Correlation between heme oxygenase-1 gene rs2071746 polymorphism and long-term outcome in patients with ischemic stroke / 国际脑血管病杂志

Objective To investigate the association between heme oxygenase-1 (HO-1) gene rs2071746 polymorphism and long-term clinical outcome in patients with ischemic stroke.Methods Between July 2015 and June 2017,consecutive patients with acute ischemic stroke admitted to the Department of Neurology,the Third Affiliated Hospital of Soochow University were enrolled prospectively.TOAST classification was performed for all patients.Genotyping of the HO-1 gene rs2071746 polymorphism was performed using a modified multiplex ligase detection reaction technique.The patients were followed up.The primary endpoint events included ischemic stroke,vascular death,and myocardial infarction.Multivariate Cox proportional hazard regression model was used to analyze the independent influencing factors for primary endpoint events.Results A total of 1 698 patients with successful genotyping and follow-up information were enrolled.Genotyping showed that the frequency of rs2071746 A allelewas 44.91％.They were followed up for 15.21 ± 7.39 months,and 168 patients (9.89％) had primary endpoint events.The incidence of primary endpoint events in A allele carriers was significantly lower than that in non-A allele carriers (8.80％ vs.12.40％;P =0.018).Multivariate Cox proportional risk regression model showed that after adjusting for age,gender,hypertension,diabetes mellitus,smoking,alcohol consumption,and genotype,A allele was an independent protective factor for primary endpoint events in patients with acute ischemic stroke (hazard risk [HR] 0.693,95％ confidence interval [CI]0.506-0.949;P=0.022).Subgroup analysis showed that carrying the A allele was an independent protective factor for primary endpoint events in patients with large atherosclerotic stroke (HR 0.651,95％ CI 0.425-0.997;P=0.048),while rs2071746 polymorphism was not associated with long-term outcome in other etiological subtypes.Conclusion The HO-1 gene rs2071746 A allele may be a protective factor for the long-term outcome in patients with acute ischemic stroke and large atherosclerotic stroke.

Microcalcification and vulnerability of atherosclerotic plaques / 国际脑血管病杂志

It has been previously thought that calcification is a feature of the stability of atherosclerotic plaques. However, recent studies have shown that microcalcification in atherosclerotic plaques is significantly associated with plaque vulnerability. The relationship between atherosclerotic plaques and calcification is unclear, and the specific role of calcification in atherosclerotic plaques remains controversial.

White matter change in diffusion tensor imaging of amnestic mild cognitive impairment / 中华神经科杂志

Objective To investigate the features of white matter impairment and its relationship with cognition in patients with amnestic mild cognitive impairment (aMCI).Methods Eighty-three cases of aMCI and 85 normal aging volunteers were scanned with diffusion tensor imaging (DTI) using MR system.All subjects completed the neuropsychological battery.We analyzed the differences between two groups using tract-based spatial statistics and the association between regions in difference and cognition using correlation analysis.Results There were significant differences between aMCI and normal control in the neuropsychological battery including the Mini-Mental State Examination(26.2 ± 2.6 vs 28.3 ± 1.3,F =43.224,P =0.000),Mattis Dementia Rating Scale-2 (131.4 ± 6.9 vs 138.0 ± 3.5,F =62.308,P =0.000),Auditory Verbal Learning Test-delayed recall(2.4 ± 1.6 vs 7.5 ± 2.0,F =324.018,P =0.000),Boston Naming Test(8.7 ± 1.4 vs 9.2 ± 1.0,F =6.821,P =0.010),Rey-Osterrich Complex Figure Test (12.1 ± 7.3 vs 18.5 ± 6.1,F =40.674,P =0.000),Symbol Digit Modulation Test (30.0 ± 10.1 vs 38.6 ± 9.8,F =30.786,P =0.000),Trail-Making Test Part B ((256.8 ± 124.5) s vs (178.1 ± 59.0) s,F =27.601,P =0.000).Significantly higher diffusivity indexes and radial diffusivity were also found in aMCI subjects compared to healthy elders in the parahippocampal,superior longitudinal fasciculus,inferior longitudinal fasciculus,superior fronto-occipital fasciculus,inferior fronto-occipital fasciculus,unciform fasciculus,corticospinal tract,corpus callosum,cingulum,corona radiate.We also found that axial diffusivity was significantly increased in the parahippocampal,superior longitudinal fasciculus,inferior longitudinal fasciculus,superior fronto-occipital fasciculus,inferior fronto-occipital fasciculus,unciform fasciculus,corticospinal tract and corpus callosum,whereas fractional anisotropy changes were not observed in aMCI.Diffusivity indexes values in bilateral frontal lobe (left r =0.67 ; right r =0.70),left cingulum (r =0.63),parietal white matter (r =0.69) and radial diffusivity values in left parietal (r =0.68) were significantly related to Trail Making Test A among aMCI (all P ＜ 0.05).Conclusions In aMCI patients,there was a wide range of white matter damage,with no brain region-specific.Executive function deficit was related to the white matter impairment in bilateral frontal lobe,left cingulate and parietal lobe.The specificity and sensitivity of four DTI parameters fordetecting white matter lesions are variant.Trial registration Clinical Research Center of Jiangsu Province (BL2013025)

Association study of candidate gene polymorphisms of tau protein pathway with amnestic mild cognitive impairment / 中华神经科杂志

Objective To investigate the relationship between amnestic mild cognitive impairment and functional genes associated with hyperphosphorylated tau protein.Methods One hundred and sixteen amnestic mild cognitive impairment (aMCI) patients and 93 normal controls were recruited for the study.Multi-dimension neuropsychologic tests were used to assess the cognitive function extensively.MassARRAY and iPlex systems were used to measure candidate SNP polymorphisms,analyze genotypic,allelic or haplotypic distributions and their interaction with ApoE ε4 and the correlation with the cognitive function in the subjects.Results ( 1 ) The scores of neuropsychologic tests in memory domain ( Auditory Verbal Learning Test (AVLT)-first immediate recall,AVLT-second immediate recall,AVLT-second immediate recall,AVLT-5 minute delayed recall,AVLT-20 minute delayed recall,AVLT-recognition,Rey-Osterrich Comolex Test-delay) in aMCI patients ( 3.0 ( 0-7.0 ),5.0 ( 1.0-10.0),6.0 ( 1.0-11.0 ),4.0 (0-11.0),3.0(0-10.0),20.0(8.0-24.0),11.2 ±8.3) were significantly lower than those in the normal controls(4.0(0-9.0),7.0(2.0-11.0),9.0(3.0-12.0),8.0(0-12.0),8.0(0-12.0),22.0 (10.0-24.0),16.1±8.0) (Z=-3.592,-6.802,-6.408,-8.173,-8.533,-5.647 andt=4.216 respectively,all P ＜0.01 ) ; (2) Genotypic distributions of rs242562 GG in aMCI (7.826％ ) were significantly lower than those in normal controls (20.65％,OR =0.3525,95％ CI 0.1411-0.8807,P =0.024 98),however there were no differences in the genotypic,allelic or haplotypic distributions between aMCI patients and controls of glycogen synthase kinase-3β,cyclin dependent protein kinase-5,calcium and calmodulin-dependent protein kinase-Ⅱ,cell division cycle 2,dual-specificity tyrosine-phosphorylation regulated kinase 1A and low density lipoprotein receptor-related protein 6; (3) MAPT/STH rs242562 genotype was correlated with AVLT-immediate recall,AVLT-delayed recall,Rey-Osterrieth Complex Test,Rey-Osterrieth Complex Test-delayed recall and Clock Drawing Test (H =9.763,12.258,10.508,9.624,10.767,F =3.700,3.123 and H =6.591 respectively,all P ＜ 0.05 ) ; (4) There were no differences in the distributions of MAPT/STH rs242562 GG genotype and ApoE ε4 haplotype between aMCI patients and normal controls.Conclusions MAPT/STH rs242562 GG genotype decreases the genetic risk of aMCI,which might have important role in memory function in aMCI.The interaction between rs242562 GG and ApoE ε4 doesn' t affect the susceptibility to aMCI.

Association of single nucleotide polymorphisms in inflammation-related genes with amnestic mild cognitive impairment / 中华行为医学与脑科学杂志

ObjectiveTo examine whether the single nucleotide polymorphisms in inflammation-related genes are associated with the risk of amnestic mild cognitive impairment (aMCI).MethodsThe study recruited 116 aMCI patients and 93 matched healthy controls.All subjects underwent extensive assessment of cognitive function,genotyping was carried out on the platform of matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry.Results ( 1 ) There was prominent discrepancy between aMCI and controls in the memory,attention and executive functions,20 minutes delayed recall of auditory verbal memory test (AVMT) (3.0(0.0 ～ 10.0 ),8.0 (0.0 ～ 12.0),t =- 8.533,P ＜ 0.05 ),recall of Rey-Osterrieth complex figure test ( R-O CFT) (11.2 ±8.3,16.1 ±8.0,t=4.216,P＜0.05),digit span test (DST) (12.0(7.0 ～ 19.0),13.0(7.0 ～20.0),Z=-2.516,P＜0.05),trail making test A (TMTA) (80.0s(35.0 ～200.0)s,72.0s(29.0 ～512.0)s,Z=-3.113,P＜0.05),trail making test B (TMTB) ((180.1 ±72.7)s,(141,7 ±52.1)s,t=-4.385,P＜0.05 ).(2) No significant differences were found in frequencies of alleles,genotypes and hapolotypes of inflammation mediator genes ( interleukin 10,interleukin 1 A,interleukin 1 B,tumor necrosis factor,interleukin 6,α1- an-tichymotrypsin gene,transforming growth factor B1 ) between aMCI and controls (P ＞ 0.05 ).ConclusionThe results indicate that polymorphisms in the inflammation-related candidate genes do not appear to be involved in the risk of developing aMCI.

Feasibility study of the Montreal cognitive assessment of Chinese version for the detection of vascular cognitive impairment-no dementia in Han population / 中华行为医学与脑科学杂志

Objective To explore feasibility of the Chinese version of MoCA for the detection of vascular cognitive impairment-no dementia (VaCIND) and control in a cross-sectional study. Methods One hundred and three Chinese Han were assessed by the MoCA and MMSE. 64 met criteria for VaCIND and 39 were considered cognitively normal. Sensitivities and specificities were calculated using the recommended cut-off scores,and ROC curve analyses were performed to determine optimal sensitivity and specificity. Results No differences were found between groups on age,gender,education degrees. According to their MoCA scores,cognitive impairments including memory,visuospatial, executive function, attention, language, and orientation sub-scores in VaCIND ((0.44 ± 0.96), (2.13 ±1.40), (1.90 ±1.02), (4.61 ±1.41), (4.23 ±1.40), (5.38 ±1.15)) significantly decreased compared with that in controls((2.92 ± 1.42) ,(3.16 ± 1.08) ,(3.32 ± 1.07) ,(5. 87 ±0.41) ,(5.34 ±0.75), (5.79 ±0. 70)) (P<0. 05). The MMSE scale was insensitive to cognitive impairment as compared with MoCA scale. Using cut-off score of 24,the MoCA exhibited excellent sensitivity (0.923) and specificity (0.906). Conclusion MoCA is a more sensitive instrument than the MMSE for the detection of VaCIND and warrants further investigation regarding its applicability in large group and varying ethnic groups.

Cognitive changes in amnestic mild cognitive impairment:a follow-up study / 中华行为医学与脑科学杂志

Objective To investigate outcome and cognitive changes of amnestic mild cognitive impairment (aMCI) in a follow-up study. Methods A cross-sectional and longitudinal parallel cohort study design was conducted among 109 aMCI patients and 104 matched normal controls. Multi-dimension neuropsychologic tests were used to extensively assess the cognitive function. Results The scores of neuropsychologic tests in aMCI patients were significantly lower than those in the normal controls( all P＜0.01 ) ,with the largest impairment on 20minutes delayed recall of the auditory verbal memory test ( AVMT), which reflects episodic memory ( aMCI pa-tients :2.50 ± 1.48, normal controls :7.85 ± 1.59, Z = - 12.697, P ＜ 0.01 ); AD was diagnosed in 15 of the 69aMCI patients with a prevalence rate of 22% ,but none was converted to AD in the normal controls. The cognitivechanges of performance in AVMT, CDT, MMSE of the patients in aMCI group (( 3.77 ± 60.83 )%, (6.89 ±28.24) %, (6.13 ± 16.89) % respectively) were significantly poorer than those of the controls group(( - 10.75 ±27.46) %, ( - 5.23 ± 14.05 ) %, ( - 1.11 ± 8.26 ) % respectively) ( all P ＜ 0.05 ). At baseline, demented aMCIperformed poorer in AVMT, CFT, TMT, SDMT, CDT, MMSE when compared to stable. During the follow-up, demented aMCI groups performed significantly poorer than did stable subjects in AVMT, CFT, DST, VFT, SDMT,MMSE ( all P ＜ 0.05 ). Conclusion aMCI is a prodromal period of AD and characterized by episodic memory impairment. The neuropsychologic test is a predictive factor for aMCI to develop AD.