Differential association of cerebral blood flow and anisocytosis in APOE ε4 carriers at midlife.

Cerebral hemodynamic alterations have been observed in apolipoprotein ε4 (APOE4) carriers at midlife, however the physiological underpinnings of this observation are poorly understood. Our goal was to investigate cerebral blood flow (CBF) and its spatial coefficient of variation (CoV) in relation to APOE4 and a measure of erythrocyte anisocytosis (red blood cell distribution width - RDW) in a middle-aged cohort. Data from 563 participants in the PREVENT-Dementia study scanned with 3 T MRI cross-sectionally were analysed. Voxel-wise and region-of-interest analyses within nine vascular regions were run to detect areas of altered perfusion. Within the vascular regions, interaction terms between APOE4 and RDW in predicting CBF were examined. Areas of hyperperfusion in APOE4 carriers were detected mainly in frontotemporal regions. The APOE4 allele differentially moderated the association between RDW and CBF, an association which was more prominent in the distal vascular territories (p - [0.01, 0.05]). The CoV was not different between the considered groups. We provide novel evidence that in midlife, RDW and CBF are differentially associated in APOE4 carriers and non-carriers. This association is consistent with a differential hemodynamic response to hematological alterations in APOE4 carriers.

Déclaration de conflit d'intérêts

Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: The authors report no competing interests related to this study. Unrelated to this work, JTOB has received honoraria for work as DSMB chair or member for TauRx, Axon, Eisai, has acted as a consultant for Lilly and Biogen, has received honorarium for talks from GE Healthcare and research support from Alliance Medical and Merck. IK has received honoraria for talks by NovoNordisk and is a paid medical advisor for digital technology companies in the Alzheimer's disease space (Five Lives SAS, Cognetivity Ltd and Mantrah Ltd). PM has received an honorarium for a talk from GE Healthcare.