Brainppt课件.pptx

LOGOGenetic impact on cognition and brain function in newly diagnosed Parkinsons disease:ICICLE-PD study Lab of Neuroscience of West China Hospital Zhao Xiaoyan 2014.09.271.Contents 1Spatial Rotations Task2Memory Encoding Task3 Functional MRI4Tower of London Task2.Tower of London Taskv Prefrontal executive function；three levels of difficulty；No feedback；The dependent variables were the latency of response3.Spatial Rotations TaskSpatial impairmentsThis task to probe posterior cortical function(后皮质)4.Memory Encoding Task5.Memory Encoding Task Memory deficits in PD are most related to encodingLinked to hippocampal function 5 15 s of six images for 4 s each 30 different images in the scanner18 of them appeared once,12 appeared twice 6.AbbreviationsDLPFC=dorsolateral prefrontal cortex 背外侧前额叶皮层ICICLE-PD=Incidence of Cognitive Impairment in Cohorts with Longitudinal Evaluation Parkinsons Disease 在PD的纵向队列研究中认知功能障碍的发生率LEDD=levodopa equivalent daily doseMMSE=Mini-Mental State Examination 简易精神状态测试MOCA=Montreal Cognitive Assessment 蒙特利尔认知评估量表NART=National Adult Reading TestMDS-UPDRS=Unified Parkinsons Disease Rating Scale7.Inclusion and exclusion Exclusion1.Parkinsonism diagnosed before the onset of the incidence study2.insufficient working knowledge of English to perform the neuropsychological assessment3.dementia at presentation 4.criteria for dementia or Movement Disorder 5.history or examination suggestive of dementia with Lewy bodies,MSA,PSP,repeated strokes or stepwise progression of symptoms indicative of vascular parkinsonismInclusionincident Parkinsons disease UKPDS:the United Kingdom Parkinsons Disease Society Brain Bank diagnostic criteria8.PreparationvParticipants undertook clinical and neuropsychological assessments：vthe Unified Parkinsons Disease,MDS-UPDRS,MMSE,NART estimate of premorbid IQ;verbal fluency for words and semantic fluency,LEDD value vPatients were assessed ON their usual dopaminergic medication.vDNA was extracted from peripheral bloodvGenotyping for rs4680(COMT Val 158 Met),rs9468(MAPT H1 versus H2 haplotype)rs429358 plus rs7412(APOE genotype 14)9.ResultsFig 1Activity during planning minus control condition on Tower of London TaskActivity during rotations minus baseline on Spatial Rotations Task Activity during encoding minus baseline on the Encoding Memory Task Figures show areas of signal change above a threshold of P=0.05 after FDR correction for the whole brain volume Basic condition10.Results1.Gender,age,MOCA and MMSE scores were matched between groups and sites11.2.For years of education,fewer years at Site 2,and a main effect of disease group:controls spent longer in formal education 3.category and letter fluency scores,there were differences between groups(higher score in controls)and sites(higher scores at Site 1)4.an interaction between disease and site for category fluency with relatively higher scores in controls at Site 1.Results12.Behavioral performance by groups Results Tower of LondonFig 2 (A)Latency of response Tower of London,difficulty manipulated by number of movements required13.ResultsFunctional MRI regional activity of Tower of LondonA significant interaction between genotype and LEDD,in the right DLPFC,left DLPFC,right frontopolar,right caudate and left caudate14.Figure 3Tower of London Task,the activation in regions of interest is presented separately by COMT genotype and LEDD(above versus below 275 mg/day)in patientsResults Tower of London15.Company Logo1 1 More difficult planning items required longer response times2 23 3 Conclusion 1 A shorter response latency in younger subjects with a higher number of years of education,higher MMSE,higher MOCA and greater letter fluencyA stepwise multiple regression indicated:the MMSE explained significant variance in latency a model of explanatory variables that included years of education,MOCA,NART,explaining 24.5%of the variance16.Results Spatial Rotations Task Behavioral performance by groups(B)Spatial Rotations Task Difficulty manipulated by the complexity of the items to rotate Repeated-measures ANOVA revealed a significant effect of site(about accuracy)but no effect of disease Patients need longer times to perform more difficult items than controls.17.Results Spatial Rotations Task 18.ResultsFunctional MRI regional activity of Spatial Rotations TaskResults Spatial Rotations Task 19.Figure 5 For the Spatial Rotations Task,the activation within each region of interest is plotted separately for H1 patient homozygotes and H2 patient carriers.Results Spatial Rotations Task 20.Company Logo1 1 Accuracy was higher in younger volunteers and those with higher category fluency,with weak trends for years of education2 2 The Parkinsons disease group with lower UPDRS-III score achieved higher accuracy and there was a weak trend for shorter duration of disease3 3Significant effects were localized to the left parietal and precuneus H2 carriers reached significantly higher values than H1 homozygotes in the right caudate,left caudate and left parietalConclusion 221.Results Encoding Memory Task (C)Encoding Memory Task,difficulty manipulated by the number of expositions C1 shows responses times during the post-scan test for patients and controls C2 shows the number of correct responses for patients and controls *Significant interaction 22.Results Encoding Memory Task 23.Figure 6 Regional activation in the Encoding Memory Task,illustrating the significant interaction between regional activation and APOE genotype in Parkinsons disease patients TPO=temporo-parieto-occipital Results Encoding Memory Task 24.1 1duration of disease explained 12.4%of the variance.2 2 Patients have lower activations in the left hippocampus,left inferior frontal gyrus,right inferior frontal gyrus pars triangularis,right inferior frontal gyrus pars opercularis left parietal left occipital and TPO-areas3 3An interaction between region of interest and APOE genotype with APOE4 carriers manifesting lower activation.Conclusion 325.1.Soon after diagnosis,already changes in brain function and cognitive performance2.The regional activations associated with three major cognitive domains interact with genotype in the context.3.The anatomical,functional,genetic and behavioural data support the dual syndrome hypothesis:(i)an executive syndrome that is frontally mediated,dopamine-dependant and modulated by COMT genotype(ii)a temporo-parietal system subject to MAPT and APOE,but not dopaminergic modulationConclusion 426.LOGO27.