Claims of a 'breakthrough' for Alzheimer's patients lack merit

"Is this the solution to Alzheimer's?" asks the Mail Online. Sadly, the headline is an overblown reaction to a small, poor-quality and arguably overhyped study.

Researchers tested 2 mixtures of nutritional supplements on 25 patients with Alzheimer's disease. There was no comparison group taking a placebo supplement or alternative treatment.

The potential benefits aren't based on a validated mental health assessment, but seem to rely on reports from patients' carers, some of whom told nurses that the patients had improved memory, sight and mood.

When you read the study, it becomes clear it wasn't designed to measure the effect these supplements had on the symptoms of Alzheimer's disease, but to see how supplements affected the levels of nutrients in the patients' blood.

The supplements included xanthophyll carotenoids and omega-3 fatty acids, found in vegetables and fish.

Unsurprisingly, researchers found that taking supplements increased the blood levels of these nutrients.

They said they noticed "very striking differences" in the health of patients taking one supplement mixture, so decided to include these findings in the study.

Other dementia experts have described the study as "not much more than low-grade anecdotal evidence" and the associated self-promotion of the study as "either naive or deeply cynical".

Where did the story come from?

The study was carried out by researchers from the Waterford Institute of Technology and University Hospital Waterford in Ireland, and the Howard Foundation in the UK.

It was published in the peer-reviewed Journal of Alzheimer's Disease.

The study was funded by the Howard Foundation. One of the study's authors, Alan N Howard, is founder and chairman of the Howard Foundation.

According to its website, the Howard Foundation Group of Companies is based on intellectual property owned by the Howard Foundation and is managed by Howard Foundation Holdings Limited, a UK company.

It holds patents in nutritional supplements, including carotenoid supplements. This could be seen as a conflict of interest.

But Dr Howard stated on his conflict of interest declaration for this study that he had nothing to disclose.

The lead author, Professor John Nolan, has reported receiving payments from MacuHealth, a company that sells some of the supplements used in the study.

Both of these researchers are mentioned in a press release issued by a company called Memory Health, which plans to sell a mixture of some of the supplements used in the study.

While the Mail Online report gave prominence to the study's findings and comments from Dr Howard that "this represents one of the most important medical advancements of the century", the article also quotes a number of experts who were highly critical of the study.

What kind of research was this?

This study had an unusual design in that it sought to make comparisons between groups of people taking different combinations of supplements, but didn't carry out a randomised controlled trial.

Instead, the researchers recruited 3 groups of people separately and gave them one of the supplement combinations.

Everyone in the study knew what they were taking, and no-one was taking a placebo supplement. This introduced many possible sources of bias, which makes the results less reliable.

What did the research involve?

Researchers used 2 groups of Alzheimer's disease patients who'd been involved in their previous research, and another group of people who didn't have Alzheimer's disease and were recruited through advertising.

Patients had a standard mini-mental state examination (MMSE) at the start of the study, which assesses cognitive functions like memory and language skills.

They also had tests to measure for levels of xanthophyll carotenoids and omega-3 fatty acids in the blood.

The first Alzheimer's disease group (12 people) and the non-Alzheimer's group (15 people) were given supplements containing the xanthophyll carotenoids lutein, zeaxanthin and meso-zeanthin, found in vegetables including spinach, broccoli and peppers.

The second Alzheimer's disease group (13 people) were given the xanthophyll carotenoid supplement plus fish oil containing omega-3 fatty acids.

After 6 months, people were given another blood test. After 18 months, nurses carried out an assessment of people's health status, but didn't repeat the MMSE.

People were then diagnosed as having mild, moderate or severe Alzheimer's disease, but it's not clear what criteria was used to do this.

The study said the research nurses assessed people's health status and function by interviewing their carers.

Researchers also compared the results of the blood tests between the groups.

They then looked at the number of people designated as having mild, moderate or severe Alzheimer's disease at the start of the study and after 18 months.

They used a statistical test to see if the difference between the 2 groups was statistically significant.

What were the basic results?

Unsurprisingly, people had higher blood levels of omega-3 fatty acids and xanthophyll carotenoids after taking supplements for 6 months.

Those who took the combined supplement had higher levels of carotenoids after 6 months than those who just had the carotenoid supplement.

This may suggest that adding omega-3 fatty acids improves uptake of carotenoids into the bloodstream.

The researchers said at the start of the study:

• 4 people in the carotenoid-only supplement group had mild Alzheimer's disease and 8 had moderate Alzheimer's disease
• 2 people in the carotenoid plus omega-3 supplement group had mild Alzheimer's disease, 10 had moderate Alzheimer's disease, and 1 had severe Alzheimer's disease

After 18 months, the nurses' assessment of the patients found:

• 2 people in the carotenoid-only supplement group had mild Alzheimer's disease, 5 had moderate Alzheimer's disease, and 5 had severe Alzheimer's disease
• 4 people in the carotenoid plus omega-3 supplement group had mild Alzheimer's disease, 8 had moderate Alzheimer's disease, and 1 had severe Alzheimer's disease

The results state that 5 people in the carotenoid-only group dropped out of the trial because of a decline in their health, so it's unclear how assessments were made for these people.

The authors said the differences in outcomes between the groups were statistically significant.

They also said some carers "reported functional benefits in memory, sight and mood" and had requested continued access to the carotenoid plus omega-3 supplement after the study ended.

How did the researchers interpret the results?

The researchers said: "The results from the current study suggest that the improvements we identified in patients with AD were uniquely achieved only when a combination of the xanthophyll carotenoids and omega-3 fatty acids were provided to the patients", and that the results were "very promising".

Conclusion

Any study that reports improvements in Alzheimer's disease patients is likely to attract widespread attention, as so many people are living with or caring for people with this devastating disease.

Unfortunately, the desire for a cure is so strong that it can lead people to overlook the need for strong scientific evidence.

There are so many flaws in this poorly conducted study that it would be hard to list them all. Here are some of the most important.

We don't know how the researchers selected the patients to receive which supplement.

They weren't randomly assigned to one or the other, meaning there could be differences in the disease and the circumstances of the 2 groups of patients, making one group more likely than the other to progress to more severe disease.

The study compared 2 groups of people given combinations of supplements, all of whom knew what they were being given.

The nurses who carried out the assessments also knew what supplements people were taking. This introduces the strong possibility of bias.

For example, carers would expect to see an improvement with the combined supplement, or would perhaps give a more positive report to the nurses knowing that was what the researchers wanted to hear.

We don't know exactly how the nurses made their assessments of patients' status at 18 months.

The researchers didn't use the standard MMSE test, a screening test used to diagnose dementia, or any more in-depth validated cognitive assessment tools.

That makes it very hard to assess how reliable their division of people into mild, moderate or severe disease categories was.

The study was very small. In a clinical trial comparing 2 drugs, you'd expect to see hundreds or thousands of patients, not fewer than 20 in each group.

Smaller numbers usually means study results are much less reliable.

Previous studies looking at omega-3 supplements for preventing dementia found no evidence that they worked, which is another reason to be cautious about these results.

But until we see a proper randomised controlled trial of these supplements, we simply don't know whether they're any use or not.

Further complicating the picture, the study's lead authors are mentioned in a press release produced by a company called Memory Health, which appears to be planning to sell some of the supplements used in the study.

Find out more about how to reduce the chances of getting dementia