{"doi":"10.1002/alz.70554","title":"Arterial stiffness moderates the link between NfL and cognition: The IGNITE study","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.","journal":"Alzheimer s & Dementia","year":2025,"id":524099,"datarank":0.2515738783043557,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.010158191439240577,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.010158191439240577,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":2,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9384,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT02875301"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":291344,"name":"Lewis A. 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Billinger","orcid":"0000-0002-1618-7207","position":18,"is_corresponding":false},{"id":68016,"name":"Jeffrey M. Burns","orcid":"0000-0001-7609-8954","position":19,"is_corresponding":false},{"id":363262,"name":"Anna L. Marsland","orcid":"0000-0001-8951-7513","position":20,"is_corresponding":false},{"id":271300,"name":"Chaeryon Kang","orcid":"0000-0001-9442-8515","position":21,"is_corresponding":false},{"id":225312,"name":"Kirk I. Erickson","orcid":"0000-0001-8736-981X","position":22,"is_corresponding":false},{"id":1106772,"name":"Amani M. 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