Major Lifetime Discrimination Exposure Accelerates Brain Microstructural Aging: Diffusion MRI Evidence From MIDUS

Abstract

Objective: Experiencing discrimination is associated with faster biological aging, as reflected in telomere shortening and DNA methylation. However, the impact of discrimination on brain aging processes remains unclear. Here, we tested whether individuals who reported at least one major lifetime discrimination event would exhibit steeper age-related associations in microstructural metrics within whole-brain white matter and the hippocampus, consistent with accelerated brain microstructural aging, compared with those with no such experiences.

Methods: We analyzed multi-shell diffusion-weighted MRI data from the Midlife in the United States (MIDUS) cohort ( n =147, mean age=65 years, range: 48 to 95 years) to assess brain microstructure using complementary statistical and biophysical diffusion models. Diffusion kurtosis imaging representation was used to derive diffusion tensor imaging (DTI) and white matter tract integrity (WMTI) measures. Additional microstructural health indices were derived using the neurite orientation dispersion and density imaging (NODDI) model. Permutation analyses of linear models were run within the whole-brain white matter and bilateral hippocampi, adjusting for sex, race, and education.

Results: Participants who reported at least one major discriminatory experience during their lifetime exhibited accelerated age-associated changes in white matter microstructural measures, including higher mean and radial diffusivities, extra-axonal radial diffusivity, and free water fraction compared with those with no such experiences.

Conclusions: These converging findings from complementary measures of brain microstructure suggest that major discrimination experiences may contribute to accelerated brain microstructural aging.

Keywords: MIDUS; aging; brain microstructure; diffusion weighted imaging; major lifetime discrimination.