'Technology, food additives and air pollution are causing people to develop dementia earlier than ever,' reports the Mail Online website. But this is a claim with little to no evidence to support it.

The study the Mail reports on looked at death rates in 10 developed countries, including the UK and the US. The researchers specifically focused on what they termed "neurological deaths". These are deaths arising from conditions that affect the brain and nervous system, such as motor neurone disease and dementia.

This study found that the overall death rate has fallen over the past 30 years. But levels of neurological deaths have risen significantly when comparing data from 2008-10 to comparative data from 1979-81.

It is not clear why there has been such a rise in the number of deaths from neurological disorders. The researchers speculate that the fact that people are living longer, there have been major improvements in diagnostic techniques, and significant changes in lifestyle and the environment – such as the increased use of food additives, more pollution, and new technologies such as wi-fi and mobile phones – could all contribute to the rising numbers.

It is the claim about modern technology that captured the Mail's imagination the most. But the key word here is "speculate": more research is needed to see whether factors such as "technology, food additives and air pollution" could be held responsible for the rise in neurological deaths.

Where did the story come from?

The study was carried out by researchers from Bournemouth University and Southampton University. There was no funding to declare. It was published in the peer-reviewed journal, Public Health.

This story was covered poorly by the Mail Online website. Speculation about the possible causes of the increase in deaths from neurological diseases was reported as fact.

What kind of research was this?

This was an observational study that aimed to see how total deaths (mortality) and deaths specifically from neurological causes in older adults (aged 55 to 74 years) varied between the periods 1979-81 and 2008-10 in 10 major developed countries (Australia, Canada, France, Germany, Italy, Japan, Netherlands, Spain, the UK and the US).

This type of study can tell us how death rates and deaths from neurological causes vary over time, but it cannot tell us why these rates vary.

In order to investigate whether any of the factors suggested by the Mail Online – such as electronic devices, food additives and air pollution – play a role, ideally a randomised controlled trial, or more likely a cohort study, would have to be performed.

Even these types of studies could be difficult to carry out. Given that certain technologies such as mobile phones are now a global phenomena, it would be hard to isolate a mobile-free control group.

What did the research involve?

The researchers compared World Health Organization (WHO) data on total mortality and deaths due to neurological causes in people aged between 55 and 74 years old for the period 1979-81 with data from 2008-10 (or for the latest years available) in 10 major developed countries.

Neurological deaths were analysed as a whole, or divided into "nervous disease deaths" and "Alzheimer's and other dementia deaths". Nervous disease deaths included deaths from various conditions where there was inflammation or degeneration of the nervous system, including multiple sclerosis, motor neurone disease and Parkinson's disease.

What were the basic results?

The researchers found that total mortality for people aged between 55 and 74 years old fell substantially in every country over the 30-year period. On average, there was a fall of 45% from 25,620 deaths per million men in 1979-81, to 14,158 deaths per million men in 2008-10. For women, there was a decrease of 54% from 13,591 deaths per million in 1971-81 compared with 6,195 deaths per million in 2008-10.

In contrast, in people aged between 55 and 74 years old deaths from neurological causes rose by at least 10% in men in seven countries, and in women in eight countries. Total neurological deaths for both women and men rose significantly in Australia, Canada, Germany, Italy, Spain, the UK and the US.

Total neurological deaths increased significantly only in women in the Netherlands. On average, there were 275 deaths per million due to neurological causes in men in 1979-81. This rose to 332 deaths per million in 2008-10, an increase of 21%. In women, there were 101 deaths per million due to neurological causes on average in 1971-81, rising to 260 deaths per million in 2008-10, an increase of 29%.

When deaths from nervous diseases and Alzheimer's and other dementias were considered separately:

• In men, deaths from nervous diseases rose from 144 deaths per million in 1979-81 to 203 deaths per million in 2008-10 on average across the 10 countries surveyed.
• Seven countries had at least 10% increases in death rates from nervous diseases in men. Rates fell by at least 10% in the other three countries.
• In women, deaths from nervous diseases rose from 104 deaths per million to 137 deaths per million on average. Six countries had at least 10% increases in the rate of death from nervous diseases in women. Rates fell by at least 10% in two other countries.
• In men, deaths from Alzheimer's and other dementias rose slightly from 128 deaths per million in 1979-81 to 130 deaths per million in 2008-10 on average. Death rates from Alzheimer's and other dementias rose by at least 10% in men in five countries, and fell by at least 10% in three countries.
• In women, deaths from Alzheimer's and other dementias rose from 86 deaths per million to 123 deaths per million on average.
• Death rates from Alzheimer's and other dementias rose by at least 10% in women in seven countries, and fell by at least 10% in two countries.

How did the researchers interpret the results?

The researchers conclude that in contrast to major reductions in general mortality, mortality due to neurological deaths has increased in the majority of the countries analysed. They state that, "These results pose a major public health problem".

The researchers go on to discuss potential explanations for the increase in neurological deaths seen, including:

• the fact that people are living longer, making it more likely that they will develop and possibly die from some of the diseases considered to be diseases of older people
• improved diagnostic techniques, allowing more diagnoses of neurological diseases to be made
• lifestyle or environmental factors, which may increase the risk of developing some of these diseases

Conclusion

This research has found that the death rate in people aged between 55 and 74 years old has fallen over the past 30 years in 10 developed countries (Australia, Canada, France, Germany, Italy, Japan, Netherlands, Spain, the UK and the USA). However, during this period deaths from neurological disorders such as Alzheimer's and other dementias (such as vascular dementia), Parkinson's disease and multiple sclerosis have increased on average.

The reasons for this increase in neurological deaths can only be speculated about. The researchers suggest that the fact that people are living longer, improvements in diagnostic techniques, and changes in lifestyle and the environment could contribute to the increase.

However, although this type of study can tell us how death rates and deaths from neurological causes are varying over time, it cannot tell us why these rates might be varying. More research is required to see whether factors such as "technology, food additives and air pollution" really are responsible for the increase in death rates due to neurological disorders.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter.

Links To The Headlines

Technology, food additives and air pollution are causing people to develop dementia earlier than ever, says leading scientist. Mail Online, May 13 2013

Links To Science

Pritchard C, Mayers A, Baldwin D. Changing patterns of neurological mortality in the 10 major developed countries – 1979-2010. Public Health. Published online April 19 2013

"Children brought up by two parents are more intelligent," is the baseless claim on the Mail Online website.

The headline fails to mention that the research the story is based on involved only mice. Not until eight paragraphs into the news story does the Mail reveal this crucial point.

The scientific study involved housing baby mice with either their mother only, with both 'parents' or with their mother and a matched female 'parent'. These baby mice were then subjected to a series of tests designed to assess their development. After the testing, researchers took tissue samples from the brains of the mice.

The researchers found that:

• male mice housed with two parents seemed to have better threat-recognition abilities than those who were raised by a single mouse mum
• female mice housed with two parents seemed to have better motor co-ordination
• being housed with two parents did seem to affect brain development, although the pattern of development differed between male and female mice

Interesting as this is, it is hard to see how it applies to human families. This study cannot be used to conclude that children raised by one parent will have behavioural differences from, or will be less intelligent than, those raised by two parents.

Where did the story come from?

The study was carried out by researchers from the University of Calgary in Canada and was funded by the Canadian Institutes of Health Research and awards from Alberta Innovates Health Solutions.

The study was published in the peer-reviewed scientific journal PLOS one, which is free to read for all on an open-access basis.

The Mail’s story exaggerates the findings of this unusual animal study. Most of the article reads as if the research were directly relevant to humans or carried out in humans. The Mail encourages this idea by illustrating the story with a picture of a couple with their toddler. It is only in the eighth paragraph of the Mail’s report that the fact that the study was in mice is revealed. The paper offers no thoughts about how relevant research on mice is to humans.

However, much of the exaggeration in the Mail’s reporting can be traced back to a press release about the research issued by the University of Calgary.

What kind of research was this?

This was animal research aiming to investigate the effect that early life experiences can have on brain development, emotions and social behaviour.

In particular, the researchers were interested in the theory that low maternal care leads to changes in the area of the brain involved with memory and emotions (the hippocampus). This may then lead to increased stress and increased sensitivity to changes in emotion and mood (emotional reactivity).

They say that previous studies have shown that when pregnant rodents have been exposed to stress the female offspring developed a smaller hippocampus. As the effect was not seen in male offspring this suggested there may be some gender difference.

This study aimed to see whether parental care offered by two rodent parents rather than one had an effect on brain cell development. Further, the researchers wanted to see whether any changes in development had an effect on the behaviour of the offspring, and whether the effect was different in male and in female offspring. 

This study may be of interest to scientists and psychologists, and offers a possible insight into the factors that may influence animal brain development and behaviour. But it is hard to determine if, or how, the results can ever be applied directly to humans.

What did the research involve?

This research involved eight-week-old female and male mice, who were fed a normal diet and housed under 12-hour light/dark conditions. They were allowed to mate freely. Pregnant females were removed and placed in different parental conditions for the duration of pregnancy, through birth and until weaning at 21 days. In total, 269 animals were involved.

The three conditions were:

• maternal-only condition – the offspring were housed with their mother only
• maternal-virgin condition – the offspring were housed with their mother and an age-matched virgin female mouse
• maternal-paternal condition – the offspring were housed with the mated male-female pair

When housed under the three conditions the researchers observed the time that the parent mice spent in parenting behaviours, such as nursing, licking and grooming, and nest building.

When the offspring were weaned at 21 days they were housed with their littermates. They then completed a series of behavioural tasks ranging from least to most stressful. The tasks included:

• different maze tasks, including water mazes
• light-dark tasks (seeing how long mice spent in light and dark compartments when allowed to navigate freely)
• horizontal ladder tests (looking at how well they walked across the differently-spaced rungs of a ladder)
• tests of social preference (looking at interest in exploring different objects that stimulated the senses)
• tests of passive avoidance (of an electric shock)
• tests of fear conditioning (observing their time spent frozen and motionless when they were exposed to different shocks and sounds)

The researchers also examined tissue samples from the brains of the offspring mice to investigate any biological differences in their brain development.

What were the basic results?

Before weaning, the researchers observed that the parenting behaviour of the mother mouse was no different in the three conditions. Nor did the displays of parenting behaviour from the virgin-female and father-mouse differ from each other in those two respective conditions.

When the researchers worked out the average time spent licking and grooming the offspring (a marker of parental attention), the offspring in the two-parent conditions (either maternal-virgin or maternal-parent) received more attention than those in the maternal-only condition.

Overall, they found effects of parenting upon offspring behaviour and brain cell development differed between male and female offspring. In the various tasks, males raised in the two-parent conditions showed more fear conditioning, by displaying more freezing behaviour than males raised in the maternal-only condition. Meanwhile, females raised in the two-parent conditions showed better co-ordination when walking across the ladder than females in the maternal-only condition. The two-parent females also displayed more interest in exploring different objects.

This suggests that being raised in an environment with the biological mother and another adult mouse (male or female), may improve or accelerate some, but not all, developmental skills.

Two-parent care also had more effect on the male mouse brain. Male offspring in both the two-parent conditions had more growth of cells in a certain part of the hippocampus (the dentate gyrus). Parenting experience didn’t seem to have an effect on the hippocampus of the female offspring. However, females raised under the two-parent conditions did show greater proliferation of the white matter (the nerve fibres) of the brain.

How did the researchers interpret the results?

The researchers say that early life experiences can have an effect on brain development and behaviour, and that this persists through life. Male and female offspring appear to be affected in different ways.

They note in the abstract of their published research article (but do not describe in detail in the main research methods or results) that some of the brain development and behavioural advantages due to two-parent upbringing can stay with the mice throughout life and can be transmitted to the next generation.

Conclusion

This animal study suggests that male and female mice raised in two-parent conditions display differences in their brain cell development and behaviour compared with mice raised with only their mother.

While there are similarities between mice and men, it would be a mistake to assume that the findings in this mice study can be applied to humans. There are many important differences between the parenting of mice and people, and many differences in biology and social development that make it impossible to translate these findings to people.

Nonetheless, this study will be of interest to scientists and psychologists and offers a possible insight into the factors that may influence animal brain development and behaviour. Future research can build on these findings.

It should not be assumed from this study that children raised by one parent will have behavioural differences from those raised by two parents. The Mail Online also mistakenly suggests that this study supports the idea that children brought up by two parents are more intelligent. Apart from the fact that it was a rodent study, the study did not examine the ‘intelligence’ of the mice, so this assumption is groundless.

The main differences observed were that male mice from two-parent families seemed to freeze more when exposed to a perceived threat, and that female mice from two-parent families were more interested in exploring objects and better at walking over a ladder. It is a distortion of the evidence to conclude from this that children from two-parent families are more intelligent.

If you are shocked by the reporting of this study, first by the University of Calgary’s press office (or to be specific, its Hotchkiss Brain Institute) and then by the Mail Online, you may want to read about a study published in 2012. It found that half of all health reporting is subject to some sort of ‘spin’ with researchers and academic press offices shouldering a large proportion of the blame.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter.

Links To The Headlines

Children brought up by two parents are more intelligent - because they develop more brain cells. Mail Online, May 2 2013

Links To Science

Mak GK, Antle MC, Dyck RH, Weiss S. Bi-Parental Care Contributes to Sexually Dimorphic Neural Cell Genesis in the Adult Mammalian Brain. PLoS One. Published online May 1 2013

'Babies that are abnormally heavy or underweight are at 62% greater risk' of developing autism, reports the Daily Mail. The news is based on a large study of Swedish children with and without autism spectrum disorder (ASD).

Researchers compared healthy children up to the age of 17 with children who had a diagnosis of ASD. They examined whether there were any differences between the children in terms of how quickly they grew while in the womb (foetal growth) and the length of the pregnancy.

They found that babies with unusually low and unusually high levels of foetal growth had an increased risk of ASD (with or without intellectual disability).

This large study does suggest a possible association between foetal growth and ASD, but it does not prove a direct cause and effect. It could well be that there are underlying factors that cause both abnormal foetal growth and ASD.

While the researchers did try to account for a number of factors that could be linked to both foetal growth and ASD, this is not an exact science.

However, this study does raise interesting questions about how development in the womb could affect a child's risk of ASD, and will hopefully lead to further research in this field.

Where did the story come from?

The study was carried out by researchers from Manchester and Bristol Universities, Karolinska University Hospital in Sweden, Columbia University in the US, and other institutions. Sources of funding were not reported. It was published in the peer-reviewed American Journal of Psychiatry.

The study was covered by the Daily Mail, whose reporting was arguably not as clear as it could have been. While the main findings of the study were reported accurately, there was no discussion about the limitations of the study, or that other factors could have been at play.

The headline and much of the reporting also focuses on birth weight. However, the researchers specifically did not want to use birth weight as the prime measurement, as they said this is often prone to inaccuracy and misinterpretation. This is why they took the decision to focus on foetal growth.

What kind of research was this?

This was a nested case-control study within the Stockholm Youth Cohort study looking at the associations between the growth of babies in the womb, gestational age (length of the pregnancy) and ASD.

Autism spectrum disorder (ASD) is the name given to a group of developmental disorders that start in very early childhood and tend to have characteristic impairments in three main areas:

• social interaction, such as having difficulty understanding emotions
• communication and language difficulties
• a restricted, repetitive collection of interests and activities, or set routines or rituals

ASD includes both autism and Asperger syndrome. The main difference between the two disorders is that children with autism tend to have some degree of learning difficulty or intellectual impairment, while this is less common in Asperger syndrome.

In some cases, children with Asperger syndrome can be particularly gifted in certain areas, such as mathematics or computer science, though this is less common than the media would lead you to believe.

The causes of ASD are not known. Current thinking on the matter speculates that a combination of genetic and environmental factors disrupts the development of the brain during pregnancy.

A nested case-control study is a special type of cohort study where people who have the condition (cases) and a selected matched group who don't (controls) are selected from the same population, or cohort, of people (nested).

In contrast to non-nested case-control studies, data is usually collected prospectively, which means that researchers can be sure of when certain exposures or outcomes happened. This also avoids the difficulties or biases of participants remembering past events. Also, as cases and controls are selected from the same cohort, this means that they should be better matched than if researchers identified cases and controls separately.

What did the research involve?

The researchers used data from the Stockholm Youth Cohort study, which included all children up to the age of 17 who lived in Stockholm county between 2001 and 2007.

They identified 4,283 children with ASD (cases) and compared them with 36,588 healthy children randomly selected from the community (controls).

The cases were matched to controls by age and sex. For each child with ASD, there were nine children without the condition.

Of the children with ASD, 1,755 had an intellectual disability and 2,528 did not. Children who had been adopted or had missing data were excluded from the study.

Children with ASD were determined by linking with national registries containing information about all assessments or care of ASD in Stockholm county. The researchers say that children in Stockholm have assessments of development carried out by nurses or paediatricians at the ages of 1, 2, 6, 10-12, 18, 36, 48 and 60 months, or when there is concern about a child's development.

They say the type of care a child receives following a diagnosis of ASD is determined by whether the child also has an intellectual disability or not. This allowed the researchers to determine how many children with ASD also had an intellectual disability.

The researchers then collected information on the birth weight of each child and the length of the pregnancy (gestational age). The length of the pregnancy was determined using ultrasound dating.

They used information from the national registry of births to determine averages of foetal growth by gestational age, so they could determine which children were above or below these averages.

The researchers analysed the results to determine the risk of developing ASD (with and without intellectual disability). Results were adjusted for known factors that may have influenced the results (confounders), including:

• parent age when the baby was born
• country of birth
• socioeconomic status
• household income
• family psychiatric history
• whether the mother had diabetes or high blood pressure during pregnancy
• congenital disorders

What were the basic results?

The main results of this study were:

• below-average foetal growth was associated with an increased risk of ASD – the poorer the growth, the higher the risk
• foetal growth that was higher than average was associated with an increased risk of ASD, but only when the growth was in the extreme ranges of higher than normal
• these findings were for children with and without intellectual disability, although below-average foetal growth was more strongly associated with ASD with intellectual disability than without
• following adjustment, children who were born small or large for their gestational age were at greater risk of developing ASD with intellectual disability, irrespective of the length of the pregnancy
• preterm birth increased the risk of ASD independent of foetal growth

The researchers also found:

• parents of children with ASD were more likely to have experienced admission to hospital for psychiatric reasons (18.7%) compared with parents of children without ASD (11.3%)
• children with ASD were more likely to have congenital malformations compared with children without ASD

How did the researchers interpret the results?

The authors concluded that foetal growth above or below the average in Stockholm is an independent risk factor for developing ASD. They say this risk is greatest when growth is well below or above average, as well as for ASD with intellectual disability.

The researchers suggest these findings may allow for the possibility of early intervention in order to reduce poor developmental outcomes, through monitoring as well as follow-up, screening and the management of children who may be most at risk. 

Lead researcher Professor Kathryn Abel from Manchester University is reported as saying, "We think this increase in risk associated with extreme abnormal growth of the foetus shows that something is going wrong during development, possibly with the function of the placenta."

Conclusion

This large study suggests a possible link between foetal growth and very low or very high birth weight and ASD, with or without intellectual disability. However, it only observes an association and does not prove cause and effect.

Parents expecting a baby who is showing below- or above-average foetal growth, or who have a baby born with below- or above-average birth weight, should not be overly concerned that their child may be at risk of developing ASD.

If there is a direct link between foetal growth and ASD, the reasons why this may be the case are not clear. The authors' suggestions of possible reasons, such as the function of the placenta, are only theories.

Importantly, although the authors have tried to adjust for possible confounders, there could be other factors at play that may have affected the results. These include genetic, environmental or health-related conditions that the child or mother were exposed to during the pregnancy or after the birth.

Examples of possible factors not taken into consideration include alcohol and substance misuse, and obesity or weight gain around the time of the birth.

The study also only relates to a Swedish population sample. There may be environmental and population health differences between Sweden and elsewhere, meaning that care should be taken when generalising results to other countries.

Overall, the possible causes of autism spectrum disorder remain unknown, and further research is needed.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter.

Links To The Headlines

Babies born weighing more than 9lb 14oz or under 5lb 5oz have a higher chance of developing autism. Daily Mail, May 1 2013

Links To Science

Abel KM, Dalman C, Svensson AC, et al. Deviance in Fetal Growth and Risk of Autism Spectrum Disorder. The American Journal of Psychiatry. Published online April 1 2013

The health benefits of a Mediterranean-style diet have hit the headlines, with The Daily Telegraph reporting we should, 'Eat oily fish to prevent memory loss,' while the Mail Online focuses on how oily fish can keep the memory 'sharp'.

These somewhat overenthusiastic headlines are based on a large study that looked at how eating habits similar to those seen in Mediterranean countries could affect your chances of developing cognitive impairment.

Researchers found that older adults from the US who followed a Mediterranean-style diet were 13% less likely to have impaired cognitive abilities. This was still the case even after adjustment for other health and lifestyle factors that could also have an influence. However, this association was not seen in people with diabetes.

The Mediterranean diet has been linked to a lower risk of developing several diseases, including cardiovascular conditions such as heart disease and stroke, and forms of dementia (such as Alzheimer's disease).

Drawing conclusions from research into associations between diet and health is difficult, as it is hard to measure the influence of dietary habits properly.

In the case of this study, the diet measurements may be quite specific to the US, so the findings may not apply to British people's diets in the same way.

Overall, however, this large well-conducted study suggests that sticking to a largely Mediterranean-style diet may have benefits for the cognitive functioning of people who do not have diabetes.

Where did the story come from?

The study was carried out by researchers from the University of Athens, the University of Alabama at Birmingham, and other research institutes in the US and the Czech Republic. It was funded by the US National Institutes of Health and was published in the peer-reviewed medical journal Neurology.

The media headlines regarding the importance of eating oily fish instead of red meat do not fully capture the research results. While oily fish is part of the Mediterranean diet, there are many other components that could also have beneficial effects. This study assessed all the components together rather than focusing on oily fish alone, as the media suggests – in fact, the word 'fish' does not appear once in the Neurology article.

Additionally, the 19% reduction in risk quoted by both The Daily Telegraph and the Daily Mail is incorrectly attributed to "people who adhere to a Mediterranean-style diet". This figure actually only applies to non-diabetic people. The risk reduction for the entire study sample was a more moderate 13% reduction in odds. However, both newspapers covered the main methods of the study well.

What kind of research was this?

This was a prospective cohort study that assessed the relationship between how much people adhered to a Mediterranean diet and their odds of developing cognitive impairment over time.

The Mediterranean diet involves eating lots of fruit, vegetables and olive oil, and eating few saturated fats, meat and dairy products. According to the study's authors, the diet has been associated with longer lifespan and a reduced risk of heart conditions, some cancers and Alzheimer's disease. It is the frequent subject of research into the influence of lifestyle on health and longevity.

As a prospective cohort study, this research can tell us how people's diet is linked to new cases of cognitive impairment over time. It also confirms that diet preceded any change in cognitive function, a key factor in assessing causality.

What did the research involve?

As part of the Reasons for Geographic and Racial Difference in Stroke (REGARDS) study, researchers recruited more than 30,000 individuals over the age of 45 from various regions of the United States. At the beginning of the study (baseline), individuals completed a version of the food frequency questionnaire (FFQ) that assessed their dietary habits. It was adapted specifically around foods commonly eaten in the US. Their cognitive functioning was also assessed using the six-item screener (SIS).

Participants were excluded if:

• they had a history of stroke
• there was missing data from the diet questionnaire
• they completed fewer than two cognitive assessments during the study
• the baseline tests revealed impaired cognitive status

The participants were asked to complete the FFQ several times over the first year to validate the results of the baseline diet assessment. The questionnaire was scored on a 10-point scale (0 to 9), with higher scores indicating higher adherence to a Mediterranean diet.

The SIS cognitive assessment was carried out at baseline and on a yearly basis to detect changes in cognitive status and new cases of cognitive impairment. For the statistical analyses, the researchers defined incident (new) cognitive impairment as a change from intact cognitive functions (an SIS score of 5 to 6) to impaired cognitive status during follow-up assessment (an SIS score of 4 or less).

Using data from the FFQ scores, the researchers separated participants into two categories according to their adherence to a typical Mediterranean diet. Scores of 0 to 4 were taken to indicate low adherence, while scores of 5 to 9 indicated high adherence.

The researchers then calculated the odds of new onset cognitive impairment in the group with high diet adherence, and compared this with the odds of new cognitive impairment in the low adherence group.

They adjusted the analyses to control for factors shown to be associated with new-onset cognitive impairment, including:

• demographic factors, such as age, race and sex
• socioeconomic factors, such as region of residence, household income and education
• health status, such as history of heart disease, diabetes, atrial fibrillation, blood pressure, high cholesterol, use of blood pressure medications, symptoms of depression, and perceived general health
• other risk factors, such as body mass index (BMI), waist circumference, smoking status, alcohol use and physical activity level

They also assessed how having diabetes influenced the relationship between diet and cognitive impairment. For this, they carried out two separate analyses similar to those described above: one for individuals with diabetes, and the other for diabetes-free participants only.

What were the basic results?

Main analysis

Links To The Headlines

Eat oily fish to prevent memory loss, researchers claim. The Daily Telegraph, April 29 2013

Want your memory to stay sharp in old age? Eat less red meat and more oily fish. Daily Mail, April 29 2013

Links To Science

Tsivgoulis G, Judd S, Letter AJ, et al. Adherence to a Mediterranean diet and risk of incident cognitive impairment. Neurology, April 30 2013

"Forget popping pills – the best way to boost your brainpower is a crossword or sudoku," the Mail Online website states. The website reports that fish oils and ginkgo supplements won’t prevent cognitive decline, but that brain training games might.

The story is based on a well-conducted review of previous research that looked at prevention of cognitive decline. Researchers found 32 relevant studies investigating the use of different treatments, including drug treatments, supplements, physical activity and cognitive exercises, for preventing cognitive decline.

Interestingly, there was no firm evidence that pharmacological treatments (such as cholinesterase inhibitors and vitamin pills) were of any benefit for preventing cognitive decline. In fact, the available research suggested that certain treatments, such as hormonal therapies, may worsen memory.

The researchers also found inconsistent evidence for the supposed benefits of physical activity for preventing cognitive problems.

However, they did find some evidence (from three studies) that brain training exercises could help prevent cognitive decline. It is important to note that none of the research looked at sudoku or crosswords and that the ‘brain training’ involved was of a more intensive and long-lasting nature.

The bad news is that most things that have been tried to prevent cognitive decline don’t appear to work (or are even harmful), while the probable benefits of cognitive training are also uncertain. However, further research into ways to improve or maintain cognitive function may well change this view.

Where did the story come from?

This was a systematic review that looked at a total of 32 randomised controlled trials (RCTs) that studied treatments for cognitive decline. It was carried out by researchers from the Divisions of Geriatric Medicine and General Internal Medicine at the University of Toronto. No competing interests or sources of financial support were reported.

The study was published in the peer-reviewed Journal of the Canadian Medical Association.

The Mail Online’s reporting generally represented this research well. However, the headline that you should "forget popping pills – the best way to boost your brainpower is a crossword or sudoku" is misleading. The studies included in the review did not use puzzles of this nature. They instead used cognitive exercises that were described by the researchers as “labour and resource intensive” – less laid back than completing a crossword puzzle or sudoku grid.

What’s more, there are currently no pills you can “pop” to “boost your brainpower”.

What kind of research was this?

The researchers say that, as the population as a whole is ageing, it is becoming increasingly important to find ways of preventing or limiting cognitive decline in healthy older adults. In this review they looked at evidence on how effective drug treatments and non-pharmacological interventions might be.

Because this was a well-conducted systematic review we can be fairly sure that the researchers identified all available RCTs that have evaluated the effectiveness of different interventions for preventing cognitive decline. However, the quality of the individual studies is likely to vary, which limits the strength of any conclusions that can be made.  

What did the research involve?

The researchers searched four literature databases up to October 2011 using search terms such as ‘cognitive decline’, ‘dementia’ and ‘mild cognitive impairment’ to find relevant RCTs. They defined these as RCTs looking at pharmacological or non-pharmacological interventions in people aged 65 years or older who had normal cognition or mild cognitive impairment at the start of the study.

Studies were eligible if they looked at the effect of the intervention on any form of cognitive decline, including the development of mild cognitive impairment (if the person had normal cognition at study start), worsening cognitive function on cognitive testing, or progression to dementia. The focus of their review, however, was on people with normal cognition at study start.

A total of 5,205 articles were initially identified but, when reviewed, only 32 were eligible for inclusion. The researchers assessed the quality of these studies using valid criteria.

What were the basic results?

The researchers found 26 studies on pharmacological interventions for cognitive problems. These were:

• Three studies on cholinesterase inhibitors and NMDA (N-methyl-D-aspartate) receptor antagonists, which included 89 people and lasted between three and 15 months. These drugs are sometimes used to treat people with neurodegenerative disorders, such as Alzheimer's disease. From these studies they found no evidence of an overall effect on memory.
• Thirteen studies on various hormonal therapies. Seven studies were on oestrogen therapies and included a total of 10,792 women. These studies lasted between two weeks and five years. These studies overall showed that oestrogen treatments actually worsened memory. Three studies were on testosterone therapies. These studies lasted between three months and three years and included 144 men. These studies provided inconsistent evidence of any effect of testosterone on memory. Three studies were on DHEA (a synthetically produced version of a natural hormone produced by the adrenal glands). These studies lasted between six weeks and one year and included 317 people. These studies provided inconsistent evidence of any effect of DHEA on memory.
• Two studies on ginkgo (a type of herb found in China), including 348 people and lasting between six weeks and 3.5 years. These studies provided no evidence of any effect on memory.
• Four studies of vitamins and fatty acids, including 6,779 people and lasting between four weeks and 9.6 years. These studies provided no evidence of any effect on memory.
• Four studies of miscellaneous pharmacological interventions (including various anti-inflammatories and heart drugs), including 7,530 people and lasting between four weeks and 3.7 years. These studies provided inconsistent evidence of an effect on memory.

The following studies of non-pharmacological interventions were identified:

• Three studies on physical exercise, including 244 people and lasting between six months and one year. These studies provided inconsistent evidence on exercise.
• Three studies on cognitive training (mental exercises), including 3,321 people and lasting between three weeks and five years. These studies showed significant improvements in auditory memory (processing spoken information) and attention.

How did the researchers interpret the results?

The researchers concluded that there is no consistent evidence that any pharmacological treatment is beneficial in preventing cognitive decline in healthy older adults. Furthermore, studies investigating oestrogen therapies have suggested that these treatments may actually cause a decline in memory.

They also said that there is weak evidence to suggest that physical activity can have an effect in preventing cognitive decline and that formal cognitive training exercises may have some potential benefit in preventing cognitive decline.

Conclusion

As the researchers say, there are various products on the market that claim to prevent cognitive decline. These range from physical and mental activities to prescription and non-prescription medications.

However, as the researchers mention, the evidence supporting the benefits of these interventions can be limited, and studies into these types of intervention are often of poor quality.

This review usefully clarifies what scientific evidence is available for these interventions, and what this evidence shows.

Researchers found no firm evidence that any pharmacological interventions would be of benefit in preventing cognitive decline. In fact, certain treatments including oestrogen therapies may even worsen memory.

Looking at exercise, there was evidence from one study on resistance training that this may improve memory, but in a study of resistance and balance training and another of aerobic exercise there was no effect. However, three studies on cognitive training or mental exercises did suggest that these may be beneficial.

The studies in the review used labour- and resource-intensive cognitive training exercises. They did not assess more readily available puzzles such as crosswords or sudoku, as the headlines suggest. The studies in question appear to involve the level of cognition and memory equivalent to learning a foreign language, rather than simply filling out a crossword. So the headline that the “best way to boost your brainpower is a crossword or sudoku” is not accurate.

This may have been extrapolated from the suggestion by the researchers that further research is needed to address the potential impact of more readily accessible puzzles, such as crosswords.

While this research shows the state of the current evidence on the effects of treatments to prevent cognitive decline in older people, uncertainties remain. Further, high-quality evidence may well change our understanding of what can and cannot help prevent cognitive decline.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter.

Links To The Headlines

Forget popping pills - the best way to boost your brainpower is a crossword or sudoku. Mail Online, April 16 2013

Links To Science

Naqvi R, Liberman D, Rosenberg J, et al. Preventing cognitive decline in healthy older adults. Canadian Medical Association Journal. Published online April 15 2013

Much of the media is reporting on an interview given by broadcaster and journalist Andrew Marr, who is recovering from a stroke he had in January 2013.

In the interview, Marr explained that he had two 'mini-strokes' – or transient ischaemic attacks – the year before, but he "hadn't noticed".

Marr suggested that his stroke was triggered by vigorous exercise on a rowing machine, saying, "I'm frankly lucky to be alive".

But can exercise actually be bad for your health? It all depends on the type of exercise you are doing and your individual circumstances. It is worth noting that almost all of us can safely reduce our stroke risk through moderate exercise.

What are strokes and mini-strokes?

A stroke is a serious medical emergency where the supply of blood to the brain is disrupted. In over 80% of cases, strokes usually happen because a blood clot blocks the blood supply to the brain. They can also happen when a weakened blood vessel that supplies the brain bursts and causes brain damage, known as a haemorrhagic stroke.

From the account given in his interview, Andrew Marr could have had either an ischaemic or a haemorrhagic stroke: "I'd torn the carotid artery, which takes blood into the brain, and had a stroke overnight."

A mini-stroke, or transient ischaemic attack (TIA), is similar to a stroke but the symptoms only last a few minutes. Due to the short duration of symptoms, many people are unaware they have had a TIA, as was the case with Marr.

While not as serious as a stroke, a TIA is a serious warning sign that you need to make significant changes to your lifestyle or start taking medication, and usually both.

If left unaddressed, people who have had TIAs will often go on to have a full-blown stroke.

Is it unusual for men of Andrew Marr's age to have a stroke?

Strokes are uncommon, but certainly not rare in men in their fifties, like Andrew Marr. While the majority of strokes occur in over-65s, around one in four strokes occur in people under the age of 65.

The main risk factor for a haemorrhagic stroke is high blood pressure (hypertension) as the excess pressure can weaken the arteries in the brain and make them prone to splitting or rupturing.

In turn, risk factors for high blood pressure include:

• being overweight or obese
• smoking
• drinking excessive amounts of alcohol
• lack of exercise
• stress

Is Andrew Marr 'lucky to be alive'?

Yes. Even with prompt treatment a stroke can often be fatal. The fact that Andrew Marr left it until the next morning to seek treatment makes him extremely lucky to have lived to tell the tale.

Thankfully for Marr, he seems to be on the road to making a good recovery, although he has described difficulty walking. He does not appear to have developed the very serious after effects that often occur after a stroke, such as permanent physical disability and cognitive impairment.

Can exercise really cause a stroke?

Andrew Marr has described how he felt the symptoms of his stroke after he went on a rowing machine and "gave it everything I had". This, and other references to short bursts of intense exercise, suggests that he was undertaking some very vigorous exercise in the belief that this would benefit his health.

Most health advice actually focuses on simple, moderate levels of exercise, which raises the heart level and leaves you feeling slightly out of breath. Jogging, cycling and swimming are all good forms of moderate exercise. However, recent research has suggested that intense bursts of exercise may be just as good for you as the recommended 150 minutes per week of moderate exercise.

Almost everyone can safely take part in moderate exercise, and moderate exercise is one of the most effective and proven methods of reducing stroke risk. Just 30 minutes of moderate exercise five times a week can significantly reduce your risk of stroke.

Vigorous exercise is not safe or suitable for everyone. It is not usually recommended for people with a history of TIAs who have not received treatment to reduce their stroke risk.

If you have not been exercising regularly, it may be a good idea to first check with your GP that it is safe to take part in a course of vigorous exercise.

Despite the media emphasis on the stroke risk exercise could pose, it should also be borne in mind that Andrew Marr has said that he had been "heavily overworked". Stress is a known risk factor for high blood pressure, and it is possible that this may have played a part in his condition.

What do the experts say about Andrew Marr's stroke?

Nikki Hill, deputy director of communications for the Stroke Association, said: "We are delighted to see Mr Marr back on our screens. He's testimony to the recovery that is possible after stroke.

"Regular exercise is an important factor in stroke prevention and recovery. We have heard anecdotally that some activities like vigorous exercise can sometimes cause blood vessels to burst. We need more research on the underlying factors that might make that happen.

"We do know that high blood pressure itself is the single biggest cause of stroke. Until more research is done on specific triggers, we'd suggest getting your blood pressure checked and taking steps to keep it under control – exercise can help with that."

How can I reduce my stroke risk?

The best way of preventing a stroke is to eat a healthy diet, exercise regularly, avoid drinking too much and stop smoking.

It is never too late to take up exercise, eat more healthily, stop smoking or cut down on alcohol.

Read more about reducing your stroke risk.

Edited by NHS Choices. Follow Behind the Headlines on Twitter.

Links To The Headlines

Does Andrew Marr's stroke tell us it's time to slow down? The Daily Telegraph, April 14 2013

Andrew Marr's stroke caused by intense exercise. The Daily Telegraph, April 14 2013

Andrew Marr makes first TV appearance since stroke. The Guardian, April 14 2013

Andrew Marr says he's lucky to be alive after stroke. BBC News, April 14 2013

Andrew Marr says 'I'm lucky to be alive' following stroke. The Sun, April 14 2013

'I'm lucky to be alive,' says Andrew Marr as he makes first public appearance since suffering massive stroke which left him unable to walk. Daily Mail, April 14 2013

"A major breakthrough has been made by researchers seeking treatments for…illnesses such as Parkinson's disease," is the exciting news on the Mail Online website.

This headline is based on early stage research into the structure of an enzyme that has been implicated in the development of brain disorders including Alzheimer’s disease, Parkinson’s disease and Huntington's disease (a genetic condition that causes progressive loss of brain function).

The incidence of Alzheimer’s and Parkinson’s increases with age, and more people are being diagnosed with these conditions as the population ages. This rise, combined with the limitations of current treatment options for these and other ‘neurodegenerative diseases’, makes the search for effective therapies particularly important.

After years of work, scientists have discovered both the structure of this enzyme and a compound that has been shown to block the enzyme’s harmful effects. This makes the enzyme an attractive target for potential drug therapies for these diseases.

The compound that has been found to block the enzyme’s toxic effects is not currently suitable for use as a drug as it is too big to enter the brain. The study of both the compound and the enzyme’s structure should help in the ongoing quest to develop treatments.

Where did the story come from?

The study was carried out by researchers from the University of Manchester, the University of Leicester and other institutions in Portugal, France and Germany. No funding information was reported.

The study was published in the peer-reviewed journal Nature.

The research was covered by the Mail Online website and it provided a measured headline and reported on the study’s findings and implications well.

The 'breakthrough' claim may be overstating how important the findings are, although, in this case, the Mail Online was simply reflecting the researchers' own enthusiasm.

What kind of research was this?

This was laboratory research that sought to determine the structure of an enzyme thought to play a key role in the development of several degenerative brain disorders.

Scientists suspect that a particular ‘molecular pathway’ is involved in the development of conditions such as Huntington’s, Parkinson’s and Alzheimer’s disease.

Molecules produced by this ‘pathway’ (known as ‘metabolites’) have been noted for their effect on the brain. One particular metabolite (an enzyme called kynurenine 3-monooxygenase or KMO, which is produced in certain brain cells) has been previously identified as an attractive target for potential drug therapies for brain disorders.

Previous studies using yeast, fruit fly and mouse models of these conditions suggest that inhibiting the activity of KMO may improve certain symptoms associated with these neurodegenerative diseases.

Although these previous studies have shown that some known chemical compounds can block (inhibit) the activity of KMO, scientists do not know precisely how this occurs on a molecular level.

The current study sought to characterise how the inhibition occurs, and to provide a detailed description of the KMO enzyme in the hope that potentially effective drug compounds can be identified in the future.

This research is at a very early stage in the drug discovery and development process. While a potential drug target has been identified (KMO), scientists have yet to discover compounds or drugs that can interact with that target in a clinically meaningful way.

What did the research involve?

The researchers produced several versions of the enzyme KMO in an attempt to determine its molecular structure, both on its own and when bound to a compound called UPF 648. This compound has been used in previous laboratory and animal studies, and has been shown to inhibit KMO.

Unfortunately, UPF 648 is too large to pass between the blood and the cerebrospinal fluid (because of the blood-brain barrier), which is a vital characteristic for potential drugs directed at the brain.

What were the basic results?

After several attempts, the researchers were able to crystallise KMO on its own, and with UPF 648.

Having generated these ‘crystal structures’ of the enzyme and one of its inhibitors, the researchers hope to be able to screen known compounds with similar molecular structures to identify potential drug compounds that could pass the blood-brain barrier.

How did the researchers interpret the results?

The researchers concluded that discovery of KMO’s crystal structure, both on its own and with a known inhibitor, “is a major breakthrough for new KMO inhibitor design”.

Conclusion

This research represents an exciting development for scientists studying neurodegenerative disorders and those attempting to develop therapies for their treatment.

The researchers say that this new detailed knowledge of KMO’s structure and, in particular, knowledge about the binding of KMO and one of its inhibitors will allow for the development of screens that can sift through collections of chemicals to help identify other compounds that may both bind with KMO and pass the blood-brain barrier.

These new compounds could then be investigated as potential drugs targeting KMO for the treatment of diseases such as Huntington’s, Parkinson’s and Alzheimer’s.

It is important to remember that this is a very early stage of the drug development process. While a potential drug target has been identified, scientists have yet to discover, let alone develop, compounds or drugs that can effectively interact with that target.

This research serves as an important and useful step in the drug discovery process, but there are still many years of research ahead before this new knowledge may lead to drugs for these devastating illnesses.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter.

Links To The Headlines

Degenerative disease researchers make breakthrough in bid to find treatment for Parkinson's and Huntington's. Mail Online, April 10 2013

Brain disease breakthrough. Daily Express, April 11 2013

Links To Science

Amaral M, Levy C, Heyes DJ, et al. Structural basis of kynurenine 3-monooxygenase inhibition. Nature. Published online April 10 2013

“Appetite control could be rewired, say researchers”, BBC News reports, based on findings that it notes “could eventually offer a permanent solution for tackling obesity”.

The news comes from complex cellular research looking at a part of the brain called the hypothalamus, which helps regulate appetite.

This research confirms suggestions that the nerve cells in the hypothalamus are not ‘fixed’ from birth, but can be generated later. Researchers identified a type of cell known as ‘Fgf10-expressing tanycytes’ that could add new nerve cells to the hypothalamus after birth in mice.

This provides clues as to how this part of the brain could be adapted. The researchers suggest that this knowledge could eventually be used to develop novel treatments for obesity and other eating disorders.

However, these experiments were performed in mice, and the researchers did not investigate whether they could control the generation of new nerve cells to control the appetite of obese mice. For these reasons, any chance of ‘rewiring’ human appetite – as the researchers point out – is an incredibly long way off.

Where did the story come from?

The study was carried out by researchers from the University of East Anglia, UK; the University of Helsinki, Finland; University Justus Liebig, Germany; and the University of Los Angeles, US. It was funded by the Wellcome Trust.

The study was published in the peer-reviewed Journal of Neuroscience.

The story was covered by the BBC News, the Daily Express and the Mail Online. BBC News strikes an appropriate note of caution in its coverage and includes a quote from one of the researchers pointing out that this is just a single first step towards a possible, and by no means certain, treatment for obesity in humans.

The coverage in the Mail Online and the Express is a bit more excitable; with claims in their headlines that an ‘obesity pill’ may be available ‘within years’.

Although this research suggests the appetite and energy-balance regulating centres in the brain are not fixed at birth and could possibly adapt, a safe and effective ‘obesity pill’ in humans is still the stuff of science fiction, at least until further research is carried out. The genes and processes involved in this cell addition, and how they could be modified, need to be investigated first.

What kind of research was this?

This was animal-based research studying a type of cell found in the brain, called Fgf10-expressing tanycytes (Fgf stands for fibroblast growth factor-10).

The researchers wanted to see if Fgf10- expressing tanycytes could act in the same way as stem cells or progenitor cells in the production of new cells. They specifically wanted to see if they could stimulate formation of nerve cells (neurons) in a part of the brain called the hypothalamus, after birth. The hypothalamus regulates sleep cycles, appetite, thirst and other critical biological functions.

Some areas of the brain can change and adapt over the course of a lifetime (this is known as plasticity) while others remain relatively unchanged. Until recently it was thought that the majority of the nerve cells in hypothalamus were generated during the embryonic period. However, there is increasing evidence, that this study adds to, that new nerve cell formation occurs after birth and into adulthood.

Animal studies are ideal for investigating this type of question. However, further experimental studies will have to be performed in mice to find out which genes and processes are involved and whether these can be modified.

While it is likely that similar processes to those observed in mice occur in humans, this also needs to be confirmed. The ability to ‘rewire’ the human appetite seems a long way off.

What did the research involve?

The researchers looked at what happened to Fgf10- expressing tanycytes and their ‘daughter’ cells (new cells produced from Fgf10- expressing tanycytes) in the brains of mice.

What were the basic results?

The researchers found that Fgf10- expressing tanycytes resemble neuron stem cells and can divide and generate neurons and glial cells (cells that support and protect neurons).

The researchers found that Fgf10- expressing tanycytes continually add new neurons to the parts of the hypothalamus that regulate appetite and energy balance. Some of these cells expressed a signalling molecule involved in the regulation of appetite.

Some cells responded to fasting, as well as responding to signals from the hormone leptin, which inhibits appetite.

How did the researchers interpret the results?

The researchers conclude that this study provides evidence that new neurons grow in the hypothalamus after birth, into adulthood. They also conclude that they identified Fgf10- expressing tanycyte cells as a source of these neurons, and that these cells have a possible role in appetite and energy balance.

Conclusion

In this study, researchers identified a type of cell that – in mice – can add new nerve cells to the hypothalamus after birth. The new neurons were created in parts of the hypothalamus with a role in regulating appetite, energy balance and feeling full.

Some cells also expressed a signalling molecule involved in the regulation of appetite, and that some cells responded to fasting and signals from the hormone leptin (which inhibits appetite).

Until recently, it was thought all the nerve cells in the brain associated with appetite regulation were produced during the embryonic stage of development so the circuitry controlling appetite was believed to be ‘fixed’.

However, this new research adds to increasing evidence that new nerve cell formation occurs after birth, and into adulthood in the hypothalamus of mammals. Adding new cells could mean there may be ways to adapt appetite, energy balance and satiety, and if these processes could be modified, may lead to treatments for obesity and other eating disorders.

There are, however, a couple of points worth noting; firstly, the researchers did not investigate whether the creation of these additional cells actually had any effect on the appetite or weight of overweight or obese mice. It will also need to be determined if, and how, the process of cell generation in the hypothalamus could be modified. Secondly, and probably more importantly, results of animal studies do not necessarily ‘translate’ over into humans.

Further experimental studies will have to be performed in mice before any studies in humans could be considered. The ability to ‘rewire’ human appetite seems a long way off.  

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter.

Links To The Headlines

Appetite control could be rewired, say researchers. BBC News, April 6 2013

Obesity pill that re-wires the brain so it feels full could be available within years after scientific breakthrough. Mail Online, April 8 2013

Diet pill to re-wire the brain into feeling full. Daily Express, April 6 2013

Links To Science

Haan N, Goodman T, Najdi-Samiei A, et al. Fgf10-Expressing Tanycytes Add New Neurons to the Appetite/Energy-Balance Regulating Centers of the Postnatal and Adult Hypothalamus. The Journal of Neuroscience. Published online April 3 2013

BBC News reports that low levels of a particular protein may contribute to some of the characteristics of Down's syndrome. The news comes from a study that builds on previous research into the condition, which found abnormalities in the connections between nerve cells in the brains of people with Down's syndrome.

In this study, mice were genetically engineered to lack the protein (SNX27) involved in this nerve cell connection. The researchers found that mice lacking the protein were less able to learn and memorise how to navigate a maze.

Further examination of their brains showed that a lack of the protein led to a loss of certain chemical (glutamate) receptors involved in nerve cell connections. These connections were in areas of the brain thought to play an important role in learning and memory.

Similar examination of brain samples taken from people with Down's syndrome revealed that they also had reduced amounts of the SNX27 protein and a loss of glutamate receptors.

This research offers possible new insights into how chemical signalling between nerve cells may function in people with Down's syndrome, but it has no current implications for the treatment or prevention of the condition.

Where did the story come from?

The study was carried out by researchers from Sanford-Burnham Medical Research Institute, La Jolla, California, and other research institutions in the USA, China and Malaysia. The research received financial support from various sources, including the US National Institutes of Health.

It was published in the peer-reviewed journal Nature Medicine.

BBC News provided a simple, but accurate, summary of this complex research.

What kind of research was this?

Down's syndrome is a genetic condition where a person has an extra copy of chromosome 21. People affected by Down's syndrome usually have characteristic physical features, tend to have some degree of learning or developmental difficulty, and can also have various other medical problems, including heart conditions.

The reason why the chromosome abnormality occurs is not clear. The one idenitifed risk factor for the condition is maternal age – the older the mother, the higher the risk that her child will develop Down's syndrome. It is estimated that women aged 45 years old have a one in 30 chance of conceiving a child with the condition.

This current piece of research in mice centred on a type of protein called sorting nexin 27 (SNX27). SNX proteins are said to have a function in the connections between nerve cells in the brain. The researchers say that examination of the brains of humans affected by Down's syndrome, and a similar mouse model of the disease, revealed various abnormalities inside the brain. These abnormalities were associated with the connections between nerve cells, including:

• dendrites – the branches at the ends of the nerve cells
• synapses – the gaps that electrical signals are passed across to the next nerve cell

This research aimed to look at "a new role for SNX27 in the dysregulation of synaptic function in Down's syndrome" using mice genetically engineered to lack the SNX27 protein.

What did the research involve?

Initially the researchers looked at the brains of normal newborn mice to see how the SNX27 protein is produced inside the brain. They compared normal mice with those genetically engineered to lack protein SNX27, and found mice completely lacking the protein survived well after birth until 14 days. After this point their growth rate slowed, and they died by four weeks. Examination of their brains revealed they had degenerating nerve cells in the brain.

The researchers said that in the immediate period following birth, there is a period of increased brain development (specifically, dendritic branching and synapse formation) that is greatly compromised when the SNX27 protein is lacking.

Because mice genetically engineered to lack the SNX27 protein (labelled Snx27-/-) had such a limited lifespan, the researchers studied mice carrying just one copy of the gene that helps to make the protein (labelled Snx27+/-) so they could examine the effect of a lack of the protein on learning and memory. These mice had a similar life expectancy to the normal mice (labelled Snx27+/+).

The researchers set the mice behavioural tests, such as maze tests, to assess their learning and memory. They then examined the brains of Snx27+/- mice to look at the function of their nerve cells, focusing on the synaptic connections. Finally, the researchers examined brain samples from people with and without Down's syndrome to see if the observations from the mouse experiments were also seen in humans.

What were the basic results?

In the maze test, the researchers found that a week after training, Snx27+/- mice made more errors and had less spatial awareness than normal mice, and also spent less time exploring new objects. However, they were no different in terms of movement ability or vision.

When looking at brain samples from the Snx27+/- mice, they found that these mice had decreased chemical signalling across the synapses compared with normal mice. On further examination, the defect seemed to be on the 'postsynaptic' side.

This means there is a defect with the electrical signal being received by the next nerve cell, rather than a defect with the initial transmission of the electrical signal across the synapse.

They found that loss of the SNX27 protein leads to the breakdown of certain glutamate receptors in the postsynaptic nerve membranes.

When examining human brain samples, the researchers discovered that the amount of SNX27 protein and certain postsynaptic glutamate receptors were markedly decreased in the brains of people with Down's syndrome.

How did the researchers interpret the results?

The researchers conclude that a loss of SNX27 protein contributes to synaptic dysfunction by modulating the glutamate receptors. They say that their "identification of the role of SNX27 in synaptic function establishes a new molecular mechanism of Down's syndrome [disease development]".

Conclusion

This scientific research offers a new insight into how chemical signalling between nerve cells may function in some people with Down's syndrome. Dysfunction of the signalling between nerve cells has previously been suggested to play a role in various neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease.

The researchers say they plan further laboratory research exploring how a lack of SNX27 protein affects postsynaptic receptors.

However, this research does not provide the whole answer to the biological processes behind all of the developmental and physical characteristics of Down's syndrome.

Although the brain samples from people with Down's syndrome were also found to lack SNX27 protein and have reduced glutamate receptors, there may be other biochemical differences that this study has not explored.

Down's syndrome is complex, so it is unlikely that one protein or one chemical signalling pathway will be responsible for all the characteristics – many different biological process are likely to contribute.

The main limitation of this research is that it was mainly in mice. However, some of the experiments used samples of human brain. Further studies in humans are needed to further explore the biological underpinnings of Down's syndrome.

Despite being of scientific interest, this research has no immediate implications for the prevention of Down's syndrome, or for the treatment of any aspects of the condition. However, it does tell us more about the complex causes of this condition.

Research like this, which explores the underlying biology of Down's syndrome, could eventually lead to novel treatments for the condition. However, this is an aspiration rather than a certainty.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter.

Links To The Headlines

Down's syndrome 'linked to brain protein loss'. BBC News, March 24 2013

Links To Science

Wang X, Zhao Y, Zhang X, et al. Loss of sorting nexin 27 contributes to excitatory synaptic dysfunction by modulating glutamate receptor recycling in Down's syndrome. Nature Medicine. Published online March 24 2013

“Parkinson's drug 'helps' the elderly think younger and reap the rewards from the choices they make,” according to the Mail Online. It reports that as you age you lose the ability to learn from experiences, which can lead to poor decision making. But the drug levodopa, used to treat Parkinson’s disease, could help the elderly to think again in a ‘younger manner’, it says.

Researchers speculate that the lower levels of dopamine found as people grow older could be harmful to the part of the brain that judges whether choices lead to beneficial rewards. Levodopa can increase levels of dopamine, so researchers wanted to see if it improved decision making skills.

In this study, a small group of older people performed tasks where making the correct decision could win them money. The researchers then looked at the effect that dopamine treatment had on their performance. They also compared the performance of these older adults with 22 healthy young adults.

They found that half of the older people improved performance with levodopa, but there was no improvement in the other half.

The research doesn’t tell us much more than how ageing may affect the chemical processes of the brain. Levodopa is only licensed for use in Parkinson’s conditions. Given the side effects of the drug, and that in this small study it only gave some benefit to half the participants, it is very unlikely that its use would ever be extended to all older adults, simply to boost decision making.

Where did the story come from?

The study was carried out by researchers from University College London and other institutions in the UK and Europe. Funding was provided by the Wellcome Trust.

The study was published in the peer-reviewed Nature Neuroscience.

Overall, the Mail Online’s reporting takes this small scientific research study a step too far, suggesting that the Parkinson’s drug can be used to treat older adults to help improve their decision making. This was scientific research exploring the chemical processes in the brain and how they may affect decision making, but it certainly has no therapeutic implications. Levodopa is licensed only for the treatment of Parkinson’s disease and related conditions.

Even if the medication was found to be effective (which is unproven by this study) it is unlikely it would be used simply to aid decision making, as the small benefits of the drug are unlikely to outweigh the risks. Most people would be unwilling to tolerate the side effects that can occur after levodopa use, such as nausea, vomiting, tiredness and dizziness.

What kind of research was this?

The researchers’ report that older adults are worse at making decisions when there are outcomes with different probability of reward led them to question what accounts for this poor decision making. Evidence from previous human and animal study suggests that an area of the middle of the brain, called the nucleus accumbens, has a key role in any decisions that may involve the likelihood of potential rewards and pleasurable emotions.

The nucleus accumbens is targeted by the chemical dopamine. Previous studies of brain samples of older adults have shown that there is a loss of dopamine nerve cells in certain areas of the brain that increases with age. So the reduction in dopamine levels and the subsequent effects on the nucleus accumbens may be responsible for the poorer reward-based decision making associated with ageing.

The current research used a sample of healthy older adults and gave them a task where they had two choices. At the same time they had functional magnetic resonance images (fMRI) taken, which measures the blood flow in the brain to show what areas of the brain are active.

They also had another special type of MRI scan called diffusion tensor imaging (DTI), which can identify any areas of the brain that are lacking oxygen. For this reason DTI is useful for examining people who have had a stroke, but also is a good technique for looking at conditions involving the nerve fibres (white matter).

The researchers compared the results for the older adults with the results from a sample of adults in their 20s. They also examined the effect of a placebo or the chemical levadopa (L-dopa - which is converted to dopamine in the brain and used in the treatment of Parkinson’s disease) on the older adults’ performance in the tasks.

What did the research involve?

The study involved 32 healthy adults aged 65-75 years. These people attended the study centre on two occasions, one week apart, and performed the same task on both occasions. They were randomised to receive in random order either placebo or L-dopa (both mixed into an orange juice drink).

Participants performed five practise trials of the two-armed bandit task before performing the same task before placebo or L-dopa. The task involved being shown two images, selecting one of these and being shown what the monetary reward of this image was. They used statistical tests to compare task performance (how much money was won) under L-dopa or placebo, in addition to monitoring brain activity using fMRI and DTI. Participants were also monitored for any adverse effects of the drugs.

They also compared the performance of the older adults with 22 healthy young adults (average age 25 years) who performed the tasks without taking L-dopa or placebo.

What were the basic results?

The researchers found that the older adults had similar choice reaction times after taking L-dopa and placebo, but overall they had slower reaction times than the younger participants.

Overall there was also no significant difference in the amount of money won by the older participants when L-dopa was given compared to placebo. Fifteen older people won more money with L-dopa than placebo, and 17 won less with L-dopa than placebo. When they analysed in more detail the differences between these two groups they found that those with lower baseline task performance with no treatment (on placebo) improved when they were given L-dopa. However, those older adults who had higher baseline performance with no treatment did not improve with L-dopa.

Those older participants who improved with L-dopa then had similar task performance to the younger participants. Those who did not improve with L-dopa had similar task performance to the younger participants without treatment.

Of those who won more on L-dopa, L-dopa appeared to be improving their learning behaviour with successive tasks. Meanwhile, in those who did not perform better with L-dopa, the drug did not seem to be having any effect on their learning behaviour.

Looking at the fMRI images, the researchers found that older adults had less of a ‘reward prediction error’ signal in the nucleus accumbens. This reward prediction error is thought to be a spike in dopamine levels that occurs when the brain experiences an unexpected reward.

Using DTI to look at the dopamine nerves supplying the nucleus accumbens, they found that within individuals, the structure of their nerve connections was related to whether they had an RPE signal. In older adults with poorer nerve connections, giving L-dopa restored the RPE signal.
 
Four of the 32 older participants experienced vomiting a few hours after taking L-dopa, but they were still to take part in the tasks before experiencing this side effect.

How did the researchers interpret the results?

The researchers conclude that their results identify that chemical signalling problems in the dopamine nerves underlie the abnormal reward processing in older adults, and suggest that this problem can be modulated by the drug L-dopa.

Conclusion

Overall, this research is of scientific interest – it furthers our understanding how ageing may affect the chemical processes of the brain. Specifically it suggests that the reason our ability to make rewards-based choices declines as we age may, in part, be related to poor dopamine signalling to the nucleus accumbens.

However, this small study in 32 older adults tells us little more than that.

These older adults were healthy and were not reported to be suffering from any cognitive impairment. Their results cannot be generalised to all older adults, and not to those who may be suffering from neurodegenerative conditions such as Alzheimer’s disease.

While levodopa has been hailed by the media as a solution for making better decisions in older age, the drug is currently licensed only for conditions related to Parkinson’s disease. It is associated with adverse effects and would not be suitable for everyone. 

It should be noted that taking levodopa did not actually improve the decision-making ability of everyone – for half the older adults who had similar decision making ability to younger participants, taking levadopa reduced their decision making ability instead.

 It is highly unlikely that this will ever be offered as a treatment for every person over a particular age to preserve their decision making ability.

Overall, this research has no immediate implications for the prevention or treatment of cognitive decline or dementia in older adults.   

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on twitter.

Links To The Headlines

Parkinson's drug 'helps' the elderly think younger and reap the rewards from the choices they make. Mail Online, March 25 2013

Links To Science

Chowdhury R, Guitart-Masip M, Lambert C, et al. Dopamine restores reward prediction errors in old age. Nature Neuroscience. Published online March 24 2013