Faculty Collaboration Database

Functional network endophenotypes unravel the effects of apolipoprotein E epsilon 4 in middle-aged adults. PLoS One 2013;8(2):e55902

Date

02/21/2013

Pubmed ID

23424640

Pubmed Central ID

PMC3570545

DOI

10.1371/journal.pone.0055902

Scopus ID

2-s2.0-84873739878 (requires institutional sign-in at Scopus site)   49 Citations

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.

Author List

Goveas JS, Xie C, Chen G, Li W, Ward BD, Franczak MB, Jones JL, Antuono PG, Li SJ

Authors

Piero G. Antuono MD Professor in the Neurology department at Medical College of Wisconsin
Malgorzata Franczak MD Professor in the Neurology department at Medical College of Wisconsin
Joseph S. Goveas MD Professor in the Psychiatry and Behavioral Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Apolipoproteins E
Basal Metabolism
Cognition
Endophenotypes
Executive Function
Female
Functional Neuroimaging
Humans
Male
Memory, Episodic
Middle Aged
Nerve Net
Neuropsychological Tests