Common cause of dementia may be treatable

A new study — led by the University of Edinburgh in the United Kingdom — has now uncovered how a disease that affects the brain's small blood vessels contributes to dementia and stroke.

The disease in question is called cerebral small vessel disease (CSVD).

In a paper now published in the journal Science Translational Medicine, researchers led by Prof. Anna Williams, who heads the MRC Centre for Regenerative Medicine at the university, note how they studied molecular features of the disease in rats.

They made some important discoveries. They identified, for example, a mechanism through which blood vessel changes from CSVD harm the myelin covering of nerve fibers that carry signals between brain cells.

The scientists also showed how certain drugs reversed the blood vessel changes and prevented damage to the nerve fibers in the rats' brains.

Brain scans of individuals with dementia often show abnormalities in white matter, which consists mostly of nerve fibers and their myelin covering.

But until this study, the underlying mechanisms implicating CSVD as a driver of myelin damage in white matter were unknown.

Should the mechanism be the same in human CSVD, these findings could pave the way to new treatments for dementia and stroke.

Dr. Sara Imarisio, who is head of research at Alzheimer's Research UK — one of the organizations that sponsored the study — says that the findings point to "a promising direction for research into treatments that could limit the damaging effects of blood vessel changes and help [to] keep nerve cells functioning for longer."

Dementia is a major cause of disability

Dementia is a general term for a group of conditions in which brain function worsens over time. As the condition progresses, it diminishes ability to remember, think, interact socially, make decisions, and lead an independent life.

Worldwide, there are 50 million people with dementia and "10 million new cases every year."

Dementia is a major cause of disability in older people and is the main reason that they become dependent on others. The social and economic burden of the condition also affects carers, families, and the wider community.

The majority of dementia cases are caused by Alzheimer's, a progressive disease in which toxic proteins build up in the brain.

Other conditions that directly or indirectly damage the brain — such as stroke — also cause dementia.

'Dysfunction of endothelial cells'

CSVD is common among older individuals. Not only does it directly cause stroke and dementia, but it can also worsen the effects of Alzheimer's disease and give rise to depression and problems with gait.

For a long time, it was thought that the "different features" of CSVD were signs of "different types of tissue changes." But more recently, scientists have come to realize that these features likely share many similar changes that affect small blood vessels.

And, as imaging technology advances, they are finding it easier to explore underlying mechanisms.

Prof. Williams and her colleagues discovered that CSVD causes dysfunction of endothelial cells, which are the cells that form the inner lining of blood vessels.

They also found that dysfunctional endothelial cells stop precursor cells from maturing into cells that make the myelin covering on nerve fibers.

'A potential therapeutic approach'

Closer investigation revealed that the rats that developed CSVD had a mutated form of an enzyme called ATPase, and that this led to dysfunction of their endothelial cells. The mutation has also been found in the brain tissue of humans with CSVD.

In a final set of experiments, the scientists showed how using drugs to stabilize the endothelial cells "could reverse the white matter abnormalities in early-stage SVD in the rat model, suggesting a potential therapeutic approach."

Prof. Williams and team explain that more research is now needed to find out whether the drugs work after CSVD has established itself and whether they might also "reverse the symptoms of dementia."

"There are currently no drugs that slow down or stop Alzheimer's disease and no treatments to help people living with vascular dementia."

Dr. Sara Imarisio