Stiff Arteries May Amplify Early Memory Decline in Older Adults

Findings from the multisite IGNITE clinical trial suggest that arterial stiffness, which occurs when large blood vessels lose their natural flexibility, may be linked to greater injury effects to brain nerve fibers in older adults without cognitive impairment. Understanding this relationship may help researchers and clinicians identify older adults who could be more at risk of developing cognitive decline.

The study, “Arterial stiffness moderates the link between NfL and cognition: The IGNITE study,” published in Alzheimer’s & Dementia, included 570 cognitively unimpaired older adults. Researchers examined plasma levels of neurofilament light chain, a blood biomarker that reflects damage to nerve fibers in the brain. NfL levels rise naturally with age, but higher-than-expected levels may signal accelerated brain aging or increased risk of cognitive decline.

The team also measured arterial stiffness using carotid-femoral pulse wave velocity, a measure of how fast blood flows from the heart to the legs. Stiff arteries cannot absorb the force of each heartbeat adequately, increasing strain on the heart. Over time, this added stress can harm organs that depend on a consistent blood supply — especially the brain.

The researchers found that greater arterial stiffness was associated with poorer performance in specific areas of thinking, including episodic memory (recalling past events), working memory (holding and manipulating information), and processing speed (how quickly the brain handles information). Importantly, participants with both higher arterial stiffness and elevated NfL showed the strongest associations with memory difficulties. In this group, higher NfL levels were tied to significantly worse memory functions, suggesting that stiff arteries may magnify the effects of nerve fiber damage on cognition.

Implications and caution

These findings suggest that vascular health may influence how nerve fiber damage in the brain translates to cognitive difficulties, even before dementia symptoms appear. However, the study is observational and cross-sectional, meaning it shows associations at a single point in time rather than cause-and-effect. Further research is needed to determine whether reducing arterial stiffness could lessen the impact of nerve damage on memory and thinking skills.

“These results reinforce the idea that brain aging is not only marked by damage to nerve fibers, reflected in biomarkers like NfL, but also about the health of the blood vessels that support the brain,” said Lewis A. Lipsitz, MD, director of the Hinda and Arthur Marcus Institute for Aging Research and chief academic officer at Hebrew SeniorLife. “While we can’t yet say that reducing arterial stiffness will reverse or halt cognitive decline, our findings suggest that stiff arteries may make the brain more vulnerable to damage. Protecting vascular health through the treatment of hypertension, high cholesterol, and other vascular risk factors could be an important piece of maintaining memory as we age.”

Lead author Amani M. Norling, PhD, BCBA, postdoctoral research fellow at the Marcus Institute and Harvard Medical School, highlighted the combined impact of the two risk factors. “Our findings suggest that when both nerve fiber damage and arterial stiffness are present, the brain may be especially vulnerable,” she said. “This means that a person with early signs of nerve fiber injury could face greater risks of cognitive decline if their arteries are also stiff, underscoring the importance of a two-pronged approach: monitoring brain health with biomarkers like NfL while also protecting vascular health through prevention and treatment. Together, these strategies may help us better identify who is most at risk for cognitive decline and how to intervene earlier.”

Senior author and principal investigator of the IGNITE study, Kirk Erickson, PhD, director of translational neuroscience at AdventHealth Research Institute, underscored the broader significance of the findings. “Understanding why some individuals experience more rapid cognitive decline in late adulthood than others remains a critical area of research, as it could help us develop medical treatments that more precisely target those at greatest risk. These exciting findings offer new insight into how both NfL and arterial stiffness may work together to influence certain aspects of cognition. While additional research is needed to confirm these relationships, this study represents an important first step toward that goal.”

Many older adults worry about cognitive decline, but early changes are often subtle and occur before dementia symptoms develop. This study offers preliminary evidence that maintaining vascular health may help preserve memory and cognitive function.

The Investigating Gains in Neurocognition in an Intervention Trial of Exercise, or IGNITE, is a large, multi-site randomized clinical trial that examines how different doses of aerobic exercise affect brain structure, biomarkers, and cognitive function in older adults.

In addition to Lipsitz and Norling, researchers include: Alyssa B. Dufour, PhD, senior scientist, Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife; Thomas G. Travison, PhD, director of biostatistics, Marcus Institute, Hebrew SeniorLife; Kelsey R. Sewell, PhD, research scientist, AdventHealth Research Institute, Neuroscience; Audrey M. Collins, research assistant, AdventHealth Research Institute, Neuroscience; Lu Wan, PhD, research scientist, AdventHealth Research Institute, Neuroscience; George Grove, PhD, Department of Psychology, University of Pittsburgh; Haiqing Huang, MD, research scientist, AdventHealth Research Institute, Neuroscience; Lauren E. Oberlin, PhD, AdventHealth Research Institute, Neuroscience; Shivangi Jain, MPH, research associate, AdventHealth Research Institute, Neuroscience; Thomas K. Karikari, PhD, Department of Psychiatry, School of Medicine, University of Pittsburgh; Jill K. Morris, PhD, associate professor, Department of Neurology, University of Kansas Medical Center, and investigator, University of Kansas Alzheimer’s Disease Research Center; John M. Jakicic, PhD, professor, Department of Internal Medicine, Division of Physical Activity and Weight Management, University of Kansas Medical Center; Edward McAuley, PhD, professor, Department of Health and Kinesiology and Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign; Arthur F. Kramer, PhD, senior research scientist, Beckman Institute for Advanced Science and Technology, University of Illinois; Charles H. Hillman, PhD, professor, Department of Psychology, Center for Cognitive & Brain Health, and Department of Physical Therapy, Movement, & Rehabilitation Sciences, Northeastern University, Boston, MA; Eric D. Vidoni, PhD, associate professor, Department of Neurology, and Investigator, Alzheimer’s Disease Research Center, University of Kansas Medical Center; Sandra A. Billinger, PhD, PT, professor, Department of Neurology, and Investigator, Alzheimer’s Disease Research Center, University of Kansas Medical Center; Jeffrey M. Burns, MD, MS, professor, Department of Neurology, and Investigator, Alzheimer’s Disease Research Center, University of Kansas Medical Center; Anna L. Marsland, PhD, professor, Department of Psychology, University of Pittsburgh; Chaeryon Kang, PhD, associate professor, Department of Psychiatry, University of Pittsburgh; and Kirk I. Erickson, PhD, director of translational neuroscience and senior scientist, AdventHealth Research Institute, Neuroscience.

About Hebrew SeniorLife
Hebrew SeniorLife, an affiliate of Harvard Medical School, is a national senior services leader uniquely dedicated to rethinking, researching, and redefining the possibilities of aging. Hebrew SeniorLife cares for more than 4,500 seniors a day across seven campuses throughout Greater Boston. Locations include: Hebrew Rehabilitation Center-Boston and Hebrew Rehabilitation Center-NewBridge in Dedham; NewBridge on the Charles, Dedham; Orchard Cove, Canton; Simon C. Fireman Community, Randolph; Center Communities of Brookline, Brookline; Jack Satter House, Revere; and Leyland Community, Dorchester. Founded in 1903, Hebrew SeniorLife also conducts influential research into aging at the Hinda and Arthur Marcus Institute for Aging Research, which has a portfolio of more than $98 million, making it one of the largest gerontological research facilities in the U.S. in a clinical setting. It also trains more than 500 geriatric care providers each year. For more information about Hebrew SeniorLife, follow us on our blog, Facebook, Instagram, Threads, and LinkedIn.