Showing papers by "Bernard Mazoyer published in 2012"
University of Washington1, University of California, Davis2, University of Iceland3, Erasmus University Rotterdam4, Centre national de la recherche scientifique5, University of Bordeaux6, University of Texas Health Science Center at Houston7, Boston University8, French Institute of Health and Medical Research9, Harvard University10, Broad Institute11, Medical University of Graz12, University of Tasmania13, Monash University14, Rush University Medical Center15, university of lille16, Mayo Clinic17, Université de Montréal18, Wake Forest University19, University of Queensland20, Illinois Institute of Technology21, Leiden University22, University of Mississippi23, Delft University of Technology24, University of California, Los Angeles25, QIMR Berghofer Medical Research Institute26, Radboud University Nijmegen27, National Institutes of Health28, Royal Children's Hospital29, University of Pittsburgh30, German Center for Neurodegenerative Diseases31, University of Bonn32
TL;DR: In this article, a genome-wide association study (GWAS) of dementia-free persons (n = 9,232) identified 46 SNPs at four loci with P values of <4.0 × 10(-7).
Abstract: Aging is associated with reductions in hippocampal volume that are accelerated by Alzheimer's disease and vascular risk factors. Our genome-wide association study (GWAS) of dementia-free persons (n = 9,232) identified 46 SNPs at four loci with P values of <4.0 × 10(-7). In two additional samples (n = 2,318), associations were replicated at 12q14 within MSRB3-WIF1 (discovery and replication; rs17178006; P = 5.3 × 10(-11)) and at 12q24 near HRK-FBXW8 (rs7294919; P = 2.9 × 10(-11)). Remaining associations included one SNP at 2q24 within DPP4 (rs6741949; P = 2.9 × 10(-7)) and nine SNPs at 9p33 within ASTN2 (rs7852872; P = 1.0 × 10(-7)); along with the chromosome 12 associations, these loci were also associated with hippocampal volume (P < 0.05) in a third younger, more heterogeneous sample (n = 7,794). The SNP in ASTN2 also showed suggestive association with decline in cognition in a largely independent sample (n = 1,563). These associations implicate genes related to apoptosis (HRK), development (WIF1), oxidative stress (MSR3B), ubiquitination (FBXW8) and neuronal migration (ASTN2), as well as enzymes targeted by new diabetes medications (DPP4), indicating new genetic influences on hippocampal size and possibly the risk of cognitive decline and dementia.
238 citations
TL;DR: IL-6, and, to a lesser degree, CRP levels were associated with WMH severity as well as global markers of brain atrophy, suggesting that an inflammatory process may be involved in both age-associated brain alterations.
Abstract: Objective: The relation between inflammation and brain MRI findings in the elderly remains poorly known. We investigated the association of circulating interleukin-6 (IL-6) and C-reactive protein (CRP) levels with baseline and longitudinal white matter hyperintensities (WMH), silent brain infarction, and brain volumes in community-dwelling elderly free of dementia. Methods: We included 1,841 participants aged 65 to 80 years from the Three City-Dijon cohort. Participants followed an MRI examination at baseline and after a 4-year follow-up (n = 1,316). IL-6 and CRP concentrations were measured at baseline from fasting blood samples. WMH were detected with an automatic imaging processing method and gray matter, hippocampal, white matter, and CSF volumes were estimated with voxel-based morphometry. Silent brain infarctions were assessed visually and defined as focal lesions of ≥3 mm in the absence of stroke. We used analysis of covariance and logistic regression to model the associations between inflammatory biomarkers and brain MRI findings adjusting for potential confounders. Results: In cross-sectional analyses, higher IL-6 levels were associated with higher WMH volumes ( p p = 0.001) and hippocampal ( p = 0.01) volumes, and increasing CSF volumes ( p = 0.002) in a dose-relationship pattern. Similar but weaker relations were observed for CRP. We observed no associations between baseline inflammatory biomarker levels and the evolution of MRI findings over 4 years. Conclusions: IL-6, and, to a lesser degree, CRP levels were associated with WMH severity as well as global markers of brain atrophy. These results suggest that an inflammatory process may be involved in both age-associated brain alterations.
234 citations
TL;DR: Evidence is provided that modulation of spontaneous low-frequency fluctuations in the brain is at least partially explained by spontaneous conscious cognition while at rest, and mind wandering can be characterized by widespread modular segregation.
104 citations
TL;DR: The potential of a joint DTI and SVM pipeline for fast, objective classification of healthy older and MCI subjects is demonstrated and may be useful for large scale drug trials in Alzheimer's disease.
Abstract: Few studies have looked at the potential of using diffusion tensor imaging (DTI) in conjunction with machine learning algorithms in order to automate the classification of healthy older subjects and subjects with mild cognitive impairment (MCI). Here we apply DTI to 40 healthy older subjects and 33 MCI subjects in order to derive values for multiple indices of diffusion within the white matter voxels of each subject. DTI measures were then used together with support vector machines (SVMs) to classify control and MCI subjects. Greater than 90% sensitivity and specificity was achieved using this method, demonstrating the potential of a joint DTI and SVM pipeline for fast, objective classification of healthy older and MCI subjects. Such tools may be useful for large scale drug trials in Alzheimer's disease where the early identification of subjects with MCI is critical.
96 citations
TL;DR: The amygdala, which develops neuropathology in the early stage of AD and is involved in the pathogenesis of depression, may be an important brain structure involved inThe association between EPA and cognitive decline and depressive symptoms.
Abstract: Objective: The long-chain -3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are potential candidates for interventions to delay Alzheimer disease (AD), but evidence from clinical studies is mixed. We aimed at determining whether plasma levels of EPA or DHA predict atrophy of medial temporal lobe (MTL) gray matter regions in older subjects. Methods: A total of 281 community dwellers from the Three-City Study, aged 65 years or older, had plasma fatty acid measurements at baseline and underwent MRI examinations at baseline and at 4 years. We studied the association between plasma EPA and DHA and MTL gray matter volume change at 4 years. Results: Higher plasma EPA, but not DHA, was associated with lower gray matter atrophy of the right hippocampal/parahippocampal area and of the right amygdala (p 0.05, familywise error corrected). Based on a mean right amygdala volume loss of 6.0 mm 3 /y (0.6%) ,a1S Dhigher plasma EPA (0.64% of total plasma fatty acids) at baseline was related to a 1.3 mm 3 smaller gray matter loss per year in the right amygdala. Higher atrophy of the right amygdala was associated with greater 4-year decline in semantic memory performances and more depressive symptoms. Conclusion: The amygdala, which develops neuropathology in the early stage of AD and is involved in the pathogenesis of depression, may be an important brain structure involved in the association between EPA and cognitive decline and depressive symptoms. Neurology ® 2012;79:642–650
92 citations
TL;DR: The 3C-Dijon study results underline the role of gray matter subcortical structures, in particular of the caudate nucleus, in the age-related decline of motor performances among community-dwelling elderly subjects.
60 citations
TL;DR: These findings suggest that emotional speech comprehension results from interactions between language, ToM and emotion processing networks, and that the language network, active during both tasks, would be involved in the extraction of lexical and prosodic emotional cues.
31 citations
University of Washington1, University of California, Davis2, University of Iceland3, Erasmus University Rotterdam4, Centre national de la recherche scientifique5, University of Bordeaux6, University of Texas Health Science Center at Houston7, French Institute of Health and Medical Research8, Boston University9, Harvard University10, Broad Institute11, Medical University of Graz12, University of Tasmania13, Monash University14, Rush University Medical Center15, university of lille16, Mayo Clinic17, Université de Montréal18, Wake Forest University19, University of Queensland20, Illinois Institute of Technology21, Leiden University22, University of Mississippi23, Delft University of Technology24, University of California, Los Angeles25, QIMR Berghofer Medical Research Institute26, Radboud University Nijmegen27, National Institutes of Health28, Royal Children's Hospital29, University of Pittsburgh30, University of Bonn31, German Center for Neurodegenerative Diseases32
TL;DR: These associations implicate genes related to apoptosis (HRK), development (WIF1), oxidative stress (MSR3B), ubiquitination (FBXW8) and neuronal migration (ASTN2), as well as enzymes targeted by new diabetes medications (DPP4), indicating new genetic influences on hippocampal size and possibly the risk of cognitive decline and dementia.
Abstract: Aging is associated with reductions in hippocampal volume that are accelerated by Alzheimer's disease and vascular risk factors. Our genome-wide association study (GWAS) of dementia-free persons ( n = 9,232) identified 46 SNPs at four loci with P values of −7 . In two additional samples ( n = 2,318), associations were replicated at 12q14 within MSRB3 - WIF1 (discovery and replication; rs17178006; P = 5.3 × 10 −11 ) and at 12q24 near HRK - FBXW8 (rs7294919; P = 2.9 × 10 −11 ). Remaining associations included one SNP at 2q24 within DPP4 (rs6741949; P = 2.9 × 10 −7 ) and nine SNPs at 9p33 within ASTN2 (rs7852872; P = 1.0 × 10 −7 ); along with the chromosome 12 associations, these loci were also associated with hippocampal volume ( P n = 7,794). The SNP in ASTN2 also showed suggestive association with decline in cognition in a largely independent sample ( n = 1,563). These associations implicate genes related to apoptosis ( HRK ), development ( WIF1) , oxidative stress ( MSR3B ), ubiquitination ( FBXW8 ) and neuronal migration ( ASTN2 ), as well as enzymes targeted by new diabetes medications ( DPP4 ), indicating new genetic influences on hippocampal size and possibly the risk of cognitive decline and dementia.
29 citations
TL;DR: DTI data suggest that the same degree of cognitive impairment is associated with greater structural damage in men compared with women as well as women with mild cognitive impairment.
Abstract: Previous PET and MRI studies have indicated that the degree to which pathology translates into clinical symptoms is strongly dependent on sex with women more likely to express pathology as a diagnosis of AD, whereas men are more resistant to clinical symptoms in the face of the same degree of pathology. Here we use DTI to investigate the difference between male and female white matter tracts in healthy older participants (24 women, 16 men) and participants with mild cognitive impairment (21 women, 12 men). Differences between control and MCI participants were found in fractional anisotropy (FA), radial diffusion (DR), axial diffusion (DA) and mean diffusion (MD). A significant main effect of sex was also reported for FA, MD and DR indices, with male control and male MCI participants having significantly more microstructural damage than their female counterparts. There was no sex by diagnosis interaction. Male MCIs also had significantly less normalised grey matter (GM) volume than female MCIs. However, in terms of absolute brain volume, male controls had significantly more brain volume than female controls. Normalised GM and WM volumes were found to decrease significantly with age with no age by sex interaction. Overall, these data suggest that the same degree of cognitive impairment is associated with greater structural damage in men compared with women.
28 citations
TL;DR: This work proposes a method based on group analysis of individual ICA components, using a multi-scale clustering (MICCA), which proved to be reproducible in a random splitting of the data sample and more robust than the classical concatenation method.
Abstract: Functional connectivity-based analysis of functional magnetic resonance imaging data (fMRI) is an emerging technique for human brain mapping. One powerful method for the investigation of functional connectivity is independent component analysis (ICA) of concatenated data. However, this research field is evolving toward processing increasingly larger database taking into account inter-individual variability. Concatenated data analysis only handles these features using some additional procedures such as bootstrap or including a model of between-subject variability during the preprocessing step of the ICA. In order to alleviate these limitations, we propose a method based on group analysis of individual ICA components, using a multi-scale clustering (MICCA). MICCA start with two steps repeated several times: 1) single subject data ICA followed by 2) clustering of all subject independent components according to a spatial similarity criterion. A final third step consists in selecting reproducible clusters across the repetitions of the two previous steps. The core of the innovation lies in the multi-scale and unsupervised clustering algorithm built as a chain of three processes: robust proto-cluster creation, aggregation of the proto-clusters, and cluster consolidation. We applied MICCA to the analysis of 310 fMRI resting state dataset. MICCA identified 28 resting state brain networks. Overall, the cluster neuroanatomical substrate included 98% of the cerebrum gray matter. MICCA results proved to be reproducible in a random splitting of the data sample and more robust than the classical concatenation method.
17 citations
TL;DR: It is suggested that the 3T magnet remains a valuable tool to analyze neural pathways in the macaque brain under light anesthesia and the use of spatially resolved fMRI in higher visual areas of anesthetized monkeys is reported.