We investigated the impact of APOE genotype on cerebral blood flow (CBF) in older and younger adults. Forty cognitively normal older adults (16 ε4 carriers, 24 non-ε4 carriers) and 30 younger adults (15 ε4 carriers, 15 non-ε4 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 ε4 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 ε4 carriers and increased CBF in young ε4 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 ε4 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.

Using whole-brain pulsed arterial spin labeling magnetic resonance imaging, resting cerebral blood flow (CBF) was measured in 20 mild cognitive impairment (MCI; 11 e3 and 9 e4) and 40 demographically matched cognitively normal (CN; 27 e3 and 13 e4) participants. An interaction of apolipoprotein (APOE) genotype (e3 and e4) and cognitive status (CN and MCI) on quantified gray-matter CBF corrected for partial volume effects was found in the left parahippocampal and fusiform gyri (PHG/FG), right middle frontal gyrus, and left medial frontal gyrus. In the PHG/FG, CBF was elevated for CN e4 carriers but decreased for MCI e4 carriers. The opposite pattern was seen in frontal regions: CBF was decreased for CN e4 carriers but increased for MCI e4 carriers. Cerebral blood flow in the PHG/FG was positively correlated with verbal memory for CN e4 adults (r = 0.67, P = 0.01). Cerebral blood flow in the left medial frontal gyrus was positively correlated with verbal memory for MCI e4 adults (r = 0.70, P = 0.05). Findings support dynamic pathophysiologic processes in the brain associated with Alzheimer's disease risk and indicate that cognitive status and APOE genotype have interactive effects on CBF. Correlations between CBF and verbal memory suggest a differential neurovascular compensatory response in posterior and anterior cortices with cognitive decline in e4 adults.

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Vascular risk factors and cerebral blood flow (CBF) reduction have been linked to increased risk of cognitive impairment and Alzheimer's disease (AD); however the possible moderating effects of age and vascular risk burden on CBF in late life remain understudied. We examined the relationships among elevated vascular risk burden, age, CBF, and cognition. Seventy-one non-demented older adults completed an arterial spin labeling MR scan, neuropsychological assessment, and medical history interview. Relationships among vascular risk burden, age, and CBF were examined in a priori regions of interest (ROIs) previously implicated in aging and AD. Interaction effects indicated that, among older adults with elevated vascular risk burden (i.e., multiple vascular risk factors), advancing age was significantly associated with reduced cortical CBF whereas there was no such relationship for those with low vascular risk burden (i.e., no or one vascular risk factor). This pattern was observed in cortical ROIs including medial temporal (hippocampus, parahippocampal gyrus, uncus), inferior parietal (supramarginal gyrus, inferior parietal lobule, angular gyrus), and frontal (anterior cingulate, middle frontal gyrus, medial frontal gyrus) cortices. Furthermore, among those with elevated vascular risk, reduced CBF was associated with poorer cognitive performance. Such findings suggest that older adults with elevated vascular risk burden may be particularly vulnerable to cognitive change as a function of CBF reductions. Findings support the use of CBF as a potential biomarker in preclinical AD and suggest that vascular risk burden and regionally-specific CBF changes may contribute to differential age-related cognitive declines.