Regional Atrophy of Transcallosal Prefrontal Connections in Cognitively Normal APOE ε4 Carriers

Abstract

Purpose: To investigate the possible effect of the APOE ε4 allele on age-related regional volume loss within the corpus callosum (CC) in healthy ε4 allele carriers compared with noncarriers. Materials and Methods: A total of 211 subjects, ages 27 to 83 years, 51 ε4 carriers and 160 noncarriers underwent T1-weighted MRI scan. All subjects had normal MRI scan and performed within normal range on a neuropsycholog- ical battery of tests. CC was segmented into seven function- ally relevant regions using a previously published probabi- listic map of the CC connectivity. We measured the volumes of the CC and its subregions. We used a regression model (with volumes as dependent and age as independent vari- ables) and compared the slopes between carriers and non- carriers using an analysis of covariance model. We also carried out voxel-based-morphometry analysis to investi- gate the possible effect of the APOE ε4 gene on the gray matter. Results: We found that the volume of the CC and all sub- regions decreased with increasing age in both groups. The slope was steeper in the APOE ε4 carriers compared with- the noncarriers particularly in the prefrontal region (P = 0.02). No gray matter differences were observed between the two groups. Conclusion: APOE ε4 polymorphism is associated with ac- celerated age-related volume loss in the prefrontal callosal tracts without gray matter loss. This result suggests the role of APOE ε4 in the brain aging by primarily affecting white matter structures particularly in the frontal lobe. © 2009.