O’Donnell Brain Institute experts highlight hope for dementia patients, power of music at UTSW-Dallas Opera event
Investigators in UT Southwestern’s Peter O’Donnell Jr. Brain Institute shed light on the science that drives dementia, brain research, future treatments for neurodegenerative disorders, and the role of music in keeping patients connected during a panel discussion at the Winspear Opera House in Dallas.
W. P. Andrew Lee, M.D., Executive Vice President for Academic Affairs, Provost, and Dean of UT Southwestern Medical School, moderated “Melodies of Hope: Music, Dementia, and Brain Science,” which drew more than 700 people to the event co-sponsored by UT Southwestern and The Dallas Opera. The presentation featured four O’Donnell Brain Institute experts in Alzheimer’s and other brain diseases.
The discussion was a prelude to the opera company’s upcoming production of Orpheus and Eurydice, which has been reimagined in a contemporary setting by director Joachim Schamberger. In the new version, Eurydice has dementia and her husband, Orpheus, is her caregiver, using the power of music to rescue her from darkness. Attendees heard a brief excerpt from the opera performed by Madison Leonard, the soprano who portrays Eurydice. The opera will be performed Feb. 7, 9, 12, and 15.
William Dauer, M.D., inaugural Director of the O’Donnell Brain Institute and Professor of Neurology and Neuroscience, spoke to the theme of the evening, saying music provides resilience to the brain and activates a broad range of its areas. He said music’s ability to evoke emotions and strengthen brain processing gives dementia patients a cognitive boost. Brendan Kelley, M.D., Professor and Clinical Vice Chair of Neurology, said some of his patients’ families have shared that music has helped their loved ones maintain connectedness and reduce behavioral distress.
“I think it’s quite clear that, when dementia patients listen to music, it continues to activate those emotional parts of the brain that remain intact,” Dr. Dauer said. “It’s a way for them to connect in ways they otherwise can’t because things like language and memory areas are unfortunately damaged by the disease.”
A ‘golden era’ for research
Marc Diamond, M.D., founding Director of UT Southwestern’s Center for Alzheimer’s and Neurodegenerative Diseases and Professor of Neurology and Neuroscience, discussed what Dr. Lee called “a golden era for brain research.” Dr. Diamond said a deeper understanding of the molecular processes that cause dementia, and clinical trials targeting them before they cause symptoms, fuel significant hope for the future of treatment.
“The optimism within our field after decades of no real progress with clinical therapies is unbelievable,” Dr. Diamond said. “In the world that we are trying to create within our Center, we will find evidence of the disease at a biochemical level before there’s any cognitive impairment.”
The future of treatments includes ongoing research into blood tests that can screen for dementia risk, Dr. Diamond said, adding that “this is not a pipe dream.” He told the audience about a new generation of dementia medications in development that are even more effective than the handful already in use, targeting the amyloid beta proteins that build up in the brain and initiate dementia.
In the future, “you will go to your primary care doctor, have blood drawn, and a panel of pathologic proteins will be searched for,” Dr. Diamond said. “If you score positive, you will be directed for further testing and interventions that will stop the process before you have cognitive impairment.
“These blood tests already exist – we have the ability to predict who will get Alzheimer’s. What we don’t have is assurance that the interventions we would give someone are safe and effective. Those clinical trials are going on right now and will read out in the next few years.”
Dr. Diamond explained the processes behind Alzheimer’s disease, the most common cause of dementia. The trigger, he said, is accumulation of amyloid beta, which is one of the earliest biological changes caused by Alzheimer’s and can start forming plaques in brain tissue 20 years before the onset of dementia. What Dr. Diamond called the “bullet” is the subsequent accumulation and replication of a second protein called tau, which builds assemblies in brain nerve cells and damages the neurons responsible for sending and receiving electrical signals.
Dr. Kelley listed some early signs of dementia that should prompt a doctor’s visit before the disease advances. These differ from the common changes that occur with aging, such as forgetting a word, a name, or where you put your keys. If you begin repeating questions/answers or have difficulty keeping track of appointments or making decisions you’ve always made, brain disease may be present.
People who may be developing dementia can have positron emission tomography (PET) scans to detect accumulation of amyloid, Dr. Kelley said. Family history and previous head injuries can heighten dementia risk. He also referenced studies showing that lifestyle factors such as a healthy diet and regular physical activity can help reduce risk, along with managing blood pressure, cholesterol, and blood sugar levels.
“All of these seemingly mundane things can substantially reduce our risk of developing Alzheimer’s,” Dr. Kelley said.
Certain mutations in the gene that produces amyloid give some patients a 100% likelihood of having Alzheimer’s while others with different mutations are protected, Dr. Diamond said. Trials treating patients who have mild cognitive impairment with certain medications have shown a slowing of Alzheimer’s progression, and he said the hope is that using these treatments before issues occur will also have an impact.
Imaging deeper into the brain
Sarah Shahmoradian, Ph.D., Assistant Professor in the Center for Alzheimer’s and Neurodegenerative Diseases and of Biophysics, discussed how advanced imaging technologies are helping scientists better understand dementia by providing a more detailed view inside the brain. One such technology is cryo-electron microscopy (cryo-EM), which she described as having “a unique ability to visualize the molecular structure of proteins and identify features that may be linked to disease.”
Dr. Shahmoradian used the analogy of Google Maps highlighting buildings with structural issues. “With cryo-EM, we can see defects in proteins much like how cracks in bricks can weaken a building,” she explained. “Some of these defects may make proteins unstable or prone to forming harmful aggregates in the brain.
“Just as engineers assess buildings for structural risks, scientists use these imaging techniques to study how protein abnormalities could contribute to brain cell dysfunction. By identifying these molecular weak points, we can gain insight into how diseases like Alzheimer’s develop and explore ways to intervene before significant damage occurs.”
Dr. Diamond cited “amazing successes” in research involving other neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig’s disease, which stems from buildup of a different protein. He said he was inspired to work on brain disease because of ALS, a fast-progressing disorder that damages nerve cells in the brain and spinal cord, causing loss of muscle function and later paralysis.
Dr. Dauer highlighted the O’Donnell Brain Institute’s multidisciplinary approach to treating dementia and other brain diseases, including autism, tumors, and concussions.
“There is no greater priority at the Peter O’Donnell Brain Institute than tackling the problem of dementia,” he said.