Effect of sex on the APOE4-aging interaction in the white matter microstructure of cognitively normal older adults using diffusion-tensor MRI with orthogonal-tensor decomposition (DT-DOME)

Abstract

The influence of the apolipoprotein E ε4 allele (APOE4) on brain microstructure of cognitively normal older adults remains incompletely understood, in part due to heterogeneity within study populations. In this study, we examined white-matter microstructural integrity in cognitively normal older adults as a function of APOE4 carrier status using conventional diffusion-tensor imaging (DTI) and the novel orthogonal-tensor decomposition (DT-DOME), accounting for the effects of age and sex. Age associations with white-matter microstructure did not significantly depend on APOE4 status, but did differ between sexes, emphasizing the importance of accounting for sex differences in APOE research. Moreover, we found the DT-DOME to be more sensitive than conventional DTI metrics to such age-related and sex effects, especially in crossing WM fiber regions, and suggest their use in further investigation of white matter microstructure across the life span in health and disease.

Sex, racial, andAPOE-ε4 allele differences in longitudinal white matter microstructure in multiple cohorts of aging and Alzheimer’s disease

“…Despite the role of APOE in lipid homeostasis, studies do not consistently find an association between APOE -ε4 and worse white matter integrity. 61-63 In previous work, we have shown that the FW measure, particularly in limbic tracts, is sensitive to abnormal aging. 28,49 This study extends this work by showing that APOE -ε4 carriers, who are known to be at greater risk for AD, show these same changes in the FW metric in limbic tracts.…”

Modeling the impact of genotype, age, sex, and continuous navigation on pathway integration performance

“…These morphological and physiological variations within different age and gender groups consequently yield divergent impacts on PI performance, a function involving the entorhinal cortex (Powell et al, 2021)(a Meta-analysis by (Farrer et al, 1997)). Beyond the entorhinal cortex, various other factors such as neurofibrillary tangle (NFT) formation (Ghebremedhin et al, 2001), cerebrospinal fluid (CSF) composition (Altmann et al, 2014), amyloid fibril levels (Cacciaglia et al, 2022), white matter microstructure (Srisaikaew et al, 2023), and functional connectivity within the default mode network (DMN) (Damoiseaux et al, 2012), are similarly influenced by age, gender, and APOE4. Consequently, they could also potentially influence the performance of path integration tasks.…”