Abstract
INTRODUCTION: Arterial stiffness (carotid-femoral pulse wave velocity [cfPWV]) and plasma neurofilament light (NfL), markers of vascular and neuroaxonal aging, are linked to cognitive decline. Whether higher cfPWV amplifies the NfL-cognition relationship remains unclear. METHODS: Cognitively unimpaired older adults (N = 570) were assessed using composite cognitive scores from confirmatory factor analysis. cfPWV was dichotomized at the median. Plasma NfL was quantified on a Single Moleculte Array-High Definition, model X (SIMOA-HD X). RESULTS: Higher NfL correlated with poorer performance across all cognitive domains (p < 0.05), and higher cfPWV was linked to worse episodic memory, working memory, and processing speed (p < 0.05). NfL× cfPWV interactions were significant for episodic (β = 0.289, p = 0.048) and working memory (β = 0.287, p = 0.025), with stronger NfL-cognition associations in the higher cfPWV group (episodic memory: β = -0.324, p < 0.01; working memory: β = -0.343, p < 0.01). DISCUSSION: Greater cfPWV amplified the association between NfL-related axonal degeneration and cognitive decline. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02875301 HIGHLIGHTS: Neurofilament light (NfL) and carotid-femoral pulse wave velocity (cfPWV) each correlate with poorer cognitive function in older adults. Higher cfPWV exacerbates the link between NfL and cognitive deficits. Arterial stiffness may worsen NfL-related cognitive decline. Findings reveal synergy between vascular and neurodegenerative aging markers. Examining NfL or cfPWV alone may miss their synergistic effects on cognition.