Sex Differences in the Association between Repetitive Negative Thinking, Allostatic Load and Neurofilament Light

Emerging evidence suggests that Repetitive Negative Thinking (RNT; i.e., worry and ruminative brooding) is associated with biomarkers of Alzheimer’s disease. However, it is neither known whether RNT may be a marker of neurodegenerative disease more generally, nor the mechanism through which RNT may act. Given that women have greater risk of many neurodegenerative diseases, this study aimed to investigate (I) the relationships between worry and ruminative brooding and a blood-based biological correlate of neurodegeneration, neurofilament light chain (NfL), (II) whether this relationship differs by sex, and (III) the extent to which allostatic load, a marker of chronic stress, may mediate this relationship. Cross-sectional baseline data from 134 cognitively healthy older adults (61.2% women) enrolled in the Age-Well clinical trial were utilised. Worry and brooding were assessed by the Penn State Worry Questionnaire and the Rumination Response Scale brooding subscale, respectively. Plasma NfL levels were quantified using a Meso Scale Discovery assay. A composite measure of allostatic load was calculated using 18 biomarkers spanning five sub-categories (anthropometric, cardiovascular and respiratory, metabolic, immune, neuroendocrine). Associations were examined using linear regressions adjusted for demographic characteristics. We found a positive interaction between brooding and ex on NfL, with higher brooding associated with greater NfL levels in women. No associations were observed with worry or allostatic load. These results offer preliminary support that RNT is associated with worse brain health, specifically in women. Further research is needed to elucidate the underlying mechanisms that explains the association between RNT and markers of dementia risk in women.