Objective:To investigate the plasma differential protein expressions between patients with Alzheimer's disease (AD) and normal controls, and to search plasma protein markers or protein combinations with screening or diagnostic significance.Methods:Plasma samples from 98 patients with dementia of Alzheimer type (DAT), 102 patients with mild cognitive impairment (MCI) and 101 normal controls (NC) were collected from Wuxi Mental Health Center and Shanghai Mental Health Center from 2016 to 2018.The expression levels of 50 kinds of plasma proteins in all plasma samples were detected by Milliplex MAP assays(xMAP).Analysis of variance, regression analysis, discriminant analysis, and ROC analysis on the data were performed using SPSS 20.0 software.Results:(1)Compared with the NC group, 26 plasma proteins were up-regulated and 4 proteins were down-regulated in DAT group, while 6 proteins were up-regulated and 4 proteins were down-regulated in MCI group(all P<0.05).Compared with the NC group, 6 proteins were upregulated in both MIC group and DAT group, which were clusterin(Clust) (613.41(278.89), 761.76(358.60), 473.01(321.73)), cystatin C(Cys C) (691.88(441.34), 852.28(551.75), 548.64(545.28)), transthyretin(TTR) (207.10(168.60), 220.95(151.20), 152.89(162.70)), complement factor H(Com FH) (331.67(218.37), 361.69(124.64), 225.79(236.82)), soluble intercellular adhesion molecule-1(sICAM1) (109.30(49.47), 137.21(50.36), 87.06(57.59), and apolipoprotein E(APOE) (79.33(78.13), 79.31(68.85), 54.88(67.34)).The serum amyloid P component(SAP) was downregulated in both DAT and MCI groups(121.23(311.31), 92.39(156.62), 125.00(242.82)) compared with NC group.(2)Three sets of protein combination were screened by differential analysis, regression analysis, and discriminant analysis, including 8 proteins, 9 proteins and 7 proteins, respectively.And SAP, angiotensin (AGT), osteopontin (OPN), and complement C4 (Com C4) were the compared with NC group most frequently selected protein.The screening correct rate of three protein combinations were respectively 67.4%-71.4% for AD, 82.4%-88.4% for DAT, and 60.6%-63.5% for MCI. Conclusions:A variety of plasma proteins such as Clust, Cys C, TTR, Com FH, sICAM1, APOE are upregulated, while SAP is downregulated in AD patients.These differential protein combinations can help with early diagnosis of dementia with Alzheimer type.SAP, AGT, OPN and Com C4 may be potential markers for early screening or diagnosis of AD.

Objective:To evaluate association of peripheral blood brain-derived neurotrophic factor (BDNF) with Alzheimer's disease (AD) .Methods:Databases including Pubmed, Cochrane library, Web of science, Embase, China National Knowledge Infrastructure, CBM disc, VIP-CSTJ and Wanfang Data were used to collect case-control studies related to the concentration of BDNF in peripheral blood of dementia patients with Alzheimer's type(DAT) and mild cognitive impairment(MCI). After extracting data and appraising the quality of the included studies, meta-analysis were conducted using Review Manager 5.3 and CMA 3.0.Results:A total of 51 articles were included in the analysis, with a total subjects of 7 182, including 2 673 subjects in DAT group, 1 506 subjects in MCI group, and 3 003 subjects in control group.The Meta-analysis showed that the levels of peripheral blood BDNF in patients with DAT were significantly lower than normal control group(SMD=-0.71, 95% CI : -0.99--0.43, P<0.001) ( n=5 111), and there were no statistical differences in peripheral blood BDNF levels between MCI group and control group and between DAT group and MCI group.The subgroup analysis showed that the level of serum BDNF in patients with DAT (SMD=-0.85, 95% CI: -1.15--0.55, P<0.001)( n=4 425) and MCI(SMD=-0.38, 95% CI: -0.62--0.14, P=0.002)( n=2 476) was significantly lower than that in normal control group, and the level of serum BDNF (SMD=-0.76, 95% CI: -1.37--0.16), P=0.01)( n=1 630) in patients with DAT was lower than that in MCI; However, there were no statistical difference among DAT, MCI and control groups in the level of plasma BDNF( P>0.05). Conclusion:The patients with DAT and mild cognitive impairment have lower level of serum BDNF, which suggesting that serum BDNF level may be a potential biomarker for early diagnosis of AD.

Objective:To investigate the mechanism of subjective cognitive decline(SCD)in resting-state by using regional homogeneity(ReHo)and functional connectivity(FC)in SCD patients.Methods:Resting-state functional magnetic resonance imaging(RS-fMRI)was performed in 25 SCD patients and 30 normal controls matched by sex, education and nationality.DPARSFA2.3 and SPM8 software were used to analyze and screen the brain areas with abnormal ReHo values in SCD group, with the posterior cingulated(PCC)/paruneus as seed points for whole-brain FC analysis.Results:Compared with the normal control group, the SCD group showed that ReHo values of right occipital gyrus and left precuneus were increased, and ReHo values of right inferior temporal gyrus, right orbital inferior frontal gyrus and bilateral thalamus were decreased(Voxel level, Alphasim correction, P<0.05). Using PCC/ precuneus as seed voxels, the whole brain functional connectivity analysis showed that the functional connectivity with cerebelum Crus 2 R was increased, and the functional connectivity with right orbital inferior frontal gyrus, left inferior temporal gyrus and temporal pole was reduced(Voxel level, Alphasim correction, all P<0.05). Conclusions:Default mode network may play an important role in the mechanism of SCD, and abnormalities in brain areas may first occur in PCC/precuneus.

Objective:To develop the screening checklist of brief interview for autism disorder suitable for Chinese children and evaluate its reliability and validity.Methods:Based on existed research results and diagnostic criteria for autism spectrum disorder of DSM-5, the screening checklist of brief interview for autism spectrum disorder(SCAD) was developed. A sample of 238 children were selected for investigation and 28 of them were retested for test-retest reliability with 2-4 weeks interval. Cronbach's α coefficient, split-half correlation coefficient, test-retest reliability, and evaluator consistency were used to test the reliability of the scale. Content validity, construct validity and empirical validity were used to test the validity of the scale.All statistical analysis were conducted by SPSS 22.0 and AMOS 17.0.Results:The SCAD contains two components and six dimensions, with a total of 25 items. The Cronbach's α coefficient was 0.936 for the total scale and were 0.938, 0.771 for the two components. The split-half coefficient for the total scale and the two components were 0.962, 0.938 and 0.794. The test-retest reliability for the total scale and the two components were 0.806, 0.795 and 0.766. The Kendall coefficient for the total scale and the two components were 0.968, 0.982 and 0.950. The SCAD item-level content validity index (I-CVI) ranged from 0.66 to 0.98 and the Kappa value ranged from 0.66 to 0.98. The scale-level content validity S-CVI/UA and S-CVI/Ave were 0.89 and 0.94. The correlations between SCAD and calibration tests such as ABC, CARS and M-CHAT were 0.54, 0.53 and 0.87, and the correlation coefficients with the M-CHAT-R/F between the two components were 0.87 and 0.76 respectively (both P<0.01). The result of CFA demonstrated that the model fitted the data with well construct validity(χ 2/ df=0.910, RMR=0.049, AGFI=0.974, RMSEA=0.010, PNFI=0.530, PCFI=0.533, NFI=0.994, RFI=0.988, CFI=1.000). The correlation coefficient of the two components was 0.88 and that with the total scale were 0.97 and 0.90, each dimensions with the total scale ranged from 0.72 to 0.93. Conclusion:The SCAD has a good reliability and validity, and it can be used as a clinical screening tool for children with autism spectrum disorder.

Objective:To investigate regional homogeneity(ReHo)and whole brain functional connectivity(FC)in patients with mild cognitive impairment(MCI), and to explore the mechanisms of MCI in the resting state.Methods:Resting-state functional magnetic resonance imaging(RS-fMRI)was performed on 24 patients with MCI and 30 age, gender and nationality-matched normal controls.Abnormal brain areas in the MCI group were screened and analyzed by using the DPARSFA2.3 and SPM8 software programs.Whole brain FC analysis was performed with the posterior cingulate cortex(PCC)/precuneus as the seed points.Results:Compared with the control group, MCI subjects displayed higher ReHo values in the frontal-middle-Left, precentral-Left, postcentral-Left, rolandic-opercular-Left, and frontal-inferior-opercular-Left and lower ReHo values in the temporal-superior-right, temporal-middle-right, postcentral-right, and temporal -pole -superior -right(Voxel level, Alphasim correction, P<0.05). Whole brain FC analysis showed greater functional connectivity of PCC/precuneus with fusiform-right, thalamus-right, lingual-right and parahippocampal-right in subjects with MCI, and less functional connectivity of the PCC/precuneus with temporal-middle-Left, angular-Left, temporal-superior-Left and occipital-middle-Left in subjects with MCI(Voxel level, Alphasim correction, P<0.05). Conclusions:Abnormalities of the default mode network may be associated with the onset of MCI, and abnormalities in posterior cingulate/precuneus connectivity may be helpful in finding imaging evidence with high sensitivity to MCI.

Objective:To verify the validity of the clinical dementia rating(CDR) for early screening of Alzheimer's disease in the community.Methods:One thousand two hundred and eighty-one community volunteers (580 males and 701 females) came to hospital for clinical interviews, laboratory tests and a series of psychological assessment, including CDR, brief elderly cognitive screening inventory (BECSI), quickly cognitive screening scale for elderly (QCSS-E), mini-mental state examination (MMSE) and core neurocognitive test (CNT). According to clinical interview, assessment and DSM-5 criteria, 623 normal cognition, 570 mild cognitive impairment (MCI) and 88 dementia with Alzheimer's type (DAT) were screened.Results:(1) The results of CDR-global scores (CDR-GS)in the community volunteers showed that 506 (39.5%) scored 0, 688 (53.7%) scored 0.5, 72 (5.6%) scored 1, and 15 (1.2%) scored 2 or more.(2) There were significantly differences on the BECSI score, QCSS-E score, MMSE score and CNT score among people with different CDR-GS ( P<0.01). In the total or dementia sample, CDR-sum of box score (CDR-SB) and CDR-GS were significantly correlated with BECSI score ( r=0.577-0.639), QCSS-E score ( r=-0.586--0.680), MMSE score ( r=-0.570--0.764) and CNT score ( r=-0.244--0.357)( P<0.01). (3) The accuracy (95.8%) and specificity (99.8%) of the CDR-GS screening DAT were slightly higher than those of the CDR-SB(91.1%, 92.0%), and its sensitivity (65.9%) was lower than that of CDR-SB(82.5%). The accuracy (72.6%), sensitivity (81.9%) and specificity (64.0%)of the CDR-GS were close to those of CDR-SB(72.1%, 83.3%, and 61.8% respectively) in screening MCI. Conclusion:The CDR can be used for screening of AD in community populations.CDR-GS and CDR-SB have their own advantages, and combination of both advantages can improve the screening efficiency.

Objective: To investigate the neurocognitive characteristics and related factors in the elderly with subjective cognitive decline. Methods: Among the 1 850 elderly volunteers aged over 50, 377 cognitive normal elderly (NC group), 234 subjective cognitive decline (SCD Group) and 291 patients with mild cognitive impairment (aMCI Group) were screened with the brief elderly cognitive screening questionnaire and the elderly rapid cognitive screening scale.They were all received clinical interview and examination and core neurocognitive test. Results: (1) There were statistically significant differences in the three groups on the age, education, occupation, HAMD, low density lipoprotein and blood pressure (P<0.01). (2) The score of the picture-symbol association in SCD group(8.94±4.05)was lower than that in NC group(9.83±4.18)and higher than that in aMCI group (7.12±4.17)(all P<0.05), while the scores of the other neuropsychological tests were higher than those in aMCI group.There were no statistically significant difference between SCD group and NC group on the other neuropsychological tests(P>0.05). (3)The SCD was mainly influenced by age(β=0.063, OR=1.065, 95%CI=1.033-1.099), depression(β=0.182, OR=1.199, 95%CI=1.084-1.327)and hypertension(β=0.473, OR=1.604, 95%CI=1.185-2.171)(all P<0.01). And the aMCI was mainly influenced by age(β=0.078, OR=1.081, 95%CI=1.048-1.115), education(β=-0.174, OR=0.840, 95%CI=0.778-0.907), occupation(β=-0.406, OR=0.666, 95%CI=0.535-0.830)and low density lipoprotein(β=-0.451, OR=0.637, 95%CI=0.497-0.816)(all P<0.01 ). Conclusion Objective neurocognitive function of the elderly with subjective cognitive decline is basically normal.Age, depression and hypertension are risk factors of subjective cognitive decline.

Objective: To verify the criteria validity and effectiveness of the QCSS-E for screening of mild cognitive impairment (MCI) and early dementia with Alzheimer's type (DAT) among the elderly in community. Methods: With stratified convenient sampling, 1 298 elderly aged 55 and over recruited from Wuxi community, who finished the clinical interviews, laboratory examination and psychological tests such as QCSS-E, ADL, MMSE, ADAS-cog, CDR, and Core Neuropsychological Test.Then they were divided into health control group(HC), MCI group and DAT group by the diagnostic criteria of Peterson’s MCI and DSM-5 AD dementia.The criteria validity and screening efficacy of QCSS-E were verified and the optimal cut off value for detecting MCI and DAT were explored. Results: There were statistically significant differences in age, education level, marital status, family structure, occupation, and scores of MMSE, ADAS-cog, CNT, and QCSS-E total score and domain scores among three groups (all P<0.01). The total score and every domains score of QCSS-E were significantly correlated with test scores such as MMSE, ADAS-cog and CNT (all P<0.01). Using the total QCSS-E score to discriminate MCI from health control, the area under the curve (AUC) was 83.5%. When the cut off value was 74.5, the accuracy rate of classification was the highest (75.0%). Using the total QCSS-E score to discriminate DAT from health control, the AUC was 83.5%. When the cut off value was 64.5, the accuracy rate of classification was the highest (94.2%). Conclusion The QCSS-E has better criteria validity and higher effectiveness in screening MCI and DAT.

Objective To develop anxiety scale suitable for Chinese pregnant women and evaluate its reliability and validity. Methods Based on existing research results and clinical experience,this study compiled pregnancy anxiety scale(PAS). A sample of 509 pregnant women were selected for investigation and 65 of them were randomly retested for test-retest reliability with 2 week interval. Item analysis was con-ducted to screen valid items. Then the construct validity of the scale was tested by exploratory factor analysis ( EFA) and confirmatory factor analysis(CFA). Finally the reliability and criterion validity of the scale were evaluated using Cronbach's α coefficient,retest reliability coefficient and Pearson correlation coefficient. Re-sults The PAS was composed of 27 items in four factors,including worry about delivery,worry about them-selves,worry about fetal health and general anxiety. The four factors were extracted by EFA which could ex-plain 62. 48% of the total variance. Besides,the result of CFA demonstrated that the model fitted the data with well construct validity (χ2/df=1. 89,RMR=0. 04,RMSEA=0. 06,IFI=0. 92,TLI=0. 91,CFI=0. 92, PGFI=0. 70,PNFI=0. 74,PCFI=0. 81). The score of the pregnancy-related anxiety scale and its factors scores were positively correlated with the scores of pregnancy-related anxiety questionnaire(PAQ) and child-birth attitudes questionnaire(CAQ). The correlation coefficients were 0. 60-0. 80 and 0. 50-0. 78 respectively (all P<0. 01). The Cronbach's α coefficient was 0. 93 for the total scale and that of the four factors ranged from 0. 82 to 0. 90. The test-retest reliability was 0. 68 for the total scale and ranged from 0. 54 to 0. 75 for the four factors. Conclusion The PAS has a good reliability and validity,and it can be used as a valid tool to measure the anxiety level of pregnant women.

Objective To investigate the comprehensive effect and impact path of family environment,rearing style and personality on adolescents with mental disorder.Methods A sample of 200 adolescents with mental disorders and 228 normal adolescents were tested with Family Environment Scale (FESCV),Family Upbringing Style Questionnaire (FUSO),Big Five Personality Questionnaire (NEO-FFI-R) and Psychological Symptom Inventory-100(PSI-I00).Regression analysis and path analysis were used to explore influence and path of rearing style,family environment and personality on mental health.Results The total score PSI-100 in case group (204.0±68.6) was higher than that in control group (146.9±38.4)(t=10.43,P＜0.01).Regression analysis revealed that mental health was affected by rearing style (R2 =0.208) such as mother supervision-control (β =-0.249),father understands-blame (β =-0.195),mother warmth-wildness (β=-0.228) and mother acceptance-rejection (β=0.201),family environment (R2 =0.244) such as conflict (β=0.309),organization (β=-0.196) and expressiveness (β=-0.141),and personality traits (R2 =0.452)such as neuroticism (β=0.412),agreeableness (β=-0.237) and conscientiousness (β=-0.203).Path Analysis showed that personality traits directly affected mental health (β=-0.90),parenting style indirectly influenced mental health (β=0.51) by personality,the family environment had direct (β=0.20) and indirect (β=0.72) effects on mental health,and the model fits well (x2/df =2.160,RMSEA =0.052,GFI =0.88,AGFI =0.84,PGFI =0.67,NFI =0.91,RFI =0.89,IFI =0.95,TLI =0.94,CFI =0.95),and three factors explained 61％ of variation on symptom total score.Conclusion The family environment,family upbringing style and personality traits have significant effect on the adolescent's mental disorder.The personality traits are the most important variables affecting mental health family upbringing style affect mental health indirectly through personality traits,and family environment directly and indirectly affected on the mental health.