Could epilepsy drug help treat Alzheimer's disease?

Behind the Headlines

Tuesday March 17 2015

Could epilepsy drug help treat Alzheimer's disease?

Overactivity in some parts of the brain is linked to dementia, says study

A drug commonly used to treat epilepsy could help "slow down" the progress of Alzheimer's disease, reports The Daily Express. According to the news story, the drug levetiracetam was shown to "help restore brain function and memory". 

The story is based on a study analysing the short-term effect of the drug in 54 people with mild cognitive impairment (MCI). This is where people have problems with their memory and are at an increased risk of developing dementia, including Alzheimer's disease.

Dementia is a common condition that affects about 800,000 people in the UK. Most types of dementia cannot be cured.

Researchers found people with the condition showed overactivity in one part of the brain during one memory test involving image recognition.

This overactivity and performance on the test was better when participants had been taking 125mg of levetiracetam twice a day for two weeks, compared with when they had taken inactive "dummy" capsules.

This study was small, short-term and showed improvement on a single memory test. It is not possible to say from this study whether continuing to take the drug would reduce a person's chances of developing dementia.

Larger and longer-term trials would be needed to assess this. For now, levetiracetam remains a prescription-only medication that is only licensed for the treatment of epilepsy.

Where did the story come from?

The study was carried out by researchers from the Johns Hopkins University, and was funded by the US National Institutes of Health. It was published in the peer-reviewed medical journal NeuroImage: Clinical.

The Daily Express' headline, "Epilepsy drug found to slow down slide into Alzheimer's", overstates the findings of this study. It did not assess whether the drug affected a person's risk of Alzheimer's disease.

The study actually focused on how the drug affected short-term performance on one memory test in people with a specific type of MCI.

The news story also refers to "younger victims", but it is not clear what this means – the participants in this study were, on average, aged in their 70s.

What kind of research was this?

The main part of this study was a crossover randomised controlled trial looking at the effect of the anti-epileptic drug levetiracetam on brain function in people with amnestic mild cognitive impairment (aMCI). This type of study design is suitable if testing a drug or intervention that does not have lasting effects. 

The researchers report that previous studies have suggested people with aMCI have more activity in one part of one area of the brain (the dentate gyrus/CA3 region of the hippocampus) during certain memory tasks relating to recognising patterns.

Levetiracetam had been shown to reduce activity in these areas in animal research, so the researchers wanted to test whether low doses could reduce this excess activity and improve performance in memory tests in people with aMCI.

MCI is a decline in cognitive abilities (such as memory and thinking) that is greater than normal, but not severe enough to be classed as dementia. aMCI mainly affects a person's memory. A person with MCI is at an increased risk of developing dementia, including Alzheimer's disease.

What did the research involve?

The researchers recruited 69 people with aMCI and 24 controls (people of similar ages who did not have the condition). They gave levetiracetam to the people with aMCI and then tested their cognitive ability and monitored their brain activity with a brain scan (MRI).

They then repeated these tests with identical-looking dummy pills (placebo) and compared the results. They also compared the results with those of the controls taking the dummy pills.

All participants completed standard cognitive tests, such as the mini-mental status exam and other verbal and memory tests, as well as brain scans, at the start of the study.

Those with aMCI had to meet specific criteria – such as impaired memory, but without problems carrying out their daily activities – but not meet criteria for dementia. The control participants were tested to make sure they did not have MCI or dementia.

People with aMCI were randomly allocated to have either the levetiracetam test first and then the placebo test four weeks later, or the other way around. This aims to make sure that the order the tests were carried out does not affect the outcomes of the study.

In each test, participants took the capsules twice a day for two weeks before doing the cognitive test while having a brain scan. The researchers used three different doses of levetiracetam in their study (62.5mg, 125mg or 250mg, twice a day).

The cognitive test called the "three-judgement memory task" involved being shown pictures of common objects, such as a frying pan, beach ball, or a piece of luggage, shown one after the other.

Some of the pictures in the sequence were identical, some were similar but not identical (for example, different coloured beach balls), and most were unique pictures with no similar pictures shown.

The participants were asked whether each picture was new, identical to the one they had seen before, or similar to the one they had seen before. During the test, their brains were scanned using MRI to see which parts of the brain were active.

The researchers were able to analyse data from 54 people with aMCI and 17 controls, as some people dropped out of the study or did not have useable data – for example, if they moved too much while the brain scans were being taken.

What were the basic results?

After taking a placebo, people with aMCI tended to incorrectly identify more items as identical to ones they had seen before than control participants on the three-judgement memory task.

They identified fewer items as being similar to ones shown before compared with the control participants. This suggested people with aMCI were not as good at discriminating between items that were just similar to ones they had seen before and those that were identical.

When people with aMCI had been taking 62.5mg or 125mg of levetiracetam twice a day, they performed better on the three-judgement memory task than when they took placebo.

They correctly identified more items as being similar and fewer items incorrectly as similar, and performed similar to the controls. The highest dose of levetiracetam (250mg twice a day) did not improve test performance in people with aMCI.

Brain scans showed that when people with aMCI who had been taking placebo recognised identical items, they showed more activity in one area within a part of the brain called the hippocampus than controls recognising a match.

Taking 125mg of levetiracetam twice a day reduced this activity compared with placebo, but the lower and higher doses of levetiracetam did not.

The researchers say levetiracetam did not affect the performance of people with aMCI on standard neuropsychological tests. Results on these tests were not reported in detail.

How did the researchers interpret the results?

The researchers concluded that people with aMCI have overactivity of the dentate gyrus/CA3 region of the hippocampus during an image recognition memory task. Low doses of the epilepsy drug levetiracetam reduced this activity and improved performance on the tasks.

Conclusion

This small-scale study found that low doses of the epilepsy drug levetiracetam improved performance on an image recognition task for people with aMCI. This condition causes memory problems, and people who have it are at an increased risk of developing dementia.

While the news reporting has focused on the potential for levetiracetam to slow the onset of dementia, this is not something the research has assessed or focused on.

It instead focused on the short-term impact of the drug on a single test of memory, plus brain activity. There was reported to be no impact on other neuropsychological tests, which appeared to include other memory tests.

It's also important to note that the effect of taking the drug for two weeks was not lasting. It is not possible to say from this study whether continuing to take the drug would reduce a person's chances of developing dementia. Larger and longer-term trials would be needed to assess this. 

The researchers noted that they only looked at very specific brain areas, and this will not capture wider changes in brain networks.

Testing an existing drug that already has approval for treating another condition means that we already know it is safe enough for use in humans. This can mean that human trials can get started more quickly than if a completely new drug was being tested.

However, the benefits and risks still need to be weighed up for each new condition a drug is used for.

For now, levetiracetam remains a prescription-only medication that is only licensed for the treatment of epilepsy.

Analysis by Bazian. Edited by NHS ChoicesFollow Behind the Headlines on TwitterJoin the Healthy Evidence forum.

Analysis by Bazian

Edited by NHS Choices

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