Two widely available and affordable drugs may provide the first treatment for a type of stroke associated with nearly half of all dementia cases, scientists have found.
The drugs, isosorbide mononitrate and cilostazol, used worldwide for treating heart and circulatory diseases, are believed to improve outcomes after a lacunar stroke, a debilitating condition affecting thousands each year.
Researchers from the University of Edinburgh, the University of Nottingham, and the UK Dementia Research Institute conducted a year-long trial involving participants who had experienced a lacunar stroke.
This type of stroke is caused by cerebral small-vessel disease, a condition affecting small blood vessels deep within the brain, which can lead to cognitive impairment and dementia.
Prof Joanna Wardlaw, the lead researcher, told The National: “This type of stroke is different from other types due to problems in the small vessels in the brain. When these blood vessels do not function properly, the brain's supply of oxygen and nutrients can become compromised.
"These two drugs help improve the function of the lining of the small blood vessels, thus enhancing their ability to dilate and contract when necessary, improving blood flow.”
Currently, there are no specific effective treatments for lacunar strokes, making this study a potential game-changer in stroke and dementia treatment.
If the trial's results are confirmed in subsequent studies, these two drugs, within five years, could be widely available as a treatment for lacunar strokes.
“Participants who took both drugs were nearly 20 per cent less likely to have problems with their thinking and memory compared with the group that did not take either drug,” Prof Wardlaw said.
“Moreover, those individuals reported better independence and improved quality of life. Even more encouraging was that those who took isosorbide mononitrate were less likely to have further strokes at one year than those who did not take the drug.”
Effect on recurrent strokes
The implications of patients being less likely to suffer further strokes at one year post-treatment are significant, Prof Wardlaw told The National.
“Anyone who's had any type of stroke is at higher risk of having another stroke. The more strokes you have, the more damage your brain is acquiring.
“The fact that one of the drugs reduces recurrent stroke in this group is really important, because it could be the first time that we've been able to show that this approach helps reduce recurrent stroke in this group of people.”
Unveiling the mechanism
The trial, funded by the British Heart Foundation, focused on cilostazol and isosorbide mononitrate because the hypothesis is that these drugs enhance the function of the inner lining of blood vessels, believed to be crucial in small-vessel disease.
When taken separately, each drug had beneficial effects on the patients' cognitive abilities, independence, mood, and overall quality of life. However, beneficial effects were significantly amplified when the drugs were taken together.
Addressing potential barriers to the widespread adoption of this treatment, Prof Wardlaw emphasised the importance of proceeding with cautious optimism.
She told The National that the accessibility and affordability of the drugs should not be a barrier.
“Both drugs are available worldwide. Isosorbide mononitrate has been used for decades in ischemic heart disease and is inexpensive. Cilostazol, while slightly more expensive, is widely used in Asia Pacific countries.
“Both drugs are off patent, and the cost is not prohibitive like some Alzheimer's drugs. If we confirm the results in a larger trial, then the adoption into clinical practice should be fairly straightforward.”
Safety concerns and side effects
As with any medicinal treatment, potential side effects and safety concerns are a valid inquiry.
“We monitored safety very closely during the trial. We couldn't find any safety concerns,” Prof Wardlaw told The National.
“While these drugs can cause headaches, palpitations, nausea, among other symptoms, only two symptoms were increased in people taking one or the other of the drugs, which did not get any worse when people were taking both drugs.
“These symptoms also tended to settle down over time, and they didn’t stop people from taking the drugs. Therefore, we don't think that safety or symptoms are a major concern.”
Next steps
After these promising findings, the research team is preparing for a larger, four-year clinical trial, scheduled to commence by the end of 2023.
They are also planning to explore whether these drugs are effective in treating other conditions associated with small-vessel disease, including vascular cognitive impairment and dementia.
“As a scientist, it's exhilarating to witness the potential repurposing of common drugs to treat conditions that currently have no specific treatments,” the lead researcher said. “The implication of our findings for thousands of patients suffering from lacunar strokes and associated dementia is profound. We look forward to validating these findings in our upcoming trial.”
The research team is also interested in exploring whether these drugs are effective in other ways in which small-vessel disease can present.
“If these drugs work in the way that they have in this particular type of small-vessel disease, then there's a possibility that they might also work in other presentations”, Prof Wardlaw said.
“For instance, they could be beneficial in cases where small-vessel disease is detected during memory clinic visits or through scans done for other reasons. We're keen to do feasibility trials in these other patient types to potentially pave the way for larger Phase 3 trials in those populations as well, should this approach prove to be effective.”
