Sleep loss precedes Alzheimer’s symptoms

Sleep is disrupted in people who likely have early Alzheimer’s disease but do not yet have the memory loss or other cognitive problems characteristic of full-blown disease, researchers at Washington University School of Medicine in St. Louis report March 11 in JAMA Neurology.

The finding confirms earlier observations by some of the same researchers. Those studies showed a link in mice between sleep loss and brain plaques, a hallmark of Alzheimer’s disease. Early evidence tentatively suggests the connection may work in both directions: Alzheimer’s plaques disrupt sleep, and lack of sleep promotes Alzheimer’s plaques.

“This link may provide us with an easily detectable sign of Alzheimer’s pathology,” says senior author David M. Holtzman, MD, the Andrew B. and Gretchen P. Jones Professor and head of Washington University’s Department of Neurology. “As we start to treat people who have markers of early Alzheimer’s, changes in sleep in response to treatments may serve as an indicator of whether the new treatments are succeeding.”

Sleep problems are common in people who have symptomatic Alzheimer’s disease, but scientists recently have begun to suspect that they also may be an indicator of early disease. The new paper is among the first to connect early Alzheimer’s disease and sleep disruption in humans.

(Image: iStockphoto)

Sleep Discovery Could Lead to Therapies That Improve Memory

A team of sleep researchers led by UC Riverside psychologist Sara C. Mednick has confirmed the mechanism that enables the brain to consolidate memory and found that a commonly prescribed sleep aid enhances the process. Those discoveries could lead to new sleep therapies that will improve memory for aging adults and those with dementia, Alzheimer’s and schizophrenia.

The groundbreaking research appears in a paper, “The Critical Role of Sleep Spindles in Hippocampal-Dependent Memory: A Pharmacology Study,” published in the Journal of Neuroscience.

Earlier research found a correlation between sleep spindles — bursts of brain activity that last for a second or less during a specific stage of sleep — and consolidation of memories that depend on the hippocampus. The hippocampus, part of the cerebral cortex, is important in the consolidation of information from short-term to long-term memory, and spatial navigation. The hippocampus is one of the first regions of the brain damaged by Alzheimer’s disease.

Mednick and her research team demonstrated, for the first time, the critical role that sleep spindles play in consolidating memory in the hippocampus, and they showed that pharmaceuticals could significantly improve that process, far more than sleep alone.

In addition to Mednick the research team includes: Elizabeth A. McDevitt, UC San Diego; James K. Walsh, VA San Diego Healthcare System, La Jolla, Calif; Erin Wamsley, St. Luke’s Hospital, St. Louis, Mo.; Martin Paulus, Stanford University; Jennifer C. Kanady, Harvard Medical School; and Sean P.A. Drummond, UC Berkeley.

“We found that a very common sleep drug can be used to increase verbal memory,” said Mednick, the lead author of the paper that outlines results of two studies conducted over five years with a $651,999 research grant from the National Institutes of Health. “This is the first study to show you can manipulate sleep to improve memory. It suggests sleep drugs could be a powerful tool to tailor sleep to particular memory disorders.”

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Suzanne Dickson: Brain mechanisms of food reward

Studying what makes us want to eat, could help devise approaches to prevent obesity, which is becoming widespread in Europe.

Suzanne Dickson is a Professor of physiology and neuroendocrinology at the Institute of Neuroscience and Physiology, based at the Sahlgrenska Academy at the University of Gothenburg, Sweden. She tells youris.com about her involvement in the EU funded NeuroFAST project. Her focus is on the impact of appetite-regulating gut hormones on parts of the brain that influence food preference and food reward.

This research is also driven by the huge unmet need of treating the growing group of obese patients.

What is the focus of your work relating to food and the brain?
We work on food reward, which involves neurobiological circuits linked to the addiction process. We decided to work on this because increasing evidence linked excessive over-eating to brain pathways involved in reward, including pathways known to be targets for addictive drugs.  Over-eating can be influenced by genetic predisposition traits, psychiatric diseases, cues from the environment that trigger expectation of a food reward. Other factors include socio-economic pressures, stressful lifestyle including stress in the workplace or home.

What is the nature of food reward?
Our specific focus is on the property of the reward value. If animals find food rewarding, they will display altered behaviours that indicate that the reward value of the food is changed. Members of our team are working with sugars, fats and combinations of the above. We have also been working in clinical projects with foods of similar taste but with altered caloric value. By targeting brain mechanisms involved in food reward, we hope to reveal new mechanisms that will help develop new treatment strategies for obesity.

We have studied an area of the brain called ventral tegmental area (VTA) is a key node in the brain’s reward pathway. It is the home of the dopamine cells that are activated by rewards, including food rewards. Its role is very complex. Many believe that these cells are involved in food searching behaviours or food motivation, for example. However, they also can be activated simply by cues associated with foods akin to deciding to consume a chocolate bar by the sight of one at the cashier in a supermarket and novelty of the reward stimulus appears to play a role.

Did you identify the difference between the brain’s pleasure center and hunger center?
The pleasure centres are involved in food intake that is linked to its reward value. Whether we are hungry or fed, by raising the reward value of food the reward system encourages us to eat more, especially rewarding food. This system has been critical during the evolution process to ensure survival from famine. In our modern environment that generates obesity, food reward is no longer our friend as it encourages us to over-indulge in sweet and fatty food, even when we are not hungry.

By contrast, the hunger pathways can be considered more primitive. They detect and respond to nutrient deficit. If we enter negative energy balance, homeostatic pathways become activated informing higher feeding networks to initiate feeding behaviours.

What strategies have studied to try and find ways to limit over-eating?
We have recently learned from the field of bariatric—weight loss—surgery that it is possible to change reward behaviour towards food. This involves unknown mechanisms that are likely linked to the brain’s food reward system. We focus particularly on a hormone called ghrelin whose secretion is altered after bariatric surgery. We hope to reveal new information that is of clinical and therapeutic relevance for future drug strategies for this disease area.

So far, in the laboratory, we have learned a lot about the basic brain mechanisms controlling food reward and the role played by gut hormones in regulating these. We therefore know a lot more about mechanisms—namely about the brain systems and circuits underpinning over-eating—especially for calorie dense foods.

(Image credit: Zorrilla Laboratory, The Scripps Research Institute)

Monday’s medical myth: alcohol kills brain cells

Do you ever wake up with a raging hangover and picture the row of brain cells that you suspect have have started to decay? Or wonder whether that final glass of wine was too much for those tiny cells, and pushed you over the line?

Well, it’s true that alcohol can indeed harm the brain in many ways. But directly killing off brain cells isn’t one of them.

The brain is made up of nerve cells (neurons) and glial cells. These cells communicate with each other, sending signals from one part of the brain to the other, telling your body what to do. Brain cells enable us to learn, imagine, experience sensation, feel emotion and control our body’s movement.

Alcohol’s effects can be seen on our brain even after a few drinks, causing us to feel tipsy. But these symptoms are temporary and reversible. The available evidence suggests alcohol doesn’t kill brain cells directly.

There is some evidence that moderate drinking is linked to improved mental function. A 2005 Australian study of 7,500 people in three age cohorts (early 20s, early 40s and early 60s) found moderate drinkers (up to 14 drinks for men and seven drinks for women per week) had better cognitive functioning than non-drinkers, occasional drinkers and heavy drinkers.

But there is also evidence that even moderate drinking may impair brain plasticity and cell production. Researchers in the United States gave rats alcohol over a two-week period, to raise their alcohol blood concentration to about 0.08. While this level did not impair the rats’ motor skills or short-term learning, it impacted the brain’s ability to produce and retain new cells, reducing new brain cell production by almost 40%. Therefore, we need to protect our brains as best we can.

Excessive alcohol undoubtedly damages brain cells and brain function. Heavy consumption over long periods can damage the connections between brain cells, even if the cells are not killed. It can also affect the way your body functions. Long-term drinking can cause brain atrophy or shrinkage, as seen in brain diseases such as stroke and Alzheimer’s disease.

There is debate about whether permanent brain damage is caused directly or indirectly.

We know, for example, that severe alcoholic liver disease has an indirect effect on the brain. When the liver is damaged, it’s no longer effective at processing toxins to make them harmless. As a result, poisonous toxins reach the brain, and may cause hepatic encephalopathy (decline in brain function). This can result in changes to cognition and personality, sleep disruption and even coma and death.

Alcoholism is also associated with nutritional and absorptive deficiencies. A lack of Vitamin B1 (thiamine) causes brain disorders called Wernicke’s ncephalopathy (which manifests in confusion, unsteadiness, paralysis of eye movements) and Korsakoff’s syndrome (where patients lose their short-term memory and coordination).

So, how much alcohol is okay?

To reduce the lifetime risk of harm from alcohol-related disease or injury, the National Health and Medical Research Council recommends healthy adults drink no more than two standard drinks on any day. Drinking less frequently (such as weekly rather than daily) and drinking less on each occasion will reduce your lifetime risk.

To avoid alcohol-related injuries, adults shouldn’t drink more than four standard drinks on a single occasion. This applies to both sexes because while women become intoxicated with less alcohol, men tend to take more risks and experience more harmful effects.

For pregnant women and young people under the age of 18, the guidelines say not drinking is the safest option.

So while alcohol may not kill brain cells, if this myth encourages us to rethink that third beer or glass of wine, I won’t mind if it hangs around.

You’re such a jerk

If that headline makes you feel bad, an expert says it’s because we’re genetically wired to take offense.

Insults are painful because we have certain social needs. We seek to be among other people, and once among them, we seek to form relationships with them and to improve our position on the social hierarchy. They are also painful because we have a need to project our self-image and to have other people not only accept this image, but support it. If we didn’t have these needs, being insulted wouldn’t feel bad. Furthermore, although different people experience different amounts of pain on being insulted, almost everyone will experience some pain. Indeed, we would search long and hard to find a person who is never pained by insults—or who himself never feels the need to insult others.

These observations raise a question: why do we have the social needs we do? According to evolutionary psychologists, our social needs—and, more generally, our psychological propensities—are the result of nature rather than nurture. More precisely, they are a consequence of our evolutionary past. The views of evolutionary psychologists are of interest in this, a study of insults, for the simple reason that they allow us to gain a deeper understanding of why it is painful when others insult us and why we go out of our way to cause others pain by insulting them.

We humans find some things to be pleasant and other things to be unpleasant. We find it pleasant, for example, to eat sweet, fattening foods or to have sex, and we find it unpleasant to be thirsty, swallow bitter substances, or get burned. Notice that we don’t choose for these things to be pleasant or unpleasant. It is true that we can, if we are strong-willed, voluntarily do things that are unpleasant, such as put our finger in a candle flame. We can also refuse to do things that are pleasant: we might, for example, forgo opportunities to have sex. But this doesn’t alter the basic biological fact that getting burned is painful and having sex is pleasurable. Whether or not an activity is pleasant is determined, after all, by our wiring, and we do not have it in our power—not yet, at any rate—to alter this wiring.

Why are we wired to be able to experience pleasure and pain? Why aren’t we wired to be immune to pain while retaining our ability to experience pleasure? And given that we possess the ability to experience both pleasure and pain, why do we find a particular activity to be pleasant rather than painful? Why, for example, do we find it pleasant to have sex but unpleasant to get burned? Why not the other way around? I have given the long answer to these questions elsewhere. For our present purposes—namely, to explain why we have the social needs we do—the short answer will suffice.

We have the ability to experience pleasure and pain because our evolutionary ancestors who had this ability were more likely to survive and reproduce than those who didn’t. Creatures with this ability could, after all, be rewarded (with pleasurable feelings) for engaging in certain activities and punished (with unpleasant feelings) for engaging in others. More precisely, they could be rewarded for doing things (such as having sex) that would increase their chances of surviving and reproducing, and be punished for doing things (such as burning themselves) that would lessen their chances.

This makes it sound as if a designer was responsible for our wiring, but evolutionary psychologists would reject this notion. Evolution, they would remind us, has no designer and no goal. To the contrary, species evolve because some of their members, thanks to the genetic luck-of-the-draw, have a makeup that increases their chances of surviving and reproducing. As a result, they (probably) have more descendants than genetically less fortunate members of their species. And because they spread their genes more effectively, they have a disproportionate influence on the genetic makeup of future members of their species.

Evolutionary psychologists would go on to remind us that if our evolutionary ancestors had found themselves in a different environment, we would be wired differently and as a result would find different things to be pleasant and unpleasant. Suppose that getting burned, rather than being detrimental to our evolutionary ancestors, had somehow increased their chances of surviving and reproducing. Under these circumstances, those individuals who were wired so that it felt good to get burned would have been more effective at spreading their genes than those who were wired so that it felt bad. And as a result we, their descendants, would also be wired so that it felt good to get burned.

Evolutionary psychologists would also remind us that the evolutionary process is imperfect. For one thing, although the wiring we inherited from our ancestors might have allowed them to flourish on the savannahs of Africa, it isn’t optimal for the rather different environment in which we today find ourselves. Our ancestors who had a penchant for consuming sweet, fattening foods, for example, were less likely to starve than those who didn’t. The problem is that we who have inherited that penchant live in an environment in which sweet, fattening foods are abundant. In this environment, being wired so that it is pleasant to consume, say, ice cream, increases our chance of getting heart disease and other illnesses, and thereby arguably lessens our chance of surviving.

The Hidden Costs of Cognitive Enhancement

Gentle electrical zaps to the brain can accelerate learning and boost performance on a wide range of mental tasks, scientists have reported in recent years. But a new study suggests there may be a hidden price: Gains in one aspect of cognition may come with deficits in another.

Researchers who study transcranial electrical stimulation, which uses electrodes placed on the scalp, see it as a potentially promising way to enhance cognition in neurological patients, struggling students, and perhaps even ordinary people. Scientists have used it to speed up rehab in people whose speech or movement has been affected by a stroke, and DARPA has studied it as a way to accelerate learning in intelligence analysts or soldiers on the lookout for bad guys and bombs.

Until now, the papers coming out of this field have reported one good-news finding after another.

“This is the first paper to my knowledge to show a cost associated with the gains in cognitive function,” said neuropsychologist Rex Jung of the University of New Mexico, who was not associated with the study. “It’s a really nice demonstration.”

Cognitive neuroscientist Roi Cohen Kadosh of the University of Oxford, who led the study, has been investigating brain stimulation to boost mathematical abilities. He has applied for a patent on a brain stimulator he hopes could help math-challenged students get a better grip on the basics, or even help the mathematically inclined perform even better.

Cohen Kadosh and his colleague Teresa Iuculano investigated 19 volunteers as they learned a new numerical system by trial and error. The new system was based on arbitrary symbols: A cylinder represented the number five, for example, and a triangle represented the number nine. In several training sessions the volunteers viewed pairs of symbols on a computer screen and pressed a key to indicate which one represented a bigger quantity. At first they had to guess, but they eventually learned which symbols corresponded with which numbers.

All of the volunteers wore electrodes on their scalp during these training session. Some received mild electrical stimulation that targeted the posterior parietal cortex, an area implicated in previous studies of numerical cognition. Others received stimulation of the dorsolateral prefrontal cortex, an area involved in a wide range of functions, including learning and memory. A third group received sham stimulation that caused a slight tingling of the skin but no change in brain activity.

Those who had the parietal area involved in numerical cognition stimulated learned the new number system more quickly than those who got sham stimulation, the researchers report in the Journal of Neuroscience. But at the end of the weeklong study their reaction times were slower when they had to put their newfound knowledge to use to solve a new task that they hadn’t seen during the training sessions. ”They had trouble accessing what they’d learned,” Cohen Kadosh said.

The volunteers who had the prefrontal area involved in learning and memory stimulated showed the opposite pattern. They were slower than the control group to learn the new numerical system, but they performed faster on the new test at the end of the experiment. The bottom line, says Cohen Kadosh, is that stimulating either brain region had both benefits and drawbacks. ”Just like with drugs, there seem to be side effects,” he said.

Going forward, Cohen Kadosh says, more work is needed on how to maximize the benefits and minimize the costs of electrical brain stimulation. He thinks the approach has promise, but only when it’s used strategically, by picking the right brain regions to target and stimulating them while a person is training on the skill they want to improve. ”I think it’s going to be useless unless you pair it with some type of cognitive training,” he said.

But that’s not stopping some people from giving it a try on their own. Although it should be obvious that DIY brain stimulation is a bad idea, both Jung and Cohen Kadosh say there seems to be growing interest in the general public in using it for cognitive enhancement.

“There are some do it yourself websites I’ve stumbled across that are pretty frightening,” Jung said. “People are definitely tinkering around with this in their garage.”

The new study suggests one way that could backfire. And that’s not all, said Jung. ”You can burn yourself if nothing else.”