Individuals who suffer from a type of stroke linked to nearly half of all dementia cases could be treated for the first time by repurposing two affordable and widely available drugs, according to trial results.
The study discovered that isosorbide mononitrate and cilostazol, drugs already employed to address other heart and circulatory ailments, can safely ameliorate the debilitating outcomes typically observed after lacunar stroke.
If the results are validated in subsequent trials, these two drugs, which proved to be more effective when combined, could become a treatment for lacunar strokes within the next five years, experts suggest.
Lacunar strokes, affecting at least 35,000 individuals in the UK annually, are a consequence of cerebral small vessel disease, where small blood vessels deep in the brain are damaged and cease to function properly. This disease is also a frequent cause of cognitive impairment and dementia.
The strokes can be quite distressing, as patients may experience cognitive and memory issues, motor difficulties, and even dementia. At present, there are no specific effective treatments available.
The Universities of Edinburgh and Nottingham, along with the UK Dementia Research Institute, spearheaded the trial, which involved 363 individuals who had suffered a lacunar stroke.
Participants received their standard stroke prevention treatment for a year, along with either isosorbide mononitrate or cilostazol individually, both drugs in tandem, or neither.
The trial, funded by the British Heart Foundation, examined cilostazol and isosorbide mononitrate as they potentially enhance the function of the inner lining of blood vessels, a role researchers believe to be critical in small vessel disease.
Participants who took both drugs were nearly 20 per cent less likely to exhibit cognitive and memory issues compared to the group that did not take either drug. They also demonstrated more independence and reported an improved quality of life.
Furthermore, individuals who took isosorbide mononitrate were less likely to have had additional strokes at one year compared to those who did not take the drug.
Administered individually, isosorbide mononitrate improved cognitive and memory skills, as well as quality of life, while cilostazol enhanced independence and mood. These effects were amplified when the two drugs were used in combination, according to the researchers.
The team is now preparing to conduct a larger four-year clinical trial with these drugs, which they aim to initiate by the end of 2023. They also plan to assess the effectiveness of the drugs in different conditions associated with small vessel disease, such as vascular cognitive impairment and dementia.
The findings are published in the journal JAMA Neurology. This work also received support from the Alzheimer’s Society and Stroke Association.
Professor Joanna Wardlaw, Chair of Applied Neuroimaging at the University of Edinburgh and Foundation Chair at the UK Dementia Research Institute, said: “Now we understand more about what is triggering these small vessel 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.”
Professor Sir Nilesh Samani, Medical Director at the British Heart Foundation, said: “These promising findings provide a long-awaited positive step towards the first treatments becoming available for lacunar strokes, offering much needed hope for thousands of people. Lacunar strokes are not the only way that cerebral small vessel disease can affect someone. These findings also open new avenues of research into other conditions related to small vessel disease, such as vascular dementia.”
