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Peer-reviewedCC BY-NC 4.0Alzheimer's & Dementia : Diagnosis, Assessment & Disease Monitoring

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

  • Amani M. Norling1,2
  • Audrey M. Collins1
  • Kelsey R. Sewell1,3
  • Lu Wan1
  • George Grove4
  • Haiqing Huang1
  • Timothy M. Hughes5
  • Adam D. Gepner6,7
  • Akira Sekikawa8
  • Lauren E. Oberlin1,9
  • Thomas K. Karikari10,11,12
  • Jill K. Morris13,14
12 more authors
  • John M. Jakicic15
  • Renee J. Rogers15
  • Daniel E. Forman16
  • Edward McAuley17,18
  • Arthur F. Kramer17
  • Charles H. Hillman19,20,21
  • Eric D. Vidoni13,14
  • Sandra A. Billinger13,14
  • Jeffrey M. Burns13,14
  • Anna L. Marsland4
  • Chaeryon Kang10,22
  • Kirk I. Erickson1
22 affiliations
  1. 1AdventHealth Research Institute, Neuroscience Orlando Florida USA
  2. 2The Hinda and Arthur Marcus Institute for Aging Research Hebrew SeniorLife Boston Massachusetts USA
  3. 3Centre for Healthy Ageing, Health Futures Institute Murdoch University Perth Western Australia Australia
  4. 4Department of Psychology University of Pittsburgh Pittsburgh Pennsylvania USA
  5. 5Wake Forest University School of Medicine Winston‐Salem North Carolina USA
  6. 6Department of Medicine–Division of Cardiovascular Medicine William S. Middleton Memorial Veteran's Hospital Madison Wisconsin USA
  7. 7Department of Medicine, Division of Cardiovascular Medicine University of Wisconsin School of Medicine and Public Health Madison Wisconsin USA
  8. 8Department of Epidemiology, School of Public Health University of Pittsburgh Pittsburgh Pennsylvania USA
  9. 9Department of Psychiatry Weill Cornell Medicine New York New York USA
  10. 10Department of Psychiatry, School of Medicine University of Pittsburgh Pittsburgh Pennsylvania USA
  11. 11Alzheimer's Disease Research Center University of Pittsburgh Pittsburgh Pennsylvania USA
  12. 12Biofluid Biomarker Laboratory Western Psychiatric Hospital, University of Pittsburgh Medical Center Pittsburgh Pennsylvania USA
  13. 13Alzheimer's Disease Research Center University of Kansas Kansas City Kansas USA
  14. 14Department of Neurology University of Kansas Medical Center Kansas City Kansas USA
  15. 15Department of Internal Medicine, Division of Physical Activity and Weight Management University of Kansas Medical Center Kansas City Kansas USA
  16. 16Department of Medicine (Geriatrics and Cardiology) and the Pittsburgh Geriatric Research Education and Clinical Center, VA Pittsburgh Healthcare System University of Pittsburgh Pittsburgh Pennsylvania USA
  17. 17Beckman Institute for Advanced Science and Technology University of Illinois at Urbana Champaign Urbana Illinois USA
  18. 18Department of Health and Kinesiology University of Illinois at Urbana Champaign Urbana Illinois USA
  19. 19Department of Psychology Northeastern University Boston Massachusetts USA
  20. 20Institute for Cognitive & Brain Health Northeastern University Boston Massachusetts USA
  21. 21Department of Physical Therapy, Movement, & Rehabilitation Sciences Northeastern University Boston Massachusetts USA
  22. 22Department of Biostatistics and Health Data Science, School of Public Health University of Pittsburgh Pittsburgh Pennsylvania USA
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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

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Cite

BibTeXRIS
BibTeX
@article{norling2026decomposed,
  title = {{Decomposed arterial stiffness and NfL–cognition association in older adults: The IGNITE study}},
  author = {Amani M. Norling and Audrey M. Collins and Kelsey R. Sewell and Lu Wan and George Grove and Haiqing Huang and Timothy M. Hughes and Adam D. Gepner and Akira Sekikawa and Lauren E. Oberlin and Thomas K. Karikari and Jill K. Morris and John M. Jakicic and Renee J. Rogers and Daniel E. Forman and Edward McAuley and Arthur F. Kramer and Charles H. Hillman and Eric D. Vidoni and Sandra A. Billinger and Jeffrey M. Burns and Anna L. Marsland and Chaeryon Kang and Kirk I. Erickson},
  journal = {Alzheimer's \& Dementia : Diagnosis, Assessment \& Disease Monitoring},
  year = {2026},
  month = nov,
  doi = {10.1002/dad2.70507},
  url = {https://doi.org/10.1002/dad2.70507},
  note = {CC BY-NC 4.0},
}
RIS
TY  - JOUR
TI  - Decomposed arterial stiffness and NfL–cognition association in older adults: The IGNITE study
AU  - Amani M. Norling
AU  - Audrey M. Collins
AU  - Kelsey R. Sewell
AU  - Lu Wan
AU  - George Grove
AU  - Haiqing Huang
AU  - Timothy M. Hughes
AU  - Adam D. Gepner
AU  - Akira Sekikawa
AU  - Lauren E. Oberlin
AU  - Thomas K. Karikari
AU  - Jill K. Morris
AU  - John M. Jakicic
AU  - Renee J. Rogers
AU  - Daniel E. Forman
AU  - Edward McAuley
AU  - Arthur F. Kramer
AU  - Charles H. Hillman
AU  - Eric D. Vidoni
AU  - Sandra A. Billinger
AU  - Jeffrey M. Burns
AU  - Anna L. Marsland
AU  - Chaeryon Kang
AU  - Kirk I. Erickson
PY  - 2026
DA  - 2026/11/02
JO  - Alzheimer's & Dementia : Diagnosis, Assessment & Disease Monitoring
DO  - 10.1002/dad2.70507
UR  - https://doi.org/10.1002/dad2.70507
AB  - 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
SN  - 2352-8729
ER  -