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Abstract Details

Effects of APOE Genotypes on Periventricular White Matter Cerebral Blood Flow in Cognitively Intact Adults
Aging, Dementia, and Behavioral Neurology
P3 - Poster Session 3 (11:45 AM-12:45 PM)
3-004
This study aimed to investigate the association between APOE genotype and cerebral blood flow (CBF) in periventricular white matter (PVWM) as a potential marker of small vessel disease (SVD) in cognitively intact (CI) individuals.
Alzheimer’s dementia (AD) and vascular dementia share common risk factors. The ε4 allele of the APOE gene is the most significant genetic risk factor for AD; however, its role in SVD remains underexplored. SVD is associated with alterations in CBF, which can be non-invasively measured using arterial spin labeling (ASL) MRI, offering valuable insights into vascular integrity. Notably, Reduced CBF in PVWM, which is vulnerable to microvascular dysfunction due to its exclusive supply by vessels smaller than 100μ in diameter, may serve as an early marker of SVD.
We utilized advanced background-suppressed 3D ASL MRI data from 179 CI participants (mean age±SD: 72.3±5.8 years; 65.4% female) to quantify CBF across various regions of interest (ROI), including gray matter, white matter, PVWM, precuneus, posterior cingulate cortex, and hippocampus. CBF values were normalized to global CBF to account for individual variations. Additional analyses excluded voxels containing white matter hyperintensity lesions to measure CBF in normal-appearing PVWM (NA-PVWM). Participants were categorized based on APOE genotype into three groups: ε4 non-carriers, heterozygous, and homozygous. Group comparisons were conducted to assess regional CBF differences across APOE genotypes, adjusting for age and sex.

ROI-based analyses indicated that participants homozygous for the APOE ε4 showed significantly lower CBF in PVWM and NA-PVWM, and significantly higher CBF in the hippocampus, compared to non-carriers and heterozygous groups (p<0.05). No significant differences were observed in other ROIs. Voxel-wise analyses demonstrated consistent findings across spatial regions.
The findings support the hypothesis that APOE ε4 contributes to the pathogenesis of both SVD and AD and suggest that APOE genotype may contribute to vascular-related cognitive decline through microvascular changes.
Authors/Disclosures
Shokufeh Sadaghiani, MD
PRESENTER 		Dr. Sadaghiani has nothing to disclose.
Mohammad Taghvaei (University of Pennsylvania) No disclosure on file
Sudipto Dolui, PhD (University of Pennsylvania) Dr. Dolui has nothing to disclose.
Banafsheh Shakibajahromi, MD (University of Pennsylvania, Department of Neurology) Dr. Shakibajahromi has nothing to disclose.
Sandhitsu R. Das, PhD Dr. Das has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Nia Therapeutics. The institution of Dr. Das has received research support from NIH.
Paul Yushkevich (University of Pennsylvania) No disclosure on file
David A. Wolk, MD, FAAN (University of Pennsylvania) Dr. Wolk has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly. Dr. Wolk has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Functional Neuromodulation. Dr. Wolk has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for GSK. The institution of Dr. Wolk has received research support from Biogen. Dr. Wolk has received publishing royalties from a publication relating to health care. Dr. Wolk has received personal compensation in the range of $5,000-$9,999 for serving as a CME speaker with Eli Lilly.
John A. Detre, MD (Hosp of the Univ of Penn) Dr. Detre has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Hura Imaging. The institution of Dr. Detre has received research support from NIH. Dr. Detre has received personal compensation in the range of $500-$4,999 for serving as a grant proposal reviewer with NIH, VA, European Science Foundation,Deutsche Forschungsgemeinschaft.