting-state functional MRI (rs-fMRI) in patients with amnestic mild cognitive impairment(aMCI) based on a prospective cohort study.@*Methods@#An average of 20 months of prospective observations were conducted on 16 ApoE-ε4-carriers and 24 non-carriers of aMCI. Neuropsychological assessments and rs-fMRI data were collected at both baseline and follow-up. All participants were assessed by a battery of neuropsychological tests and underwent rs-fMRI. Two core regions of the default mode network (DMN), the left posterior cingulate cortex (PCC) and the medial prefrontal cortex (mPFC), were selected as seeds to calculate the functional connectivity. Two-way repeated measures analysis of variance was used to assess the effects of ApoE genotype(ε4-carriers, nonε4-carriers), interval and the interaction between these two factors for functional connectivity extracted from changed region found by t-test.Conversion rates of dementia were compared between ApoE-ε4-carriers and nonε4-carriers at follow-up using Chi-square test. For the comparison of functional connectivity and clinical data between ApoE-ε4-carriers and nonsε4-carriers in baseline and follow-up, the normal distribution test was carried out first. If the normal distribution was fitted, the two-sample t test was used, otherwise, the Mann-Whitney rank sum test was used. Finally, the general linear model was used to assess the relationships between alterations in functional connectivity and in neuropsychological assessments as well as the interaction effect.@*Results@#(1)Significant decline in memory domains were found in ApoE-ε4-carriers as compared to non-carriers at both baseline and follow-up. The ApoE-ε4-carriers (14/16) presented a higher conversation rate than non-carriers(13/24, χ2=4.862, P=0.027) at follow-up. (2)Functional imaging analysis revealed that ApoE-ε4-carriers exhibited significantly higher functional connectivity between the left PCC and the left angular (ApoE-ε4-carriers: 0.23±0.11, non-carriers: -0.03±0.13, t=4.800, cluster size: 1 944 mm3, P=0.004), and between the left mPFC and the left angular (ApoE-ε4-carriers: 0.33±0.21, non-carriers: 0.08±0.18, t=5.040, cluster size:1 836 mm3, P=0.006) as compared to non-carriers at follow-up. We detected significant effect for the interaction interval by ApoE-ε4 on functional connectivity between the left angular and the left PCC (F=10.833, P=0.002)as well as the left mPFC (F=7.280, P=0.010). (3)The alteration of functional connectivity value between the left mPFC and the left angular in ApoE-ε4-carriers was positively correlated with the changes ofimmediate memory (r=0.692, P=0.018). The correlation was not statistically significant in ApoE-ε4-noncarriers (r=-0.198, P=0.417) and the integration effect was significant (F=8.632, P=0.006).@*Conclusions@#The ApoE-ε4 actually accelerates the deterioration of cognitive function in aMCI patients and carriers presented relatively reserved functional connectivity between the left angular and other core regions within DMN, which indicated the disruption of functional connectivity may be one of the underline mechanisms of ApoE-ε4 during AD process.
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Objective To explore a new index for reflecting the topological information of brain functional networks in patients at high risk of Alzheimer disease using characteristics of resting-state functional connectivity strengths(FCS) in patients with amnestic mild cognitive impairment(aMCI). Methods Thirty-one aMCI patients and 42 age, gender and years of education matched normal controls were enrolled between September 2009 and April 2011 in this study. The resting-state functional MRI (rs-fMRI) data of all participants were acquired and preprocessed. Then the whole-brain functional connectivities were constructed for exploring the distribution characteristics of hub regions which had higher FCS values. Using two-sample t test to compare group differences in age, years of education and each neuropsychological assessment. In addition, using Chi-squared test to compare group differences in gender. Group differences in FCS values were analyzed by general linear model. Finally, correlation analyses were used to evaluate the relationships between the FCS values of the brain regions with group differences and behavioral scores in aMCI patients. Results The hub regions of the functional networks in the aMCI patients were mainly located in the association cortices such as the precuneuses, posterior cingulate cortices, medial prefrontal cortices, angular gyri, superior occipital gyri, fusiform gyri and lingual gyri. The distribution models in the aMCI patients were consistent with those in the normal controls. However, the FCS values of these brain regions were significantly lower in the aMCI patients than those in the normal controls. In comparison to the normal controls, the aMCI patients had significantly decreased FCS values in the bilateral fusiform gyri, lingual gyri, superior occipital gyri, left middle occipital gyrus and postcentral gyrus (the cluster was 389, 230, 187 and 107 voxels, respectively;P<0.05, respectively), and they had decreased trends of FCS values in the bilateral posterior cingulate cortices and right insulas. The correlation analysis with uncorrected conditions showed that the FCS values of the left postcentral gyri were correlatid with the clock drawing test (CDT) scores (r=0.436, P=0.026). Conclusions aMCI mainly attacks the hub regions of brain functional networks. The changes of functional connectivities in aMCI may reflect the early pathophysiologic alterations of AD.
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Along with the development of biomarkers, the diagnostic criterion for early AD is continuously progressing until the preclinical stage of AD, on the base of which, the conception of subjective cognitive decline was raised.In order to highlight new ideas of the early diagnosis for AD in its preclinical stage, the current paper will talk about SCD in connection with neuroimaging tech-niques and examination of cerebrospinal fluid.
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Objective To investigate the changes of interleukin(IL)-2 and interferon(IFN)-γin serum and synovial fluid of patients with joint injure with Kashin-Beck disease(KBD), and study the roles of IL-2 and IFN-γ in KBD joint injure. Methods In accordance with the "Diagnostic Criteria of Kashin-Beck disease"(GB16003-1995),48 cases of KBD patients and 26 healthy people(control group) from KBD endemic area in Long county Shaanxi province were enrolled in the study. KBD patient were 24 males and 24 females, respectively, aged 40 to 65 years (mean age 51 years). Forty-eight serum specimens and 28 synovial fluid specimens of patients(14 males and 14 females,respectively) were collected. Healthy control group were 13 males and 13 females, respectively. Twenty-six serum specimens of healthy controls were collected. Serum and synovial fluid IL-2 and IFN-γ levels were determined by enzyme-linked immunosorbent assay(ELISA). Results In healthy controls and KBD patients, the midian of serum IL-2 were 46.8 ng/L and 55.7 ng/L, respectively, and IFN-γ were 52.3 ng/L and 48.8 ng/L, respectively. The difference was not statistically significant between healthy controls and KBD patients(t = 0.62, 0.70, all P ＞ 0.05).In synovial fluid of KBD patient, the midian of IL-2 and IFN-γwere 48.3 ng/L and 44.1 ng/L, respectively. The difference was not statistically significant between serum and synovial fluid in KBD patients(t = 0.69, 1.72, all P ＞0.05). Conclusion Serum and synovial fluid IL-2 and IFN-γare not significantly increased in KBD patients with articular damage, indicating that IL-2 and IFN-γare not involved in KBD joint injury.
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<p><b>OBJECTIVE</b>To investigate the anti-inflammatory effect of bone marrow stromal cells (MSCs) transfected with recombinant adenovirus-mediated ciliary neurotrophic factor (CNTF) gene in C57BL/6 mice with experimental allergic encephalomyelitis (EAE).</p><p><b>METHODS</b>An adenovirus vector containing CNTF gene Ad-CNTF-IRES-GFP was constructed and transfected in the MSCs (MSC-CNTF). After examination of CNTF expression, the transfected cells were transplanted in C57BL/6 mice with MOG 35-55-induced EAE, which were monitored for the changes in the symptoms scores. The levels of tumor necrosis factor-alpha (TNF-alpha), inteferon-gamma (IFN-gamma), interleukin-12P35 (IL-12P35), and IL-10 in the peripheral blood of the mice were detected, and the number of MSC-CNTF cells in the spleen and spinal cord was counted. CD3+ T cell infiltration and TNF-alpha and IFN-gamma expressions in the lesions were also observed after the cell transplantation.</p><p><b>RESULTS</b>CNTF gene transfection resulted in significantly increased CNTF expression in the MSCs. The mice receiving MSC-CNTF transplantation exhibited significantly improved symptoms with shortened disease course and lessened disease severity. The cell transplantation also resulted in significantly decreased peripheral blood TNF-alpha levels, ameliorated CD3+T cell infiltrations and lowered TNF-alpha expression in the lesions, while the levels of IFN-gamma underwent no significant changes.</p><p><b>CONCLUSION</b>Transplantation of CNTF gene-transfected MSCs results in decreased peripheral blood TNF-alpha and IFN-gamma levels and reduced inflammatory cells, CD3-positive cells and TNF-alpha expression in the lesion of EAE, therefore providing better effect than MSCs in relieving the symptoms of EAE in mice.</p>
Subject(s)
Animals , Female , Mice , Adenoviridae , Genetics , Metabolism , Bone Marrow Cells , Metabolism , Ciliary Neurotrophic Factor , Genetics , Therapeutic Uses , Encephalomyelitis, Autoimmune, Experimental , Therapeutics , Genetic Therapy , Interferon-gamma , Blood , Mice, Inbred C57BL , Random Allocation , Stromal Cells , Metabolism , T-Lymphocytes , Allergy and Immunology , Transfection , Tumor Necrosis Factor-alpha , BloodABSTRACT
Objectives To investigate fluoride in drinking waters and fluorosis status and evaluate the effectiveness of fluoride-reducing projects in Shaanxi Province from 2005 to 2007. Methods In the Shaanxi province-wide, the 10 endemic areas of fluorosis were chosen according to historical data as focusing areas for investigation. The village was considered as investigation spot, 5 water samples were collected from each village for investigating of fluoride content. Four water samples were collected from each fluoride-reducing project for evaluating its effectiveness. Fluoride concentrations in drinking water were measured by fluoride-selective electrode method or speetrophotometry. When fluoride content in drinking water was greater than 1.00 mg/L, the epidemical study wasd conducted to investigate fluorosis patients, focusing on investigating of dental fluorosis prevalence in 8 to 12-year-old children and skeletal fluorosis prevalence in adults. Dental fluorosis of children was diagnosed by using Dean's method, and adult skeletal fluorosis was diagnosed according to National Standard for Clinical Diagnosis of Endemic Skeletal Fiuorosis(GB 16396-1996). Results The fluoride content in drinking water from 6390 villages was measured. The fluoride content of drinking water of 2619 villages ranged from 1.0 to<2.0 mg/L, where 1 654 998 people exposed. Additionally, the fluoride content of water of 845 villages ranged from 2.0 to<4.0 mg/L, where 355 623 people exposed. Moreover, the fluoride contents of water of 272 villages exceeded 4.0 mg/L, where 111 466 people exposed. The median of fluoride content in drinking water was 1.15% in the whole province, and fluoride content in drinking water exceeded 1.00 mg/L in Weinan, Xianyang and Yulin where were concentrated distribution areas of high fluoride water. Among 3115 fluoride-reducing projects, the fluoride content of drinking water of 1269 projects ranged from 1.0 to<2.0 mg/L, where 1 415 877 people exposed. Additionally, the fluoride content of drinking water of 120 projects ranged from 2.0 to<4.0 mg/L, where 43 888 people exposed. Moreover, the fluoride content of drinking water of 14 projects exceeded 4.0 mg/L, where 5960 people exposed. The detectable rate of dental fluorosis of 8 to 12 year-old children and skeletal fluorosis of adults reached 37.4%(16 489/44 081) and 5.1%(15 877/310 993), respectively. Conclusions The widely distribution of high-fluoride in drinking water still contributes to the prevalence of fluorosis in Shaanxi Province. The quality of fluoride-reducing projects should be further improved.