Older spousal caregivers of persons with cognitive impairment are at increased risk of dementia and accelerated neurodegeneration. Although plasma neurofilament light chain(NfL) is a sensitive blood biomarker of neurodegeneration in the AT(N) framework, previous studies have not consistently shown a direct association between caregiving burden and NfL.

We proposed that caregiving burden may influence NfL through behavioral and metabolic intermediaries. Prior independent studies have suggested separate links between caregiving burden and poorer diet, poorer diet and lower blood protein levels, and lower blood protein levels and higher NfL. However, these pathways had not been examined together in a single cohort.

Using serial mediation analysis, we found that higher caregiving burden was associated with poorer dietary intake, lower blood protein levels, and subsequently higher plasma NfL. This pathway remained robust in additional analyses, including models using albumin as an alternative marker.

Our findings suggest that nutrition may be a modifiable pathway linking caregiving burden to neurodegeneration, highlighting the potential importance of dietary support for protecting caregivers’ brain health.