Higher pulse pressure was significantly associated with lower cerebral blood flow in the hippocampus, entorhinal cortex, and inferior parietal cortex only among participants homozygous for the APOE ε4 allele.
Cross-Sectional (n=144)
Yes
Does the association between pulse pressure and regional cerebral blood flow vary by APOE ε4 gene dose in older adults without dementia?
Higher pulse pressure is associated with lower regional cerebral blood flow specifically in older adults who are homozygous for the APOE ε4 allele, highlighting a genetic vulnerability to vascular risk factors.
Effect estimate: Simple slope -1.11 (entorhinal cortex), -0.92 (hippocampus), -0.78 (inferior parietal cortex) for two ε4 alleles
p-value: p=0.003 (entorhinal), 0.005 (hippocampus), 0.002 (inferior parietal)
This study assessed whether the effect of vascular risk on cerebral blood flow (CBF) varies by gene dose of apolipoprotein (APOE) ε4 alleles. 144 older adults without dementia from the Alzheimer's Disease Neuroimaging Initiative underwent arterial spin labeling and T1-weighted MRI, APOE genotyping, fluorodeoxyglucose positron emission tomography (FDG-PET), lumbar puncture, and blood pressure (BP) assessment. Vascular risk was assessed using pulse pressure (systolic BP - diastolic BP). CBF was examined in six AD-vulnerable regions: entorhinal cortex, hippocampus, inferior temporal cortex, inferior parietal cortex, rostral middle frontal gyrus, and medial orbitofrontal cortex. Linear regressions tested the interaction between APOE ε4 dose and pulse pressure on CBF in each region, adjusting for age, sex, cognitive classification, antihypertensive medication use, FDG-PET, reference CBF region, and AD biomarker positivity. There was a significant interaction between pulse pressure and APOE ɛ4 dose on CBF in the entorhinal cortex, hippocampus, and inferior parietal cortex, such that higher pulse pressure was associated with lower CBF only among ε4 homozygous participants. These findings demonstrate that the association between pulse pressure and regional CBF differs by APOE ε4 dose, suggesting that targeting modifiable vascular risk factors may be particularly important for those genetically at risk for AD.
Edwards et al. (Mon,) conducted a cross-sectional in Older adults without dementia (Cognitively Unimpaired and Mild Cognitive Impairment) (n=144). Elevated pulse pressure and APOE ε4 allele dose vs. Lower pulse pressure and zero or one APOE ε4 allele was evaluated on Interaction between pulse pressure and APOE ε4 dose on regional cerebral blood flow (CBF) (Simple slope -1.11 (entorhinal cortex), -0.92 (hippocampus), -0.78 (inferior parietal cortex) for two ε4 alleles, p=0.003 (entorhinal), 0.005 (hippocampus), 0.002 (inferior parietal)). Higher pulse pressure was significantly associated with lower cerebral blood flow in the hippocampus, entorhinal cortex, and inferior parietal cortex only among participants homozygous for the APOE ε4 allele.