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Thursday, November 24, 2016

Obesity alters brain structure and function

November 23, 2016

It’s not just your waistline that suffers as you put on weight. Researchers are beginning to find puzzling new links between obesity, memory loss and dementia

 A growing body of evidence links obesity to brain inflammation, reduced brain volume, and memory deficits. Photo: Alamy

Lucy Cheke and her colleagues at the University of Cambridge recently invited a few participants into her lab for a kind of ‘treasure hunt’.
The participants navigated a virtual environment on a computer screen, dropping off various objects along their way. They then answered a series of questions to test their memory of the task, such as where they had hidden a particular object
When examining what might have influenced their performance, you might expect that Cheke would have been more concerned with the participant’s IQ – not their waistline. Yet she found a clear relationship between their Body Mass Index – a measure of your weight relative to your height – and apparent memory deficits: the higher a participant’s BMI, the worse they performed on the Treasure Hunt task.
In doing so, Cheke has contributed to a small but growing body of evidence showing that obesity is linked to brain shrinkage and memory deficits. This research suggests that obesity may contribute to the development of neurodegenerative conditions such as Alzheimer’s Disease.
Surprisingly, it also seems to show that the relationship between obesity and memory is a two-way street: being overweight or obese not only impacts on memory function, but may also affect future eating behaviour by altering our recollections of previous eating experiences.
Cheke’s interest in the subject began unexpectedly. “At the time I was looking at the ability to imagine a future state, particularly in terms of making decisions about food,” says Cheke. “If you’re hungry, you’ll imagine your future self as being hungry, too, but obese people seem to make such decisions on fact-based judgements rather than imagining.”
One possibility was that the obesity might have been damaging their capacity for “mental time travel”. Scientific research has long shown that memory and imagination are intimately linked, as we piece together fragments of past recollections to predict how future events might pan out.
The link made sense, she says, with some signs that obesity affects areas of the brain known to be used in memory and imagination. In 2010, for instance, researchers at Boston University School of Medicine reported that healthy, middle-aged adults with increased abdominal fat tend to have slightly lower overall brain volume. In particular, the hippocampus, a deep brain structure sometimes called the brain’s printing press thanks to its role learning and memory, was significantly smaller in obese people compared to leaner individuals.
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There were also some hints from animal studies. “In studies focusing on weight changes and eating behaviours in rodents, the animals were terrible at learning tasks such as the Morris water maze,” explains Cheke. “The more I looked into it, the more I expected to see memory deficits, but that question was still very much open.”
Hence her experiment with the treasure hunt. Sure enough the obese participants found it particularly difficult to remember the location of the different objects – adding some important evidence for her hypothesis, and supporting earlier findings that indirectly linked obesity to impairments of cognitive function.
More recently, a brain scanning study including more than 500 participants confirmed that being overweight or obese is associated with a greater degree of age-related brain degeneration. These effects were biggest in middle-aged people, in whom the obesity-related changes corresponded to an estimated increase in ‘brain age’ of 10 years
Obesity is a complex condition with many contributing factors, however; so exactly how it might affect brain structure and function is still unclear.
“Body fat is the defining feature of obesity, but you’ve also got things like insulin resistance, hypertension, and high blood pressure,” says Cheke. “These can go hand in hand with behavioural factors [such as overeating and lack of exercise] and they can all potentially cause changes in the brain.”
“For example, insulin is an important neurotransmitter, and there’s a lot of evidence that diabetes is associated with changes in learning and memory,” she adds, “but there’s also evidence that high body fat on its own leads to inflammation in the brain, which can also cause problems.”
Inflammation is another potential culprit. Psychologists from the University of Arizona examined data from more than 20,000 participants in the English Longitudinal Ageing Study, in which measures of memory, BMI, and blood plasma levels of an inflammatory marker called C-reactive protein were collected every 2 years between 1998 and 2013.
They found that greater body mass was associated with a decline in memory function, and also with higher levels of the inflammatory protein. Although these links are indirect, the results suggest that brain inflammation is one plausible mechanism by which differences in body mass might influence cognitive functionin otherwise healthy, aging adults. 
Animal studies support this idea. Alexis Stranahan of Augusta University and her colleagues surgically removed abdominal fat from obese mice then transplanted it into lean animals, and found that it induced brain inflammation, altered synaptic function, and cognitive deficits in the recipients. 
They went on to show that obesity activates microglia, the brain’s resident immune cells, to strip synapses from the hippocampus. This not only links the inflammation associated with obesity to the brain volume reductions seen in other studies, but also reveals the underlying cellular mechanism.Two-way street
This should be of particular concern, given recent evidence that the path between memory and obesity may go both ways, as attention and memory control our appetite and eating behaviour. In other words, a deficit in your memory could cause you to gain weight.
Early evidence that memory plays an important role in eating behaviour came from a 1998 study showing that patients with severe amnesia will readily eat multiple meals one after the other, because they could not remember that they had just eaten. 
“This shows that when we’re deciding how much to eat we’re not just basing those decisions on physiological signals about how much food there is in our stomach, but also on cognitive processes like memory,” says experimental psychologist Eric Robinson of the University of Liverpool.
“If your memory’s impaired or just not very good then you might overeat,” he adds. “I wanted to know if this could be reversed. If you improve a person’s memory, could that be a useful way of getting them to eat less?”
Robinson and his colleagues recruited 48 overweight or obese people and invited them to eat lunch in the lab. The participants were randomly divided into two groups, and given audio recordings to listen to while they ate.
Those in one group listened to audio instructing them to pay attention to their food, while those in the other listened to an audio book with non-food related content. 
The researchers then invited them back the following day, presented with some high-energy snacks, and measured how much they ate. They found that those who had been instructed to focus on their lunchtime meal the previous day ate nearly one third less of the snacks than those who had been distracted by the audio book.
A larger follow-up study confirmed these findings. This time, Robinson and his colleagues randomly assigned a total of 114 women to one of two groups, and tried to manipulate the extent to which they were aware of their eating behaviour.
Again, they gave all participants the same lunchtime meal, consisting of a ham sandwich, mini sausage rolls, a packet of crisps, rice cakes, chocolate chip cookies and seedless grapes.
Before sitting down to eat, the participants in one group were told that they were taking part in a study of eating behaviour, and that the amount of food they ate would be measured. The rest were told that they were taking part in a study of how their thought processes and moods change during the course of the day.
The researchers found no overall difference between how much participants in both groups ate. Those who had been told that they were taking part in a study of eating behaviour tended to eat fewer cookies than those in the other group, however, apparently because their awareness of their own food consumption was heightened.
each other, but they are closely linked – we cannot remember something that we did not pay attention to and, by the same token, our memories of something tend to be more vivid the more we attend to it.
It’s therefore possible that a vivid memory of lunch could reactivate the body’s physiological state, so that we do not feel so hungry, and consequently eat less at dinner. On the other hand, someone who was distracted during lunch would form weak memories of the meal, and so thinking about it at dinner might make them feel hungrier and eat more.
In one 2011 study, for instance, half the participants played Solitaire on a computer while eating their lunch. Sure enough, they had hazier memories of their lunch and went on to eat significantly more biscuits later on than those who did not.
This is particularly interesting, given the evidence that over-eating can impair your memory, with both the over-eating and the memory problems reinforcing each other, pushing you down a slippery slope. “Our research suggests that you might eat more if you have an impaired memory,” says Robinson, “so you end up in a vicious cycle where memory’s impaired by an unhealthy lifestyle, and then that impairment promotes over-consumption.”
He points out that we still have to be careful not to draw firm conclusions, though, until we have stronger proof that this vicious cycle exists and has a real effect on people’s health. “This idea makes sense intuitively, but there’s still no direct evidence for it.”

Staging an intervention

In the meantime, the finding that food memories and awareness can influence eating behaviour does at least suggest a novel way of helping people lose weightand maintain a healthy BMI, and Robinson and his colleagues have developed a smartphone app that encourages people to eat more attentively.
“There’s now convincing evidence that attention and memory affect how much people eat, but this comes from laboratory studies,” says Robinson.“We’re trying to see if the lab findings translate to the real world. Our app encourages people to take photos of what they’re eating and answer questions about their meals, the idea being that creating vivid memories will make them less likely to overeat during the day.”
Cheke and her colleagues are now following up their initial findings by trying to pick apart the various factors that contribute to obesity, in order to try to determine which are likely to influence brain structure and function.
They are also using a smartphone app to collect information about people’s lifestyles and behaviour, and are recruiting volunteers in and around Cambridge to help them gather the data they need.
“One person may be obese because they don’t do any exercise and eat a lot of junk food,” says Cheke. “Another might be obese for genetic reasons but actually eat really well and do lots of exercise, and yet another may be obese because they have insulin problems.”
“We’re trying to get all these different variables to see the relative contribution, so we’ve got people out wearing activity monitors and filling food diaries for us. Doing studies like this is the only way we’ll be able to tease these things apart.”
https://www.theguardian.com/science/neurophilosophy/2016/nov/23/obesity-alters-brain-structure-and-function

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