People with gout have lower risk of Alzheimer’s disease

"Gout could help prevent Alzheimer's, research shows," The Independent reports. Researchers think that uric acid, which causes gout, may have a protective effect against Alzheimer's disease.

Uric acid is a waste product that is normally passed out of the body. In cases of gout, the acid builds up around one or more joints, forming tiny crystals. This can then trigger the symptoms of gout, which are typically a sudden severe pain and swelling around the affected joint(s).

Previous research has found that uric acid is also an antioxidant (which helps to protect against cell damage), so researchers wanted to see if uric acid protected against Alzheimer’s.

The researchers used information from a UK database of more than 3.7 million patients. They matched people aged over 40 who developed gout with controls who did not, and followed them, on average, for five years to see how many were diagnosed with Alzheimer’s disease. They took multiple factors into account when analysing the results, such as medication use and age.

They found that 309 out of the 59,224 people with gout (0.5%) developed Alzheimer’s disease, compared to 1,942 out of 238,805 people without gout (0.8%), which translates into a 24% reduction in risk.

The study does not prove that gout is protective against Alzheimer’s, as there could be unmeasured factors that affected the results.

Where did the story come from?

The study was carried out by researchers from Boston University School of Medicine, Harvard Medical School, Harvard School of Public Health, and the University of British Columbia. It was funded by these institutes and the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

The study was published in the peer-reviewed medical journal Annals of the Rheumatic Diseases.

In general, the media reported the story accurately, though did not discuss the limitations of this type of study – that it can look for associations, but not prove cause and effect. The Independent helpfully provided expert opinion from Dr Laura Phipps from Alzheimer’s Research UK, who is reported to have said: "while this work does suggest a positive impact of gout on brain health, many of the risk factors related to gout, including obesity and diabetes, are also linked to increased dementia risk. Current evidence suggests that the best ways to maintain a healthy brain are to keep a healthy weight, exercise regularly, not smoke, eat a balanced diet, drink in moderation, and keep blood pressure and cholesterol in check."

What kind of research was this?

This was a case-controlled cohort study, which aimed to see if people with gout were less likely to develop Alzheimer’s disease.

Gout is a type of arthritis that most commonly affects the big toe, causing swelling and inflammation. It is due to a build-up of uric acid crystals in the blood. Uric acid is a breakdown product of purines, which are in all cells in the body and consumed in the diet, especially in beer, seafood, oily fish and liver.

However, uric acid is also an antioxidant and has previously been thought to protect against some neurodegenerative conditions, such as Parkinson’s disease and dementia. The researchers wanted to specifically see if higher levels of uric acid were associated with a reduced risk of Alzheimer’s disease.

This is an appropriate style of study to assess any link between higher levels of uric acid (people with gout) and risk of Alzheimer’s disease. Deliberately giving people an intervention to increase uric acid levels would be unethical, as this could lead to painful symptoms and joint damage.

What did the research involve?

The researchers compared the incidence of Alzheimer’s disease in people with and without a new diagnosis of gout during the study period.

The researchers used data from the Health Improvement Network database, which holds medical records from 580 GP practices in the UK. All the data is anonymised, so no personal data was provided to researchers.

The study period started in 1995 and the data for more than 3.7 million people aged 40 or more with no history of gout or dementia were eligible to be included in the study. When someone then had a diagnosis of gout, they entered the study. Five people of the same age and body mass index (BMI) who did not have gout entered the study at the same time, to act as controls. The researchers then followed these people up to 2013, comparing the incidence of Alzheimer’s disease between the two groups.

They took the following potential confounding factors into account when analysing the results:

• age and sex
• history of ischaemic heart disease, stroke, hypertension, hyperlipidaemia and diabetes
• BMI
• smoking status
• alcohol consumption
• social deprivation
• use of cardiovascular medication
• use of non-steroidal anti-inflammatory drugs (NSAIDs)

They repeated the process for people who developed osteoarthritis as a control, to see if the process was robust, as there has been no previous link between these diseases. 

What were the basic results?

There was a 24% reduced risk of developing Alzheimer’s for people with gout compared to those without, after adjusting for the potential confounders listed above (hazard ratio (HR) 0.76, 95% confidence interval (CI) 0.62 to 0.87).

Alzheimer’s disease occurred in:

• 309 out of the 59,224 people with gout (0.5%)
• 1,942 of the 238,805 people without gout (0.8%)

The average age was 65 in both groups and 71% were male. They were followed up for an average of five years.

There was no association between osteoarthritis and Alzheimer’s disease.

How did the researchers interpret the results?

The researchers concluded that their "findings provide the first population-based evidence for the potential protective effect of gout on the risk of AD [Alzheimer’s disease] and support the purported neuroprotective role of uric acid." They say that "if confirmed by future studies, a therapeutic investigation that has been employed to prevent progression of PD [Parkinson’s disease] may be warranted".

Conclusion

This population-based study has found that people with gout had a 24% reduced risk of developing Alzheimer’s disease. It was a well-designed study, in that there were large numbers of people in each group and multiple potential confounding factors were taken into account. The validation of the study was also valuable in showing the expected lack of a link between osteoarthritis and Alzheimer’s disease.

However, there are some limitations with this type of study, with a major one being that it cannot prove cause and effect. While some potential confounding factors were accounted for in the statistical analysis, there could be others which influenced the results.

The study participants were followed for an average of five years, so there will be a number of cases of early Alzheimer’s disease that would not have been picked up or fully diagnosed.

Gout was used as a proxy for increased levels of uric acid. However, gout is an inflammatory type of arthritis and some people only have one attack, or attacks that are spread out over a number of years. Therefore, it is not clear that a high level of uric acid caused the results seen.

It is not advisable that you try to increase your levels of uric acid through your diet, as this could increase your risk of developing gout, which is a very painful condition. The best way to reduce the risk of Alzheimer’s and other types of dementia are all the usual suspects: stop smoking, drink alcohol within recommended limits, be physically active, eat a balanced diet, reduce weight if you are overweight or obese, and keep blood pressure and cholesterol down.

Read more about reducing your dementia risk