New blood test could help identify patients at risk for cognitive impairment

To identify and monitor blood vessel-related changes in the brain that contribute to cognitive impairment and dementia, researchers and doctors typically rely on MRI to evaluate “downstream” biological markers – those at the end of a series of events. But a multicenter study led by UCLA researchers could lead to a cost-effective blood test to identify changes at the top of the chain, potentially identifying at-risk patients at an earlier stage.

“We studied a protein in the blood that is crucial in blood vessel formation, but which also appears to play a role in vascular permeability associated with cognitive decline. We evaluate data from a large group of patients with a range of vascular risk profiles and cognition ranging from unimpaired to mild dementia, we discovered that plasma levels of this protein, placental growth factor (PlGF), could potentially be used as a biomarker for screening and monitoring cognitive impairment and dementia,” said Jason Hinman, M.D., PhD, a vascular neurologist at UCLA Health, interim co-director of the Mary S. Easton Center for Alzheimer’s Research and Care at the David Geffen School of Medicine at UCLA and senior author of an article in Alzheimer’s and Dementia: The Journal of the Alzheimer’s Association.

Dysfunctional cells lining blood vessels in the brain are increasingly recognized as a key driver of processes leading to cerebral small vessel disease (CSVD), a major contributor to cognitive decline and dementia. It is believed that the leaky blood vessels allow fluid and inflammatory molecules to seep into the brain tissue. CSVD is typically diagnosed via expensive brain MRI, in which areas of vascular-mediated brain injury appear as bright spots on clinical MRI sequences – so-called white matter hyperintensities or WMH. WMH and other structural changes are late markers of vascular brain injury.

The researchers studied possible associations involving several factors: plasma levels of PlGF, a highly sensitive research MRI measure of fluid accumulation in the brain called white matter free water (FW), white matter hyperintensities, and patients’ scores on cognitive assessments. The results were consistent with models suggesting that increased PlGF increases vascular permeability, leading to fluid accumulation in the white matter of the brain, the development of white matter hyperintensities, and subsequent cognitive impairment.

As a biomarker for cerebral small vessel disease and the vascular contributions to cognitive impairment and dementia (VCID), PlGF could be used as a cost-effective screening tool for identifying patients at risk for vascular brain injury before the insidious onset of cognitive decline. As a simple blood test, such a tool would be valuable not only for patients and physicians, but also for researchers identifying patients for clinical trials,” he said.

Kyle Kern, MD, first author, vascular neurologist at UCLA Health and researcher at the David Geffen School of Medicine at UCLA

The study was conducted by researchers involved with MarkVCID, a multi-site consortium established to validate candidate biomarkers for CSVD by recruiting participants from diverse racial and ethnic backgrounds, with a range of vascular risk factors, and across the spectrum of cognitive disorders. Participants were 55 years or older and had undergone a brain MRI and blood tests to measure PlGF levels.

The authors said that while the study’s multicenter design and large, diverse sample support the use of PlGF as a biomarker, additional longitudinal studies are needed to draw conclusions about causation and timing in the relationships between PlGF, FW, WMH, and cognition. Ideally, PlGF could be used to screen younger populations for whom currently available treatments and lifestyle modifications can prevent or reverse the deleterious effects of vascular injury before the onset of cognitive dysfunction. The research group is recruiting patients for future studies.