Reducing caloric intake delays nerve cell loss

Activating an enzyme known to play a role in the anti-aging benefits of calorie restriction delays the loss of brain cells and preserves cognitive function in mice, according to a study published in the May 22 issue of The Journal of Neuroscience. The findings could one day guide researchers to discover drug alternatives that slow the progress of age-associated impairments in the brain.

Previous studies have shown that reducing calorie consumption extends the lifespan of a variety of species and decreases the brain changes that often accompany aging and neurodegenerative diseases such as Alzheimer’s. There is also evidence that caloric restriction activates an enzyme called Sirtuin 1 (SIRT1), which studies suggest offers some protection against age-associated impairments in the brain.

In the current study, Li-Huei Tsai — director of the Picower Institute for Learning and Memory and Picower Professor of Neuroscience at MIT — along with postdoc Johannes Gräff and others at MIT tested whether reducing caloric intake would delay the onset of nerve cell loss that is common in neurodegenerative disease, and if so, whether SIRT1 activation was driving this effect. The group not only confirmed that caloric restriction delays nerve cell loss, but also found that a drug that activates SIRT1 produces the same effects.

“There has been great interest in finding compounds that mimic the benefits of caloric restriction that could be used to delay the onset of age-associated problems and/or diseases,” says Dr. Luigi Puglielli, who studies aging at the University of Wisconsin, Madison, and was not involved in this study. “If proven safe for humans, this study suggests such a drug could be used as a preventive tool to delay the onset of neurodegeneration associated with several diseases that affect the aging brain.”

In the study, Tsai’s team first decreased the normal diets of mice genetically engineered to rapidly undergo changes in the brain associated with neurodegeneration by 30 percent. Following three months on the diet, the mice completed several learning and memory tests. “We not only observed a delay in the onset of neurodegeneration in the calorie-restricted mice, but the animals were spared the learning and memory deficits of mice that did not consume reduced-calorie diets,” Tsai says.

Curious if they could recreate the benefits of caloric restriction without changing the animals’ diets, the scientists gave a separate group of mice a drug that activates SIRT1. Similar to what the researchers found in the mice exposed to reduced-calorie diets, the mice that received the drug had less cell loss and better cellular connectivity than the mice that did not receive the drug. Additionally, the mice that received the drug treatment performed as well as normal mice in learning and memory tests.

“The question now is whether this type of treatment will work in other animal models, whether it’s safe for use over time, and whether it only temporarily slows down the progression of neurodegeneration or stops it altogether,” Tsai says.

B vitamins could delay dementia

Despite spending billions of dollars on research and development, drug companies have been unable to come up with effective treatments for dementia and Alzheimer’s Disease (AD). Now, A. David Smith at the University of Oxford and his colleagues have discovered that, in some patients experiencing mild cognitive impairment (MCI), a cocktail of high-dose B vitamins could prevent gray matter loss associated with progression to AD. The study appears in the Proceedings of the National Academy of Sciences.

The World Health Organization predicts that between 2010 and 2050 the number of dementia cases will increase from 26 million to 115 million worldwide. Although there is an urgent demand for treatment, pharmaceutical companies have been unable to develop drugs that will delay or cure dementia. So far, approved drugs merely ease symptoms.

Smith and his team wanted to see if B vitamins reduced the risk of AD by lowering total homocysteine (tHcy) levels. There is a positive correlation between high tHcy levels and risk of cognitive impairment and AD.

The researchers studied 156 subjects over 70 in Oxford, England who suffered from MCI. The subjects received either a placebo or a high-dose B vitamin cocktail consisting of 20 milligrams of vitamin B6, 0.5 milligrams of vitamin B12 and 0.8 milligrams of folic acid.

Over a two-year period, subjects in both the experimental and control groups lost gray matter in the medial temporal, lateral temporoparietal and occipital regions and in the anterior and posterior cingulate cortex.

However, those receiving B vitamin treatment experienced significantly less atrophy in regions of the brain most affected in people with AD and people with MCI who go on to develop AD. These include the bilateral hippocampus, the parahippocampal gyrus, the retrosplenial precuneus, the lingual gyrus, the fusiform gyrus and the cerebellum. The placebo group experienced a 3.7 percent loss of gray matter in these regions, compared with a 0.5 percent loss among the experimental group.

When they looked at baseline tHcy levels, Smith and his colleagues found that B-vitamin treatment did not significantly reduce gray matter atrophy among subjects with tHcy levels below the median. The B-vitamin cocktail did have a significant effect on high-tHcy participants: those receiving the cocktail experienced only a 0.6 percent loss of gray matter, while high-tHcy participants in the placebo group experienced a 5.2 percent loss.

The team found a correlation between gray matter loss and worsening of scores on tests that measure cognitive function.

A causal Bayesian network analysis showed that B vitamins lower tHcy levels. This decreases gray matter atrophy, which delays cognitive decline.

Drugs found to both prevent and treat Alzheimer’s disease in mice

Researchers at USC have found that a class of pharmaceuticals can both prevent and treat Alzheimer’s Disease in mice.

The drugs, known as “TSPO ligands,” are currently used for certain types of neuroimaging.

"We looked at the effects of TSPO ligand in young adult mice when pathology was at an early stage, and in aged mice when pathology was quite severe," said lead researcher Christian Pike of the USC Davis School of Gerontology. "TSPO ligand reduced measures of pathology and improved behavior at both ages."

The team’s findings were published online by the Journal of Neuroscience on May 15. Pike’s coauthors include USC postdoctoral scientists Anna M. Barron, Anusha Jayaraman and Joo-Won Lee; as well as Donatella Caruso and Roberto C. Melcangi of the University of Milan and Luis M. Garcia-Segura of the Instituto Cajal in Spain.

The most surprising finding for Pike and his team was the effect of TSPO ligand in the aged mice. Four treatments—once per week over four weeks—in older mice resulted in a significant decrease of Alzheimer’s-related symptoms and improvements in memory – meaning that TSPO ligands may actually reverse some elements of Alzheimer’s disease.

"Our data suggests the possibility of drugs that can prevent and treat Alzheimer’s," Pike said. "It’s just mouse data, but extremely encouraging mouse data. There is a strong possibility that TSPO ligands similar to the ones used in our study could be evaluated for therapeutic efficacy in Alzheimer’s patients within the next few years."

Next, the team will next focus on understanding how TSPO ligands reduce Alzheimer’s disease pathology. Building on the established knowledge that TSPO ligands can reduce inflammation—shielding nerve cells from injury and increasing the production of neuroactive hormones in the brain—the team will study which of these actions is the most significant in fighting Alzheimer’s disease so they can develop newer TSPO ligands accordingly.

Waiting for a sign? Researchers find potential brain ‘switch’ for new behavior

You’re standing near an airport luggage carousel and your bag emerges on the conveyor belt, prompting you to spring into action. How does your brain make the shift from passively waiting to taking action when your bag appears?

A new study from investigators at the University of Michigan and Eli Lilly may reveal the brain’s “switch” for new behavior. They measured levels of a neurotransmitter called acetylcholine, which is involved in attention and memory, while rats monitored a screen for a signal. At the end of each trial, the rat had to indicate if a signal had occurred.

Researchers noticed that if a signal occurred after a long period of monitoring or “non-signal” processing, there was a spike in acetylcholine in the rat’s right prefrontal cortex. No such spike occurred for another signal occurring shortly afterwards.

"In other words, the increase in acetylcholine seemed to activate or ‘switch on’ the response to the signal, and to be unnecessary if that response was already activated," said Cindy Lustig, one of the study’s senior authors and an associate professor in the U-M Department of Psychology.

The researchers repeated the study in humans using functional magnetic resonance imaging (fMRI), which measures brain activity, and also found a short increase in right prefrontal cortex activity for the first signal in a series.

To connect the findings between rats and humans, they measured changes in oxygen levels, similar to the changes that produce the fMRI signal, in the brains of rats performing the task.

They again found a response in the right prefrontal cortex that only occurred for the first signal in a series. A follow-up experiment showed that direct stimulation of brain tissue using drugs that target acetylcholine receptors could likewise produce these changes in brain oxygen.

Together, the studies’ results provide some of the most direct evidence, so far, linking a specific neurotransmitter response to changes in brain activity in humans. The findings could guide the development of better treatments for disorders in which people have difficulty switching out of current behaviors and activating new ones. Repetitive behaviors associated with obsessive-compulsive disorder and autism are the most obvious examples, and related mechanisms may underlie problems with preservative behavior in schizophrenia, dementia and aging.

The findings appear in the current issue of Journal of Neuroscience.

UCSB Study Shows Where Scene Context Happens in our Brain

In a remote fishing community in Venezuela, a lone fisherman sits on a cliff overlooking the southern Caribbean Sea. This man –– the lookout –– is responsible for directing his comrades on the water, who are too close to their target to detect their next catch. Using abilities honed by years of scanning the water’s surface, he can tell by shadows, ripples, and even the behavior of seabirds, where the fish are schooling, and what kind of fish they might be, without actually seeing the fish. This, in turn, changes where the boats go, and how the men fish.

Though a seemingly simple and intuitive strategy, the lookout’s visual search function –– a process that takes mere seconds for the human brain –– is still something that a computer, despite technological advances, can’t do as accurately.

"Behind what seems to be automatic is a lot of sophisticated machinery in our brain," said Miguel Eckstein, professor in UC Santa Barbara’s Department of Psychological & Brain Sciences. "A great part of our brain is dedicated to vision."

Over the millennia of human evolution, our brains developed a pattern of search based largely on environmental cues and scene context. It’s an ability that has not only helped us find food and avoid danger in humankind’s earliest days, but continues to aid us today, in tasks as banal as driving to work, or shopping; or as specialized as reading X-rays.

Where this –– the search for objects using scene and other objects –– occurs in the brain is little understood, and is for the first time discussed in the paper, “Neural Representations of Contextual Guidance in Visual Search of Real-World Scenes,” published recently in the Journal of Neuroscience.

The researchers flashed hundreds images of indoor and outdoor scenes before observers, and instructed them to search for certain objects that were consistent with those scenes. Half of the images, however, did not contain the target object. During the trials, the subjects were asked to indicate whether the target object was present in the scene.

The researchers were particularly interested in the images that did not contain the target. Another measure was taken to determine where subjects expected specific objects to be in target-absent scenes. Invariably, the subjects would indicate similar areas: If presented with a living room scene and told to look for a clock or a painting, they would indicate the wall; if shown a photo of a bathroom and told to indicate where to expect a hand soap or toothbrush, they would indicate the sink.

The searched object’s contextual location in the scenes, according to the study, is represented in the area called the lateral occipital complex (LOC), a place that corresponds roughly to the lower back portion of the head, toward the side. This area, according to Eckstein, has the ability to account for other objects in the scene that often appear in close spatial proximity with the searched object –– something computers are only recently being taught to do.

"So, if you’re looking for a computer mouse on a cluttered desk, a machine would be looking for things shaped like a mouse. It might find it, but it might see other objects of similar shape, and classify that as a mouse," Eckstein said. Computer vision systems might also not associate their target with specific locations or other objects. So, to a machine, the floor is just as likely a place for a mouse as a desk.

The LOC, on the other hand, would contain the information the brain needs to direct a person’s attention and gaze first toward the most likely place that a mouse might be, such as on top of the desk, or near the keyboard. From there, other visual parts of the brain go to work, searching for particular characteristics, or determining the target’s presence.

So strong is the scene context in biasing search, said Eckstein, that if another similar-looking object was placed in the location where the mouse is likely to be, and that scene briefly flashed before your eyes, you would likely –– erroneously –– interpret that object as the mouse.

While scene context information has been found highly active in the LOC, other visual areas of the brain are also influenced by context to certain degrees, including the interparietal sulcus, located near the top of the head; and the retrosplenial cortex, found in the brain’s interior.

"Since contextual guidance is a critical strategy that allows humans to rapidly find objects in scenes, studying the brain areas involved in normal humans might help us to gain a better understanding of neural areas involved in those with visual search deficits, such as brain-damaged patients and the elderly," Eckstein said. "Also, a large component of becoming an expert searcher –– like radiologists or fishermen –– is exploiting contextual relationships to search. Thus, understanding the neural basis of contextual guidance might allow us to gain a better understanding about what brain areas are critical to gain search expertise."

Mediterranean diet seems to boost ageing brain power

A Mediterranean diet with added extra virgin olive oil or mixed nuts seems to improve the brain power of older people better than advising them to follow a low-fat diet, indicates research published online in the Journal of Neurology Neurosurgery and Psychiatry.

The authors from the University of Navarra in Spain base their findings on 522 men and women aged between 55 and 80 without cardiovascular disease but at high vascular risk because of underlying disease/conditions.

These included either type 2 diabetes or three of the following: high blood pressure; an unfavourable blood fat profile; overweight; a family history of early cardiovascular disease; and being a smoker.

Participants, who were all taking part in the PREDIMED trial looking at how best to ward off cardiovascular disease, were randomly allocated to a Mediterranean diet with added olive oil or mixed nuts or a control group receiving advice to follow the low-fat diet typically recommended to prevent heart attack and stroke

A Mediterranean diet is characterised by the use of virgin olive oil as the main culinary fat; high consumption of fruits, nuts, vegetables and pulses; moderate to high consumption of fish and seafood; low consumption of dairy products and red meat; and moderate intake of red wine.

Participants had regular check-ups with their family doctor and quarterly checks on their compliance with their prescribed diet.

After an average of 6.5 years, they were tested for signs of cognitive decline using a Mini Mental State Exam and a clock drawing test, which assess higher brain functions, including orientation, memory, language, visuospatial and visuoconstrution abilities and executive functions such as working memory, attention span, and abstract thinking.

At the end of the study period, 60 participants had developed mild cognitive impairment: 18 on the olive oil supplemented Mediterranean diet; 19 on the diet with added mixed nuts; and 23 on the control group.

A further 35 people developed dementia: 12 on the added olive oil diet; six on the added nut diet; and 17 on the low fat diet.

The average scores on both tests were significantly higher for those following either of the Mediterranean diets compared with those on the low fat option.

These findings held true irrespective of other influential factors, including age, family history of cognitive impairment or dementia, the presence of ApoE protein—associated with Alzheimer’s disease—educational attainment, exercise levels, vascular risk factors; energy intake and depression.

The authors acknowledge that their sample size was relatively small, and that because the study involved a group at high vascular risk, it doesn’t necessarily follow that their findings are applicable to the general population.

But they say, theirs is the first long term trial to look at the impact of the Mediterranean diet on brain power, and that it adds to the increasing body of evidence suggesting that a high quality dietary pattern seems to protect cognitive function in the ageing brain.

Practice makes perfect? Not so much

Turns out, that old “practice makes perfect” adage may be overblown.

New research led by Michigan State University’s Zach Hambrick finds that a copious amount of practice is not enough to explain why people differ in level of skill in two widely studied activities, chess and music.

In other words, it takes more than hard work to become an expert. Hambrick, writing in the research journal Intelligence, said natural talent and other factors likely play a role in mastering a complicated activity.

“Practice is indeed important to reach an elite level of performance, but this paper makes an overwhelming case that it isn’t enough,” said Hambrick, associate professor of psychology.

The debate over why and how people become experts has existed for more than a century. Many theorists argue that thousands of hours of focused, deliberate practice is sufficient to achieve elite status.

Hambrick disagrees.

“The evidence is quite clear,” he writes, “that some people do reach an elite level of performance without copious practice, while other people fail to do so despite copious practice.”

Hambrick and colleagues analyzed 14 studies of chess players and musicians, looking specifically at how practice was related to differences in performance. Practice, they found, accounted for only about one-third of the differences in skill in both music and chess.

So what made up the rest of the difference?

Based on existing research, Hambrick said it could be explained by factors such as intelligence or innate ability, and the age at which people start the particular activity. A previous study of Hambrick’s suggested that working memory capacity – which is closely related to general intelligence – may sometimes be the deciding factor between being good and great.

While the conclusion that practice may not make perfect runs counter to the popular view that just about anyone can achieve greatness if they work hard enough, Hambrick said there is a “silver lining” to the research.

“If people are given an accurate assessment of their abilities and the likelihood of achieving certain goals given those abilities,” he said, “they may gravitate toward domains in which they have a realistic chance of becoming an expert through deliberate practice.”

New study finds blind people have the potential to use their ‘inner bat’ to locate objects

New research from the University of Southampton has shown that blind and visually impaired people have the potential to use echolocation, similar to that used by bats and dolphins, to determine the location of an object.

The study, which is published in the journal Hearing Research, examined how hearing, and particularly the hearing of echoes, could help blind people with spatial awareness and navigation. The study also examined the possible effects of hearing impairment and how to optimise echolocation ability in order to help improve the independence and quality of life of people with visual impairments.

Researchers from the University of Southampton’s Institute of Sound and Vibration Research (ISVR) and University of Cyprus conducted a series of experiments with sighted and blind human listeners, using a ‘virtual auditory space’ technique, to investigate the effects of the distance and orientation of a reflective object on ability to identify the right-versus-left position of the object. They used sounds with different bandwidths and durations (from 10–400 milliseconds) as well as various audio manipulations to investigate which aspects of the sounds were important. The virtual auditory space, which was created in ISVR’s anechoic chamber, allowed researchers to remove positional clues unrelated to echoes, such as footsteps and the placement of an object, and to manipulate the sounds in ways that wouldn’t be possible otherwise (e.g. get rid of the emission and present the echo only).

Dr Daniel Rowan, Lecturer in Audiology in ISVR and lead author of the study, says: “We wanted to determine unambiguously whether blind people, and perhaps even sighted people, can use echoes from an object to determine roughly where the object is located. We also wanted to figure out what factors facilitate and restrict people’s abilities to use echoes for this purpose in order to know how to enhance ability in the real world.”

The results showed that both sighted and blind people with good hearing, even if completely inexperienced with echolocation, showed the potential to use echoes to tell where objects are. The researchers also found that hearing high-frequency sounds (above 2 kHz) is required for good performance, and so common forms of hearing impairment will probably cause major problems.

Dr Daniel Rowan adds: “Some people are better at this than others, and being blind doesn’t automatically confer good echolocation ability, though we don’t yet know why. Nevertheless, ability probably gets even better with extensive experience and feedback.

“We also found that our ability to use echoes to locate an object gets rapidly worse with increasing distance from the object, especially when the object is not directly facing us. While our experiments purposely removed any influence of head movement, doing so might help extend ability to farther distances. Furthermore, some echo-producing sounds are better for determining where an object is than others, and the best sounds for locating an object probably aren’t the same as for detecting the object or determining what, and how far away, the object is.”

The knowledge gained from this study will help researchers to develop training programmes and assistive devices for blind people and sighted people in low-vision situations. The team is also extending their research to investigate finding of objects in three-dimensional space and why some blind people seem to be able to outperform others, including sighted people.