To track blood vessel-related alterations in the brain that lead to cognitive decline and dementia, researchers and healthcare professionals often depend on MRI to assess ‘downstream’ biological markers—those found at the conclusion of a series of events. However, a recent multicenter study spearheaded by UCLA researchers might pave the way for an economical blood test aimed at detecting changes happening earlier in the sequence, which could help recognize patients at risk sooner.
To track blood vessel-related alterations in the brain that lead to cognitive decline and dementia, researchers and healthcare professionals often depend on MRI to assess “downstream” biological markers—those found at the end of a series of events. However, a recent multicenter study conducted by researchers from UCLA may open the door to an affordable blood test designed to detect changes occurring earlier in the process, potentially enabling the identification of at-risk patients sooner.
“We investigated a protein present in the blood that is essential for blood vessel formation and also seems to influence vascular permeability linked to cognitive decline. By analyzing data from a large cohort of patients with varying vascular risk profiles and cognitive conditions ranging from normal to mild dementia, we discovered that the levels of this protein, placental growth factor (PlGF), might serve as a biomarker for screening and monitoring cognitive issues and dementia,” stated 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 senior author of a study published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.
Faulty cells that line the blood vessels in the brain are increasingly recognized as significant contributors to conditions that cause cerebral small vessel disease (CSVD), which severely impacts cognitive function and can lead to dementia. These malfunctioning vessels are believed to let fluids and inflammatory substances leak into the brain tissue. CSVD is traditionally diagnosed through expensive brain MRIs, which reveal areas of brain injury linked to vascular issues as bright spots on the scans, known as white matter hyperintensities (WMH). WMH and other structural alterations are indicators of late-stage vascular brain injury.
The study explored potential links between several elements: levels of PlGF in plasma, a sensitive MRI measure of fluid accumulation in the brain (known as white matter free water), WMH, and cognitive assessment scores of the patients. The findings aligned with models proposing that higher levels of PlGF lead to increased vascular permeability, which results in fluid buildup in the brain’s white matter, the formation of white matter hyperintensities, and subsequent cognitive decline.
“As a biomarker for cerebral small vessel disease and the vascular contributions to cognitive impairment and dementia (VCID), PlGF holds promise as an affordable screening tool for identifying patients at risk of vascular brain injury before the gradual onset of cognitive decline,” remarked Kyle Kern, MD, the first author and a vascular neurologist at UCLA Health and researcher at the David Geffen School of Medicine at UCLA. “Such a simple blood test would not only be beneficial for patients and doctors, but it would also aid researchers in finding suitable participants for clinical trials,” he added.
The research was part of MarkVCID, a multi-site consortium aimed at validating candidate biomarkers for CSVD by recruiting participants from various racial and ethnic backgrounds, with different vascular risk factors, and a spectrum of cognitive conditions. Participants were aged 55 and above and underwent both brain MRI and blood tests for PlGF levels.
The authors emphasized that while the study’s design and the diverse sample size support the viability of PlGF as a biomarker, further long-term studies are necessary to establish causal relationships and timing among PlGF, free water, WMH, and cognitive performance. Ideally, PlGF could help screen younger demographics where existing treatments and lifestyle changes could mitigate or reverse the harmful effects of vascular injury before cognitive impairment manifests. The research team is actively seeking participants for future studies.
