Increased Cerebral Blood Flow in Cognitively Intact APOE4 Carriers Predicts Cerebral Amyloid Burden
Oana Dumitrascu1, Gina Dumkrieger1, Leslie Baxter1, Bryan Woodruff1, Yuxiang Zhou1, Richard Caselli1, Simona Nikolova1
1Mayo Clinic
Objective:
To evaluate the impact of APOE4 genotype on cerebral perfusion and the relationship between region-specific cerebral blood flow (CBF) changes and amyloid-PET in cognitively intact individuals.
Background:
Region-of-interest-based CBF measurements could differentiate Alzheimer’s disease (AD) from healthy controls. Although APOE4 may trigger blood-brain barrier dysfunction and AD pathogenesis, cerebral blood flow patterns in presymptomatic AD are poorly characterized.
Design/Methods:
We analyzed the cerebral perfusion on pseudo-continuous arterial spin labeling (pCASL) in 71 cognitively intact individuals that underwent APOE and amyloid-PET testing. T1-weighted MR images were acquired on a 3T Siemens Skyra System. CBF was acquired using 5-delay pCASL with TR=4100ms, TE=37.0ms, FA=120 degrees, 3.5mm isotropic resolution and field of view of 224x 224mm2. Whole-brain CBF differences between APOE4 carriers and non-carriers were interrogated using two group F-test (significance set as p<0.001, cluster forming threshold of 10 voxels). The CBF in the strongest discriminatory brain regions were used in a logistic regression model to predict amyloid-PET positive status (Standardized Uptake Value Ratio centiloid>20), along with age, sex, APOE4 carrier, and vascular comorbidities.
Results:
APOE4 carriers (n=31, 17 (55%) amyloid-PET positive) exhibited significantly greater CBF in 35 brain regions compared to non-carriers (n=40, 8 (20%) amyloid-PET positive), after correcting for age, sex and vascular risk factors. APOE4 carriers were significantly more likely to have increased cerebral amyloid (chi-square t-test, P=0.0023). The CBF from the top four most discriminative brain regions (right cerebellum, left post central gyrus, right middle temporo-occipital, right anterior orbital gyrus) were included in the brain amyloid-PET predictive model. Left post-central CBF (p=0.07, b = 0.01), age (p=1.3e-05, b = 0.03), and APOE4 status (p=0.003, b =0.24) had the greatest predictive magnitude for amyloid-PET (AUROC of 0.924).
Conclusions:
The increased region-specific cerebral perfusion in APOE4 carriers significantly predicts cerebral amyloid burden in cognitively intact individuals at genetic risk for AD.
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