Sex differences in the association between repetitive negative thinking and neurofilament light

Abstract

Emerging evidence suggests that repetitive negative thinking (RNT; i.e., worry and ruminative brooding) is associated with biomarkers of Alzheimer’s disease. Given that women have a greater risk of many neurodegenerative diseases, this study investigated whether worry and brooding are associated with general neurodegeneration and whether associations differ by sex. Exploratory analyses examined whether allostatic load, a marker of chronic stress, mediates any observed relationships. Baseline data from 134 cognitively healthy older adults in the Age-Well clinical trial were utilised. Worry and brooding were assessed using questionnaires. Plasma neurofilament light chain (NfL), a biomarker of neurodegeneration, was quantified using a Meso Scale Discovery assay. We found a positive interaction between brooding and sex on NfL, with higher brooding associated with greater NfL levels in women. No associations were observed between worry/ruminative brooding and allostatic load. These results offer preliminary support that RNT is associated with worse brain health, specifically in women.