Interaction of Age and APOE Genotype on Cerebral Blood Flow at Rest

We investigated the impact of APOE genotype on cerebral blood flow (CBF) in older and younger adults. Forty cognitively normal older adults (16 epsilon 4 carriers, 24 non-epsilon 4 carriers) and 30 younger adults (15 epsilon 4 carriers, 15 non-epsilon 4 carriers) completed a resting-state whole-brain pulsed arterial spin labeling magnetic resonance scan. Main effects of aging were demonstrated wherein older adults had decreased gray matter CBF corrected for partial volume effects compared to younger adults in widespread brain regions. Main effects of APOE genotype were also observed wherein epsilon 4 carriers displayed greater CBF in the left lingual gyrus and precuneus than non-carriers. An interaction between age and APOE genotype in the left anterior cingulate cortex (ACC) was characterized by reduced CBF in older epsilon 4 carriers and increased CBF in young epsilon 4 carriers. Increased CBF in the left ACC resulting from the interaction of age group and APOE genotype was positively correlated with executive functioning in young epsilon 4 adults (r = 0.61, p = 0.04). Results demonstrate APOE genotype differentially impacts cerebrovascular function across the lifespan and may modify the relationship between CBF and cognition. Findings may partially support suggestions that the gene exerts antagonistic pleiotropic effects.