The influence of Apolipoprotein E ε4 carrier status on posterior cingulate cortex thickness and learning

Abstract

AbstractBackgroundThinning of the posterior cingulate cortex (PCC) is implicated in Alzheimer’s disease (AD). Though some evidence suggests ApolipoproteinE (APOE) ε4 carriers (ε4+) have thinner PCCs than non‐carriers (ε4‐), the evidence is conflicting and lacks association with learning outcomes relevant to AD.MethodA subset from an ongoing clinical trial (NIH/NIA: R01AG058919) was used for analyses and included 26 ε4+ (73% female, Agemean=55.81±5.53) and 42 ε4‐ (88% female, Agemean= 57.54±5.10), who were all cognitively normal, sedentary, and had a family history of AD. Genetic sampling was completed via passive drool. Structural MRI was completed to assess PCC cortical thickness, and the Rey Auditory Verbal Learning Task (AVLT) was used to assess learning. Brain segmentation was completed with Freesurfer’s automated pipeline, and left and right PCC cortical thickness was extracted for analysis. A learning over trials (LOT) composite score from the AVLT was calculated to represent learning. An analysis of covariance was completed to assess the effect of carrier status on left/right PCC thickness, controlling for age and sex. Linear regressions were completed to assess main effects and interaction of carrier status and left/right PCC thickness in predicting LOT when controlling for age and sex.Resultε4+ had less cortical thickness in the left PCC (F(1,64)=5.07, p=.03), but not the right PCC (p=.33), relative to ε4‐. Carrier status predicted LOT (Left: F(1,62)=10.37, p<.01; Right: F(1,62)=10.66, p<.01), however this was superseded by significant interactions between carrier status and PCC thickness predicting LOT (Left: F(1,62)=10.72, p<.01; Right: F(1, 62)=11.10, p<.01), with post‐hoc analyses demonstrating PCC thickness predicts LOT for ε4+ (Left:β=‐21.07, p=.04; Right:β=‐24.33, p<.01), but not ε4‐ (p’s>.09).ConclusionIn cognitively normal sedentary adults with a family history of AD, carrying the APOE ε4 allele was associated with a thinner left PCC. Further, thinner bilateral PCCs in ε4+ were associated with greater learning during the AVLT task. This suggests that ε4+ may have compensatory neural pathways to account for losses in the PCC, which temporarily bolster learning to delay the onset of AD. However, additional research is needed to continue understanding the neural mechanisms affected by carrying the APOE ε4 allele.