Grant funds diabetes and dementia research


Researchers plan to find a measurable indicator of dementia in people with diabetes, which will aid in developing early treatments for dementia. (Simon Park | Daily Trojan file photo)

A group of researchers from the Keck School of Medicine received a $3.7 million grant from the National Institute on Aging to investigate the link between Type 2 diabetes and a higher risk of developing dementia in 200 Hispanic adults between the ages 50 and 65. 

The study will focus on Hispanic adults, a group that not only has been historically understudied in the medical field, but also has a higher incidence of diabetes due to multiple causes, including environmental factors such as stress and air pollution.

The age demographic of this cohort — 50 to 65 years old — is a period of life where there can be changes in the glucose tolerance of adults due to Type 2 diabetes, but before the cognitive decline associated with dementia begins.

“Ultimately, we are trying to establish biomarkers that can be reversed,” said Dr. Hussein Yassine, an associate professor of medicine at the Keck School of Medicine and co-principal investigator of the study. “So let’s say you’ve got somebody with diabetes or prediabetes, and you reverse diabetes by weight loss or by medication. Does that translate into the brain getting better? Does that translate into [a] lower [incidence of] Alzheimer’s diseases?” 

Dr. Yassine and his team will begin recruiting the study cohort soon, which will be comprised of Hispanic people both with and without Type 2 diabetes, a form of diabetes which tends to develop during adulthood. From there, participants will take cognitive tests conducted by Dr. Yassine and Dr. Lina D’Orazio, an assistant professor of clinical neurology at Keck and co-investigator of the study. 

Participants will then undergo a blood draw to identify baseline glucose and insulin levels, other testing to identify risk factors for Alzheimer’s disease and an initial resting state fMRI scan — a tool which helps researchers observe how parts of the brain work together.

After preliminary tests are conducted, participants will then undergo the central experiment of this study: drinking a sugary drink. People with diabetes experience a blood sugar spike — known as hyperglycemia — in response to ingesting sugar, which is higher and more prolonged than a person without diabetes — this sugary drink will allow researchers to observe the effect of hyperglycemia on the brain.

“There are some things that you might not be able to see when a person’s system isn’t stressed,” said Dr. Meredith Braskie, an assistant professor of neurology at Keck and co-principal investigator of the study. “But when you’re giving them this glucose drink, it might uncover things that you wouldn’t be able to see otherwise.”

Two hours later, participants will undergo another MRI scan and another blood draw to find a potential link between the brain and blood response to the glucose drink.

Dr. Matthew Borzage, an assistant professor of research pediatrics at Keck and co-principal investigator of the study, will help analyze cerebrovascular reactivity — a measure of how well blood vessels expand to let more blood through in response to a stimulus. Researchers will also perform neuroimaging analysis of the blood-brain barrier and conduct arterial spin labeling, a process that measures blood flow in the brain.

Observing the brain’s response to hyperglycemia, the researchers suggest, is a potential way of identifying a link between adults with Type 2 diabetes and dementia. After two years, the participants will return to undergo more cognitive testing and brain scans.

“In this way, we can look at the different measures that we’re measuring at baseline,” Dr. Braskie said, “[We can] look at how their brain is responding to glucose and see to what extent those measures are predicting longitudinal changes in our brain or cognition.”

The study operates under both the Alzheimer’s Disease Research Institute, which helps facilitate aspects of the study such as neuropsychological testing, recruitment and community outreach, and USC’s Mary Stevens Neuroimaging and Informatics Institute, where the MRI scanning will take place. 

Community outreach is particularly important in addressing the historical injustices faced by the Hispanic community, said Dr. Yassine, who works with patients in the demographic often in his clinic in East Los Angeles.

“What we have discovered out of experience is that if we have full-time staff in the community, having events, talking about Alzheimer’s, talking about diabetes, building relationships, answering questions to get their trust,” Dr. Yassine said, “they’re willing to [go] the extra mile.”

Although much of the study has yet to take place, the researchers hope to use this critical period in the lives of people with and without Type 2 diabetes to identify a measurable indicator of dementia in people with diabetes — a biomarker — which may be used as an intervention point to help in the development of early treatments for dementia.

“Being able to see [biomarkers] in the short term,” Dr. Borzage said, “and [knowing] that they should lead to long-term improvements in a community that really deserves that same level of attention and care is really exciting.”