To identify and track blood vessel-related changes in the brain that contribute to cognitive impairment and dementia, researchers and clinicians typically rely on MRI to assess “downstream” biomarkers – those found at the end of a cascade of events. But a multicenter study led by UCLA researchers could lead to a cost-effective blood test that can identify changes occurring near the top of the chain, potentially identifying at-risk patients at an earlier stage.

“We studied a protein in the blood that is essential for blood vessel formation, but also appears to play a role in vascular permeability associated with cognitive decline. Evaluating data from a large group of patients with a range of profiles vascular risk and cognition ranging from unimpaired to mild dementia, we found that plasma levels of this protein, placental growth factor (PlGF), could potentially be used as a biomarker to screen and monitor cognitive impairment and dementia,” said Jason Hinman, MD, 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 lead 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 factor in the processes leading to cerebral small vessel disease (CSVD), a major contributor to cognitive decline and dementia. Leaky vessels are thought to allow fluids and inflammatory molecules to seep into brain tissue. CSVD is usually diagnosed by an expensive brain MRI, where areas of vascular-related brain damage appear as bright spots on clinical MRI sequences – called white matter hyperintensities, or WMHs. WMH and other structural changes are late markers of cerebrovascular injury.

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

As a biomarker of cerebral small vessel disease and vascular contributions to cognitive impairment and dementia (VCID), PlGF could be used as a cost-effective screening tool to identify patients at risk for vascular brain injury before onset insidiousness of cognitive decline. As a simple blood test, such a tool would be valuable not only to patients and clinicians, but also to 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 undertaken by researchers involved in MarkVCID, a multisite consortium established to validate candidate biomarkers for CSVD through the recruitment of participants from diverse racial and ethnic backgrounds, with a range of vascular risk factors, and across the spectrum of cognitive disorders. Participants were aged 55 or older and had brain MRI and blood tests to determine PlGF levels.

The authors stated 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 the causality and timing of relationships between PlGF , FW, WMH and cognition. Ideally, PlGF could be used to screen younger populations for whom currently available treatments and lifestyle modifications could prevent or reverse the deleterious effects of vascular damage before the onset of cognitive dysfunction. The research group is recruiting patients for future studies.