Latest documents http://publikationen.ub.uni-frankfurt.de/index/index/ Tue, 11 Dec 2012 11:04:53 +0100 Tue, 11 Dec 2012 11:04:53 +0100 http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/27301 The E4 allele of the ApoE gene has consistently been shown to be related to an increased risk of Alzheimer's disease (AD). The E4 allele is also associated with functional and structural grey matter (GM) changes in healthy young, middle-aged and older subjects. Here, we assess volumes of deep grey matter structures of 22 healthy younger ApoE4 carriers and 22 non-carriers (20–38 years). Volumes of the nucleus accumbens, amygdala, caudate nucleus, hippocampus, pallidum, putamen, thalamus and brain stem were calculated by FMRIB's Integrated Registration and Segmentation Tool (FIRST) algorithm. A significant drop in volume was found in the right hippocampus of ApoE4 carriers (ApoE4+) relative to non-carriers (ApoE4−), while there was a borderline significant decrease in the volume of the left hippocampus of ApoE4 carriers. The volumes of no other structures were found to be significantly affected by genotype. Atrophy has been found to be a sensitive marker of neurodegenerative changes, and our results show that within a healthy young population, the presence of the ApoE4+ carrier gene leads to volume reduction in a structure that is vitally important for memory formation. Our results suggest that the hippocampus may be particularly vulnerable to further degeneration in ApoE4 carriers as they enter middle and old age. Although volume reductions were noted bilaterally in the hippocampus, atrophy was more pronounced in the right hippocampus. This finding relates to previous work which has noted a compensatory increase in right hemisphere activity in ApoE4 carriers in response to preclinical declines in memory function. Possession of the ApoE4 allele may lead to greater predilection for right hemisphere atrophy even in healthy young subjects in their twenties. Laurence O'Dwyer; Franck Lamberton; Silke Matura; Colby Tanner; Monika Scheibe; Julia Miller; Dan Rujescu; David Prvulovic; Harald Hampel article http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/27301 Mon, 12 Nov 2012 11:04:53 +0100 http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/25553 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. Laurence O’Dwyer; Franck Lamberton; Arun L. W. Bokde; Michael Ewers; Yetunde O. Faluyi; Colby Tanner; Bernard Mazoyer; Desmond O’Neill; Máiréad Bartley; Rónán Collins; Tara Coughlan; David Prvulovic; Harald Hampel article http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/25553 Tue, 28 Aug 2012 15:44:07 +0200 http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/24369 The apolipoprotein E4 (ApoE4) is an established risk factor for Alzheimer's disease (AD). Previous work has shown that this allele is associated with functional (fMRI) changes as well structural grey matter (GM) changes in healthy young, middle-aged and older subjects. Here, we assess the diffusion characteristics and the white matter (WM) tracts of healthy young (20-38 years) ApoE4 carriers and non-carriers. No significant differences in diffusion indices were found between young carriers (ApoE4+) and non-carriers (ApoE4-). There were also no significant differences between the groups in terms of normalised GM or WM volume. A feature selection algorithm (ReliefF) was used to select the most salient voxels from the diffusion data for subsequent classification with support vector machines (SVMs). SVMs were capable of classifying ApoE4 carrier and non-carrier groups with an extremely high level of accuracy. The top 500 voxels selected by ReliefF were then used as seeds for tractography which identified a WM network that included regions of the parietal lobe, the cingulum bundle and the dorsolateral frontal lobe. There was a non-significant decrease in volume of this WM network in the ApoE4 carrier group. Our results indicate that there are subtle WM differences between healthy young ApoE4 carriers and non-carriers and that the WM network identified may be particularly vulnerable to further degeneration in ApoE4 carriers as they enter middle and old age. Laurence O'Dwyer; Franck Lamberton; Silke Matura; Monika Scheibe; Julia Miller; Dan Rujescu; David Prvulovic; Harald Hampel article http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/24369 Thu, 24 May 2012 11:25:17 +0200 http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/23737 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. Laurence O’Dwyer; Franck Lamberton; Arun L. W. Bokde; Michael Ewers; Yetunde O. Faluyi; Colby Tanner; Bernard M. Mazoyer; Desmond O’Neill; Máiréad Bartley; D. Rónán Collins; Tara Coughlan; David Prvulovic; Harald Hampel article http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/23737 Tue, 27 Mar 2012 08:53:19 +0200