Wednesday August 27 2014
Weight loss may help reduce inflammation inside the brain
"Weight loss surgery 'reduces chance of Alzheimer's disease'," reports The Daily Telegraph. This misleading headline reports on a small Brazilian study of severely obese women before and after weight loss surgery. None of the women had any signs or symptoms of Alzheimer's.
Seventeen women with an average body mass index (BMI) of 50kg/m² had neuropsychological tests, blood tests and a brain scan before surgery and again six months later, when their average BMI had reduced to 37kg/m². Their results were compared with those of 16 women of a normal weight – the "controls".
All of the women had normal neuropsychological tests. The obese women performed one of the tests more quickly after weight loss surgery, but it cannot be assumed this is a direct result of their weight loss. It could be they were faster simply because this was the second time they had done the test. The control group of women did not repeat the test, so we do not know if they also would have performed better.
Small changes in the rate of metabolism were seen in brain scans after surgery in two areas of the obese women's brains. But because the women were not followed up over time, it is not possible to say whether this means the women were at less risk of dementia or Alzheimer's disease as a result.
Losing weight can improve cardiovascular function, which in turn can protect against some types of dementia. But, based on this very small study, weight loss surgery cannot be recommended as an effective preventative measure against dementia.
Where did the story come from?
The study was carried out by researchers from the University of São Paulo, Brazil and was funded by the Brazilian National Council for Scientific and Technological Development.
It was published in the peer-reviewed Journal of Clinical Endocrinology and Metabolism on an open access basis, so it is free to read the paper online (PDF, 443kb).
The media headlines overstated the results of this study – it was not able to show that weight loss "boosts brain power" or reduces the risk of Alzheimer's disease. A more accurate – if less exciting – headline would have been "Weight loss surgery may make you perform slightly better in one of several neuropsychological tests".
But credit should go to the Mail Online for including a quote from an independent expert, who warned against reading too much into the results of this small study.
What kind of research was this?
This was a before and after study looking at the effect of weight loss surgery on brain (cognitive) function and metabolism in severely obese people. Severe obesity is when a person has a BMI of 40 or above.
The researchers say there is a link between obesity and Alzheimer's disease. They also report that previous research has found one area of the brain, called the posterior cingulate gyrus (believed to be involved in many brain processes), which shows reduced metabolic activity in early Alzheimer's disease.
They suggest the increased activity in this region might be a compensatory mechanism that occurs before the reduction in activity later in the disease.
The researchers wanted to assess the level of activity in this part of the brain in obese women and whether weight loss could have any impact on the metabolism.
As this study did not have a randomised control group of severely obese people who did not receive surgery, it is not able to prove cause and effect, as other confounding factors may have influenced the results.
What did the research involve?
The researchers compared the results of six neuropsychological tests, blood tests and a PET brain scan (a type of scan that assesses brain metabolism) on severely obese women before gastric bypass surgery and six months afterwards. They also compared the obese women's results with those of a group of normal-weight women.
Seventeen severely obese women aged between 30 and 50 were selected who were due to have gastric bypass surgery. The blood tests they had measured:
- indicators of metabolism – glucose (sugar) level, insulin and lipids
- markers of inflammation – C-reactive protein (CRP), Interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α)
Sixteen normal-weight women were recruited from the gynaecology unit to have the same tests on a single occasion to act as controls. They were matched to the obese women in terms of age and educational level.
What were the basic results?
The obese women lost a significant amount of weight after the surgery, but were still classified as very obese. Their average BMI was 50.1kg/m² before surgery and 37.2kg/m² six months after. The BMI of the normal-weight women was 22.3kg/m².
There was no significant difference in the neuropsychological tests between the obese women (before or after surgery) and the normal-weight women. The obese women showed improvements in one part of one of the six neuropsychological tests after surgery, however. This was the Trail Making Test – B, which assesses speed of visual scanning, attention and mental flexibility.
The obese women were able to complete the test in two-thirds of the time after surgery than they had before (average 147.8 seconds before and 96.9 seconds afterwards). Their performance was within normal limits both before and after surgery.
The brain PET scan showed an increase in metabolism in two areas of the brain before surgery compared with the normal-weight women. This difference was no longer present six months after surgery.
The two areas were the right posterior cingulate gyrus (the area that may be more active in early Alzheimer's disease) and the right posterior lobe of the cerebellum (involved in motor co-ordination).
Blood glucose, insulin levels and insulin resistance were higher in obese women than normal-weight women before surgery and improved to similar levels six months after surgery. Two of the inflammatory markers – CRP and IL-6 – were also significantly higher prior to surgery but then improved.
How did the researchers interpret the results?
The researchers concluded that, "metabolic and inflammatory properties associated with obesity in young adults are accompanied by changes in the cerebral metabolism capable of being reversed with weight loss."
They acknowledge that, "further studies are required to improve the understanding of the pathogenesis of the cognitive dysfunction related to obesity and the effects of weight loss on the occurrence of dementia."
This small short-term study has not shown that weight loss surgery reduces the risk of dementia. The women in this study were relatively young (about 41 years old on average) and all had normal neuropsychological test performance.
What this study did show is that, unsurprisingly, weight loss for severely obese women was associated with improved insulin resistance and blood glucose levels, and reduced levels of inflammation.
The main result reported by the researchers was a higher level of metabolism in two areas of the brain in severely obese women before gastric band surgery compared with normal-weight controls. This reduced to normal levels six months after surgery, when they had lost a substantial amount of weight but were still obese.
According to the researchers, one of these parts of the brain usually has reduced levels of metabolism in Alzheimer's disease, but has higher levels of metabolism in young people with a genetically increased risk of Alzheimer's disease before the levels then reduce. But they did not test any of the women for this genetic risk factor (apolipoprotein E type 4 allele).
The study also only followed the women for six months. This means it was not able to show what happened to activity in this area over a longer period of time, or whether any of the women would go on to develop Alzheimer's disease.
Overall, this study cannot show that the increased level of activity was associated with an increased risk of dementia, or that the reduction of activity after the women lost weight would change their risk.
There were improvements in the time it took the obese women to complete half of one of the six neuropsychological tests after the surgery and weight loss, but this cannot be attributed solely to weight loss. It could be that the women were quicker simply because they had done the test before and remembered how to do it.
The normal-weight women were only tested once, and there was no randomised control group of severely obese women who did not have surgery. Therefore, there was no group that allowed the researchers to compare whether completing the test for a second time would be faster, even without weight loss. There was also no difference in the women's ability to complete the other part of this test, or in the other five tests.
Further limitations of the study include:
- the small number of participants
- all the participants were women, so the results may not be applicable to men
- this was a select group of severely obese women with an average BMI of 50kg/m², so may not apply to women with other levels of obesity – a normal weight is between 19 and 25kg/m², obesity is considered for those over 30kg/m² and severe obesity for those over 40kg/m²
- it is not clear what gynaecological conditions the control women had and whether this could have affected the results
- there is no information about any other potential confounding factors that could have influenced the results, including other medical conditions, lifestyle factors such as smoking or alcohol use, or a family history of dementia
In conclusion, this study does not show that weight loss surgery reduces the risk of dementia. Despite this, the study does provide further evidence of the benefits of this type of surgery, including weight loss and improvements in insulin resistance, which would reduce the risk of diabetes.
Weight loss surgery should only be considered as a last resort. Many people can achieve significant weight loss through reducing their calorie intake and by taking regular exercise. This also has the added bonus of eliminating the risks of complications and after effects of surgery, such as excess skin.
For more information on losing weight, download the NHS Choices weight loss plan.
Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.