Clinical Trial, Phase III Journal Article Multicenter Study Randomized Controlled Trial Ppublish
PubMed: 40775489 DOI: 10.1002/alz.70554
Arterial stiffness moderates the link between NfL and cognition: The IGNITE study.
Alzheimers Dement 21(8):e70554
Authors: Amani M Norling, Lewis A Lipsitz, Alyssa B Dufour, Thomas G Travison, Kelsey R Sewell, Audrey M Collins, Lu Wan, George Grove, Haiqing Huang, Lauren E Oberlin, Shivangi Jain, Thomas K Karikari, Jill K Morris, John M Jakicic, Edward McAuley, Arthur F Kramer, Charles H Hillman, Eric D Vidoni, Sandra A Billinger, Jeffrey M Burns, Anna L Marsland, Chaeryon Kang, Kirk I Erickson
Affiliations
- The Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, Massachusetts, USA.
- Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
- AdventHealth Research Institute, Neuroscience, Orlando, Florida, USA.
- Centre for Healthy Ageing, Health Futures Institute, Murdoch University, Western Australia, Australia.
- Department of Psychology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
- Department of Psychiatry, Weill Cornell Medicine, New York, New York, USA.
- Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
- Alzheimer's Disease Research Center, University of Kansas, Kansas City, Kansas, USA.
- Department of Neurology, University of Kansas Medical Center, Kansas City, Kansas, USA.
- Department of Internal Medicine, Division of Physical Activity and Weight Management, University of Kansas Medical Center, Kansas City, Kansas, USA.
- Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana Champaign, Illinois, USA.
- Department of Health and Kinesiology, University of Illinois at Urbana Champaign, Illinois, USA.
- Department of Psychology, Northeastern University, Boston, Massachusetts, USA.
- Center for Cognitive & Brain Health, Northeastern University, Boston, Massachusetts, USA.
- Department of Physical Therapy, Movement, & Rehabilitation Sciences, Northeastern University, Boston, Massachusetts, USA.
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.
MeSH
Dementia, Memory, Short-Term, Alzheimer Disease, Cardiorespiratory Fitness, Aging, Cognitive Dysfunction, Carotid-Femoral Pulse Wave Velocity, Cognitive Aging, Memory, Cognition, Pulse, Memory, Episodic, Vascular Health
Cited by
- Arterial stiffness moderates the link between NfL and cognition: The IGNITE study. Alzheimers Dement, 2025