Memory loss after lacunar stroke: 2 drugs may boost cognition

• A stroke occurs when a bleed or blockage stops blood flow to part of the brain.
• Lacunar strokes, where a clot blocks a small artery deep in the brain, make up 25% of ischemic strokes, the most common type of stroke.
• They tend to occur in older people, are associated with high blood pressure and diabetes, and often result in cognitive impairment and dementia.
• A study has found that two cheap, common drugs used to treat heart and circulatory disorders may help improve cognitive function after a lacunar stroke.

According to the Centers for Disease Control and Prevention (CDC), almost 800,000 people have a stroke every year in the United States.

Of these cases, 87% are ischemic strokes, caused by a clot blocking an artery in the brain. And around 25% of ischemic strokes are lacunar strokes, which affect small arteries deep in the brain.

When a stroke occurs, some or all of the brain is deprived of oxygen and nutrients, so cells are damaged or die. A stroke can cause brain damage, long-term disability, and even death.

Repurposing drugs to treat lacunar strokes

Lacunar strokes, or lacunar infarcts, are more likely to occur in older people. Many other factors also increase the risk of experiencing a lacunar stroke, including:

• hypertension, or high blood pressure, which can damage the lining of arteries
• atherosclerosis: the buildup of cholesterol and other fatty materials within artery walls
• diabetes mellitus can damage blood vessels and increase the risk of high blood pressure
• smoking: Smoking tobacco damages the arteries and may lead to plaques forming in the arteries and blocking blood flow
• hyperlipidemia: High levels of fats in the blood can damage and narrow the blood vessels
• genetic factors: Certain genes and genetic conditions can significantly increase a person’s risk of stroke.

Lacunar strokes, which often result from cerebral small vessel disease (CSVD), are a common cause of vascular dementia and mild cognitive impairment.

A new trial has found that two commonly prescribed, cheap drugs reduce the risk of thinking and memory problems in people following lacunar stroke.

The study, published in JAMA Neurology, found that treatment with isosorbide mononitrate (ISMN) and cilostazol reduced cognitive impairment and improved quality of life in people who had experienced a lacunar stroke.

Using 2 common drugs for heart conditions

The two drugs used in this trial, ISMN — sold as Ismo, Monoket, or Imdur in the U.S. — and cilostazol (Pletal), are both widely used to treat heart and circulatory disorders.

ISMN is used to treat angina pectoris — the sensation of pain and squeezing in the chest that results from lack of blood and oxygen to the heart muscle — and heart failure. It works by releasing nitrogen oxide, which dilates the blood vessels to restore blood flow.

Cilostazol is prescribed for people with peripheral artery disease to relieve intermittent claudication — pain and cramping when walking due to insufficient blood flow in the legs. Like ISMN, it dilates the arteries to increase blood flow.

In this 1-year trial, the researchers gave the two drugs independently and together in addition to standard stroke prevention treatment in people who had experienced a lacunar stroke. A control group was given only a standard stroke prevention treatment.

Improved quality of life after a stroke

On its own, ISMN improved thinking and memory (cognitive) skills and quality of life. It also reduced the risk of repeat strokes during the 1-year follow-up. Cilostazol alone improved mood and independence.

However, the researchers reported the greatest impact when the two drugs were given in combination. Participants on this treatment showed similar improvements to those on the individual drugs, but the beneficial effects were enhanced on the combined treatment.

Participants taking both drugs were almost 20% less likely to have problems with thinking and memory than those in the control group. In addition, the researchers noted that the participants became more independent and reported a better quality of life.

Dr. Adam G. Kelly, an associate professor of neurology and neurosurgery at the University of Rochester Medical Center, not involved in the study, told Medical News Today: “Overall, the investigators found that both agents individually and the two collectively were safe and well tolerated, and that there were some potential signs of benefits in terms of risk of recurrent vascular events and cognitive impairment, particularly with combination therapy.”

Why the drugs reduce cognitive impairment

The findings suggest that these vascular-endothelial stabilizing drugs may reduce cognitive impairment and dependence following a lacunar stroke due to CSVD.

Dr. Kelly explained why they might have these beneficial effects.

“Dysfunction of the endothelium — the innermost lining of the blood vessel wall — is part of the pathophysiology that results in stroke, particularly strokes due to blockage of very small blood vessels up in the brain. This cerebral small vessel disease is also a major contributor to cognitive problems in many individuals,“ he told us.

“The medications used in this study, ISMN, and cilostazol, both have the potential to improve endothelial function and thus lower the risk of small vessel strokes,” he added.

Positive outlook for stroke patients

“The authors found [that] 99% of patients were retained at 1 year with good study drug adherence and no safety concerns. Isosorbide mononitrate reduced recurrent stroke and cognitive impairment, cilostazol reduced dependence, and ISMN-cilostazol reduced the composite of adverse vascular, dependence, and cognitive outcomes.”

– Dr. Steven Allder, consultant neurologist at Re:Cognition Health, not involved in the study

This was a small, phase 2 trial, but if these beneficial effects are repeated in larger studies, the medications could form a useful post-stroke therapy, as Dr. Kelly outlined.

“The hope is that these medications could be offered to patients with lacunar-type (small vessel) strokes and further lower their risk of recurrent events. Small vessel disease is also felt to be a contributor to vascular cognitive impairment and these medications may also have a role in preventing this,” said Dr. Kelly.

He went on to say: “As the authors note, both ISMN and cilostazol have been approved and used for years, so [we] have a fairly good sense of their safety profiles and potential to interact with other drugs, and both are relatively inexpensive.”

Dr. Allder agreed that the findings could be good news for those recovering from strokes: “If a full trial confirmed these results, a whole new area of post-stroke prevention would have opened up. These medications would be relevant to a large proportion of stroke patients.”

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