Abstract
Apolipoprotein E-ε4 (APOE-ε4) accentuates memory decline, structural volume loss and cerebral amyloid deposition in cognitively healthy adults. We investigated whether APOE-ε4 carriers will show disruptions in the intrinsic cognitive networks, including the default mode (DMN), executive control (ECN) and salience (SN) networks, relative to noncarriers in middle-aged healthy adults; and the extent to which episodic-memory performance is related to the altered functional connectivity (Fc) in these networks. Resting-state functional connectivity MRI (R-fMRI) was used to measure the differences in the DMN, ECN and SN Fc between 20 APOE-ε4 carriers and 26 noncarriers. Multiple linear regression analyses were performed to determine the relationship between episodic-memory performance and Fc differences in the three resting-state networks across all subjects. There were no significant differences in the demographic and neuropsychological characteristics and the gray-matter volumes in the carriers and noncarriers. While mostly diminished DMN and ECN functional connectivities were seen, enhanced connections to the DMN structures were found in the SN in ε4 carriers. Altered DMN and ECN were associated with episodic memory performance. Significant Fc differences in the brain networks implicated in cognition were seen in middle-aged individuals with a genetic risk for AD, in the absence of cognitive decline and gray-matter atrophy. Prospective studies are essential to elucidate the potential of R-fMRI technique as a biomarker for predicting conversion from normal to early AD in healthy APOE-ε4 carriers.
Highlights
Imaging genetics, a rapidly growing field in neuroscience, utilizes an imaging endophenotype to study the genetic influences on human cognitive function and behavior [1]
Gender, education, cognitive and depressive symptom scores (p.0.05) between groups, Apolipoprotein E-e4 (APOE-e4) carriers showed a trend toward lower Rey Auditory-Verbal Learning Test (RAVLT)-DR (p = 0.10) and Digit Span Test (p = 0.07) scores, when compared to non e4 carriers (Table 1)
We demonstrate for the first time that the core cognitive resting-state networks (RSNs) disruptions extend beyond the default mode network (DMN) to include the executive control network (ECN) and salience network (SN) in middle-aged individuals at genetic risk for Alzheimer’s disease (AD)
Summary
A rapidly growing field in neuroscience, utilizes an imaging endophenotype to study the genetic influences on human cognitive function and behavior [1]. Imaging endophenotypes are commonly used as biomarkers in Alzheimer’s disease (AD) research because they are powerful techniques that can indicate disease-specific changes long before clinical evidence of neurodegeneration. Functional magnetic resonance imaging (fMRI) studies in APOE-e4 carriers have shown differential patterns of brain activations during various memory tasks in the regions affected by AD, relative to noncarriers [9,10,11,12,13]. Using traditional task-driven fMRI methods, it is difficult to reveal disruptions in the large-scale distributed brain networks associated with specific cognitive functions in persons at risk for AD [14]. R-fMRI shows great promise as an imaging biomarker in preclinical and clinical AD states [21,22,23,24,25,26,27,28,29,30]
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