APOE ε4 ALLELE EFFECT ON WHITE AND GRAY MATTER PERFUSION IN COGNITIVELY NORMAL AND MCI GROUPS

Abstract

Cerebral perfusion in both white and gray matter may be an indicator of vascular dysfunction and cognition decline. In this study, simultaneous estimates of cerebral blood flow (CBF) and arterial transit time (ATT) using multiple inversion time arterial spin labeling (ASL) was analyzed in cognitively normal and mild cognitive impairment (MCI) groups. Lower CBF and shorter ATT in APOE ε4 carriers may indicate cerebrovascular functional disorder that impacts cognitive function. 87 subjects (62 cognitively normal (23% ε4+) and 25 MCI (48% ε4+); 23M/64F; age: 63.9±7.7) underwent baseline brain MRI exams as part of several on-going studies within the Wake Forest AD Center, including pseudo-continuous ASL to estimate voxel-wise whole brain CBF and ATT in white and gray matters using a partial volume correction. An example CBF and ATT maps are shown in Figure 1. All ASL images were co-registered to T1 weighted structural images and normalized into a study specific template. Age, Sex, BMI, and HbA1C were adjusted and 2-way ANOVA was performed for each voxel. A minimum cluster size was determined with p<0.05 and α=0.05. APOE ε4 carriers showed reduced CBF in a white matter cluster and four gray matter clusters as shown in Figure 2. The white matter hypo-perfusion cluster locates mainly in left sub-lobar region and extends over temporal and parietal lobes. Four small clusters in gray matter are in left hippocampus, thalamus, right lingual, and right hippocampus and amygdala (Table 1). Although were not statistically significant, ATT values measured in the clusters representing lower blood flow are also shorter in the ε4 carriers (Table 2). In addition, the group without ε4 Allele showed a trend of compensatory increased blood flow in MCI while that with ε4 Allele had impaired blood flow. In this small pilot study sample, lower CBF and shortened ATT were observed among APOE ε4 carriers in both white and gray matter and did not significantly differ by cognitive status. These data suggest evidence of that a perfusion abnormality indicative of flow dynamics of arterial stiffness / arteriolosclerosis are seen among ε4 carriers that may contribute to cerebrovascular disorders. CBF and ATT maps in GM and WM from a representative subject (82 yr. old, F). The partial volume fraction of 0.2 was applied to make the maps. Clusters in white and gray matters representing lower blood flow in the group with APOE ε4 Allele.