A team of brain scientists from UC Davis School of Medicine and The University of Texas Health Science Center at Houston (UTHealth) has been awarded a six-year grant expected to total $53.6 million from the National Institutes of Health (NIH). The researchers will use the funding to study the role of incidental white matter lesions, or WMLs, in dementia among diverse people with cognitive complaints.
The grant is the largest ever from the NIH to the UC Davis School of Medicine. It also is a new and critical part of the NIH’s Vascular Contributions to Cognitive Impairment and Dementia (VCID) research program.
“The magnitude of this NIH grant underscores UC Davis Alzheimer’s Disease Research Center’s national prominence and research leadership,” said UC Davis School of Medicine Dean Allison Brashear, a neurologist nationally known for her groundbreaking research in movement disorders. “This multi-year research award will enable us to make game-changing advancements in our understanding and treatment of dementia.”
The principal investigator is Charles DeCarli, professor of neurology, director of the UC Davis Alzheimer’s Disease Research Center and the nation’s foremost expert on the role of subcortical cerebrovascular disease in cognitive decline. In the last few years, DeCarli has been awarded national and state research grants exceeding $33 million.
UC Davis Health is a leader in Alzheimer’s research and its neurology research is ranked 18th nationally in neurosciences funding, with $79.6 million in grants in fiscal year 2017. UC Davis Health CEO David Lubarsky also is a member of the California Governor’s Alzheimer's Prevention and Preparedness Task Force.
— Charles DeCarli
DeCarli’s co-principal investigator is Myriam Fornage, professor of genetics at the Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases at McGovern Medical School at UTHealth. Fornage is a leading researcher on the molecular genetics of cerebrovascular disease.
WMLs: Common but still a mystery
WMLs occur when tissue deep in the brain becomes injured, often due to changes in small blood vessels. They are common and often found on brain MRIs of people who have concerns about their brain health.
Why or how WMLs are associated with cognitive decline is not known. It isn’t known if certain WML characteristics, such as size and location, make them greater risk factors for dementia. It also isn’t clear how comorbidities, or additional health conditions such as heart disease or diabetes, together with WMLs increase risk for cognitive decline. Defining these connections is essential to improving outcomes for the 5.7 million people in the U.S. affected by cognitive impairment and dementia.
DeCarli and Fornage’s landmark research is expected to answer these questions and lead to standards for assessing, diagnosing and treating individuals with WML-related cognitive problems.
“This grant gives us the chance to study WMLs from every angle and definitively understand their roles in age- and disease-related cognitive decline and risk for future dementia,” DeCarli said. “It’s the culmination of our three decades of research that has given us great directions, but no final answers yet.”
A study unique for its diversity
DeCarli and Fornage will conduct a study of patients with WMLs on their MRIs and concerns about cognitive symptoms, but no dementia diagnosis. It will be the first large study of a diverse population on the long-term effects of these lesions on thinking and dementia risk.
Beginning Sept. 2021, study participants will be recruited at UC Davis Health and at least 10 other locations throughout the U.S. They will be from a variety of backgrounds, so the researchers can identify how WML outcomes differ by race, ethnicity and sex, better representing those at risk for dementia.
“Our ultimate goals are to develop a ‘risk profile’ that identifies the likelihood of WML-related cognitive impairment and dementia over the course of five to 10 years and to identify clear targets for interventional trials,” DeCarli said.
Resources to advance all dementia research
Another exciting part of the grant, according to the researchers, is the chance to fund additional studies aimed at refining diagnostic and predictive tools and methods for dementia. The outcomes will enhance dementia research and clinical care worldwide.
Data and samples from these studies will be shared with the wider research community via the National Alzheimer's Coordinating Center at the University of Washington and the National Centralized Repository for Alzheimer’s Disease and Related Dementias at Indiana University. Images will be shared through Laboratory of Neuroimaging at the University of Southern California.
“Our team has been at the forefront of genetic studies of WMLs for two decades,” Fornage said. “Through the genetic risk profiles we will develop, we will have an opportunity to apply what we have discovered and improve the precision with which we identify patients with a higher prior probability of cognitive impairment and dementia. At the same time, we will be contributing new resources for dementia research everywhere.”
DeCarli and Fornage also participate in the MarkVCID Consortium, supported by the NIH’s National Institute of Neurological Disorders and Stroke. The consortium was established in 2016 to identify biological markers of vascular cognitive impairment and dementia.
Additional UC Davis Alzheimer’s Disease Research Center investigators on the project include Evan Fletcher, Danielle Harvey, Lee-Way Jin, David Johnson, Pauline Maillard and Kumar Bharat Rajan.
This award is co-sponsored by the NIH’s National Institute of Neurological Disorders and Stroke and National Institute on Aging through grant 1U19NS120384.
The UC Davis Alzheimer’s Disease Research Center is one of only 31 research centers designated and funded by the NIH’s National Institute on Aging. The center's goal is to translate research advances into improved diagnosis and treatment for patients while focusing on the long-term goal of finding a way to prevent or cure Alzheimer’s disease and other dementias. The center also allows researchers to study the effects of the disease on a uniquely diverse population. For more information, visit health.ucdavis.edu/alzheimers.
The Brown Foundation Institute of Molecular Medicine (IMM) for the Prevention of Human Diseases is part of McGovern Medical School at The University of Texas Health Science Center at Houston (UTHealth). The IMM is focused on studying and preventing diseases at the genetic, cellular and molecular levels using DNA and protein technologies and animal models. The IMM is part of the Texas Therapeutics Institute, a multi-institutional collaboration encouraging drug discovery. For more information, visit www.uth.edu/imm/mission.htm.
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