Effect of APOE ε4 status on intrinsic network connectivity in cognitively normal elderly subjects

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Abstract

Objective: To examine default mode and salience network functional connectivity as a function of APOE ε4 status in a group of cognitively normal age-, sex-, and education-matched older adults. Design: Case-control study. Subjects: Fifty-six cognitively normal APOE ε4 carriers and 56 age-, sex- and education-matched cognitively normal APOE ε4 noncarriers. Main Outcome Measure: Alterations in in-phase default mode and salience network connectivity in APOE ε4 carriers compared with APOE ε4 noncarriers ranging from 63 to 91 years of age. Results: A posterior cingulate seed revealed decreased inphase connectivity in regions of the posterior default modenetwork that included the left inferior parietal lobe, left middle temporal gyrus, and bilateral anterior temporal lobes in the ε4 carriers relative to APOE ε4 noncarriers. An anterior cingulate seed showed greater in-phase connectivity in the salience network including the cingulate gyrus, medial prefrontal cortex, bilateral insular cortex, striatum, and thalamus in APOE ε4 carriers vs noncarriers. There were no groupwise differences in brain anatomy. Conclusions: The observation of functional alterations in default mode and salience network connectivity in the absence of structural changes between APOE ε4 carriers and noncarriers suggests that alterations in connectivity may have the potential to serve as an early biomarker.

Original languageEnglish (US)
Pages (from-to)1131-1136
Number of pages6
JournalArchives of Neurology
Volume68
Issue number9
DOIs
StatePublished - Sep 2011

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Gyrus Cinguli
Sex Education
Temporal Lobe
Seeds
Parietal Lobe
Prefrontal Cortex
Thalamus
Cerebral Cortex
Case-Control Studies
Anatomy
Biomarkers
Observation
Outcome Assessment (Health Care)
Brain
Intrinsic
Connectivity
Carrier
Alteration

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

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title = "Effect of APOE ε4 status on intrinsic network connectivity in cognitively normal elderly subjects",
abstract = "Objective: To examine default mode and salience network functional connectivity as a function of APOE ε4 status in a group of cognitively normal age-, sex-, and education-matched older adults. Design: Case-control study. Subjects: Fifty-six cognitively normal APOE ε4 carriers and 56 age-, sex- and education-matched cognitively normal APOE ε4 noncarriers. Main Outcome Measure: Alterations in in-phase default mode and salience network connectivity in APOE ε4 carriers compared with APOE ε4 noncarriers ranging from 63 to 91 years of age. Results: A posterior cingulate seed revealed decreased inphase connectivity in regions of the posterior default modenetwork that included the left inferior parietal lobe, left middle temporal gyrus, and bilateral anterior temporal lobes in the ε4 carriers relative to APOE ε4 noncarriers. An anterior cingulate seed showed greater in-phase connectivity in the salience network including the cingulate gyrus, medial prefrontal cortex, bilateral insular cortex, striatum, and thalamus in APOE ε4 carriers vs noncarriers. There were no groupwise differences in brain anatomy. Conclusions: The observation of functional alterations in default mode and salience network connectivity in the absence of structural changes between APOE ε4 carriers and noncarriers suggests that alterations in connectivity may have the potential to serve as an early biomarker.",
author = "Machulda, {Mary Margaret} and Jones, {David T} and Vemuri, {Prashanthi D} and Eric McDade and Ramesh Avula and Scott Przybelski and Boeve, {Bradley F} and Knopman, {David S} and Petersen, {Ronald Carl} and Jack, {Clifford R Jr.}",
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AU - Machulda, Mary Margaret

AU - Jones, David T

AU - Vemuri, Prashanthi D

AU - McDade, Eric

AU - Avula, Ramesh

AU - Przybelski, Scott

AU - Boeve, Bradley F

AU - Knopman, David S

AU - Petersen, Ronald Carl

AU - Jack, Clifford R Jr.

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N2 - Objective: To examine default mode and salience network functional connectivity as a function of APOE ε4 status in a group of cognitively normal age-, sex-, and education-matched older adults. Design: Case-control study. Subjects: Fifty-six cognitively normal APOE ε4 carriers and 56 age-, sex- and education-matched cognitively normal APOE ε4 noncarriers. Main Outcome Measure: Alterations in in-phase default mode and salience network connectivity in APOE ε4 carriers compared with APOE ε4 noncarriers ranging from 63 to 91 years of age. Results: A posterior cingulate seed revealed decreased inphase connectivity in regions of the posterior default modenetwork that included the left inferior parietal lobe, left middle temporal gyrus, and bilateral anterior temporal lobes in the ε4 carriers relative to APOE ε4 noncarriers. An anterior cingulate seed showed greater in-phase connectivity in the salience network including the cingulate gyrus, medial prefrontal cortex, bilateral insular cortex, striatum, and thalamus in APOE ε4 carriers vs noncarriers. There were no groupwise differences in brain anatomy. Conclusions: The observation of functional alterations in default mode and salience network connectivity in the absence of structural changes between APOE ε4 carriers and noncarriers suggests that alterations in connectivity may have the potential to serve as an early biomarker.

AB - Objective: To examine default mode and salience network functional connectivity as a function of APOE ε4 status in a group of cognitively normal age-, sex-, and education-matched older adults. Design: Case-control study. Subjects: Fifty-six cognitively normal APOE ε4 carriers and 56 age-, sex- and education-matched cognitively normal APOE ε4 noncarriers. Main Outcome Measure: Alterations in in-phase default mode and salience network connectivity in APOE ε4 carriers compared with APOE ε4 noncarriers ranging from 63 to 91 years of age. Results: A posterior cingulate seed revealed decreased inphase connectivity in regions of the posterior default modenetwork that included the left inferior parietal lobe, left middle temporal gyrus, and bilateral anterior temporal lobes in the ε4 carriers relative to APOE ε4 noncarriers. An anterior cingulate seed showed greater in-phase connectivity in the salience network including the cingulate gyrus, medial prefrontal cortex, bilateral insular cortex, striatum, and thalamus in APOE ε4 carriers vs noncarriers. There were no groupwise differences in brain anatomy. Conclusions: The observation of functional alterations in default mode and salience network connectivity in the absence of structural changes between APOE ε4 carriers and noncarriers suggests that alterations in connectivity may have the potential to serve as an early biomarker.

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