The starting point is an observation that people with conditions such as high blood pressure and obesity, or who are simply getting old, have a higher risk of certain kinds of dementia and heart disease. In particular, they seem to have a greater chance of developing vascular dementia, which is associated with reduced blood flow to the brain, and diastolic heart failure, which happens when the heart muscle cannot relax properly.
Conditions such as high blood pressure and obesity can exacerbate diseases, and therefore they are referred to as co-morbidities. “It’s not known why people with these conditions are more likely to get these diseases, nor why the heart and brain are especially sensitive,” explains Professor Elizabeth Jones, from the Department of Cardiovascular Sciences, who is coordinating the project. “But one theory is that all of these co-morbidities lead to a loss in the smallest blood vessels, or micro-circulation, around these organs.”
The CRUCIAL project, funded by the European Union’s Horizon 2020 programme, will investigate this theory through fundamental research in the laboratory, and clinical research with patients.
The fundamental research will work towards understanding why blood vessels are being lost. “They don’t die from lack of blood flow,” says Professor Jones. “Instead, the blood stops flowing after the vessels disappear.”
Her group at KU Leuven will explore this further by looking at the molecular pathways that maintain the micro-circulation. “There are pathways being activated that actively make the vessels regress,” she says. “If we can stop that from happening, we can inhibit the loss of the microvessels.” This may open the way for new treatments.
The VIB-KU Leuven Center for Cancer Biology will examine the metabolic changes involved in the loss of micro-circulation. And Maastricht University Medical Centre will look at biological ageing, with a focus on dementia.
On the clinical side, the aim is to see if advanced magnetic resonance imaging (MRI) techniques can be validated as a way of measuring micro-circulatory health. “The important difference is that we are not trying to diagnose the disease, but the loss of blood vessels that we think is the cause,” says Professor Jones.
This imaging will be carried out in a large and varied population of patients, at the Academic Hospital Maastricht, the Universidad de Navarra, and University College London. Doctors who are routinely scanning patients’ hearts will be asked to examine their brains at the same time, and vice versa. This is not common practice at present. And the MRI techniques will be standardised across all the hospitals, so that the results are comparable.
“We are hoping to bring the imaging to the point where it can be diagnostic, to move these academic MRI techniques into clinical practice,” Professor Jones says. This will give doctors an important new way to personalise patient care. “Just because you have co-morbidities doesn’t mean that you will experience heart failure or dementia. So by improving the imaging technology, we hope we will be able to identify who is at risk and needs to be monitored more closely.”
At the same time, the researchers will look at alternatives to MRI that may give comparable results at lower cost. For example, optical coherence tomography angiography measures the micro-circulation in the eye. “The idea is that the eye is part of the nervous system, so if your nervous system is losing blood vessels then so will the retina, at the back of the eye.” The microcirculation can also easily be measured under the tongue, using a technology called Glycocheck. “If the loss of blood vessels is not specific to heart and brain, we may be able to identify it there as well.”
Other options involve looking at microvesicles, which are fragments of cell membrane that circulate freely in the body, or at a range of biomarkers in the blood. “These technologies have been used before to look at micro-circulation, but they have never before been assessed against MRI results.”