Annals of the Child Neurology Society · 2025
Variation in Neurodegeneration-Linked Brain Regions in Young Adult APOE E4 Carriers With Spina Bifida.
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Jasien Joan M, Stout Jacques A, Mikati Mohamad A, Anderson Robert J, Nave Brittany G, Fuchs Herbert E, Smith Brian, Badea Alexandra, Browndyke Jeffrey N
Аннотация
OBJECTIVE: 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).
METHODS: 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.
RESULTS: 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).
INTERPRETATION: 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.
METHODS: 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.
RESULTS: 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).
INTERPRETATION: 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.