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last updated: Thu, 28 Aug 2014 14:52:36 GMT

 Wed, 27 Aug 2014 11:30:00 GMT Does weight loss surgery affect dementia risk?

"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."

 

Conclusion

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.

Links To The Headlines

Weight loss surgery 'reduces chance of Alzheimer's Disease'. The Daily Telegraph, August 26 2014

Weight-loss surgery can boost brain power and 'cut the risk of developing Alzheimer's'. Mail Online, August 26 2014

Links To Science

Marques EL, Halpern A, Mancini MC, et al. Changes in Neuropsychological Tests and Brain Metabolism After Bariatric Surgery (PDF, 443kb). The Journal of Clinical Endocrinology and Metabolism. Published online August 26 2014

 Wed, 27 Aug 2014 00:00:00 GMT Antidepressant use in pregnancy linked to ADHD

“Pregnant women who take anti-depressants 'could raise their child's risk of ADHD',” reports the Mail Online, saying that this could explain “the rise in children with short attention spans”.

The study in question compared children with attention deficit hyperactivity disorder (ADHD) or autistic spectrum disorders (ASD) with children without these conditions. It found that children with ADHD, but not those with ASD, were more likely to have had mothers who took antidepressants during pregnancy. 

The main limitation to this study is that there is no certainty the antidepressants were having an effect, or whether other factors were at play. The researchers did try to take factors such as the mother’s depression itself into account, but acknowledge that other factors may have affected the findings. The fact that the link was no longer significant once the severity of women’s psychiatric illness was taking into account adds weight to the suggestion that other factors were involved.

While medications, including antidepressants, are generally avoided in pregnancy, the benefits of taking them may outweigh potential risks in some circumstances. Depression is a serious condition, which can have serious consequences if left untreated during pregnancy.

If you are taking antidepressants and are pregnant or planning to get pregnant, talk to your doctor. However, you should not stop taking your medicines unless advised to do so by your doctor.

 

Where did the story come from?

The study was carried out by researchers from Massachusetts General Hospital and other healthcare and research institutes in the US. It was funded by the US National Institute for Mental Health Research. Some of the authors declared receiving consulting fees or research support, having equity holdings or being on scientific advisory boards for various pharmaceutical companies. The study was published in the peer-reviewed medical journal Molecular Psychiatry.

The study was covered reasonably by the Mail, which highlighted early on in its story that any risk of taking antidepressants needed to be balanced against the risk of not treating a woman’s depression. It also very sensibly reported on current guidance from the National Institute for Health and Care Excellence (NICE) on when antidepressants should be used in pregnancy.

 

What kind of research was this?

This was a case-control study looking at whether exposure of a foetus to antidepressants in the womb might increase the risk of the child having ASD or ADHD in childhood. The researchers report that some previous studies have found a link, while others have not.

It would be unethical for researchers to randomly assign pregnant women with depression to receive or not receive antidepressants just to assess potential harms to the baby. Therefore, this type of study (called an observational study) is the most feasible way of investigating these links. The limitation to this type of study, however, is that factors other than antidepressants could be causing the link seen. For example, the depression itself might have an effect, or genetic factors contributing to the woman’s depression might also increase the child’s risk of ASD or ADHD. The researchers took measures to try and take some factors into account, particularly that ADHD and ASD might be associated with maternal depression itself. However, their effect may not be removed completely.

 

What did the research involve?

The researchers used data routinely collected from one healthcare group in the US. They identified children diagnosed with ADHD or ASD (cases), and compared them with similar children who did not have these conditions (controls). They looked at whether the mothers of children with these conditions were more likely to have taken antidepressants during their pregnancies. If this was the case, this would suggest that the antidepressant use might be linked to an increased risk of these conditions.

The researchers identified cases diagnosed between 1997 and 2010, among children aged from two to 19, who had been delivered at the three hospitals that were part of the healthcare group. For each case child, they identified three “control” children, who were:

  • not diagnosed with ADHD, ASD or an intellectual disability
  • born in the same year, ideally, or within three years if not enough controls could be found
  • born at the same hospital
  • born at the same term – either full-term or preterm (premature)
  • of the same sex
  • of the same race/ethnicity
  • of the same health insurance type (this acted as an indicator of socioeconomic status)

Children for whom no matching controls could be identified were excluded, but those with only one or two matched controls were included. The researchers ended up with 1,377 children with ASD, 2,243 children with ADHD and 9,653 healthy control children for analysis.

The children’s mothers were also identified from the healthcare database and birth certificate data. They identified whether the mothers had been prescribed antidepressants:

  • at any time before pregnancy
  • in the three months before conceiving the child
  • at any time during pregnancy (also broken down into first, second or third trimester prescriptions)

They also identified how long the prescription lasted (how many days’ worth of antidepressants the woman was prescribed).

The researchers then analysed whether prenatal antidepressant use was more or less common in mothers of cases or controls. These analyses took into account the factors that the children were matched for (such as gender and race) as well as maternal age and household income.

They also took into account whether the mother had been diagnosed with depression, looked at the effects of different types of antidepressant, an indicator of how severe the woman’s illness was (assessed by how much treatment she received and presence of other psychiatric diagnoses) – and exposure to two types of non-antidepressant medication (one drug to prevent vomiting that affected serotonin levels – something that some antidepressants also do – and any antipsychotics).

 

What were the basic results?

Maternal depression was associated with increased risk of ASD and ADHD in adjusted analyses.

Between 3% and 6.6% (approximately) of children with ADHD or ASD had mothers who had taken antidepressants either before pregnancy or during pregnancy, compared to 1% to 3.5% (approximately) of control children.

Before taking into account other factors, taking antidepressants before pregnancy or during pregnancy was associated with an increased risk of ASD and ADHD. After taking into account factors including maternal depression, taking antidepressants before pregnancy was associated with an increase in the odds of ASD (odds ratio (OR) 1.62, 95% confidence interval (CI) 1.17 to 2.23), but not of ADHD (OR 1.18, 95% CI 0.86 to 1.61). Taking antidepressants during pregnancy was associated with an increase in the odds of ADHD (OR 1.81, 95% CI 1.22 to 2.70) but not of ASD (OR 1.10, 95% CI 0.70 to 1.70).

The researchers found that if they took into account measures of how severe the woman’s illness was (how much treatment she was receiving, and whether she had other psychiatric conditions), the link between antidepressant exposure during pregnancy and ADHD was no longer statistically significant.

The researchers found no link between the anti-vomiting drug and ASD or ADHD risk, while there was a suggestion of a link between maternal antipsychotic use during pregnancy and ASD, but not ADHD.

 

How did the researchers interpret the results?

The researchers concluded that the association between maternal prenatal antidepressant use and ASDs in the children was probably due to the depression itself, rather than antidepressant use.

Maternal prenatal antidepressant use did appear to be associated with a modest increase in ADHD in the child, although this may still be due to other factors rather than the antidepressants themselves, they said. The researchers note that this potential risk needs to be weighed up against the considerable consequences of not treating the mother’s depression.

 

Conclusion

This study suggests a potential link between women taking antidepressants during pregnancy and an increased risk of ADHD, but not ASDs, in their children. The limitation to this type of study is that factors other than the antidepressants, such as the depression itself, or genetic factors increasing both depression and ADHD risk, might be causing the effect seen.

The researchers used various methods to take this into account, but acknowledge that other factors could still be having an effect. While the link with ADHD remained significant after taking maternal depression into account, it did not remain significant after taking into account measures of how severe the woman’s illness was.

Other limitations to the study include the following:

  • It could only assess what prescriptions the mothers received, and not whether they took them.
  • It could not directly assess how severe a woman’s illness was; they had to rely on data that was routinely collected on the types of treatment she was receiving and her previous diagnoses. This is unlikely to capture severity as well as a more direct assessment could.
  • If children or mothers were diagnosed or treated outside of the healthcare grouping being assessed, this information would not be available to the researchers, and this could affect results.

It is important to know that no one factor is likely to cause ADHD or ASD. These conditions are complex, and we are not yet entirely sure what causes the majority of cases. Both genetic and non-genetic (known as “environmental”) factors are thought to potentially play a part.

Medications are used sparingly in pregnancy to reduce any risk of harm to the developing foetus. However, if a woman’s condition could have serious consequences if untreated, then the woman and their doctor may decide that the benefits outweigh the harms.

NICE has guidance on how to treat depression if planning a pregnancy and during pregnancy and breastfeeding. In general, it recommends considering alternatives to antidepressant treatment, and considering doctor-supervised withdrawal of antidepressants for women already taking them. However, under certain circumstances it advises considering antidepressant treatment, such as if the women has not responded to non-drug therapies. 

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

Links To The Headlines

Pregnant women who take anti-depressants 'could raise their child's risk of ADHD'. Mail Online, August 26 2014

Links To Science

Clements CC, Castro VM, Blumenthal SR, et al. Prenatal antidepressant exposure is associated with risk for attention-deficit hyperactivity disorder but not autism spectrum disorder in a large health system. Molecular Psychiatry. Published online August 26 2014

 Tue, 26 Aug 2014 12:00:00 GMT Common bacteria could help prevent food allergies

"Bacteria which naturally live inside our digestive system can help prevent allergies and may become a source of treatment," BBC News reports after new research found evidence that Clostridia bacteria helps prevent peanut allergies in mice.

The study in question showed that mice lacking normal gut bacteria showed increased allergic responses when they were given peanut extracts.

The researchers then tested the effects of recolonising the mice's guts with specific groups of bacteria. They found that giving Clostridia bacteria (a group of bacteria that includes the "superbug" Clostridium difficile) reduced the allergic response.

The researchers hope the findings could one day support the development of new approaches to prevent or treat food allergies using probiotic treatments.

These are promising findings, but they are in the very early stages. Only mice have so far been studied, with a specific focus on peanut allergy and Clostridia bacteria. Further study developments from this animal research are awaited.

 

Where did the story come from?

This study was conducted by researchers from the University of Chicago, Northwestern University, the California Institute of Technology and Argonne National Laboratory in the US, and the University of Bern in Switzerland.

Funding was provided by Food Allergy Research and Education (FARE), US National Institutes of Health Grants, the University of Chicago Digestive Diseases Research Core Center, and a donation from the Bunning family.

It was published in the peer-reviewed journal PNAS.

BBC News gave a balanced account of this research.

 

What kind of research was this?

This was an animal study that aimed to see how alterations in gut bacteria are associated with food allergies.

As the researchers say, life-threatening anaphylactic reactions to food allergens (any substance that generates an allergic response) are an important concern, and the prevalence of food allergies appears to have been rising over a short space of time.

This has caused speculation about whether alterations in our environment could be driving allergic sensitivity to foods. One such theory is the "hygiene hypothesis" (discussed above).

This is the theory that reducing our exposure to infectious microbes during our early years – through overzealous sanitisation, for example – deprives people's immune systems of the "stimulation" of exposure, which could then lead to allergic disease. 

An extension of this theory is that environmental factors – including sanitation, but also increased use of antibiotics and vaccination – have altered the composition of natural gut bacteria, which play a role in regulating our sensitivity to allergens. It has been suggested that infants who have altered natural gut bacteria could be more sensitive to allergens.

This mouse study aimed to examine the role of gut bacteria in sensitivity to food allergens, with a focus on peanut allergy.

 

What did the research involve?

The researchers investigated the role gut bacteria plays in sensitivity to food allergens in different groups of mice. The research team studied mice born and raised in a completely sterile, bacteria-free environment so they were germ free.

Another group of mice were treated with a mixture of strong antibiotics from two weeks of age to severely reduce the variety and number of bacteria in their gut.

These groups of mice were then given purified extracts of roasted unsalted peanuts to assess their allergic response.

After looking at the allergic reactions in the germ-free and antibiotic-treated mice, specific groups of bacteria were reintroduced into their gut to see what, if any, effect it had on their allergic response.

The researchers focused on reintroducing Bacteroides and Clostridia groups of bacteria, which are normally present in mice in the wild.

 

What were the basic results?

Faecal samples taken from the antibiotic mice were found to have a significantly reduced number and variety of gut bacteria. These mice also had increased sensitivity to peanut allergens, demonstrating an increased immune system response that produced antibodies specific to these allergens, as well as showing symptoms of allergy.  

When the germ-free mice were exposed to peanut allergens, they demonstrated a greater immune response than normal mice and also demonstrated features of an anaphylactic reaction.

The researchers found that adding Bacteroides to the gut of the germ-free mice had no effect on the allergic reaction. However, adding Clostridia bacteria reduced sensitivity to the peanut allergen, making their allergic response similar to normal mice.

This suggests that Clostridia plays a role in protecting against sensitisation to food allergens.

This was further confirmed when Clostridia was used to recolonise the guts of the antibiotics mice and was found to reduce their allergic response.

The researchers then carried out further laboratory experiments looking at the process by which Clostridia could be offering protection. They found the bacteria increases the immune defenses of the cells lining the gut.

One specific effect seen was how Clostridia increased the activity of a particular antibody, which reduced the amount of peanut allergen entering the bloodstream by making the gut lining less permeable (so substances are less likely to pass through it).

 

How did the researchers interpret the results?

The researchers concluded that they have identified a "bacterial community" that protects against sensitisation to allergens and have demonstrated the mechanisms by which these bacteria regulate the permeability of the gut lining to food allergens.

They suggest their findings support the development of new approaches for the prevention and treatment of food allergy by using probiotic therapies to modulate the composition of the gut bacteria, and so help induce tolerance to dietary allergens.

 

Conclusion

This research examined how normal populations of gut bacteria influence mouse susceptibility to peanut allergens. The findings suggest the Clostridia group of bacteria may have a particular role in altering the immune defenses of the gut lining and preventing some of the food allergen entering the bloodstream.

The findings inform the theory that our increasingly sterile environments and increased use of antibiotics could lead to a reduction in our normal gut bacteria, which could possibly lead to people developing a sensitivity to allergens.

But these findings are in the very early stages. So far, only mice have been studied, and only their reactions to peanuts. We don't know whether similar results would be seen with other tree nuts or other foods that can cause an allergic response.

Also, although this research provides a theory, we do not know whether this theory is correct. We don't know, for example, whether people with a peanut allergy do (or did) have reduced levels of certain gut bacteria populations and whether this contributed to the development of their allergy. We also do not know whether treatments that reintroduce these bacteria could help reduce the allergy.

As the researchers say, the study does open an avenue of further study into the possible development of probiotic treatments, but there is a long way to go. 

Professor Colin Hill, a microbiologist at University College Cork, was quoted by the BBC as saying: "It is a very exciting paper and puts this theory on a much sounder scientific basis."

But he does offer due caution, saying: "We have to be careful not to extrapolate too far from a single study, and we also have to bear in mind that germ-free mice are a long way from humans."

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.

Links To Science

Gut bugs 'help prevent allergies'. BBC News, August 26 2014

Probiotics may help prevent peanut allergies, animal study shows. Fox News, August 26 2014


 

 
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