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Influence of APOE genotype on whole-brain functional networks in cognitively normal elderly.

ABSTRACT: This study aimed to investigate the influence of apolipoprotein E (APOE) ?4 allele on whole-brain functional networks in cognitively normal (CN) elderly by applying graph theoretical analysis to brain glucose metabolism. Eighty-six CN elderly [28 APOE ?4 carriers (?4+) and 58 non-carriers (?4-)] underwent clinical evaluation and resting [(18)F] fluorodeoxyglucose positron emission tomography scan. Whole-brain functional networks were constructed from correlations of the 90 regions of interest using the automated anatomical labeling template, and analyzed using graph theoretical approaches. The overall small-world property seen in ?4- was preserved in ?4+. However, both local clustering and path length were lower in ?4+ compared to ?4-. In terms of the hubs of functional networks, ?4+ showed decreased centrality of the right hippocampus but increased centrality of several brain regions associated with the default mode network compared to ?4-. Our results indicate that genetic vulnerability to Alzheimer's disease may alter whole-brain functional networks even before clinical symptoms appear.

SUBMITTER: Seo EH

PROVIDER: S-EPMC3859658 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Influence of APOE genotype on whole-brain functional networks in cognitively normal elderly.

Seo Eun Hyun EH Lee Dong Young DY Lee Jong-Min JM Park Jun-Sung JS Sohn Bo Kyung BK Choe Young Min YM Byun Min Soo MS Choi Hyo Jung HJ Woo Jong Inn JI

PloS one 20131211 12

This study aimed to investigate the influence of apolipoprotein E (APOE) ε4 allele on whole-brain functional networks in cognitively normal (CN) elderly by applying graph theoretical analysis to brain glucose metabolism. Eighty-six CN elderly [28 APOE ε4 carriers (ε4+) and 58 non-carriers (ε4-)] underwent clinical evaluation and resting [(18)F] fluorodeoxyglucose positron emission tomography scan. Whole-brain functional networks were constructed from correlations of the 90 regions of interest us ...[more]

PMID: 24349461

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Project description:IntroductionLate onset Alzheimer's disease (AD) is the most common form of dementia, in which almost 70% of patients are women.HypothesisWe hypothesized that women show worse global FC metrics compared to men, and further hypothesized a sex-specific positive correlation between FC metrics and cognitive scores in women.MethodsWe studied cognitively healthy individuals from the Alzheimer's Disease Neuroimaging Initiative cohort, with resting-state functional Magnetic Resonance Imaging. Metrics derived from graph theoretical analysis and functional connectomics were used to assess the global/regional sex differences in terms of functional integration and segregation, considering the amyloid status and the contributions of APOE E4. Linear mixed effect models with covariates (education, handedness, presence of apolipoprotein [APOE] E4 and intra-subject effect) were utilized to evaluate sex differences. The associations of verbal learning and memory abilities with topological network properties were assessed.ResultWomen had a significantly lower magnitude of the global and regional functional network metrics compared to men. Exploratory association analysis showed that higher global clustering coefficient was associated with lower percent forgetting in women and worse cognitive scores in men.ConclusionWomen overall show lower magnitude on measures of resting state functional network topology and connectivity. This factor can play a role in their different vulnerability to AD.Significance statementTwo thirds of AD patients are women but the reasons for these sex difference are not well understood. When this late onset form dementia arises is too late to understand the potential causes of this sex disparities. Studies on cognitively healthy elderly population are a fundamental approach to explore in depth this different vulnerability to the most common form of dementia, currently affecting 6.2 million Americans aged 65 and older are, which means that >1 in 9 people (11.3%) 65 and older are affected by AD. Approaches such as resting-state functional network topology and connectivity may play a key role in understanding and elucidate sex-dependent differences relevant to late-onset dementia syndromes.

Dataset Information

Influence of APOE genotype on whole-brain functional networks in cognitively normal elderly.

Publications

Influence of APOE genotype on whole-brain functional networks in cognitively normal elderly.

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