Cerebral blood flow as a biomarker of resilience in cognitively unimpaired APOE ɛ 4 carriers
Melanie Quiring, Arunima Kapoor, John Paul M. Alitin, Basant Lashin, Jillian L. Joyce, Allison C. Engstrom, Trevor Lohman, Aimée Gaubert, Fatemah Shenasa, Kevin W. Law, Farrah Ferrer, Danny J. J. Wang, Elizabeth Head, Rond Malhas, Kathleen Rodgers, S. Duke Han, Daniel A. NationAbstract
INTRODUCTION
It remains unclear whether medial temporal lobe (MTL) hyperperfusion in cognitively unimpaired apolipoprotein E ( APOE) ɛ4 carriers reflects resilience or dysfunction. We examined whether cortical MTL cerebral blood flow (CBF) relates to cognition differently in APOE ɛ4 carriers and noncarriers with and without AD pathophysiological changes.
METHODS
One hundred forty‐eight cognitively unimpaired older adults underwent pseudo‐continuous arterial spin labeling MRI to quantify MTL CBF and assessment of memory and executive function. In a subset ( n = 126), AD pathology was indexed using plasma phosphorylated tau 217 (pTau 217 ).
RESULTS
APOE ɛ4 carriers showed higher MTL CBF than noncarriers. Higher MTL CBF was associated with better executive function only in pTau 217 ‐negative APOE ɛ4 carriers. Interactions remained significant after adjusting for MTL cortical volume or white matter hyperintensities.
DISCUSSION
Hyperperfusion in cognitively unimpaired APOE ɛ4 carriers may reflect a resilience biomarker related to better cognitive function in the absence of detectable AD pathophysiological changes.
Highlights
Apolipoprotein E (
APOE)
ɛ4 carriers show elevated medial temporal lobe (MTL) cerebral blood flow (CBF).
Higher MTL CBF is linked to better executive function in
APOE
ɛ4 carriers.
This association is only observed in
APOE
ɛ4 carriers who are pTau
217
‐negative.
MTL hyperperfusion may mark resilience in
APOE
ɛ4 carriers at risk for AD.