Decomposed arterial stiffness and NfL-cognition association in older adults: The IGNITE study

Neurofilament light chain (NfL) indexes neuroaxonal injury and relates to poorer cognition. Higher carotid-femoral pulse wave velocity (cfPWV) arterial stiffness strengthens NfL-cognition associations, but reflects both pressure-standardized structural stiffness (S-PWV) and transient hemodynamic load-dependent pulse wave velocity (LD-PWV). We tested which component drives this interaction.

Plasma NfL and cfPWV were measured in 552 cognitively unimpaired older adults. cfPWV was decomposed into S-PWV and LD-PWV. Five latent cognitive domains were modeled. Linear regression tested PWV moderators of NfL-cognition associations.

NfL correlated with all domains (r = -0.116 to -0.185; P < 0.01) and was unrelated to S-PWV or LD-PWV. Total-PWV moderated NfL-working memory (β = -0.268, P = 0.019). NfL × S-PWV interactions were significant for episodic memory, working memory, and processing speed (P < 0.040), but did not meet false discovery rate correction (q ≈ 0.067). NfL × LD-PWV interactions were non-significant (P > 0.09).

Nominal interactions were more consistent for S-PWV. Findings did not provide multiplicity-adjusted evidence of component-specific moderation.ClinicalTrials.gov: NCT02875301.