LOS ANGELES—Dr. Danny J.J. Wang, an associate professor of neurology and a researcher in the Ahmanson-Lovelace Brain Mapping Center at the University of California, Los Angeles (UCLA), became interested in the mechanical properties of the brain and other organs when his father had a stroke. Understanding that his father had fragile blood vessels, Wang has spent the ensuing 20 years on the ramifications of arterial stiffness for preventing stroke and providing early diagnoses of Alzheimer’s disease.
“There are two theories about the origin of Alzheimer’s disease,” Wang explains. “One is that beta amyloid accumulates in the brain and forms plaques. The other is that the brain is unable to clear beta amyloid through the blood vessels, because the arteries are stiff. We wondered what comes first—stiffness or dementia.”
According to Wang, “Vascular compliance is a useful marker for a number of cardiovascular diseases, such as hypertension and diabetes. Growing evidence suggests intracranial vascular pathology also may be associated with the origin and progression of cerebrovascular disorders and neurodegenerative diseases, such as Alzheimer’s disease, which is the sixth leading cause of death in the United States. However, to date, few methods are available to assess it.”
Wang is working with other UCLA researchers on a noninvasive method to measure vascular compliance, or how stiff an artery is, in the human brain. In an article in NeuroImage titled “Assessing intracranial vascular compliance using dynamic arterial spin labeling (ASL),” the researchers explained that vascular compliance (VC) is an important marker for a number of cardiovascular diseases and dementia. They believe that their MRI technique for in-vivo assessment of intracranial VC is a safe, inexpensive, noninvasive method of measuring this parameter.
Using the technique, the team measured the volume of cerebral arteries using ASL to magnetically “label” the blood in arteries without the use of an external radioactive agent. In a study funded by the National Institutes of Health and the California Department of Public Health, the team measured blood flow at two time points—once at the systolic phase of the cardiac cycle, when the heart was pumping the blood into the brain, and again at the diastolic phase, when the heart was relaxing. The researchers discovered that the stiffer the arteries were, the smaller the change in the arterial blood volume between the two cardiac phases, because stiff arteries are not as able to change shape or comply with the blood pressure changes as elastic arteries are. VC mainly occurs in large arteries and gradually decreases in small arteries and arterioles.
Comparing stiffness measurements in young and elderly patients, the team found that arterial stiffness is significantly increased in elderly patients. The researchers concluded that aging is associated with stiffening of the arteries. They also discovered that increased arterial stiffness is associated with reduced cerebral blood flow, suggesting stiff arteries impair the blood supply to the brain. Additionally, they found artery stiffness is correlated with the stiffness of the largest artery of the human body, the aorta.
According to Lirong Yan, an assistant researcher in the UCLA Department of Neurology, “The development of early bio- or imaging markers for Alzheimer’s is of great importance for slowing disease progression.”
Wang hopes to commercialize the technology, which is the intellectual property of UCLA. He believes that the need for a new approach to treating Alzheimer’s disease is urgent. Alzheimer’s is the most common age-related dementia and the number of cases in the United States is expected to increase from the current number of about five to six million to 15 million by 2050. The costs to family life and on the health care system are enormous. Alzheimer’s and other dementias are projected to cost the United States $226 billion in 2015 alone, with that number rising to as high as $1.1 trillion in 2050.
“Our technology has the potential to predict Alzheimer’s disease early at a far lower cost than technologies that predict the likelihood of developing Alzheimer’s down the road, that subject patients to noise and confined spaces, that are invasive and that are not reimbursed by insurance,” Wang concluded.