White matter microstructure and cognitive functioning across healthy older adults with different APOE alleles

Abstract

Background: APOE alleles play an important neurobiological role in the development of Alzheimer’s Disease (AD), including modifying structure of white matter in the brain and cognitive decline (Gold et al., 2012; Reas et al., 2019). However, certain alleles (i.e., APOE‐e4) have be studied more than others (i.e., APOE‐e2 & e3), and have been primarily studied in individuals already diagnosed with AD, rather than in healthy older adults. While APOE‐e4 is well establish risk factor for AD, APOE‐e2 may play a role in protective mechanisms against AD, and APOE‐e3 may be neutral, yet their underlying neural mechanisms and association with cognitive functioning in the healthy aging brain are equivocal (Suri et al., 2013). Thus, the current study aimed to investigate the influence of different APOE alleles on white matter microstructure and cognition in healthy older adults. Method: White matter microstructure, memory, and executive functioning (EF) were compared between cognitively normal older adults with either APOE‐e2+ (n= 16, mean age= 76), APOE e3e3 (n= 64, mean age= 74), or APOE‐e4+ (n=35, mean age=73). White matter microstructure was compared using Diffusion Tensor Imaging (DTI) Track‐based spatial statistics (TBSS) methods to derive fractional anisotropy (FA). Whole‐brain mean FA was compared first between e3e3 and e2+ and then between e3e3 and e4+ groups. Memory and executive functioning composite scores were compared, including covariates of age, sex, and education levels, using multivariate analysis of covariance (MANCOVA). All data were retrieved from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Result: No significant differences in white matter microstructure (FA; p> 0.05, corrected) were observed. Further, groups were not significantly different in memory, EF, age, sex, or education levels (p=0.59). Conclusion: These results indicate that white matter microstructure, memory, and EF changes are not evident in the healthy brain as a function of APOE allele presence. DTI may not be sensitive to APOE‐related changes in the healthy brain; nonetheless, future investigations should evaluate whether other structural (e.g., grey matter volume) and functional (e.g., fMRI) differences are evident across different APOE alleles in this population, as well as examine other cognitive domains.