Work

Cerebral blood flow as a biomarker of resilience in cognitively unimpaired APOE ɛ 4 carriers

Year: 2026

Type: article

Abstract: 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.

Source: Alzheimer s & Dementia

DOI: 10.1002/alz.71934