Cost-Effective Blood Test Could Detect Early Brain Changes Leading to Dementia

Dysfunctional cells in the blood vessels of the brain have increasingly been identified as a major factor in the development of cerebral small vessel disease (CSVD), which is a significant cause of cognitive decline and dementia. These dysfunctional vessels are thought to allow fluid and inflammatory molecules to leak into the brain tissue. CSVD is typically diagnosed using costly brain MRI scans, which show areas of vascular-induced brain damage as bright spots known as white matter hyperintensities (WMH). These structural changes are considered late indicators of vascular brain injury. Now, a new, cost-effective blood test could potentially detect early-stage changes, identifying at-risk individuals before significant damage occurs.

A multicenter study led by researchers at UCLA Health (Los Angeles, CA, USA) examined several factors for potential associations: plasma levels of placental growth factor (PlGF), a sensitive MRI measure of fluid accumulation in the brain called white matter free water (FW), white matter hyperintensities, and cognitive assessment scores. The study was part of MarkVCID, a multisite consortium designed to validate biomarkers for CSVD, with participants drawn from diverse racial and ethnic backgrounds, varying vascular risk factors, and across different stages of cognitive impairment. The participants, aged 55 or older, had both brain MRI scans and blood tests to measure PlGF levels.

The results, published in an article in the journal Alzheimer's & Dementia, supported models suggesting that elevated PlGF increases blood vessel permeability, leading to fluid buildup in the white matter of the brain, the development of white matter hyperintensities, and subsequent cognitive decline. The researchers concluded that the study’s large, diverse sample and its multicenter design provide strong evidence for the use of PlGF as a potential biomarker. However, they noted that further longitudinal studies are needed to establish causality and the timing of the relationships between PlGF, fluid accumulation, WMH, and cognitive decline. Ideally, PlGF could be used to screen younger individuals, allowing for early intervention with treatments or lifestyle changes to prevent or reverse vascular injury before cognitive dysfunction begins. The research team is currently recruiting participants for future studies.

“We studied a protein in the blood that is critical in the formation of blood vessels but that also appears to play a role in vascular permeability associated with cognitive decline,” said Jason Hinman, MD, PhD, a vascular neurologist at UCLA Health. “Evaluating data from a large group of patients with a range of vascular risk profiles 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 for and monitor cognitive impairment and dementia.”

“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,” added Kyle Kern, MD, first author and a vascular neurologist at UCLA Health. “As a simple blood test, such a tool would be valuable not only for patients and clinicians, but also for researchers identifying patients for clinical trials.”

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