Researchers at Washington University School of Medicine in St. Louis have been awarded $7.5 million from the National Institutes of Health (NIH) to investigate a form of dementia caused by cerebral small vessel disease, the second-leading cause of dementia after Alzheimer’s disease.
The grant funds the Vascular Contributions to Cognitive Impairment and Dementia (VCID) Center, which is a National Institute of Neurological Disorders and Stroke “Center Without Walls” initiative that will coordinate researchers at six sites across the U.S.
The WashU Medicine team will apply new magnetic resonance image-processing tools and other cutting-edge “multi-omic” technologies (a technique that looks at proteins, genes, metabolites and other complex systems together) to analyze cerebrospinal fluid and brain tissues from human and animal models to precisely map mRNA within cells affected by cerebral small vessel disease (CSVD). The long-term goals are to track biomarkers that can be used to identify the onset of CSVD-linked conditions and to locate targets for drugs that might mitigate or protect against the damage caused by the disease.
Three co-investigators are leading the effort at WashU Medicine: Jin-Moo Lee, MD, PhD, the Andrew B. & Gretchen P. Jones Professor in Neurology and head of the Department of Neurology; Carlos Cruchaga, PhD, the Barbara Burton & Reuben M. Morriss Professor of Psychiatry; and Manu Goyal, MD, an associate professor of radiology in the Mallinckrodt Institute of Radiology.
CSVD occurs when small blood vessels in the brain are damaged and lose their ability to change caliber to accommodate greater or lesser amounts of blood as needed by the brain. When the vessels lose this ability, it can lead to a lack of blood flow to regions of the brain, a condition known as ischemia.
“Over a long period of time, this ischemia can lead to injury to the white matter, and result in memory loss, difficulty walking, incontinence, depression — symptoms that define vascular dementia,” Lee said.
Several conditions can lead to CSVD. These include hypertension and diabetes, which can lead to arteriolosclerosis (thickening of the walls of small vessels) or the buildup of amyloid around vessels, leading to cerebral amyloid angiopathy (CAA). This latter condition is linked to the progression of Alzheimer’s disease. The damaged areas caused by CSVD appear as bright spots called white matter hyperintensities on MRI scans of the brain.
“When we look at older patients, we routinely see indications of small vessel disease,” Goyal said. “It’s a striking thing that we’ve known about for decades, but we don’t really know how it happens precisely, and we don’t have very good treatments.”