The Mediterranean Diet Has Varied Effects on Cognitive Decline Among Different Race-Specific Populations

While the Mediterranean diet may have broad health benefits, its impact on cognitive decline differs among race-specific populations, according to a new study published in the Journal of Gerontology.

The team of researchers, including Ben-Gurion University of the Negev (BGU Prof. Danit R. Shahar RD, Ph.D, analyzed an NIH/NIA prospective cohort study [Health ABC] conducted over eight years in the U.S. to measure the effects of adherence to a Mediterranean diet. Prof. Shahar is affiliated with the BGU S. Daniel Abraham International Center for Health and Nutrition, Department of Public Health, Faculty of Health Sciences.

The Mediterranean-style diet (MedDiet) has fewer meat products and more plant-based foods and monounsaturated fatty acids from olive and canola oil (good) than a typical American diet.

To assess the association between MedDiet score and brain function, the researchers used data of several Modified Mini-Mental State Examinations (3MS) on 2,326 participating older adults (70-79). The 3MS is an extensively used and validated instrument designed to measure several cognitive domains to screen for cognitive impairment and commonly used to screen for dementia.

"In a population of initially well-functioning older adults, we found a significant correlation between strong adherence to the Mediterranean diet and a slower rate of cognitive decline among African American, but not white, older adults. Our study is the first to show a possible race-specific association between the Mediterranean diet and cognitive decline.”

The researchers note that further studies in diverse populations are necessary to confirm association between the MedDiet and cognitive decline, and to pinpoint factors that may explain these results.

(Image: Getty Images)

Understanding Consciousness

Why does a relentless stream of subjective experiences normally fill your mind? Maybe that’s just one of those mysteries that will always elude us. 

Yet, research from Northwestern University suggests that consciousness lies well within the realm of scientific inquiry — as impossible as that may currently seem. Although scientists have yet to agree on an objective measure to index consciousness, progress has been made with this agenda in several labs around the world.

“The debate about the neural basis of consciousness rages because there is no widely accepted theory about what happens in the brain to make consciousness possible,” said Ken Paller, professor of psychology in the Weinberg College of Arts and Sciences and director of the Cognitive Neuroscience Program at Northwestern.

“Scientists and others acknowledge that damage to the brain can lead to systematic changes in consciousness. Yet, we don’t know exactly what differentiates brain activity associated with conscious experience from brain activity that is instead associated with mental activity that remains unconscious,” he said.

In a new article, Paller and Satoru Suzuki, also professor of psychology at Northwestern, point out flawed assumptions about consciousness to suggest that a wide range of scientific perspectives can offer useful clues about consciousness.

“It’s normal to think that if you attentively inspect something you must be aware of it and that analyzing it to a high level would necessitate consciousness,” Suzuki noted. “Results from experiments on perception belie these assumptions.

“Likewise, it feels like we can freely decide at a precise moment, when actually the process of deciding begins earlier, via neurocognitive processing that does not enter awareness,” he said. 

The authors write that unconscious processing can influence our conscious decisions in ways we never suspect.

If these and other similar assumptions are incorrect, the researchers state in their article, then mistaken reasoning might be behind arguments for taking the science of consciousness off the table. 

“Neuroscientists sometimes argue that we must focus on understanding other aspects of brain function, because consciousness is never going to be understood,” Paller said. “On the other hand, many neuroscientists are actively engaged in probing the neural basis of consciousness, and, in many ways, this is less of a taboo area of research than it used to be.”

Experimental evidence has supported some theories about consciousness that appeal to specific types of neural communication, which can be described in neural terms or more abstractly in computational terms. Further theoretical advances can be expected if specific measures of neural activity can be brought to bear on these ideas.

Paller and Suzuki both conduct research that touches on consciousness. Suzuki studies perception, and Paller studies memory. They said it was important for them to write the article to counter the view that it is hopeless to ever make progress through scientific research on this topic.

They outlined recent advances that provide reason to be optimistic about future scientific inquiries into consciousness and about the benefits that this knowledge could bring for society.

“For example, continuing research on the brain basis of consciousness could inform our concerns about human rights, help us explain and treat diseases that impinge on consciousness, and help us perpetuate environments and technologies that optimally contribute to the well being of individuals and of our society,” the authors wrote.

They conclude that research on human consciousness belongs within the purview of science, despite philosophical or religious arguments to the contrary.

Their paper, “The Source of Consciousness,” has been published online in the journal Trends in Cognitive Sciences.

(Image: Shutterstock)

Little or poor sleep may be associated with worse brain function when aging

Research published today in PLOS ONE by researchers at the University of Warwick indicates that sleep problems are associated with worse memory and executive function in older people.

Analysis of sleep and cognitive (brain function) data from 3,968 men and 4,821 women who took part in the English Longitudinal Study of Ageing (ELSA), was conducted in a study funded by the Economic and Social Research Council (ESRC). Respondents reported on the quality and quantity of sleep over the period of a month.

The study showed that there is an association between both quality and duration of sleep and brain function which changes with age.

In adults aged between 50 and 64 years of age, short sleep (<6hrs per night) and long sleep (>8hrs per night) were associated with lower brain function scores. By contrast, in older adults (65-89 years) lower brain function scores were only observed in long sleepers.

Dr Michelle A Miller says “6-8 hours of sleep per night is particularly important for optimum brain function, in younger adults”. These results are consistent with our previous research, which showed that 6-8 hours of sleep per night was optimal for physical health, including lowest risk of developing obesity, hypertension, diabetes, heart disease and stroke”.

Interestingly, in the younger pre-retirement aged adults, sleep quality did not have any significant association with brain function scores, whereas in the older adults (>65 years), there was a significant relationship between sleep quality and the observed scores.

“Sleep is important for good health and mental wellbeing” says Professor Francesco Cappuccio, “Optimising sleep at an older age may help to delay the decline in brain function seen with age, or indeed may slow or prevent the rapid decline that leads to dementia”.

Dr Miller concludes that “if poor sleep is causative of future cognitive decline, non-pharmacological improvements in sleep may provide an alternative low-cost and more accessible Public Health intervention, to delay or slow the rate of cognitive decline”.

Running, Combined with Visual Experience, Restores Brain Function

In a new study by UC San Francisco scientists, running, when accompanied by visual stimuli, restored brain function to normal levels in mice that had been deprived of visual experience in early life.

In addition to suggesting a novel therapeutic strategy for humans with blindness in one eye caused by a congenital cataract, droopy eyelid, or misaligned eye, the new research—the latest in a series of UCSF studies exploring effects of locomotion on brain function—suggests that the adult brain may be far more capable of rewiring and repairing itself than previously thought.

In 2010, Michael P. Stryker, PhD, the W.F. Ganong Professor of Physiology, and postdoctoral fellow Cris Niell, PhD, now at the University of Oregon, made the surprising discovery that neurons in the visual area of the mouse brain fired much more robustly whenever the mice walked or ran.

Earlier this year, postdoctoral fellow Yu Fu, PhD, Stryker and a number of colleagues built on these findings, identifying and describing the neural circuit responsible for this locomotion-induced “high-gain state” in the visual cortex of the mouse brain.

Neither of these studies made clear, however, whether this circuit might have broader functional or clinical significance.

It has been known since the 1960s that visual areas of the brain do not develop normally if deprived of visual input during a “critical period” of brain development early in life. For example, in humans, if amblyopia (“lazy eye”) or other major eye problems are not surgically corrected in infancy, vision will never be normal in the affected eye—if such individuals lose sight in their “good” eye in later life, they are blind.

In the new research, published June 26, 2014 in the online journal eLife, Stryker and UCSF postdoctoral fellow Megumi Kaneko, MD, PhD, closed one eyelid of mouse pups at about 20 days after birth, and that eye was kept closed until the mice reached about five months of age.

As expected, the mice in which one eye had been closed during the critical developmental period showed sharply reduced neural activity in the part of the brain responsible for vision in that eye.

As in the previous UCSF experiments in this area, some mice were allowed to run freely on Styrofoam balls suspended on a cushion of air while recordings were made from their brains.

Little improvement was seen in the mice that had been deprived of visual input either when they were simply allowed to run or when they received visual training with the deprived eye not accompanied by walking or running.

But when the mice were exposed to the visual stimuli while they were running or walking, the results were dramatic: within a week the brain responses to those stimuli from the deprived eye were nearly identical to those from the normal eye, indicating that the circuits in the visual area of the brain representing the deprived eye had undergone a rapid reorganization, known in neuroscience as “plasticity.”

Interestingly, this recovery was stimulus-specific: if the brain activity of the mice was tested using a stimulus other than that they had seen while running, little or no recovery of function was apparent.

“We have no idea yet whether running puts the human cortex into a high-gain state that enhances plasticity, as it does the visual cortex of the mouse,” Stryker said, “but we are designing experiments to find out.”

Brain signals link physical fitness to better language skills in children

Children who are physically fit have faster and more robust neuro-electrical brain responses during reading than their less-fit peers, researchers report.

These differences correspond with better language skills in the children who are more fit, and occur whether they’re reading straightforward sentences or sentences that contain errors of grammar or syntax.

The new findings, reported in the journal Brain and Cognition, do not prove that higher fitness directly influences the changes seen in the electrical activity of the brain, the researchers say, but offer a potential mechanism to explain why fitness correlates so closely with better cognitive performance on a variety of tasks.

“All we know is there is something different about higher and lower fit kids,” said University of Illinois kinesiology and community health professor Charles Hillman who led the research with graduate student Mark Scudder and psychology professor Kara Federmeier. “Now whether that difference is caused by fitness or maybe some third variable that (affects) both fitness and language processing, we don’t know yet.”

The researchers used electroencephalography (EEG), placing an electrode cap on the scalp to capture some of the electrical impulses associated with brain activity. The squiggly readouts from the electrodes look like seismic readings captured during an earthquake, and characteristic wave patterns are associated with different tasks.

These patterns are called “event-related potentials” (ERPs), and vary according to the person being evaluated and the nature of the stimulus, Scudder said.

For example, if you hear or read a word in a sentence that makes sense (“You wear shoes on your feet”), the component of the brain waveform known as the N400 is less pronounced than if you read a sentence in which the word no longer makes sense (“At school we sing shoes and dance,” for example), Scudder said.

“We focused on the N400 because it is associated with the processing of the meaning of a word,” he said. “And then we also looked at another ERP, the P600, which is associated with the grammatical rules of a sentence.” Federmeier, a study co-author, is an expert in the neurobiological basis of language. Her work inspired the new analysis.

The researchers found that children who were more fit (as measured by oxygen uptake during exercise) had higher amplitude N400 and P600 waves than their less-fit peers when reading normal or nonsensical sentences. The N400 also had shorter latency in children who were more fit, suggesting that they processed the same information more quickly than their peers.

Most importantly, the researchers said, these differences in brain activity corresponded to better reading performance and language comprehension in the children who were more fit.

“Previous reports have shown that greater N400 amplitude is seen in higher-ability readers,” Scudder said.

“Our study shows that the brain function of higher fit kids is different, in the sense that they appear to be able to better allocate resources in the brain towards aspects of cognition that support reading comprehension,” Hillman said.

More work must be done to tease out the causes of improved cognition in kids who are more fit, Hillman said, but the new findings add to a growing body of research that finds strong links between fitness and healthy brain function.

Many studies conducted in the last decade, on children and older adults, ”have repeatedly demonstrated an effect of increases in either physical activity in one’s lifestyle or improvements in aerobic fitness, and the implications of those health behaviors for brain structure, brain function and cognitive performance,” Hillman said.

(Image caption: Omega-3 fatty acid DHA transporter protein Mfsd2a is shown here as red fluorescence along mouse brain capillaries. Credit: Long N. Nguyen)

Researchers discover how DHA omega-3 fatty acid reaches the brain

It is widely believed that DHA (docosahexaenoic acid) is good for your brain, but how it is absorbed by the brain has been unknown. That is - until now. Researchers from Duke-NUS Graduate Medical School Singapore (Duke-NUS) have conducted a new study identifying that the transporter protein Mfsd2a carries DHA to the brain. Their findings have widespread implications for how DHA functions in human nutrition.

People know that DHA is an essential dietary nutrient that they can get from seafood and marine oils. Baby formula companies are especially attuned to the benefits of DHA, with nary a baby formula marketed without it.

DHA is an omega-3 fatty acid most abundantly found in the brain that is thought to be crucial to its function. However, the brain does not produce DHA. Instead, DHA uptake in the brain happens in two ways. The developing brain receives DHA during fetal development, from a mother to her baby. The adult brain gets it through food or DHA produced by the liver.

Though DHA is postulated to benefit the brain, the mechanics of how the brain absorbs the fatty acid has remained elusive. Senior author of the research, Associate Professor David L. Silver of Duke-NUS explained the importance of unlocking this mystery.

"If we could show the link by determining how DHA gets into the brain, then we could use this information to more effectively target its absorption and formulate an improved nutritional agent."

In the study, led by post-doctoral fellow Long N. Nguyen of Duke-NUS, researchers found that mice without the Mfsd2a transporter had brains a third smaller than those with the transporter, and exhibited memory and learning deficits and high levels of anxiety. The team recognized that the learning, memory and behavioral function of these mice were reminiscent of omega-3 fatty acid deficiency in mice starved of DHA in their diet.

Then, using biochemical approaches, the team discovered that mice without Mfsd2a were deficient in DHA and made the surprising discovery that Mfds2a transports DHA in the chemical form of lysophosphatidlycholine (LPC). LPCs are phospholipids mainly produced by the liver that circulate in human blood at high levels. This is an especially significant finding as LPCs have been considered toxic to cells and their role in the body remains poorly understood. Based on this surprising new information, Dr Silver’s team showed that Mfsd2a is the major pathway for the uptake of DHA carried in the chemical form of LPCs by the growing fetal brain and by adult brain.

The findings, published online in Nature the week of May 12, 2014 marks the first time a genetic model for brain DHA deficiency and its functions in the brain has been made available.

"Our findings can help guide the development of technologies to more effectively incorporate DHA into food and exploit this pathway to maximize the potential for improved nutritionals to improve brain growth and function. This is especially important for pre-term babies who would not have received sufficient DHA during fetal development," said Dr Silver, who is from the Cardiovascular and Metabolic Disorders Program at Duke-NUS.

Functioning of aged brains and muscles in mice made younger

Harvard Stem Cell Institute (HSCI) researchers have shown that a protein they previously demonstrated can make the failing hearts in aging mice appear more like those of young health mice, similarly improves brain and skeletal muscle function in aging mice.

In two separate papers given early online release today by the journal Science—which is publishing the papers this coming Friday, Professors Amy Wagers, PhD, and Lee Rubin, PhD, of Harvard’s Department of Stem Cell and Regenerative Biology (HSCRB), report that injections of a protein known as GDF11, which is found in humans as well as mice, improved the exercise capability of mice equivalent in age to that of about a 70-year-old human, and also improved the function of the olfactory region of the brains of the older mice—they could detect smell as younger mice do.

Rubin, and Wagers, who also has a laboratory at the Joslin Diabetes Center, each said that, baring unexpected developments, they expect to have GDF11 in initial human clinical trials within three to five years.

Postdoctoral fellow Lida Katsimpardi, PhD, is the lead author on the Rubin group’s paper, and postdocs Manisha Sinha, PhD, and Young Jang, PhD, are the lead authors on the paper from the Wagers group.

Both studies examined the effect of GDF11 in two ways. First, by using what is called a parabiotic system, in which two mice are surgically joined and the blood of the younger mouse circulates through the older mouse. And second, by injecting the older mice with GDF11, which in an earlier study by Wagers and Richard Lee, MD, of Brigham and Women’s Hospital who is also an author on the two papers released today, was shown to be sufficient to reverse characteristics of aging in the heart.

Doug Melton, PhD, co-chair of HSCRB and co-director of HSCI, reacted to the two papers by saying that he couldn’t “recall a more exciting finding to come from stem cell science and clever experiments. This should give us all hope for a healthier future. We all wonder why we were stronger and mentally more agile when young, and these two unusually exciting papers actually point to a possible answer: the higher levels of the protein GDF11 we have when young. There seems to be little question that, at least in animals, GDF11 has an amazing capacity to restore aging muscle and brain function,” he said.

Melton, Harvard’s Xander University Professor, continued, saying that the ongoing collaboration between Wagers, a stem cell biologist whose focus has been on muscle, Rubin, whose focus is on neurodegenerative diseases and using patient generated stem cells as targets for drug discovery, and Lee, a practicing cardiologist and researcher, “is a perfect example of the power of the Harvard Stem Cell Institute as an engine of truly collaborative efforts and discovery, bringing together people with big, unique ideas and expertise in different biological areas.”

As Melton noted, GDF11 is naturally found in much higher concentrations in young mice than in older mice, and raising its levels in the older mice has improved the function of every organ system thus far studied.

Wagers first began using the parabiotic system in mice 14 years ago as a postdoctoral fellow at Stanford University, when she and colleagues Thomas Rando, MD, PhD, of Stanford, Irina Conboy, PhD, of the University of California, Berkley, and Irving Weissman, MD, of Stanford, observed that the blood of young mice circulating in old mice seemed to have some rejuvenating effects on muscle repair after injury.

Last year, she and Richard Lee published a paper in which they reported that when exposed to the blood of young mice, the enlarged, weakened hearts of older mice returned to a more youthful size, and their function improved. And then working with a Colorado firm, the pair reported that GDF11 was the factor in the blood apparently responsible for the rejuvenating effect. That finding has raised hopes that GDF11 may prove, in some form, to be a possible treatment for diastolic heart failure, a fatal condition in the elderly that now is irreversible, and fatal.

“From the previous work it could have seemed that GD11 was heart specific,” said Wagers, “but this shows that it is active in multiple organs and cell types. Prior studies of skeletal muscle and the parabiotic effect really focused on regenerative biology. Muscle was damaged and assayed on how well it could recover,” Wagers explained.

She continued: “The additional piece is that while prior studies of young blood factors have shown that we achieve restoration of muscle stem cell function and they repair the muscle better, in this study, we also saw repair of DNA damage associated with aging, and we got it in association with recovery of function, and we saw improvements in unmanipulated muscle. Based on other studies, we think that the accumulation of DNA damage in muscle stem cells might reflect an inability of the cells to properly differentiate to make mature muscle cells, which is needed for adequate muscle repair.”

Wagers noted that there is still a great deal to be learned about the mechanics of aging in muscle, and its repair. “I don’t think we fully understand how this happening or why. We might say that the damage is modification to the genetic material; the genome does have breaks in it. But whether it’s damaging, or a necessary part of repair, we don’t know yet.”

Rubin, whose primary research focus is on developing treatment for neurodegenerative diseases, particularly in children, said that when his group began its GDF11 experiments, “we knew that in the old mouse things were bad in the brain, there is a reduced amount of neurogenesis (the development of neurons), and it’s well known that cognition goes down. It wasn’t obvious to me that those things that can be repaired in peripheral tissue could be fixed in the brain.”

Rubin said that postdoctoral fellow Lida Katsimpardi, the lead author on his group’s paper, was taught the parabiotic experimental technique by Wagers, but conducted the Rubin group’s experiments independently of the Wagers group, and “she saw an increase in neural stem cells, and increased development of blood vessels in the brain.” Rubin said that 3D reconstruction of the brain, and magnetic resonance imaging (MRI) of the mouse brain showed “more new blood vessels and more blood flow,” both of which are normally associated with younger, healthier brain tissue.”

Younger mice, Rubin said, “have a keen sense of olfactory discrimination,” they can sense fine differences in odor. “When we tested the young mice, they avoided the smell of mint; the old mice didn’t. But the old mice exposed to the blood of the young mice, and those treated with GDF11 did.”

“We think an effect of GDF11 is the improved vascularity and blood flow, which is associated with increased neurogenesis,” Rubin said. “However, the increased blood flow should have more widespread effects on brain function. We do think that, at least in principle, there will be a way to reverse some of the cognitive decline that takes place during aging, perhaps even with a single protein. It could be that a molecule like GDF11, or GDF11 itself, could” reverse the damage of aging.

“It isn’t out of question that GDF11,” or a drug developed from it, “might be capable of slowing some of the cognitive defects associated with Alzheimer’s disease, a disorder whose main risk factor is aging itself,” Rubin said. It is even possible that this could occur without directly changing the “plaque and tangle burden” that are the pathological hallmarks of Alzheimer’s. Thus, a future treatment for this disease might be a combination of a therapeutic that reduces plaques and tangles, such as an antibody directed against the β-amyloid peptide, with a potential cognition enhancer like GDF11.

Wagers said that the two research groups are in discussions with a venture capital group to obtain funding to “be able to do the additional preclinical work” necessary before moving GDF11 into human trials.

“I would wager that the results of this work, together with the other work, will translate into a clinical trial and a treatment,” said the stem cell biologist. “But of course that’s just a wager.”

A single spray of oxytocin improves brain function in children with autism

A single dose of the hormone oxytocin, delivered via nasal spray, has been shown to enhance brain activity while processing social information in children with autism spectrum disorders, Yale School of Medicine researchers report in a new study published in the Dec. 2 issue of Proceedings of the National Academy of Sciences.

“This is the first study to evaluate the impact of oxytocin on brain function in children with autism spectrum disorders,” said first author Ilanit Gordon, a Yale Child Study Center adjunct assistant professor, whose colleagues on the study included senior author Kevin Pelphrey, the Harris Professor in the Child Study Center, and director of the Center for Translational Developmental Neuroscience at Yale.

Gordon, Pelphrey, and their colleagues conducted a double-blind, placebo-controlled study of 17 children and adolescents with autism spectrum disorders. The participants, between the ages of 8 and 16.5, were randomly given either oxytocin spray or a placebo nasal spray during a task involving social judgments. Oxytocin is naturally occurring hormone produced in the brain and throughout the body.

“We found that brain centers associated with reward and emotion recognition responded more during social tasks when children received oxytocin instead of the placebo,” said Gordon. “Oxytocin temporarily normalized brain regions responsible for the social deficits seen in children with autism.”

Gordon said oxytocin facilitated social attunement, a process that makes the brain regions involved in social behavior and social cognition activate more for social stimuli (such as faces) and activate less for non-social stimuli (such as cars).

“Our results are particularly important considering the urgent need for treatments to target social dysfunction in autism spectrum disorders,” Gordon added.