Dataset Information

Apolipoprotein E Homozygous ?4 Allele Status: A Deteriorating Effect on Visuospatial Working Memory and Global Brain Structure.

ABSTRACT: Theoretical background: The Apolipoprotein E (APOE) ?4 genotype is known to be one of the strongest single-gene predictors for Alzheimer disease, which is characterized by widespread brain structural degeneration progressing along with cognitive impairment. The ?4 allele status has been associated with brain structural alterations and lower cognitive ability in non-demented subjects. However, it remains unclear to what extent the visuospatial cognitive domain is affected, from what age onward changes are detectable and if alterations may interact with cognitive deficits in major depressive disorder (MDD). The current work investigated the effect of APOE ?4 homozygosity on visuospatial working memory (vWM) capacity, and on hippocampal morphometry. Furthermore, potential moderating roles of age and MDD were assessed. Methods: A sample of n = 31 homozygous ?4 carriers was contrasted with n = 31 non-?4 carriers in a cross-sectional design. The sample consisted of non-demented, young to mid-age participants (mean age = 34.47; SD = 13.48; 51.6% female). Among them were n = 12 homozygous ?4 carriers and n = 12 non-?4 carriers suffering from MDD (39%). VWM was assessed using the Corsi block-tapping task. Region of interest analyses of hippocampal gray matter density and volume were conducted using voxel-based morphometry (CAT12), and Freesurfer, respectively. Results: Homozygous ?4 carriers showed significantly lower Corsi span capacity than non-?4 carriers did, and Corsi span capacity was associated with higher gray matter density of the hippocampus. APOE group differences in hippocampal volume could be detected but were no longer present when controlling for total intracranial volume. Hippocampal gray matter density did not differ between APOE groups. We did not find any interaction effects of age and MDD diagnosis on hippocampal morphometry. Conclusion: Our results point toward a negative association of homozygous ?4 allele status with vWM capacity already during mid-adulthood, which emerges independently of MDD diagnosis and age. APOE genotype seems to be associated with global brain structural rather than hippocampus specific alterations in young- to mid-age participants.

SUBMITTER: Goltermann J

PROVIDER: S-EPMC6545528 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Apolipoprotein E Homozygous ε4 Allele Status: A Deteriorating Effect on Visuospatial Working Memory and Global Brain Structure.

Goltermann Janik J Redlich Ronny R Dohm Katharina K Zaremba Dario D Repple Jonathan J Kaehler Claas C Grotegerd Dominik D Förster Katharina K Meinert Susanne S Enneking Verena V Schlaghecken Emily E Fleischer Lara L Hahn Tim T Kugel Harald H Jansen Andreas A Krug Axel A Brosch Katharina K Nenadic Igor I Schmitt Simon S Stein Frederike F Meller Tina T Yüksel Dilara D Fischer Elena E Rietschel Marcella M Witt Stephanie H SH Forstner Andreas J AJ Nöthen Markus M MM Kircher Tilo T Thalamuthu Anbupalam A Baune Bernhard T BT Dannlowski Udo U Opel Nils N

Frontiers in neurology 20190527

<b>Theoretical background:</b> The Apolipoprotein E (APOE) ε4 genotype is known to be one of the strongest single-gene predictors for Alzheimer disease, which is characterized by widespread brain structural degeneration progressing along with cognitive impairment. The ε4 allele status has been associated with brain structural alterations and lower cognitive ability in non-demented subjects. However, it remains unclear to what extent the visuospatial cognitive domain is affected, from what age on ...[more]

PMID: 31191441

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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.

Dataset Information

Apolipoprotein E Homozygous ?4 Allele Status: A Deteriorating Effect on Visuospatial Working Memory and Global Brain Structure.

Publications

Apolipoprotein E Homozygous ε4 Allele Status: A Deteriorating Effect on Visuospatial Working Memory and Global Brain Structure.

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