Brainppt课件

1、Genetic impact on cognition and brain function in newly diagnosed Parkinsons disease: ICICLE-PD study,Lab of Neuroscience of West China Hospital Zhao Xiaoyan 2014.09.27,1,.,Contents,Tower of London Task,2,.,Tower of London Task,Prefrontal executive function； three levels of difficulty； No feedback ；

2、The dependent variables were the latency of response,3,.,Spatial Rotations Task,Spatial impairments This task to probe posterior cortical function (后皮质),4,.,Memory Encoding Task,5,.,Memory Encoding Task,Memory deficits in PD are most related to encoding Linked to hippocampal function 5 15 s of six i

3、mages for 4 s each 30 different images in the scanner 18 of them appeared once,12 appeared twice,6,.,Abbreviations,DLPFC = 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 = lev

4、odopa equivalent daily dose MMSE = 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 Test MDS-UPDRS= Unified Parkinsons Disease Rating Scale,7,.,Inclusion and exclusion,Exclusion 1. Parkinsonism diagnosed before the onset of the inci

5、dence study 2. insufficient working knowledge of English to perform the neuropsychological assessment 3.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 symp

6、toms indicative of vascular parkinsonism,Inclusion incident Parkinsons disease UKPDS : the United Kingdom Parkinsons Disease Society Brain Bank diagnostic criteria,8,.,Preparation,Participants undertook clinical and neuropsychological assessments ： the Unified Parkinsons Disease, MDS-UPDRS , MMSE ,

7、NART estimate of premorbid IQ; verbal fluency for words and semantic fluency, LEDD value Patients were assessed ON their usual dopaminergic medication. DNA was extracted from peripheral blood Genotyping for rs4680 (COMT Val 158 Met), rs9468 (MAPT H1 versus H2 haplotype) rs429358 plus rs7412 (APOE ge

8、notype 14),9,.,Results,Fig 1 Activity during planning minus control condition on Tower of London Task Activity 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= 0.0

9、5 after FDR correction for the whole brain volume,Basic condition,10,.,Results,Gender, age, MOCA and MMSE scores were matched between groups and sites,11,.,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

10、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.,Results,12,.,Behavioral performance by groups,Results Tower

11、 of London,Fig 2 (A) Latency of response Tower of London, difficulty manipulated by number of movements required,13,.,Results,Functional MRI regional activity of Tower of London,A significant interaction between genotype and LEDD, in the right DLPFC, left DLPFC , right frontopolar, right caudate and

12、 left caudate,14,.,Figure 3 Tower of London Task, the activation in regions of interest is presented separately by COMT genotype and LEDD (above versus below 275 mg/day) in patients,Results Tower of London,15,.,Company Logo,Conclusion 1,A shorter response latency in younger subjects with a higher nu

13、mber of years of education, higher MMSE, higher MOCA and greater letter fluency,A 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 variance,16,.,Results S

14、patial 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 difficul

15、t items than controls.,17,.,Results Spatial Rotations Task,18,.,Results,Functional MRI regional activity of Spatial Rotations Task,Results Spatial Rotations Task,19,.,Figure 5 For the Spatial Rotations Task, the activation within each region of interest is plotted separately for H1 patient homozygot

16、es and H2 patient carriers.,Results Spatial Rotations Task,20,.,Company Logo,Conclusion 2,21,.,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 o

17、f 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-

18、parieto-occipital,Results Encoding Memory Task,24,.,Conclusion 3,25,.,1. Soon after diagnosis, already changes in brain function and cognitive performance 2. The regional activations associated with three major cognitive domains interact with genotype in the context . 3.The anatomical, functional, genetic