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Brown researchers take charge in improving Alzheimer’s research, treatment
Maura Sullivan Hill for IMPACT: Research at Brown
Through collaborations with neurologists, psychiatrists, biologists and more, projects spearheaded by Brown researchers aim to improve care for those with Alzheimer’s disease and their caregivers.
Different types of sensory neurons are being studied at Brown as a way to discover and test molecules to prevent neurodegenerative diseases, including Alzheimer’s.
PROVIDENCE, R.I. [Brown University] — Stephen Salloway still remembers the day his grandmother moved into his childhood bedroom. No longer able to live alone because of her increasing dementia symptoms, she needed full-time care. The only extra bed in the house was in his room, so he saw the impact of the disease up close, as his family became her primary caregivers and he became her roommate.
“I saw what dementia was like, and the effect it had on our family," said Salloway, now a neurologist and professor of psychiatry and human behavior at Brown’s Warren Alpert Medical School. "There is a grandmother’s story lurking in the background for many Alzheimer’s researchers.”
With more than 5.6 million Americans aged 65 and older living with Alzheimer’s and other forms of dementia, the impact of the disease is widespread, and the need for new interventions and treatment is urgent. Dementia is an umbrella term for diseases that cause a decline in mental ability, and Alzheimer’s and the memory loss associated with it are the most common form of dementia. Alzheimer’s disease, the sixth-leading cause of death in the United States, according to the Alzheimer’s Association, is a progressive disease where the symptoms of memory loss, behavior changes and disorientation worsen with age, due to changes in the brain.
Although risk genes have been identified, there is no cure for Alzheimer’s, and researchers have not yet discovered the cause of the disease.
The fear of Alzheimer’s disease “can be paralyzing, but more research is synonymous with hope,” said Stephen Salloway, a neurologist and professor of psychiatry and human behavior.
Brown has emerged as a leader in the field of Alzheimer’s research and prevention through intense activity in the School of Public Health, the Warren Alpert Medical School, the Carney Institute for Brain Science and the new Center for Translational Neuroscience.
Researchers and clinicians across the university are engaged in multi-faceted, collaborative efforts to treat Alzheimer’s disease and dementia through searching for the root causes of the disease, developing drugs to treat it, or creating interventions that could prevent or slow the progress of the disease.
“It is going to take more than one drug to treat or modify the course of Alzheimer’s, so we are going to hopefully get one that works and then build on that or combine them," Salloway said. "There are a lot of challenges, but more research is synonymous with hope.”
In 2019, Brown received the largest federal grant in University history: a five-year, $53.4 million award from the National Institute on Aging (NIA) to lead a nationwide effort to improve health care and quality of life for people living with Alzheimer’s disease and related dementias, as well as their caregivers. Together with Boston-based Hebrew SeniorLife, a Harvard Medical School affiliate, researchers at Brown are creating a massive collaborative research incubator to develop clinical trials aimed at evaluating non-pharmacological interventions.
Vincent Mor, co-leader of the collaboration and a professor of health services, policy, and practice at Brown’s School of Public Health, said this grant has the potential to revolutionize how care is delivered to patients, because it will speed up the process of bringing evidence-based interventions into health care systems.
“Given how many people are going to be diagnosed with Alzheimer’s and other dementias and the number of caregivers, this is not a problem that can be solved one lone program at a time," Mor said. "We need an industrial-strength program. We have to go to scale. And anytime you go to scale, that complicates matters dramatically, both scientifically as well as operationally, and from an organizational, human engineering perspective. The goal is to figure out how to take an idea that works when researchers do it, and to see if it works when real staff do it.”
The program, dubbed the NIA Imbedded Pragmatic AD/ADRD Clinical Trials (IMPACT) Collaboratory, will fund up to 40 pilot projects in real-world health care systems beginning in 2020, generating the necessary data for even larger trials that will be supported with future federal funding. Researchers from more than two dozen universities, including Harvard, New York University, University of Michigan, and Yale, will also be collaborators on the project.
“There is a pressing need to improve care and support for people with dementia and their caregivers,” said Richard J. Hodes, director of the NIA. “The IMPACT Collaboratory will enable more effective, efficient teamwork research on finding better solutions for the millions of Americans affected by these devastating diseases.”
The collaboratory is searching for pilot projects much like Mor’s successful Music and Memory project, which found that listening to a personalized music playlist can help reduce an Alzheimer’s patient’s behavioral symptoms and need for antipsychotic medications. They reached this finding with a small pilot study, and then received additional funding to implement the program in 81 nursing homes, gathering a larger research sample while simultaneously offering a new treatment option for patients.
The IMPACT Collaboratory will offer that same opportunity to other studies that have proven successful in small trials, providing the funding and support to implement on a larger scale.
Aiding early detection
Much like the IMPACT Collaboratory, the Memory and Aging Program of Providence’s Butler Hospital, with a team led by Salloway and as an affiliate of Brown’s Warren Alpert Medical School, is focused on making treatments and preventions more widely available and accessible.
A host of clinical trials are focused on early detection, studying people who possess risk genes for Alzheimer’s to discover what contributes to the disease. As the causes are targeted, researchers are hopeful that possible prevention treatments can be developed for future generations. A key part of that effort is to get more people to participate in research studies and educate the public about potential risk genes for Alzheimer’s.
“Everybody’s afraid of Alzheimer’s — the most feared disease of aging, more than cancer,” Salloway said. “It can be paralyzing. Our volunteers who participate in these studies are valiant, dedicated, and courageous. We’ve developed tools now so that we can identify people at risk and try to modify the risk so they don’t get the memory loss and the dementia.”
The Memory and Aging program hosts what they have dubbed “swab parties” — events where the public is invited to assist in Alzheimer’s research by participating in a cheek swab that tests for genetic risk for developing Alzheimer’s. If a participant has one of the risk genes for Alzheimer’s, known as APOE e4, the Butler team will reach out to them about opportunities to participate in studies, as well as counseling them through the process of learning about their potential risk for the disease. Salloway’s team has offered swab parties in places aimed to broaden engagement, such as Brown’s alumni reunions and WaterFire in Providence.
The program also developed a disease prevention registry, and it matches willing volunteers with Alzheimer’s studies in search of participants. After potential volunteers complete a secure and confidential online questionnaire, program representatives reach out to them about how to participate in a study. Previous studies done by the program have produced important results in the fight against Alzheimer’s, including more advanced and accurate tests for the disease, like brain scans that can detect the brain plaques and tangles (or protein deposits) that lead to Alzheimer’s before memory loss sets in, and new medications in clinical trial phase, like gene-targeted therapies that shut down the production of these toxic proteins.
In addition to the Butler Hospital team’s clinical trials, John Sedivy, professor of biology and director of the Biology of Aging initiative at Brown, gained funding from the Alzheimer’s Association for a new clinical drug trial. A drug initially developed to fight HIV appears to have the potential to treat Alzheimer’s and other age-associated diseases because of how it targets inflammation. Sedivy’s research showed that the drug reduced inflammation from age-related conditions in naturally aging mice, and now a team led by Sedivy and Salloway will test it on people with Alzheimer’s.
“Many age-associated diseases are accompanied by increased inflammation," Sedivy said. "In fact, an elevated, chronic level of inflammation is one of the hallmarks of aging — normal healthy aging included. Alzheimer’s in particular has been linked with pronounced neuro-inflammation. While it is by no means clear whether this neuro-inflammation is the cause of Alzheimer’s, it is increasingly believed that it might be an important exacerbating factor. Hence, reducing or preventing neuro-inflammation might slow down the progression of the disease.”
Untangling Alzheimer's through genetics
While clinical trials search for drugs that could help treat Alzheimer’s and other dementia patients, neuroscientists are still looking for the root causes of these diseases.
When neuroscientists learn more about the gene mutations that contribute to Alzheimer’s, researchers learn new targets for drug treatments. It all requires a collaborative process, which has led to Brown’s new Center for Translational Neuroscience, which officially launched with the 2019–20 academic year.
“Really understanding gene changes offers a powerful, fresh, and new approach for dissecting complicated brain diseases like Alzheimer’s disease. Genetics is the logic and glue that brings us together and orients our path,” said Eric Morrow, a psychiatrist and professor of biology, neuroscience, and psychiatry at Brown, who leads the center alongside Brown neurologist Judy Liu, who also runs a molecular neuroscience lab. Both Morrow and Liu are physician-scientists.
Eric Morrow, an associate professor of biology, neuroscience, and psychiatry and human behavior, is using genetics to better understand brain diseases like Alzheimer’s.
The center’s goal is to advance knowledge about how brain diseases develop and to translate this knowledge into improved clinical outcomes for families affected by brain disease.
The center is paying special attention to Alzheimer’s, with two new faculty members experienced in the field of Alzheimer’s research: Alvin Huang, recruited from Stanford, and Gregorio Valdez, from Virginia Tech. Valdez has moved his established laboratory studying age-related neurological diseases to Brown, and Huang, who is also a physician-scientist and neurologist, is starting his laboratory at Brown as junior faculty focused on Alzheimer’s disease.
They will also partner with Brown’s Carney Institute for Brain Science, already a leader in research, to identify therapies for neurodegenerative diseases including Alzheimer’s, ALS and Parkinson’s.
“We are tremendously excited about the new Center for Translational Neuroscience,” said Diane Lipscombe, professor of neuroscience and the director of the Carney Institute. “The most important ingredients for success are the people — Eric Morrow and Judy Liu are a phenomenal team; they are committed to building a community of scientists with a passion for patient-centered research. Eric and Judy lead through example, and their own research has given novel insight into disease origin. The first two recruits into the Center for Translational Neuroscience, Greg Valdez and Alvin Huang, focus on cellular and molecular processes disrupted in Alzheimer’s disease, an area of great need.”
Share knowledge widely
Researchers and clinicians at Brown continue to confront Alzheimer’s through public health interventions, clinical trials and community education and genetics research. On its current trajectory, Alzheimer’s disease is estimated to afflict 14 million people by 2050, and the day-to-day reality of this work is grueling and challenging, so efforts are seen as urgent.
“I’m so excited that Brown is really getting behind Alzheimer’s research,” Salloway said. “It is setting the stage for some amazing work. It is an exciting time, the opportunity for collaboration across disciplines and to bring discoveries to people that need them.”
As different programs are tested and implemented, the goal is for them to be replicated in any kind of health care facility, including under-resourced ones.
Mor, who co-leads the IMPACT Collaboratory along with his frequent research partner, Susan Mitchell of Hebrew SeniorLife, points out that top-ranked medical centers like Brown have the resources to invest in research and clinical trials, and there is a responsibility to share this knowledge widely.
“There are other places that are going to find it much more difficult. It is critical that we design programs that are going to be implemented and embraced,” Mor said.