Plasma NfL and Cognitive Functioning in Older Adults: The Moderating Role of HDL Cholesterol

HDL cholesterol moderates the association between plasma NfL and cognitive performance in older adults. Elevated HDL levels enhance the negative impact of NfL on cognition, challenging the assumption that HDL is uniformly protective in aging. As a modifiable factor, HDL offers a clinically actionable target in efforts to delay cognitive decline. These findings align with the United States Department of Health and Human Services (HHS) priorities on biomarker-based strategies and underscore the value of integrating metabolic and neurodegenerative biomarkers for improved cognitive risk profiling and targeted interventions.