Blood Test to Measure Key Molecule Could Help Diagnose Vascular Dementia

Cerebral small vessel disease, in which damage is caused to cells lining the blood vessels in the brain, is primarily responsible for cognitive problems and dementia in older adults. However, doctors find it difficult to conclude if a patient’s cognitive impairments are mainly due to Alzheimer’s disease or vascular problems, which are the two most common causes of dementia. Doctors usually depend on MRIs or CT scans for finding evidence of brain injury to arrive at a diagnosis, which also involves some guesswork. Now, a new study has found that measuring a key blood molecule could help doctors diagnose whether or how much impaired blood flow to a patient’s brain is responsible for dementia or cognitive problems.

Researchers at UCLA Health (Los Angeles, CA, USA) have found that patients with higher levels of placental growth factor (PlGF) – a key molecule involved in the formation of new blood vessels, or angiogenesis – are more likely to have cognitive impairment or evidence of brain injury. The study represents some of the first validation results reported by a NIH-funded consortium of academic medical centers attempting to identify biomarkers related to vascular drivers that are responsible for cognitive impairment in order to help inform diagnosis and treatment. The consortium, known as MarkVCID, was formed in 2016 after researchers realized the need for a better understanding of exactly how vascular brain injury was contributing to dementia.

The researchers have identified signaling involved in angiogenesis as potential biomarkers, theorizing that the body could respond to damaged small blood vessels in the brain by increasing its efforts to grow more. For their study, the researchers focused on one of those signals, PlGF, which had been earlier associated with cerebral blood flow regulation. Data also collated by the consortium had indicated it could be a useful biomarker for identifying patients with cognitive impairment and dementia as a result of vascular brain injury.

In the study, 335 patients at UCLA and four other research sites underwent brain imaging, cognitive testing and blood collection. The researchers found that the patients in the top quartile for PlGF measurement were three times as likely to have cognitive impairment or dementia as compared to those in the bottom quartile. Each unit increase in total PlGF in the bloodstream was also associated with an increase of 22% in the possibility of having cognitive impairment and an increase of 16% in the chances of having imaging evidence of cerebral small vessel disease.

“Historically, diagnostic studies for cognitive impairment and dementia have been limited to structural brain imaging, but increasingly there’s a recognition that we can use the bloodstream as an available but imperfect tool to understand who maximally benefits from those structural and functional imaging tools,” said UCLA Associate Professor and Vice Chair of Research in Neurology Jason Hinman, MD, PhD, the study’s lead author. “It may also tell us who might be the best candidates for some of the really new emerging drugs that are available on the market to treat cognitive impairment and dementia.”

“The addition of a blood-based biomarker that is associated with the traditional measures of vascular injury could allow a provider to be able to distinguish the patient that has Alzheimer's-predominant dementia versus a significant vascular contribution,” Dr. Hinman added. “Right now it’s kind of the clinician’s best guess. This work can directly inform this diagnostic decision.”

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