- Plasma NfL associated with poorer performance across five cognitive domains in cognitively unimpaired older adults (r = -0.116 to -0.185).
- Total cfPWV moderated the NfL-working memory association (β = -0.268, P = 0.019); S-PWV showed nominal interactions with multiple domains.
- LD-PWV interactions were non-significant and no component-specific moderation survived correction for multiple comparisons.
Alzheimers Dement (Amst). 2026 Nov 2;18(4):e70507. doi: 10.1002/dad2.70507. eCollection 2026 Oct-Dec.
ABSTRACT
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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).
DISCUSSION: Nominal interactions were more consistent for S-PWV. Findings did not provide multiplicity-adjusted evidence of component-specific moderation.ClinicalTrials.gov: NCT02875301.
PMID:42979025 | PMC:PMC13728322 | DOI:10.1002/dad2.70507
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