Abstract Details

Title Increased Cerebral Blood Flow in Cognitively Intact APOE4 Carriers Predicts Cerebral Amyloid Burden

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) P4 - Poster Session 4 (5:00 PM-6:00 PM)

Poster/Presentation
Number 3-003

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.

Authors/Disclosures
Oana M. Dumitrascu, MD, FAAN (Mayo Clinic) PRESENTER	Dr. Dumitrascu has nothing to disclose.
Gina Dumkrieger, PhD (Mayo Clinic)	Gina Dumkrieger has received personal compensation for serving as an employee of Mayo Clinic. The institution of Gina Dumkrieger has received research support from NIH. The institution of Gina Dumkrieger has received research support from DOD. The institution of Gina Dumkrieger has received research support from AMGEN.
Leslie C. Baxter, PhD (Barrow Neurological Institute)	No disclosure on file
Bryan K. Woodruff, MD (Mayo Clinic)	The institution of Dr. Woodruff has received research support from National Institute on Aging.
Yuxiang Zhou, PhD	Dr. Zhou has nothing to disclose.
Richard J. Caselli, MD, FAAN (Mayo Clinic)	The institution of Dr. Caselli has received research support from NIA. The institution of Dr. Caselli has received research support from State of Arizona.
Simona Nikolova, PhD (Mayo Clinic)	Dr. Nikolova has nothing to disclose.

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