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Researchers from UC Davis School of Medicine and The University of Texas Health Science Center at Houston (UTHealth) will study the role of incidental white matter lesions (WMLs) in dementia among diverse people with cognitive complaints, through a six-year, $53.6 million NIH grant awarded this week.

Charles DeCarli, MD, professor of neurology, director of the UC Davis Alzheimer’s Disease Research Center, is the principal investigator, while the Myriam Fornage, PhD, professor of genetics at the Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases at McGovern Medical School at UTHealth, is co-principal investigator.

DeCarli and Fornage will lead studies that are expected to offer insights on the role WMLs play in cognitive decline; the extent to which WML characteristics such as size and location make them greater risk factors for dementia; and how comorbidities such as heart disease or diabetes combine with WMLs to raise the risk of cognitive decline.

In addressing those areas, the research is expected to inform new 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.”

DeCarli and Fornage will conduct the first large study of a diverse population on the long-term effects of WMLs on thinking and dementia risk. They will study patients with no dementia diagnosis who have WMLs to learn more about their MRIs and concerns about cognitive symptoms.

“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.

Beginning in September 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, with the aim of better representing those at risk for dementia.

The grant is also designed to fund additional studies designed to enhance dementia research and clinical care by refining diagnostic and predictive tools and methods for dementia.

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.

“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,” Fornage said. “At the same time, we will be contributing new resources for dementia research everywhere.”

The studies to be funded by the grant will serve as a new and key component of the NIH’s Vascular Contributions to Cognitive Impairment and Dementia (VCID) research program. DeCarli and Fornage are among participating researchers 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, and held its kickoff meeting the following year.

The grant award is being co-sponsored by the NIH’s National Institute of Neurological Disorders and Stroke and National Institute on Aging through grant 1U19NS120384.

UC Davis School of Medicine said the NIH grant is the largest one it has ever received from the agency.

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