Brain oxygen extraction by using MRI in older individuals: Relationship to apolipoprotein e genotype and amyloid burden

Zixuan Lin, Sandeepa Sur, Anja Soldan, Corinne Pettigrew, Michael Miller, Kenichi Oishi, Murat Bilgel, Abhay R Moghekar, Jay Pillai, Marilyn Albert, Hanzhang Lu

Research output: Contribution to journalArticle

Abstract

Background: Apolipoprotein E4 (APOE4) is a major genetic risk factor for late-onset Alzheimer disease. However, the mechanisms by which APOE4 affects the brain, underpinning this risk, have not been fully elucidated. Purpose: To investigate the influence of APOE4 on global cerebral oxygen extraction fraction (OEF) and possible mediation through amyloid burden by using MRI-based brain oxygen extraction technique. Materials and Methods: Participants were enrolled from a longitudinal prospective study, the Biomarkers for Older Controls at Risk for Dementia study (data collected from January 2015 to December 2017), of whom 35% (50 of 143 participants) were APOE4 carriers. OEF was measured by using a T2-relaxation-under-spin-tagging MRI technique with a 3.0-T MRI system. PET acquired with carbon 11-labeled Pittsburgh compound B tracer was available in 119 participants to measure amyloid burden. Cognitive performance was assessed by using domain-specific composite scores including executive function, episodic memory, visual-spatial processing, and language. Linear regression analysis was performed to investigate the relationship between APOE4, OEF, and amyloid burden. The association between OEF and cognitive function was studied for the entire study cohort and separately for the APOE4 carriers and noncarriers. Results: A total of 143 cognitively healthy individuals (mean age ± standard deviation, 69.1 years ± 8.2; 57 men and 86 women) were studied. APOE4 genetic status was associated with lower OEF (noncarriers, 41.1% ± 5.8; one E4 allele, 40.1% ± 4.9; two E4 alleles, 36.7% ± 4.5; P = .03). Furthermore, among APOE4 carriers, lower OEF correlated with lower executive function scores (b = 0.079 z score for each percent change in OEF; P = .03). Amyloid burden and OEF were independently associated with APOE4 but were not associated with one another, suggesting that the effect of APOE4 on OEF is not mediated by amyloid. Conclusion: MRI-based brain oxygen extraction shows that cognitively healthy carriers of the apolipoprotein E4 gene manifest diminished brain oxygen extraction capacity independent of amyloid burden.

Original languageEnglish (US)
Pages (from-to)140-148
Number of pages9
JournalRadiology
Volume292
Issue number1
DOIs
StatePublished - Jan 1 2019

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Apolipoprotein E4
Apolipoproteins
Amyloid
Genotype
Oxygen
Brain
Executive Function
Alleles
Episodic Memory
Cognition
Longitudinal Studies
Dementia
Linear Models
Alzheimer Disease
Cohort Studies
Language
Carbon
Biomarkers

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

@article{0e6a68cf2e5f441bbf91331212cfb551,
title = "Brain oxygen extraction by using MRI in older individuals: Relationship to apolipoprotein e genotype and amyloid burden",
abstract = "Background: Apolipoprotein E4 (APOE4) is a major genetic risk factor for late-onset Alzheimer disease. However, the mechanisms by which APOE4 affects the brain, underpinning this risk, have not been fully elucidated. Purpose: To investigate the influence of APOE4 on global cerebral oxygen extraction fraction (OEF) and possible mediation through amyloid burden by using MRI-based brain oxygen extraction technique. Materials and Methods: Participants were enrolled from a longitudinal prospective study, the Biomarkers for Older Controls at Risk for Dementia study (data collected from January 2015 to December 2017), of whom 35{\%} (50 of 143 participants) were APOE4 carriers. OEF was measured by using a T2-relaxation-under-spin-tagging MRI technique with a 3.0-T MRI system. PET acquired with carbon 11-labeled Pittsburgh compound B tracer was available in 119 participants to measure amyloid burden. Cognitive performance was assessed by using domain-specific composite scores including executive function, episodic memory, visual-spatial processing, and language. Linear regression analysis was performed to investigate the relationship between APOE4, OEF, and amyloid burden. The association between OEF and cognitive function was studied for the entire study cohort and separately for the APOE4 carriers and noncarriers. Results: A total of 143 cognitively healthy individuals (mean age ± standard deviation, 69.1 years ± 8.2; 57 men and 86 women) were studied. APOE4 genetic status was associated with lower OEF (noncarriers, 41.1{\%} ± 5.8; one E4 allele, 40.1{\%} ± 4.9; two E4 alleles, 36.7{\%} ± 4.5; P = .03). Furthermore, among APOE4 carriers, lower OEF correlated with lower executive function scores (b = 0.079 z score for each percent change in OEF; P = .03). Amyloid burden and OEF were independently associated with APOE4 but were not associated with one another, suggesting that the effect of APOE4 on OEF is not mediated by amyloid. Conclusion: MRI-based brain oxygen extraction shows that cognitively healthy carriers of the apolipoprotein E4 gene manifest diminished brain oxygen extraction capacity independent of amyloid burden.",
author = "Zixuan Lin and Sandeepa Sur and Anja Soldan and Corinne Pettigrew and Michael Miller and Kenichi Oishi and Murat Bilgel and Moghekar, {Abhay R} and Jay Pillai and Marilyn Albert and Hanzhang Lu",
year = "2019",
month = "1",
day = "1",
doi = "10.1148/radiol.2019182726",
language = "English (US)",
volume = "292",
pages = "140--148",
journal = "Radiology",
issn = "0033-8419",
publisher = "Radiological Society of North America Inc.",
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}

TY - JOUR

T1 - Brain oxygen extraction by using MRI in older individuals

T2 - Relationship to apolipoprotein e genotype and amyloid burden

AU - Lin, Zixuan

AU - Sur, Sandeepa

AU - Soldan, Anja

AU - Pettigrew, Corinne

AU - Miller, Michael

AU - Oishi, Kenichi

AU - Bilgel, Murat

AU - Moghekar, Abhay R

AU - Pillai, Jay

AU - Albert, Marilyn

AU - Lu, Hanzhang

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background: Apolipoprotein E4 (APOE4) is a major genetic risk factor for late-onset Alzheimer disease. However, the mechanisms by which APOE4 affects the brain, underpinning this risk, have not been fully elucidated. Purpose: To investigate the influence of APOE4 on global cerebral oxygen extraction fraction (OEF) and possible mediation through amyloid burden by using MRI-based brain oxygen extraction technique. Materials and Methods: Participants were enrolled from a longitudinal prospective study, the Biomarkers for Older Controls at Risk for Dementia study (data collected from January 2015 to December 2017), of whom 35% (50 of 143 participants) were APOE4 carriers. OEF was measured by using a T2-relaxation-under-spin-tagging MRI technique with a 3.0-T MRI system. PET acquired with carbon 11-labeled Pittsburgh compound B tracer was available in 119 participants to measure amyloid burden. Cognitive performance was assessed by using domain-specific composite scores including executive function, episodic memory, visual-spatial processing, and language. Linear regression analysis was performed to investigate the relationship between APOE4, OEF, and amyloid burden. The association between OEF and cognitive function was studied for the entire study cohort and separately for the APOE4 carriers and noncarriers. Results: A total of 143 cognitively healthy individuals (mean age ± standard deviation, 69.1 years ± 8.2; 57 men and 86 women) were studied. APOE4 genetic status was associated with lower OEF (noncarriers, 41.1% ± 5.8; one E4 allele, 40.1% ± 4.9; two E4 alleles, 36.7% ± 4.5; P = .03). Furthermore, among APOE4 carriers, lower OEF correlated with lower executive function scores (b = 0.079 z score for each percent change in OEF; P = .03). Amyloid burden and OEF were independently associated with APOE4 but were not associated with one another, suggesting that the effect of APOE4 on OEF is not mediated by amyloid. Conclusion: MRI-based brain oxygen extraction shows that cognitively healthy carriers of the apolipoprotein E4 gene manifest diminished brain oxygen extraction capacity independent of amyloid burden.

AB - Background: Apolipoprotein E4 (APOE4) is a major genetic risk factor for late-onset Alzheimer disease. However, the mechanisms by which APOE4 affects the brain, underpinning this risk, have not been fully elucidated. Purpose: To investigate the influence of APOE4 on global cerebral oxygen extraction fraction (OEF) and possible mediation through amyloid burden by using MRI-based brain oxygen extraction technique. Materials and Methods: Participants were enrolled from a longitudinal prospective study, the Biomarkers for Older Controls at Risk for Dementia study (data collected from January 2015 to December 2017), of whom 35% (50 of 143 participants) were APOE4 carriers. OEF was measured by using a T2-relaxation-under-spin-tagging MRI technique with a 3.0-T MRI system. PET acquired with carbon 11-labeled Pittsburgh compound B tracer was available in 119 participants to measure amyloid burden. Cognitive performance was assessed by using domain-specific composite scores including executive function, episodic memory, visual-spatial processing, and language. Linear regression analysis was performed to investigate the relationship between APOE4, OEF, and amyloid burden. The association between OEF and cognitive function was studied for the entire study cohort and separately for the APOE4 carriers and noncarriers. Results: A total of 143 cognitively healthy individuals (mean age ± standard deviation, 69.1 years ± 8.2; 57 men and 86 women) were studied. APOE4 genetic status was associated with lower OEF (noncarriers, 41.1% ± 5.8; one E4 allele, 40.1% ± 4.9; two E4 alleles, 36.7% ± 4.5; P = .03). Furthermore, among APOE4 carriers, lower OEF correlated with lower executive function scores (b = 0.079 z score for each percent change in OEF; P = .03). Amyloid burden and OEF were independently associated with APOE4 but were not associated with one another, suggesting that the effect of APOE4 on OEF is not mediated by amyloid. Conclusion: MRI-based brain oxygen extraction shows that cognitively healthy carriers of the apolipoprotein E4 gene manifest diminished brain oxygen extraction capacity independent of amyloid burden.

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DO - 10.1148/radiol.2019182726

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