Measuring a key blood molecule may help clinicians diagnose whether or to what extent impaired blood flow to a patient’s brain contributes to dementia or cognitive problems, according to a new study led by the University of California, Los Angeles (UCLA) Health researchers.
Cerebral small vessel disease, a common disease marked by damage to the cells lining the blood vessels in the brain, is a major driver of cognitive problems and dementia in older adults. However, it can be difficult for clinicians to determine whether a patient’s cognitive impairments stem predominantly from Alzheimer’s disease or vascular problems, the two most common causes of dementia. Clinicians typically rely on MRI or CAT scans to detect evidence of brain injury to help make that determination, but a certain amount of guesswork is involved.
In new research recently published in Alzheimer's & Dementia: The Journal of the Alzheimer's Association, researchers found that patients with higher levels of placental growth factor (PlGF)—a key molecule involved in the formation of new blood vessels, or angiogenesis—were more likely to have cognitive impairment or evidence of brain injury.
“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 Jason Hinman, MD, PhD, associate professor, vice chair of Research in Neurology at UCLA, and 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 study represents some of the first validation results reported by an NIH-funded consortium, MarkVCID, formed to help inform diagnosis and treatment. This consortium of academic medical centers working to identify biomarkers associated with vascular drivers behind cognitive impairment was formed in 2016 after researchers recognized they needed a better handle on precisely how vascular brain injury was contributing to dementia.
Angiogenesis signals as biomarkers
Researchers identified signaling involved in angiogenesis as potential biomarkers, assuming that the body may respond to damaged small blood vessels in the brain with intensified efforts to grow more. For this study, researchers focused on just one of those signals, PlGF, which was previously associated with cerebral blood flow regulation. Data, also gathered by the consortium, suggested this may be a useful biomarker for identifying patients with cognitive impairment and dementia due to vascular brain injury.
At UCLA and four other research sites, 335 patients underwent brain imaging, cognitive testing, and blood collection. Researchers found those in the top quartile for PlGF measurement were three times as likely to have cognitive impairment or dementia compared to those in the bottom quartile. Every unit increase in total PlGF in the bloodstream was also associated with a 22 percent increase in the likelihood of having a cognitive impairment and a 16 percent increase in the likelihood of having imaging evidence of cerebral small vessel disease.
“The addition of a blood-based biomarker 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,” said Hinman. “Right now it’s kind of the clinician’s best guess. This work can directly inform this diagnostic decision.”
The research consortium is still studying whether PlGF and a bundle of other angiogenic markers in the bloodstream could help predict the risk of future cognitive decline. Patients interested in enrolling in ongoing studies at UCLA can learn more and register here.
MarkVCID is supported by NIH (grant numbers: U24NS100591, UH2NS100599, UH2/UH3NS100605, UH2NS100588, UH2NS100608, UH2NS100606, UH2NS100598, UH2NS100614, UF1NS125513). Claudia L. Satizabal, PhD, and Sudha Seshadri, MD, are partly supported by P30 AG066546. Seshadri is also supported by the Bill and Rebecca Reed Endowment for Precision Therapies and Palliative Care and by an endowment from the Barker Foundation. The authors declare no competing interests.
- This press release was originally published on the UCLA Health website