Objective:

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.

Background:

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.

Design/Methods:

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.

Results:

Conclusions:

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.