A profile of brain reserve in adults at genetic risk of Alzheimer's disease

Abstract

Introduction The apolipoprotein E (APOE) epsilon 4 allele is the greatest genetic risk factor for Alzheimer's disease (AD). Our aim was to identify the structural brain measures that mitigate the negative effect of APOE epsilon 4 on cognition, which would have implications for AD diagnosis and treatment trial selection. Methods A total of 742 older adults (mean age: 70.1 +/- 8.7 years) were stratified by APOE status and classified as cognitively normal (CDR 0) or with very mild dementia (CDR 0.5). Regional brain volume and cognitive performance were measured. Results There were significant interactions between APOE and CDR on the left precuneus and on bilateral superior frontal volumes. These regions were preserved in CDR-0 epsilon 3/epsilon 4 and epsilon 4/epsilon 4 carriers but were reduced in CDR-0.5 epsilon 3/epsilon 4 and epsilon 4/epsilon 4 carriers, compared to their respective epsilon 3/epsilon 3 counterparts. Educational attainment predicted greater brain reserve. Discussion This pattern of preserved brain structure in cognitively normal epsilon 4 carriers with comprised medial temporal volume is consistent with the theory of brain reserve.