Dataset Information

Brain network local interconnectivity loss in aging APOE-4 allele carriers.

ABSTRACT: Old age and possession of the APOE-4 allele are the two main risk factors for developing later onset Alzheimer's Disease (AD). Carriers of the APOE-4 allele have known differences in intrinsic functional brain network activity across the life span. These individuals also demonstrate specific regional differences in gray and white matter gross structure. However, the relationship of these variations to whole brain structural network connectivity remains unclear. We performed diffusion tensor imaging (DTI), T1 structural imaging, and cognitive testing on aging APOE-4 noncarriers (n = 30; mean age = 63.8±8.3) and APOE-4 carriers (n = 25; mean age = 60.8 ±9.7). Fiber tractography was used to derive whole brain structural graphs, and graph theory was applied to assess structural network properties. Network communication efficiency was determined for each network by quantifying local interconnectivity, global integration, and the balance between these, the small worldness. Relative to noncarriers, APOE-4 carriers demonstrated an accelerated age-related loss of mean local interconnectivity (r = -0.64, P ? 0.01) and regional local interconnectivity decreases in the precuneus (r = -0.64), medial orbitofrontal cortex (r = -0.5), and lateral parietal cortex (r = -0.54). APOE-4 carriers also showed significant age-related loss in mean cortical thickness (r = -0.52, P < 0.05). Cognitively, APOE-4 carriers had significant negative correlations of age and performance on two episodic memory tasks (P < 0.05). This genotype-specific pattern of structural connectivity change with age thus appears related to changes in gross cortical structure and cognition, potentially affecting the rate and/or spatial distribution of AD-related pathology.

SUBMITTER: Brown JA

PROVIDER: S-EPMC3251140 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

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Brain network local interconnectivity loss in aging APOE-4 allele carriers.

Brown Jesse A JA Terashima Kevin H KH Burggren Alison C AC Ercoli Linda M LM Miller Karen J KJ Small Gary W GW Bookheimer Susan Y SY

Proceedings of the National Academy of Sciences of the United States of America 20111121 51

Old age and possession of the APOE-4 allele are the two main risk factors for developing later onset Alzheimer's Disease (AD). Carriers of the APOE-4 allele have known differences in intrinsic functional brain network activity across the life span. These individuals also demonstrate specific regional differences in gray and white matter gross structure. However, the relationship of these variations to whole brain structural network connectivity remains unclear. We performed diffusion tensor imag ...[more]

PMID: 22106308

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Project description:BACKGROUND:Subjective cognitive decline (SCD) is characterized by self-reported cognitive deficits without measurable cognitive impairment. It has been suggested that individuals with SCD exhibited brain structural alterations in widespread cortical thinning or gray matter loss in the medial temporal and frontotemporal regions. Apolipoprotein E (APOE) ?4 allele is thought to be a genetic marker associated with risk of SCD. Neuropsychiatric symptoms may provide insight in detecting higher-risk elders for early Alzheimer's disease as well. Therefore, we aim to explore the characteristics of brain morphology in SCD and to determine whether it is influenced by APOE ?4 as well as neuropsychiatric symptoms in SCD. METHODS:A total of 138 cognitively normal older individuals from the SILCODE cohort underwent a clinical interview, neuropsychological assessments, a blood test, and MRI. A two-sample t-test was used to examine the cortex volume and bilateral cortical surface area alterations between SCD (n = 65) and controls (n = 73). A general linear model analysis was used to test for both main and interaction effects of clinical phenotype (SCD vs. controls) and APOE on global and regional cortex volume and bilateral cortical surface area and thickness. A multiple linear regression analysis was conducted to determine the effects of the APOE genotype on the relationships between morphometric features and neuropsychiatric symptoms in SCD. RESULTS:Compared with controls, individuals with SCD showed decreased total cortical volumes and cortical surface area. SCD APOE ?4 carriers showed additive reduction in the right cortical surface area. The evaluation scores of anxiety symptoms were negatively associated with the right cortical surface area in SCD APOE 4 non-carriers. CONCLUSIONS:Individuals with SCD had an altered cortical surface area, and APOE genotype and anxiety symptoms are modified factors on the cortical surface area decrease in SCD. TRIAL REGISTRATION:ClinicalTrials.gov (Identifier: NCT03370744 ). Registered 15 March 2017.

Dataset Information

Brain network local interconnectivity loss in aging APOE-4 allele carriers.

Publications

Brain network local interconnectivity loss in aging APOE-4 allele carriers.

Similar Datasets

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