Vascular Brain Injury is Evident in People in Their 40s

A large, multicenter study led by the UC Davis School of Medicine for the first time has shown that people as young as their 40s have stiffening of the arteries that is associated with subtle structural damage to the brain that is implicated in cognitive decline and Alzheimer’s disease later in life.

A collaboration of UC Davis, the Framingham Heart Study and Boston University, among others, the study found that, among young healthy adults, higher aortic “stiffness” was associated with reduced white matter volume and decreased integrity of the gray matter, and in ages much younger than previously described.

“Effects of Arterial Stiffness on Brain Integrity in Young Adults from the Framingham Heart Study,” is published online today in the American Heart Association journal Stroke.

“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 prevalent diseases such as atherosclerosis, coronary artery disease or stroke having an impact,” said Pauline Maillard, UC Davis Department of Neurology and Center for Neuroscience and the study’s lead author.

“These results may be a new avenue of treatment to sustain brain health,” she said.

The study also noted that elevated arterial stiffness is the earliest manifestation of systolic hypertension.

“Measures of arterial stiffness may actually be a better measure of vascular health, and should be identified, treated and monitored throughout the lifespan,” Maillard said.

The large study involved approximately 1,900 diverse participants in the Framingham Heart Study, who underwent brain magnetic resonance imaging (MRI), as well as arterial tonometry.

Image shows brain scans.
The large study involved approximately 1,900 diverse participants in the Framingham Heart Study, who underwent brain magnetic resonance imaging (MRI), as well as arterial tonometry. Image is adapted from the UC Davis Health System press release.

The tests measured the force of arterial blood flow, the carotid femoral pulse wave velocity or CFPWV — the reference standard for noninvasive measurement of aortic stiffness — and its association with subtle injury to the brain’s white and gray matter. The research found that increased CFPWV was associated with greater injury to the brain.

The reasons this is so are complex, and more study is needed, Maillard said. However, with age high blood pressure causes the arteries to stiffen, further increasing blood pressure as well as increasing calcium and collagen deposits, which promotes atrophy, inflammation and further stiffening, decreasing blood flow to vital organs including the brain and promoting brain atrophy.

“Our results emphasize the need for primary and secondary prevention of vascular stiffness and remodeling as a way to protect brain health,” early in life, Maillard said.

About this psychology research

Other study authors are Gary F. Mitchell, Cardiovascular Engineering, Inc.; Jayandra J. Himali, the Framingham Heart Study and Boston University School of Medicine; Alexa Beiser, the Framingham Heart Study, Boston University and the Boston University School of Public Health; Connie W. Tsao, Beth Israel Deaconess Medical Center and Harvard Medical School; Matthew P. Pase, the Framingham Heart Study, Boston University School of Medicine and Swinburne University of Technology, Australia; Claudia L. Satizabal, the Framingham Heart Study and Boston University School of Medicine; Ramachandran S. Vasan, Boston University School of Medicine; Sudha Seshadri, the Framingham Heart Study and Boston University School of Medicine; and Charles DeCarli, Imaging of Dementia and Aging (IDeA) Laboratory and Department of Neurology UC Davis.

Funding The study was funded by National Institutes of Health (NIH) grants R01 AG03304 and P30 AG010129, K23 LH118529; the Framingham Heart Study; National Heart Blood and Lung Institute (NHLBI) contracts N01-HC-25195 and HHSN268201500001; by the Boston University School of Medicine; and by HL076784; G028321; HL070100; HL06040; HL080124; HL071039; HL077447; HL107385; and 2-K24-HL04334.

Source: Phyllis Brown – UC Davis Health System
Image Credit: The image is adapted from the UC Davis Health System press release.
Original Research: Abstract for “Effects of Arterial Stiffness on Brain Integrity in Young Adults From the Framingham Heart Study” by Pauline Maillard, Gary F. Mitchell, Jayandra J. Himali, Alexa Beiser, Connie W. Tsao, Matthew P. Pase, Claudia L. Satizabal, Ramachandran S. Vasan, Sudha Seshadri, and Charles DeCarli in Stroke. Published online March 10 2016 doi:10.1161/STROKEAHA.116.012949


Abstract

Effects of Arterial Stiffness on Brain Integrity in Young Adults From the Framingham Heart Study

Background and Purpose Previous work from the Framingham Heart Study suggests that brain changes because of arterial aging may begin in young adulthood and that such changes precede cognitive deficits. The objective of this study was to determine the association of arterial stiffness with measures of white matter and gray matter (GM) integrity in young adults.

Methods One thousand nine hundred three participants from the Framingham Heart Study Third Generation (mean age, 46±8.7 years) had complete tonometry measurements and brain magnetic resonance imaging (T1-weighted and diffusion tensor imaging). Tonometry measures included carotid-femoral pulse wave velocity, augmentation index, carotid-brachial pressure amplification, and central pulse pressure. Fractional anisotropy and GM density images were computed from diffusion tensor imaging and T1 images. Registration to a common anatomic template enabled voxel-based linear regressions relating measures of fractional anisotropy and GM to tonometry measures, adjusting for relevant covariables.

Results Higher carotid-femoral pulse wave velocity was associated with lower regional fractional anisotropy, including the corpus callosum and the corona radiata (8.7 and 8.6 cc, respectively, P<0.001), as well as lower GM density in the thalamus region (0.9 cc, P<0.001). Analyses did not reveal significant associations between other tonometry measures and fractional anisotropy or GM.

Conclusions Among young healthy adults, higher aortic stiffness was associated with measures of reduced white matter and GM integrity in areas implicated in cognitive decline and Alzheimer’s disease. Greater aortic stiffness may result in subclinical vascular brain injury at ages much younger than previously described.

“Effects of Arterial Stiffness on Brain Integrity in Young Adults From the Framingham Heart Study” by Pauline Maillard, Gary F. Mitchell, Jayandra J. Himali, Alexa Beiser, Connie W. Tsao, Matthew P. Pase, Claudia L. Satizabal, Ramachandran S. Vasan, Sudha Seshadri, and Charles DeCarli in Stroke. Published online March 10 2016 doi:10.1161/STROKEAHA.116.012949

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