New Alzheimer’s insights

Too often, people learn they have Alzheimer's disease (AD) when it's too late. The changes in the brain that lead to AD manifesting with symptoms have already been occurring for decades.

A new interdisciplinary study at the University of Delaware seeks to study AD by examining changes in the arteries and brain tissue in midlife adults in their 50s and 60s. The findings could identify the earliest mechanisms linking vascular aging to the loss of brain tissue integrity, leading to new targets for interventions aimed at preventing age-related cognitive impairment.

"People who develop high blood pressure or stiffening of the aorta and carotid arteries in midlife are at a much higher risk for developing cognitive impairment or dementia in late life," said Christopher Martens, the principal investigator of the study.

Martens, an associate professor of kinesiology and applied physiology in the College of Health Sciences and director of the Delaware Center for Cognitive Aging (DECCAR), is working closely with Curtis Johnson, an associate professor of biomedical engineering in the College of Engineering and leader of the neuroimaging biomarker core within DECCAR, on research funded by a nearly $4 million grant from the National Institute on Aging (NIA), a division of the National Institutes of Health (NIH).

"A lot happens as we age, so we're aiming to pinpoint the timing and exact mechanisms that cause these changes in midlife adults," Martens said.

This latest grant extends DECCAR's ongoing Delaware Longitudinal Study for Alzheimer's Prevention (DeLSAP), which seeks to study how risk and protective factors for dementia are related and change over time. Those eligible for DeLSAP could also meet the criteria for participating in the new study.

In his Neurovascular Aging Laboratory, Martens studies mechanisms leading to the stiffening of arteries, while Johnson is specifically interested in measuring the stiffness of the brain.

"As a person ages, the brain gets softer and breaks down, and we're looking to see whether changes in arterial stiffness and patterns of blood flow in the brain cause this decline," Johnson said.

Changes in blood flow to the brain come from controllable factors. Smoking, cardiovascular health, diet and exercise all impact blood flow positively and negatively.

"A lot of aging research is done at the end of life," Johnson said. "We want to look at midlife and try to predict what happens later in life so we can prevent it."

While the brain gets softer with age, arteries get stiffer.

"We hypothesize that midlife increases in stiffness in blood vessels cause damaging pulsatile pressure to enter the brain," Martens said. "We believe this is one of the reasons we start to develop cognitive issues at an older age because the brain is exposed to increased pressure; that pressure is likely inflicting damage on surrounding brain tissue."

In Johnson's Mechanical Neuroimaging Lab, researchers will use high-resolution magnetic resonance elastography (MRE) to determine where brain damage occurs and what specific brain structures may be affected.

"From an MRI perspective, most researchers look at AD and other neurodegenerative diseases like multiple sclerosis with an emphasis on detection in a hospital setting," Johnson said. "Using highly specialized techniques we've developed, we focus on the earlier side and how these changes progress into disease from the neuroscience side, emphasizing prevention."

Together, they'll seek to learn whether arterial stiffness causes the kind of cognitive impairment seen in AD or whether the decline is associated with a loss in the integrity of brain tissue.

"If we can prove arterial stiffness is playing a causal role in cognitive aging, that would provide further support for focusing on blood vessel health as an intervention for delaying AD or other forms of dementia versus solely focusing on the brain," Martens said.