Vascular dementia: Could a blood biomarker aid early diagnosis?

• Vascular dementia causes around one in 10 dementia cases in the United States.
• It is often caused by cerebral small vessel disease, which damages cells lining the blood vessels in the brain.
• The symptoms are very similar to other forms of dementia, such as Alzheimer’s disease.
• Currently, diagnosis relies on neuroimaging to identify the damage to the blood vessels.
• A new study has shown that increased levels of a biomarker in blood plasma could help identify vascular dementia in its early stages.

Alzheimer’s disease is the most common form of dementia, and the one that most people are aware of. It causes some 70% of dementia cases.

Other forms include Lewy body dementia and vascular dementia. And it can be hard for physicians to tell the different types of dementia apart.

One major cause of cognitive decline and dementia in older people is cerebral small vessel disease. This results in decreased blood flow to key areas of the brain and increased permeability of the blood-brain barrier.

The symptoms of this vascular dementia can often be confused with those of other forms of dementia, such as Alzheimer’s disease, particularly in the early stages.

And early diagnosis is difficult, requiring MRI or CT scans to identify key changes, such as white matter hyperintensities, microbleeds, and brain atrophy.

Now, a study from the University of California Los Angeles has shown that high levels of placental growth factor (PlGF) in the blood can indicate the vascular damage responsible for this type of dementia.

The study was part of the MarkVCID Consortium, established in 2016, which aims to understand exactly how vascular brain injury contributes to dementia.

The findings are published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.

Diagnosing dementia

Vascular dementia is the second most common type of dementia. According to the Alzheimer’s Association, vascular dementia alone is responsible for 5–10% of dementia cases. However, it often coexists with Alzheimer’s disease and Lewy body dementia.

Dr. Bin Xu, assistant professor at the Biomanufacturing Research Institute and Technology Enterprise (BRITE) in the Department of Pharmaceutical Sciences at North Carolina Central University, not involved in the research, welcomed the study findings

He told Medical News Today that “[i]dentifying biomarkers for the development of minimally invasive plasma-based, inexpensive tests across [Alzheimer’s disease] and [Alzheimer’s]-related other dementias is an urgent and unmet need.”

“This new discovery of placental growth factor-based biomarker has important diagnostic and prognostic significance for vascular cognitive impairment,” he added.

In vascular dementia, cognitive decline is caused by a lack of blood flow to areas of the brain. This can be a result of a sudden change, such as a stroke, or by the more gradual changes of cerebral small vessel disease.

These vascular changes cause memory loss that is very similar to that in Alzheimer’s disease, as well as impaired judgment, lack of control of emotions, and difficulty with language, so it can be difficult for physicians to differentiate between the two types of dementia.

Some medications can help relieve the symptoms of vascular dementia, but to limit damage, it is vital that the other underlying causes, such as hypertension, hyperlipidemia, or diabetes are controlled. So differentiating between the types of dementia is hugely important.

Biomarker of vascular dementia

PlGF, one of a group of proteins called vascular endothelial growth factors, is involved in angiogenesis, the development of new blood vessels from existing ones.

It is expressed primarily in the placenta during fetal development, but later in life is used during the growth and repair of blood vessels.

The researchers theorized that the body may respond to damaged small blood vessels in the brain with intensified efforts to grow more. Therefore people with vascular dementia would produce more PlGF than those without.

The researchers assessed a total of 335 participants at five research sites. All participants underwent brain imaging, cognitive testing, and blood sampling. The researchers measured PlGF concentrations in the blood plasma from these samples.

People in the top 25% of PlGF concentrations were 3 times as likely to have cognitive impairment or dementia as those in the bottom 25%. Increased PlGF was also associated with increased cognitive impairment and evidence of cerebral small vessel disease on brain imaging.

The researchers also found a consistent association between plasma PlGF and volumetric white matter hyperintensities, which are associated with cognitive decline.

Diagnostic potential

“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. Jason Hinman, UCLA associate professor and vice chair of research in neurology, lead author on the study

The biomarker is found by analysis of a simple blood sample. As well as being less distressing for people with cognitive decline than lengthy scans and cognitive tests, it has the potential to be a rapid, cost-effective method of differentiating vascular dementia from other forms of dementia.

“Further development of this unique tool, especially for early disease stages, such as mild cognitive impairment, will be particularly useful for bench-to-bedside translation,” said Dr. Xu.

Enabling targeted treatments

New treatments for Alzheimer’s disease, such as lecanemab and aducanumab, that target the beta-amyloid plaques which are believed to cause many of the symptoms, have recently been licensed by the Food and Drug Administration (FDA). But these medications will not benefit people with vascular dementia.

Most other dementia treatments are aimed at improving quality of life and trying to slow the progression of the disease.

However, by identifying if dementia has a vascular basis, physicians could implement treatments targeted at the underlying cause, as Dr. Adi Iyer, a neurosurgeon and neurointerventional surgeon at the Pacific Neuroscience Institute at Providence Saint John’s Health Center in Santa Monica, CA, told MNT.

“Dementia, and in particular vascular dementia, is a very elusive diagnosis. Any new, clinically proven tests would be extremely helpful to physicians and patients,” he commented.

“Using PlGF might help identify specific patients who may benefit from many of the new emerging drugs for vascular dementia,” added Dr. Iyer.

Commenting on the study results, Dr. Claire Sexton, senior director of scientific programs and outreach at the Alzheimer’s Association, noted:

“This study provides evidence in support of placental growth factor as a biomarker for vascular cognitive impairment which could, in combination with other measures, potentially help inform diagnosis in the future. That being said, further research is needed to validate this marker, including longitudinal studies to assess its prospective use, studies that consider possible confounders — e.g. the possible impact of renal function on measurements — and studies that investigate its performance in diverse, representative populations.”

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