USC launches large-scale dementia study


image: Hussein Yassine, MD, will oversee cohort design, recruitment, diabetes assessments, Alzheimer’s disease biomarker assessments and cognitive testing in collaboration with the Alzheimer’s Disease Research Center ‘USC.
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Credit: Photo courtesy of USC

People with type 2 diabetes are at increased risk of Alzheimer’s disease and related dementias, but the cause of this risk is poorly understood. For example, how much of this risk is related to blood vessel problems? Are high blood glucose or insulin levels linked to brain changes or damage over time?

A team of researchers from USC’s Keck School of Medicine has launched an ambitious study to answer these and other questions about the link between type 2 diabetes and dementia.

“We know that diabetes is associated with an increased risk of later dementia, but researchers aren’t quite sure why,” said Meredith N. Braskie, PhD, assistant professor of neurology at USC’s Keck School of Medicine, director of education. at USC Mark and Mary Stevens Neuroimaging and Informatics Institute and co-principal investigator of the project. “Understanding the mechanism behind this risk is an important part of how we can improve it.”

The new study will focus on Latinos, who face significant health disparities in the United States. Compared to non-Hispanic white adults, adults of Hispanic ancestry are more likely to develop diabetes or dementia, but are much less studied. The research team will use a $3.7 million grant from the National Institute on Aging — along with state-of-the-art equipment and expertise from the Keck School of Medicine — to recruit and study 200 adults of Hispanic ancestry on a period of five years. In diabetic and non-diabetic patients, they will compare data on brain structure and activity, brain blood flow, blood sugar and insulin levels, and cognitive functioning.

“We will be able to dig deeper into what is happening in the brains of patients with diabetes compared to those without diabetes and how differences between the two groups can predict changes in brain health over time,” said Hussein Yassine, MD, the Kenneth and Bette Volk Endowed Chair of Neurology, associate professor of medicine and neurology at the Keck School of Medicine and co-principal investigator of the study.

The recruitment phase

This fall, researchers began recruiting adults of Hispanic ancestry, ages 50 to 65, who are part of the East Los Angeles community. This process requires a substantial investment of time and resources, including training research staff whose native language is Spanish and building trust with a community that has long been discriminated against by of the medical community. Community engagement in educational and research activities is central to the project.

“We don’t conduct research in a vacuum. We do this in a broader community and clinical context, and we understand that this is critical to achieving our mission to support this population,” said Matthew Borzage, PhD, assistant professor of pediatric research and co-principal investigator of the project.

The team takes a strategic approach to get a clear picture of the relationship between type 2 diabetes and Alzheimer’s disease and related dementias in middle age, before the onset of Alzheimer’s disease in the brain . They study adults between the ages of 50 and 65 – younger than the age range of a typical dementia study – because existing research suggests that diabetes in your 40s contributes to dementia risk later on.

“What’s unique about our population is that we start two decades before the symptoms of the diseases of aging usually start,” Yassine said.

High resolution brain images

Once recruitment is complete, researchers will begin collecting a range of data using frontline imaging methods and technologies, including the Institute of Neuroimaging and Computer Science’s powerful 7 Tesla MRI scanner. Mark and Mary Stevens of the Keck School of Medicine, which captures ultra-high resolution images of the brain.

A key test will measure how the brain responds to glucose by comparing brain activity before and after participants consume a sugary drink. Researchers will also collect data on cerebrovascular reactivity (a measure of how well blood vessels can expand or contract to adjust blood flow) and the health of the blood-brain barrier, which regulates substances that can enter. and go out. All of these factors are thought to play a role in the onset or progression of Alzheimer’s disease and related dementias.

By analyzing brain imaging data, along with measurements of blood glucose levels, insulin levels and cognitive aging, the research team aims to better understand how blood flow and metabolism are linked to health. of the brain. They will compare data between people with and without type 2 diabetes. Participants will also receive a two-year follow-up analysis to explore how brain health changes over time.

“What we’re doing is fundamental to finding biological markers of how diabetes affects the brain,” Borzage said.

The work may also provide support for nascent efforts to use certain diabetes drugs with brain-protective properties to prevent or slow cognitive decline associated with dementia, Yassine said.

About this award

Other co-investigators on the project include Lina D’Orazio, PhD, assistant professor of clinical neurology and director of the cultural neuropsychology program at the Keck School of Medicine, who will lead the neuropsychology assessments, which measure signs of cognitive aging, and Danny Wang, PhD, professor of neurology and radiology and director of imaging technology innovation at USC Mark and Mary Stevens Neuroimaging and Informatics Institute, who will analyze data on brain blood flow and brain permeability. blood-brain barrier.

This research is supported by 1RF1AG078362-01, “Effect of diabetes and Alzheimer’s disease pathology on brain imaging and cognition in Latino adults”.

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