Dataset Information

Predicting the apolipoprotein E ε4 allele carrier status based on gray matter volumes and cognitive function.

ABSTRACT:

Background

Apolipoprotein E (ApoE) ε4 carriers have a higher risk of developing Alzheimer's disease (AD) and show brain atrophy and cognitive decline even before diagnosis.

Objective

To predict ApoE ε4 status using gray matter volume (GMV) obtained from magnetic resonance imaging images and demographic data with machine learning (ML) methods.

Methods

We recruited 74 participants (25 probable AD, 24 amnestic mild cognitive impairment, and 25 cognitively normal older people) with known ApoE genotype (22 ApoE ε4 carriers and 52 noncarriers) and scanned them with three-dimensional (3D) T1-weighted (T1W) and 3D double inversion recovery (DIR) sequences. We extracted GMV from regions of interest related to AD pathology and used them as features along with age and mini-mental state examination (MMSE) scores to train different ML models. We performed both receiver operating characteristic curve analysis and the prediction analysis of the ApoE ε4 carrier with different ML models.

Results

The best model of ML analyses was a cubic support vector machine (SVM3) that used age, the MMSE score, and DIR GMVs at the amygdala, hippocampus, and precuneus as features (AUC = .88). This model outperformed models using T1W GMV or demographic data alone.

Conclusion

Our results suggest that brain atrophy with DIR GMV and cognitive decline with aging can be useful biomarkers for predicting ApoE ε4 status and identifying individuals at risk of AD progression.

SUBMITTER: Kim HG

PROVIDER: S-EPMC10772845 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Publications

Predicting the apolipoprotein E ε4 allele carrier status based on gray matter volumes and cognitive function.

Kim Hyug-Gi HG Tian Yunan Y Jung Sue Min SM Park Soonchan S Rhee Hak Young HY Ryu Chang-Woo CW Jahng Geon-Ho GH

Brain and behavior 20240101 1

<h4>Background</h4>Apolipoprotein E (ApoE) ε4 carriers have a higher risk of developing Alzheimer's disease (AD) and show brain atrophy and cognitive decline even before diagnosis.<h4>Objective</h4>To predict ApoE ε4 status using gray matter volume (GMV) obtained from magnetic resonance imaging images and demographic data with machine learning (ML) methods.<h4>Methods</h4>We recruited 74 participants (25 probable AD, 24 amnestic mild cognitive impairment, and 25 cognitively normal older people) ...[more]

PMID: 38376028

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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.

Project description:ObjectivesTo confirm associations of apolipoprotein E (ApoE) ε4 carrier status, sex, and time-dependent cognitive status with mortality risk and to investigate these joint effects of these associations in a cohort of community-dwelling U.S. adults.DesignProspective cohort study.SettingThe Baltimore Longitudinal Study of Aging (BLSA).ParticipantsOf 3,047 BLSA participants aged 17 to 98 at first visit (60.1% male), 1,704 with complete ApoE genotype data were included, of whom 1,461 aged 50 and older with one or more visits were eligible.MeasurementsTime to death from all, cardiovascular, and noncardiovascular causes.ResultsProbability of survival was lower for ApoE ε4 carriers, particularly those who were older. A Cox proportional hazards model for all-cause mortality yielded a hazard ratio (HR) for ApoE ε4 carrier versus noncarriers of 1.31 (95% confidence interval (CI) = 1.02-1.68). This association was also found for cardiovascular mortality. Time-dependent all-cause dementia (HR = 1.73, 95% CI = 1.33-2.26) and mild cognitive impairment (HR = 1.95, 95% CI = 1.42-2.67) increased all-cause mortality risk, associations that were also detected for noncardiovascular mortality. When individuals were free of cognitive impairment, a dose-response relationship with ε4 alleles was found for all-cause mortality (HR = 1.40, 95% CI = 0.94-2.07 for 1 ε4; HR = 2.61, 95% CI = 1.12-6.07 for 2 ε4). After onset of Alzheimer's disease (AD), carrying only one ε4 allele resulted in an approximately 77% greater all-cause mortality risk than in noncarriers. ApoE ε4 carrier status increased all-cause mortality risk in men and interacted with time-dependent AD to increase the risk of this outcome (relative excess risk due to interaction = 2.15, 95% CI = 1.22-3.07).ConclusionApoE ε4 carrier status was found to increase all-cause and cardiovascular mortality risks and interacted with sex and time-dependent AD status to affect all-cause mortality.

Project description:Theoretical background: 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 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 ε4 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 ε4 carriers was contrasted with n = 31 non-ε4 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 ε4 carriers and n = 12 non-ε4 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 ε4 carriers showed significantly lower Corsi span capacity than non-ε4 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 ε4 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.

Dataset Information

Predicting the apolipoprotein E ε4 allele carrier status based on gray matter volumes and cognitive function.

Background

Objective

Methods

Results

Conclusion

Publications

Predicting the apolipoprotein E ε4 allele carrier status based on gray matter volumes and cognitive function.

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