Large multicenter study finds early arterial stiffness linked to subtle brain injury in middle-aged adults
A major, collaborative study led by the UC Davis School of Medicine has demonstrated for the first time that arterial stiffening appears in people as young as their 40s and is associated with subtle structural brain changes linked to later cognitive decline and Alzheimer’s disease.
Researchers from UC Davis, the Framingham Heart Study, Boston University and other institutions examined nearly 1,900 participants from the Framingham Heart Study. Participants were generally healthy and middle-aged when they underwent brain magnetic resonance imaging (MRI) and noninvasive arterial tonometry.
The investigators measured carotid–femoral pulse wave velocity (CFPWV), the clinical reference standard for noninvasive assessment of aortic stiffness, together with other tonometry-derived measures of central hemodynamics. They then related these vascular measures to detailed MRI-derived indices of white matter and gray matter integrity, including diffusion tensor imaging metrics such as fractional anisotropy and gray matter density maps.
Higher aortic stiffness, reflected by elevated CFPWV, was associated with lower white matter integrity in regions including the corpus callosum and corona radiata, and with reduced gray matter density centered in the thalamus. These associations were observed in adults with a mean age in the mid-40s—decades earlier than when clinicians typically expect vascular brain injury to appear.
Pauline Maillard, lead author and a neurologist and neuroscientist at UC Davis, emphasized the clinical importance: “This study shows for the first time that increasing arterial stiffness is detrimental to the brain, and that increasing stiffness and brain injury begin in early middle life, before we commonly think of diseases such as atherosclerosis, coronary artery disease or stroke having an impact.” She noted that arterial stiffening may therefore represent an early target for interventions aimed at preserving brain health.
The biological mechanisms linking arterial stiffness to brain injury are complex and require further study. Age-related elevations in blood pressure promote arterial remodeling—stiffening that is accompanied by increased calcium and collagen deposition, inflammation, and reduced arterial compliance. These changes can raise systolic pressure, limit the ability of blood vessels to buffer pulsatile flow, and ultimately reduce effective blood delivery to vulnerable brain regions, which can promote tissue loss and microstructural injury.
Because elevated arterial stiffness is an early manifestation of systolic hypertension and vascular aging, the authors suggest that measures of arterial stiffness could serve as a sensitive marker of vascular health. Early identification, monitoring and treatment of arterial stiffening across the lifespan may help prevent subclinical vascular injury to the brain and thereby reduce the risk of future cognitive decline.
The study, titled “Effects of Arterial Stiffness on Brain Integrity in Young Adults From the Framingham Heart Study,” was published in the American Heart Association journal Stroke. Key contributors include Gary F. Mitchell, Jayandra J. Himali, Alexa Beiser, Connie W. Tsao, Matthew P. Pase, Claudia L. Satizabal, Ramachandran S. Vasan, Sudha Seshadri, Charles DeCarli and others associated with the Framingham Heart Study, Boston University, UC Davis and collaborating centers.
Funding The research was supported by multiple National Institutes of Health grants, the Framingham Heart Study, the National Heart, Lung, and Blood Institute (NHLBI) contracts and institutional funding from Boston University School of Medicine and other partners.
Source: Phyllis Brown, UC Davis Health System. Image credit: adapted from the UC Davis Health System press release. Original research article: “Effects of Arterial Stiffness on Brain Integrity in Young Adults From the Framingham Heart Study,” published in Stroke (authors: Pauline Maillard et al.).
Abstract
Effects of Arterial Stiffness on Brain Integrity in Young Adults From the Framingham Heart Study
Background and Purpose: Prior work from the Framingham Heart Study suggested that brain changes related to vascular aging might begin in young adulthood and precede measurable cognitive deficits. This study aimed to determine whether arterial stiffness is associated with measures of white matter and gray matter integrity in younger adults.
Methods: A total of 1,903 participants from the Framingham Heart Study Third Generation (mean age 46 ± 8.7 years) completed arterial tonometry and brain MRI, including T1-weighted imaging and diffusion tensor imaging. Tonometry measures included carotid–femoral pulse wave velocity (CFPWV), augmentation index, carotid–brachial pressure amplification, and central pulse pressure. Voxel-based analyses related fractional anisotropy and gray matter density to tonometry measures while adjusting for relevant covariates.
Results: Higher CFPWV was linked to lower regional fractional anisotropy in white matter regions such as the corpus callosum and corona radiata and to lower gray matter density in thalamic regions. Other tonometry measures showed no significant associations with fractional anisotropy or gray matter density in these analyses.
Conclusions: In a cohort of young, generally healthy adults, greater aortic stiffness was associated with reduced white matter microstructural integrity and lower gray matter density in brain regions implicated in cognitive decline and Alzheimer’s disease. These findings indicate that subclinical vascular brain injury related to aortic stiffness may begin much earlier in life than previously recognized.