APOE Genotype, White Matter Hyperintensities, and Cerebral Microbleeds in a Cohort with Intact Cognition
Samantha Brown1, Bryan Woodruff2, Richard Caselli2, Oana Dumitrascu2
1Mayo Clinic Alix School of Medicine, Phoenix, AZ, 2Mayo Clinic
Objective:
To compare the burden of white matter hyperintensities (WMHI) and cerebral microbleeds (CMB) between APOE4 carriers and non-carriers in a population with normal cognition.
Background:
The vascular hypothesis of Alzheimer’s disease (AD) emphasizes neurovascular dysfunction as an early trigger for vascular amyloid-beta aggregation and neurodegeneration. APOE4 modulates neurovascular dysfunction in cerebrovascular disease. Despite increasing recognition for neurovascular dysfunction as an early AD biomarker, the association between APOE4 status and brain magnetic resonance imaging (MRI) markers of cerebrovascular disease, such as WMHI and CMB, in pre-clinical AD is poorly understood.
Design/Methods:
We enrolled 194 subjects with normal cognition that underwent 3.0T brain MRI, amyloid-PET and genetic testing. Demographics, APOE4 status and MRI features (WMHI count (T2-weighted), CMB count (Gradient Echo), Fazekas scale, MRI lesions (subcortical/cortical infarcts, other)) were analyzed using descriptive statistics. Chi-square and Fisher’s exact test were used to compare intergroup distribution for all variables across APOE4 heterozygotes, homozygotes, and non-carriers.
Results:
We included 66 APOE4 heterozygotes, 19 APOE4 homozygotes, and 109 APOE4 non-carriers, majority female (74.2%) and Caucasian (80.9%), mean(SD) age 66.1(10.7), mean (SD) education (years) 16.4(2.4). The 3 groups were matched for sex, age, race, education (p>0.05 for all). Most subjects (62.3%) had mild T2 WMHI burden (67.1% APOE4 carriers, 58.7% non-carriers), Fazekas grade 1 being the most common finding (38.7% periventricular, 49.0% subcortical). 92.3% had no CMBs (89.4% APOE4 carriers, 94.5% non-carriers). Only 11 (6.7%) had cerebral infarcts. There was no statistically significant difference in T2 WMHI burden (p=0.26), periventricular (p=0.63), subcortical Fazekas grade (p=0.50), and CMB count (p=0.28) between the APOE4 homozygotes, heterozygotes, and non-carriers.
Conclusions:
In a patient population with normal cognition, APOE4 status did not impact the burden of WMHI and CMB. Future studies in larger cohorts should evaluate the relationship between APOE4 status and neuroimaging markers of cerebrovascular dysfunction in preclinical AD.