Trial raises hope for Treatment of Strokes linked to Dementia

“These are vitally important results and need to be confirmed in larger trials, not just after lacunar stroke but also in other forms of stroke and small vessel disease. The results also support the belief that small vessel disease is due to problems with the lining of blood vessels and treating that may help reverse that abnormality.” Philip Bath

A clinical trial led by researchers at the University of Nottingham and the University of Edinburgh have indicated the potential of two common drugs to be repurposed for the first specific treatment for people who experience a type of stroke linked to nearly half of all dementias.

Funded by the British Heart Foundation, the trial has shown that isosorbide mononitrate and cilostazol, already used to treat other heart and circulatory diseases and particularly used in combination, can safely and effectively improve the debilitating outcomes people experience after lacunar stroke, including problems with thinking and memory, movement and even dementia.

The trial results were presented at the American Heart Association International Stroke Conference, (Feb 10).

Lacunar strokes, which at affect at least 25,000 people in the UK each year, are thought to be caused by cerebral small vessel disease (cSVD), where small blood vessels deep within the brain become damaged and stop working properly. The researchers investigated cilostazol and isosorbide mononitrate as both thought to improve the function of the inner lining of blood vessels (the endothelium). Problems with the endothelium are thought to play a role in cSVD.

If the results from this study are confirmed in further trials, research leads Professors Joanna Wardlaw (Edinburgh)and Philip Bath (Nottingham), along with the UK Dementia Research Institute, have suggested that the two drugs could become available as a treatment within five years.

The 363 people involved in the trial continued with their standard stroke prevention treatment and took either isosorbide mononitrate or cilostazol individually, both drugs together, or neither.

After one year, participants that took both drugs were nearly 20 per cent less likely to have problems with their thinking and memory compared to the group that did not take either drug. They were also more independent and reported a better quality of life.

Those who took isosorbide mononitrate were less likely to have had further strokes at one year than those who did not take the drug.

Individually isosorbide mononitrate also improved thinking and memory skills, and quality of life, while cilostazol improved independence and mood. But these effects were strengthened when the two drugs were taken together.

The team is now planning to test these drugs in a larger four-year clinical trial, which they hope to start by the end of 2023. They are also looking to test whether the drugs are effective in different conditions linked to cSVD, such as vascular cognitive impairment and dementia.

Professor Philip Bath said: “These are vitally important results and need to be confirmed in larger trials, not just after lacunar stroke but also in other forms of stroke and small vessel disease. The results also support the belief that small vessel disease is due to problems with the lining of blood vessels and treating that may help reverse that abnormality.”

Professor Joanna Wardlaw, Chair of Applied Neuroimaging at the University of Edinburgh and Foundation Chair at the UK Dementia Research Institute, said: “Up until now, lacunar strokes have been treated just like other types of stroke, but lacunar stroke is clearly different. Now we understand more about what is triggering these strokes to attack the brain, we’ve been able to focus our efforts on treatments that can put a halt to this damage.”

“We need to confirm these results in larger trials before either drug can be recommended as a treatment. However, as these drugs are already widely available for other circulatory disorders, and inexpensive, it shouldn’t take too long to move our findings from research into everyday clinical practice.”

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