1 Physics Department, Concordia University, 7141 Rue Sherbrooke W, Montréal, Québec, H4B 1R6, Canada.
2 Centre Epic and Research Center, Montreal Heart Institute, 5000 Rue Bélanger, Montréal, Québec, H1T 1C8, Canada.
3 School of Health, Concordia University, 7200 Rue Sherbrooke W, Montréal, Québec, H4B 1R6, Canada.
4 Department of Medicine, Université de Montréal, C. P. 6128, Succursale Centre-Ville, Montréal, Québec, H3C 3J7, Canada.
5 Department of Psychiatry, McGill University, 845 Rue Sherbrooke W, Montréal, Québec, H3A 0G4, Canada.
6 McConnell Brain Imaging Centre, Montreal Neurological Institute, 845 Rue Sherbrooke W, Montréal, Québec, H3A 0G4, Canada.
7 StoP-AD Centre, Douglas Mental Health Institute Research Centre, 6875 Blvd. LaSalle, Verdun, Québec, H4H 1R3, Canada.
8 Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, 3801 University Street, Montréal, Québec, H3A 2B4, Canada.
9 Physics Department, Concordia University, 7141 Rue Sherbrooke W, Montréal, Québec, H4B 1R6, Canada. claudine.gauthier@concordia.ca.
10 Centre Epic and Research Center, Montreal Heart Institute, 5000 Rue Bélanger, Montréal, Québec, H1T 1C8, Canada. claudine.gauthier@concordia.ca.
11 School of Health, Concordia University, 7200 Rue Sherbrooke W, Montréal, Québec, H4B 1R6, Canada. claudine.gauthier@concordia.ca.

The apolipoprotein E4 (APOE4) allele is the strongest genetic risk factor for Alzheimer's disease (AD) and is linked to poorer cerebrovascular health. Cerebrovascular reactivity (CVR), an indicator of vascular reserve, and cerebral pulsatility (CP), a marker of vascular stiffness, are sensitive biomarkers of early vascular dysfunction associated with aging and AD. However, the relationship between APOE4 status and these cerebrovascular metrics remains unclear. This study investigated whether the APOE genotype influences longitudinal changes in CVR and CP, and their association with cognitive performance in cognitively unimpaired individuals. We utilized the PREVENT-AD cohort, including 101 APOE4 carriers (30 males and 71 females) and 152 non-APOE4 carriers (48 males and 104 females) aged 55 and older. Relative CVR and CP were derived from resting state functional magnetic resonance imaging data, with regional values extracted from cerebral arterial territories. Results indicated significant interactions between APOE4 status and relative CVR in the left middle cerebral artery and left posterior cerebral artery (PCA) territories. APOE4 status disaggregated analyses revealed that APOE4 carriers uniquely presented a significant decline in relative CVR within the left PCA. Furthermore, sex-specific effects were identified, with female APOE4 carriers having lower relative CVR in the right anterior cerebral artery territory compared to female non-carriers. Importantly, higher relative CVR was positively associated with better cognitive performance in APOE4 carriers. No significant effects of APOE4 status on CP were found. Together, these findings suggest that relative CVR may be an important early measure of cerebrovascular health and cognition in cognitively intact APOE4 carriers.