Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
Cerebral blood flow as a biomarker of resilience in cognitively unimpaired APOE ɛ4 carriers.
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Quiring Melanie, Kapoor Arunima, Alitin John Paul M, Lashin Basant, Joyce Jillian L, Engstrom Allison C, Lohman Trevor, Gaubert Aimée, Shenasa Fatemah, Law Kevin W, Ferrer Farrah, Wang Danny J J, Head Elizabeth, Malhas Rond, Rodgers Kathleen, Han S Duke, Nation Daniel A
Аннотация
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 (pTau217).
RESULTS: APOE ɛ4 carriers showed higher MTL CBF than noncarriers. Higher MTL CBF was associated with better executive function only in pTau217-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 pTau217-negative. MTL hyperperfusion may mark resilience in APOE ɛ4 carriers at risk for AD.
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 (pTau217).
RESULTS: APOE ɛ4 carriers showed higher MTL CBF than noncarriers. Higher MTL CBF was associated with better executive function only in pTau217-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 pTau217-negative. MTL hyperperfusion may mark resilience in APOE ɛ4 carriers at risk for AD.