Variation in Neurodegeneration-Linked Brain Regions in Young Adult APOE E4 Carriers With Spina Bifida

Possible pleiotropic effects of apolipoprotein E4 (APOE E4) in individuals with congenital brain malformations are relatively unknown. Our goal was to determine if neurodegeneration-linked brain region volumes differ significantly between E4 carriers and noncarriers in young adults with spina bifida (SB).

Eleven individuals ( > 18 years), genotyped for APOE, underwent neuroimaging and neurocognitive evaluation. Primary analysis: Magnetic resonance imaging (MRI) data from 10 a priori neurodegeneration-risk regions of interest were compared between E4 carriers and noncarriers, adjusting for age, sex, and total intracranial volume (FDR-adjusted p < 0.05). Secondary analyses: Age-adjusted neurocognitive standard scores were compared between groups (p < 0.05). Post hoc analyses of NeuroQuant-derived regional brain volumes were examined for combined group differences in young adults with SB.

Comparison of a priori risk region volumes revealed significantly lower left amygdala volumes (FDR-adjusted p = 0.04) in young adult E4 carriers (n = 4) relative to noncarriers (n = 7). Neurocognitive data were not significantly different between the groups. A possible trend was detected for enlarged parietal volumes in E4 carriers (p = 0.07), while volumetric extremes ( > 95% or < 5%) were detected for the anterior cingulate (100% of cases; p = 0.001), frontal cortices (90% of cases), hippocampus (80% of cases), and entorhinal cortices (70% of cases).

Early left amygdala volumetric reduction was found in E4 carriers; combined group volume comparisons revealed frontal and temporal lobe differences in young adults with SB relative to age- and sex-matched volumetric estimates. This pilot investigation does not appear to support E4 conferring a pleiotropic benefit in young adults with SB but rather supports further investigation of MRI volumetrics as a possible biomarker for this population.