Even though vascular dementia is the second most common form of dementia and the most frequent co-morbidity with Alzheimer’s disease, researchers still have no reliable way to detect and track it. To fill this gap, the National Institutes of Health has inaugurated a new consortium to identify and validate biomarkers that reflect vascular contributions to cognitive impairment and dementia (VCID). The five-year project, dubbed MarkVCID, will be coordinated by scientists at Massachusetts General Hospital, under the guidance of the National Institute of Neurological Disorders and Stroke (NINDS) and the National Institute on Aging (NIA). “The goal is to deliver a suite of validated biomarkers that are ready to be incorporated into clinical trials,” project leader Steven Greenberg at MGH told Alzforum.

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Vascular disorders contribute to many cases of dementia. [Courtesy of NIH.]

MarkVCID grew out of the goals set by the National Alzheimer’s Project Act (NAPA), said Roderick Corriveau at NINDS. NAPA takes on AD-related dementias such as VCID, and at summits on this topic in 2012 and 2016, scientists singled out biomarkers as a pressing need for research (see Apr 2016 conference newsApr 2016 conference news). Better biomarkers would allow early detection of VCID, help select trial participants at greatest risk of progression, and indicate that treatments are working as expected, Greenberg noted.

As a result of the summits, NINDS and NIA invited proposals and co-funded seven projects. Awards for the first year total $6.8 million, and come in the form of cooperative “U” grants, in which NIH investigators help guide the science. Corriveau said the research will focus on the contribution to VCID of small vessel disease, the type of vascular disease most frequently seen in AD. Small vessels include arterioles, capillaries, and venules.

Initially, the consortium will investigate and standardize promising candidate biomarkers, a phase expected to take about two years. For example, Gary Rosenberg and colleagues at the University of New Mexico Health Science Center in Albuquerque have found that microstructural changes on MRI scans and matrix metalloproteinases in the cerebrospinal fluid correlate with subcortical ischemic vascular disease. He will look for those markers that best detect the disease and predict progression. Meanwhile, researchers led by Danny Wang at the University of Southern California, Los Angeles, are investigating whether changes in blood vessels of the retina, as seen by the widely used technique of optical coherence tomography, reflect vascular disease in the brain. Researchers led by Julie Schneider at Rush University, Chicago, will scan postmortem brain samples by MRI to look for structural changes that correlate with the person’s cognitive status during life. Other projects are led by Joel Kramer at the University of California San Francisco, Hanzhang Lu at Johns Hopkins University, Baltimore, Donna Wilcock at the University of Kentucky, Lexington, and Sudha Seshadri at Boston University. They will investigate potential markers ranging across imaging, endothelial, inflammatory, and “omics” changes.

Once promising biomarkers are in hand, each will be validated across the consortium’s various cohorts. These include huge population studies, such as Seshadri’s CHARGE consortium, which is itself a collection of several large studies. By the end of the MarkVCID project, researchers hope to have a set of biomarkers ready for therapy trials. In some cases, the biomarkers themselves may point to new therapeutic targets, Greenberg suggested. For example, an inflammatory marker might lead investigators to try an anti-inflammatory approach. “Biomarkers can help inform the design of a trial,” Greenberg said.

Researchers are eager to test vascular interventions, because epidemiological studies have correlated recent declines in dementia incidence with improvements in cardiovascular health (see Feb 2016 news). Other studies have tied vascular disease to heightened dementia risk, again suggesting a direct connection (see Feb 2012Sep 2015 newsJun 2016 news). “There is good reason to think that further treatments aimed at the vascular contribution could substantially reduce the overall burden of dementia,” Greenberg predicted.

Corriveau noted that the consortium welcomes collaborations with other vascular researchers worldwide. “The MarkVCID consortium is just the beginning of [establishing] a VCID community,” he told Alzforum. Importantly, Corriveau promised that data and analyses from the consortium will be made freely available to other researchers.—Madolyn Bowman Rogers

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References

News Citations

  1. AD-Related Dementias Summit 2016: Progress, Aims, Dollars
  2. At 2016 Summit, Field Tackles AD-Related Dementias One By One
  3. Falling Dementia Rates in U.S. and Europe Sharpen Focus on Lifestyle
  4. Silent Vascular Disease May Hasten Dementia Progression
  5. Atrial Fibrillation in Middle Age Ups Dementia Risk
  6. Microbleeds in the Brain Portend Dementia

External Citations

  1. CHARGE consortium

Further Reading