Dataset Information

Is there a significant interaction effect between apolipoprotein E rs405509 T/T and ?4 genotypes on cognitive impairment and gray matter volume?

ABSTRACT: Evidence demonstrates that the T allele of the single-nucleotide polymorphism rs405509 in the apolipoprotein E (APOE) promoter is a risk factor for Alzheimer's disease. However, it is unknown whether rs405509 T allele synergizes with the APOE ?4 allele in influencing cognition and brain structure.We analyzed the interaction effect of the rs405509 T allele and the APOE ?4 allele on cognitive ability and brain gray matter volume among elderly people. The subjects were grouped into four groups according to APOE and rs405509 genotypes.Significant interaction effects were found between rs405509 and APOE on general mental status, memory and attention. Analysis of the whole brain gray matter showed a significantly positive interaction effect between rs405509and APOE on the right inferior temporal gyrus and right fusiform gyrus (alphasim correction P < 0.001). In addition, there was a significant relationship between cognitive ability and gray matter volume.The data indicate that the APOE rs405509 T homozygote modulates the effect of APOE ?4 on both cognitive performance and brain gray matter structure.

SUBMITTER: Ma C

PROVIDER: S-EPMC4987229 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Is there a significant interaction effect between apolipoprotein E rs405509 T/T and ε4 genotypes on cognitive impairment and gray matter volume?

Ma C C Zhang Y Y Li X X Zhang J J Chen K K Liang Y Y Chen Y Y Liu Z Z Zhang Z Z

European journal of neurology 20160604 9

<h4>Background</h4>Evidence demonstrates that the T allele of the single-nucleotide polymorphism rs405509 in the apolipoprotein E (APOE) promoter is a risk factor for Alzheimer's disease. However, it is unknown whether rs405509 T allele synergizes with the APOE ε4 allele in influencing cognition and brain structure.<h4>Methods</h4>We analyzed the interaction effect of the rs405509 T allele and the APOE ε4 allele on cognitive ability and brain gray matter volume among elderly people. The subjects ...[more]

PMID: 27259692

Similar Datasets

Project description:Many studies have shown that healthy elderly subjects and patients with Alzheimer's disease (AD) who carry the apolipoprotein E (ApoE) ε4 allele have worse cognitive function and more severe brain atrophy than non-carriers. However, it remains unclear whether this ApoE polymorphism leads to changes of cognition and brain morphology in healthy young adults. In this study, we used an established model to measure verbal episodic memory and core executive function (EF) components (response inhibition, working memory and task switching) in 32 ApoE ε4 carriers and 40 non-carriers between 20 years and 40 years of age. To do this, we carried out an adapted auditory verbal learning test and three computerized EF tasks. High-resolution head magnetic resonance scans were performed in all participants and voxel-based morphometry (VBM) was used for image processing and analysis. Multivariate analysis of variance (ANOVA) performed on memory measures showed that the overall verbal episodic memory of ApoE ε4 carriers was significantly worse than non-carriers (Wilk's λ = 4.884, P = 0.004). No significant differences were detected in overall EF between the two groups. Post hoc analyses revealed group differences in terms of immediate recall, recognition and task switching, which favored non-carriers. VBM analysis showed gray matter (GM) bilateral reductions in the medial and dorsolateral frontal, parietal and left temporal cortices in the carrier group relative to the non-carrier group, which were most significant in the bilateral anterior and middle cingulate gyri. However, these changes in GM volume were not directly associated with changes in cognitive function. Our data show that the ApoE ε4 allele is associated with poorer performance in verbal episodic memory and task switching, and a reduction in GM volume in healthy young adults, suggesting that the effects of ApoE ε4 upon cognition and brain morphology exist long before the possible occurrence of AD.

Project description:BackgroundVascular risk factors like white matter lesions (WMLs) are increasingly recognized as risk factors for vascular dementia (VaD) and can predict Alzheimer's disease (AD) at least a decade before the clinical stage of the disease. This study aimed to predict cognitive decline and use machine learning techniques to classify older individuals (aged 50 years or older) with WMLs as having vascular mild cognitive impairment (VaMCI), VaD, or in good cognitive health (CH).MethodsA total of 79 individuals with WMLs were selected for this study and categorized into the following 3 groups: CH (n=25), VaMCI (n=33), and VaD (n=21). Data from the entire cohort was then divided into a training dataset (n=56) and testing dataset (n=23). The data were extracted from gray matter (GM) segmentations using voxel-based morphometry (VBM). A relevance vector regression (RVR) approach was used to test the relationship between the structural brain images and clinical scores. To predict the individual-level subtypes, we applied 2 different machine learning-based classifiers: support vector machine (SVM) and Gaussian process classification (GPC). All predictive models were trained on the training dataset and then validated on the testing dataset of age-matched participants.ResultsMulti-domain cognitive performance could be predicted based on the pattern of GM atrophy in older people with WMLs using a RVR approach. The classification of VaD versus CH (cross-validation accuracy =93.94%, test set accuracy =76.92%) and VaMCI versus CH (cross-validation accuracy =95.24%, test set accuracy =87.50%) could be successfully achieved using both SVM and GPC. However, SVM (cross-validation accuracy =67.57%, test set accuracy =70.59%) performed better than GPC in the classification of VaD versus VaMCI.ConclusionsBased on the patterns of gray matter and RVR-based model could achieve prediction of cognitive test scores, and SVM and GPC could classify the severity of cognitive impairment in older people with WMLs.

Dataset Information

Is there a significant interaction effect between apolipoprotein E rs405509 T/T and ?4 genotypes on cognitive impairment and gray matter volume?

Publications

Is there a significant interaction effect between apolipoprotein E rs405509 T/T and ε4 genotypes on cognitive impairment and gray matter volume?

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets