Sleepiness and fatigue linked to brain atrophy in cognitively normal elderly

Excessive daytime sleepiness and fatigue symptoms may be clinical markers of accelerated brain aging

June 14, 2016
Science Daily/American Academy of Sleep Medicine
A new study found that normal older adults who experience excessive sleepiness during the day or significant fatigue may have more brain atrophy than expected for their age, particularly in areas of the brain that are more susceptible to aging and Alzheimer's disease.

Results show that subjects with excessive daytime sleepiness or fatigue not only had more disturbed sleep, but also significantly lower cognitive scores and more medical comorbidities.

"Our results may help to identify individuals at higher susceptibility or risk for dementia prior to symptom onset so that appropriate interventions can be undertaken early to prevent progression to dementia," said lead author, Diego Z. Carvalho, MD, a resident physician of neurology at the Mayo Clinic in Rochester, Minnesota.

The research abstract was published recently in an online supplement of the journal Sleep and will be presented Tuesday, June 14, and Wednesday, June 15, in Denver at SLEEP 2016, the 30th Anniversary Meeting of the Associated Professional Sleep Societies LLC (APSS).

In the Mayo Clinic Study of Aging, the authors identified 1,374 cognitively normal elderly aged 50 years and older who completed sleepiness and fatigue surveys and had a baseline structural magnetic resonance imaging (MRI). Excessive daytime sleepiness was defined as Epworth Sleepiness Scale of 10 or more. Fatigue severity was assessed with the Beck Depression Inventory-II.
Science Daily/SOURCE :https://www.sciencedaily.com/releases/2016/06/160614133613.htm

Possible missing link between sleep and improved memory

New study may explain why sleep improves memory

June 14, 2016
Science Daily/University of California - Riverside
A team of sleep researchers has found that the autonomic nervous system, which is responsible for control of bodily functions not consciously directed (such as breathing, heartbeat, and digestive processes) plays a role in promoting memory consolidation -- the process of converting information from short-term to long-term memory -- during sleep.

The groundbreaking study, "Autonomic Activity During Sleep Predicts Memory Consolidation in Humans," appears in the journal Proceedings of the National Academy of Sciences of the United States of America. Mednick and her team demonstrated, for the first time, that increases in autonomic nervous system (ANS) activity during sleep is correlated with memory improvement.

"Sleep has been shown to facilitate the transformation of recent experiences into long-term, stable memories," explained Mednick. "But, past studies produced contradictory evidence about which specific sleep features enhance memory performance." According to Mednick, this suggests that there may be unidentified events during sleep that play an important role in this process. Because memory during waking hours is enhanced by ANS activity, Mednick tested whether the ANS could be the missing link that explains how sleep promotes memory consolidation.

To test this idea, Mednick and the team of researchers added a memory component to a well-known creativity test called the Remote Associates Test (RAT). In between two RAT testing sessions, they gave people a nap and measured the quality of sleep and heart activity.

In the first part of the study, 81 healthy individuals were presented with RAT problems consisting of three seemingly unrelated words (e.g., cookies, sixteen, heart) and were required to find another word (e.g., sweet) that links the three words together. Some participants were also asked to complete an unrelated analogy task. The answers to the analogy task served as primes for solving some of the problems in the second RAT test that occurred after the nap. After completing these tasks, 60 of the participants took a 90-minute nap, while the remaining subjects watched a video. Later in the day, all the participants returned to the lab and completed RAT problems for a second time. The problems were either identical to the previous test (repeated condition), completely new (novel condition) or had the same answers as the analogy task (primed condition).

Individuals who had a nap were more likely to answer the creativity problems in the afternoon with words that were primed by the morning analogies task compared with people who didn't nap. In other words, a nap helped the experimental subjects think more flexibly and combine primed words in "new and useful" combinations. Importantly, while approximately 40 percent of the performance improvement due to the nap could be predicted by the amount of rapid eye movement (REM) sleep, when the researchers considered heart rate activity during REM, they could account for up to 73 percent of the performance increases.

"The findings suggest that ANS activity during REM sleep may be an unexplored contributor to sleep-related improvements in memory performance." said Mednick. These results have implications for understanding the mind/body connection and relationships between sleep, cardiovascular health and cognitive functioning.
Science Daily/SOURCE :https://www.sciencedaily.com/releases/2016/06/160614133617.htm

Pre and post testing show reversal of memory loss from Alzheimer's disease in 10 patients

Small trial succeeds using systems approach to memory disorders

June 16, 2016
Science Daily/Buck Institute for Research on Aging
A small trial of 10 patients using a personalized systems approach to memory disorders shows an unprecedented reversal of memory loss in those diagnosed with early stage Alzheimers. Pre and post results are based on quantitative MRI and neuropsychological testing. The study is based on a protocol dubbed 'metabolic enhancement for neurodegeneration.'

https://images.sciencedaily.com/2016/06/160616071933_1_540x360.jpg
This is the first study to objectively show that memory loss in patients can be reversed, and improvement sustained, using a complex, 36-point therapeutic personalized program that involves comprehensive changes in diet, brain stimulation, exercise, optimization of sleep, specific pharmaceuticals and vitamins, and multiple additional steps that affect brain chemistry.
Credit: © vchalup / Fotolia

Results from quantitative MRI and neuropsychological testing show unprecedented improvements in ten patients with early Alzheimer's disease (AD) or its precursors following treatment with a programmatic and personalized therapy. Results from an approach dubbed metabolic enhancement for neurodegeneration are now available online in the journal Aging.

The study, which comes jointly from the Buck Institute for Research on Aging and the UCLA Easton Laboratories for Neurodegenerative Disease Research, is the first to objectively show that memory loss in patients can be reversed, and improvement sustained, using a complex, 36-point therapeutic personalized program that involves comprehensive changes in diet, brain stimulation, exercise, optimization of sleep, specific pharmaceuticals and vitamins, and multiple additional steps that affect brain chemistry.

"All of these patients had either well-defined mild cognitive impairment (MCI), subjective cognitive impairment (SCI) or had been diagnosed with AD before beginning the program," said author Dale Bredesen, MD, a professor at the Buck Institute and professor at the Easton Laboratories for Neurodegenerative Disease Research at UCLA, who noted that patients who had had to discontinue work were able to return to work and those struggling at their jobs were able to improve their performance. "Follow up testing showed some of the patients going from abnormal to normal."

One of the more striking cases involved a 66-year old professional man whose neuropsychological testing was compatible with a diagnoses of MCI and whose PET scan showed reduced glucose utilization indicative of AD. An MRI showed hippocampal volume at only the 17th percentile for his age. After 10 months on the protocol a follow-up MRI showed a dramatic increase of his hippocampal volume to the 75th percentile, with an associated absolute increase in volume of nearly 12 percent.

In another instance, a 69-year old professional man and entrepreneur, who was in the process of shutting down his business, went on the protocol after 11 years of progressive memory loss. After six months, his wife, co-workers and he noted improvement in memory. A life-long ability to add columns of numbers rapidly in his head returned and he reported an ability to remember his schedule and recognize faces at work. After 22 months on the protocol he returned for follow-up quantitative neuropsychological testing; results showed marked improvements in all categories with his long-term recall increasing from the 3rd to 84th percentile. He is expanding his business.

Another patient, a 49-year old woman who noted progressive difficulty with word finding and facial recognition went on the protocol after undergoing quantitative neuropsychological testing at a major university. She had been told she was in the early stages of cognitive decline and was therefore ineligible for an Alzheimer's prevention program. After several months on the protocol she noted a clear improvement in recall, reading, navigating, vocabulary, mental clarity and facial recognition. Her foreign language ability had returned. Nine months after beginning the program she did a repeat of the neuropsychological testing at the same university site. She no longer showed evidence of cognitive decline.

All but one of the ten patients included in the study are at genetic risk for AD, carrying at least one copy of the APOE4 allele. Five of the patients carry two copies of APOE4 which gives them a 10-12 fold increased risk of developing AD. "We're entering a new era," said Bredesen. "The old advice was to avoid testing for APOE because there was nothing that could be done about it. Now we're recommending that people find out their genetic status as early as possible so they can go on prevention." Sixty-five percent of the Alzheimer's cases in this country involve APOE4; with seven million people carrying two copies of the ApoE4 allele.

Bredesen' s systems-based approach to reverse memory loss follows the abject failure of monotherapies designed to treat AD and the success of combination therapies to treat other chronic illnesses such as cardiovascular disease, cancer and HIV. Bredesen says decades of biomedical research, both in his and other labs, has revealed that an extensive network of molecular interactions is involved in AD pathogenesis, suggesting that a broader-based therapeutic approach may be more effective. "Imagine having a roof with 36 holes in it, and your drug patched one hole very well--the drug may have worked, a single 'hole' may have been fixed, but you still have 35 other leaks, and so the underlying process may not be affected much," Bredesen said. "We think addressing multiple targets within the molecular network may be additive, or even synergistic, and that such a combinatorial approach may enhance drug candidate performance, as well."

While encouraged by the results of the study, Bredesen admits more needs to be done. "The magnitude of improvement in these ten patients is unprecedented, providing additional objective evidence that this programmatic approach to cognitive decline is highly effective," Bredesen said. "Even though we see the far-reaching implications of this success, we also realize that this is a very small study that needs to be replicated in larger numbers at various sites." Plans for larger studies are underway.

Cognitive decline is often listed as the major concern of older adults. Already, Alzheimer's disease affects approximately 5.4 million Americans and 30 million people globally. Without effective prevention and treatment, the prospects for the future are bleak. By 2050, it's estimated that 160 million people globally will have the disease, including 13 million Americans, leading to potential bankruptcy of the Medicare system. Unlike several other chronic illnesses, Alzheimer's disease is on the rise--recent estimates suggest that AD has become the third leading cause of death in the United States behind cardiovascular disease and cancer.
Science Daily/SOURCE :https://www.sciencedaily.com/releases/2016/06/160616071933.htm

New clues about the aging brain's memory functions

June 29, 2016
Science Daily/Umea University
Dopamine D2 receptor is linked to the long-term episodic memory, which function often reduces with age and due to dementia, report researchers. This new insight can contribute to the understanding of why some but not others are affected by memory impairment, they say.

A European study led by Umeå University Professor Lars Nyberg, has shown that the dopamine D2 receptor is linked to the long-term episodic memory, which function often reduces with age and due to dementia. This new insight can contribute to the understanding of why some but not others are affected by memory impairment. The results have been published in the journal PNAS.

Using brain-imaging technologies (PET and MRI), memory tests and statistical analyses, Professor Lars Nyberg and his colleagues are trying to capture what happens to our memory and our brain as we grow old. The neurotransmitter dopamine is of significance to our motor functions but also to memory and other cognitive functions. The D1 receptor system has been linked to functions mediated by the frontal lobe, but it has been unknown what specific role the D2 receptor system has.

In this study, a PET camera was used to examine individual differences in the D2 system in a vast group consisting of 181 healthy individuals between the age of 64 and 68. All participants also had to take part in an all-inclusive performance test of the long-term episodic memory, working memory and processing speed along with an MRI assessment (which was used to measure the size of various parts of the brain).

Researchers could see that the D2 system was positively linked to episodic memory, but not to working memory or to processing speed by relating PET registrations to the cognitive data. Researchers could also see that the D2 system affects the functioning of the hippocampus in the brain. The hippocampus is since long linked to long-term episodic memory.

"Our results link the dopamine D2 receptor to long-term episodic memory, likely via hippocampus functioning. Episodic memory is often reduced with age and in people with dementia. Hence, impairment of the dopamine system are important to consider when attempting to understand the bases of impaired cognitive abilities due to aging," says Lars Nyberg, professor in Neuroscience and Director at Umeå Centre for Functional Brain Imaging (UFBI).
Science Daily/SOURCE :https://www.sciencedaily.com/releases/2016/06/160629095605.htm

Cinnamon may aid learning ability

Spice consumption made mice better learners

July 12, 2016
Science Daily/Rush University Medical Center
Cinnamon is a delicious addition to toast, coffee and breakfast rolls. Eating the tasty household spice also might improve learning ability, according to new study.
https://images.sciencedaily.com/2016/07/160712214659_1_540x360.jpg
Cinnamon sticks and cinnamon powder.
Credit: © pershing / Fotolia

The study by neurological scientists at Rush University Medical Center found that feeding cinnamon to laboratory mice determined to have poor learning ability made the mice better learners.

"This would be one of the safest and the easiest approaches to convert poor learners to good learners," said Kalipada Pahan, PhD, the lead researcher of the study and the Floyd A. Davis Professor of Neurology at Rush.

Some people are born naturally good learners, some become good learners by effort, and some find it hard to learn new tasks even with effort. Little is known about the neurological processes that cause someone to be a poor learner and how to improve performance in poor learners.

"Understanding brain mechanisms that lead to poor learning is important to developing effective strategies to improve memory and learning ability," Pahan said.

Cinnamon role reversal

The key to gaining that understanding lies in the hippocampus, a small part in the brain that generates, organizes and stores memory. Researchers have found that the hippocampus of poor learners has less CREB (a protein involved in memory and learning) and more alpha5 subunit of GABAA receptor or GABRA5 (a protein that generates tonic inhibitory conductance in the brain) than good learners.

The mice in the study received oral feedings of ground cinnamon, which their bodies metabolized into sodium benzoate, a chemical used as a drug treatment for brain damage. When the sodium benzoate entered the mice's brains, it increased CREB, decreased GABRA5, and stimulated the plasticity (ability to change) of hippocampal neurons.

These changes in turn led to improved memory and learning among the mice.

"We have successfully used cinnamon to reverse biochemical, cellular and anatomical changes that occur in the brains of mice with poor learning," Pahan said.

The researchers used a Barnes maze, a standard elevated circular maze consisting of 20 holes, to identify mice with good and bad learning abilities. After two days of training, the mice were examined for their ability to find the target hole. They tested the mice again after one month of cinnamon feeding.

The researchers found that after eating their cinnamon, the poor learning mice had improved memory and learning at a level found in good learning mice. However, they did not find any significant improvement among good learners by cinnamon.

"Individual difference in learning and educational performance is a global issue," Pahan said. "We need to further test this approach in poor learners. If these results are replicated in poor learning students, it would be a remarkable advance."

Cinnamon also may aid against Parkinson's disease

Cinnamon has been a sweet spot for Pahan's research. He and his colleagues previously that cinnamon can reverse changes in the brains of mice with Parkinson's disease.

These studies have made the researchers spice connoisseurs: They used mass spectrometric analysis to identify the purer of the two major types of cinnamon widely available in the United States -- Chinese cinnamon (Cinnamonum cassia) and original Ceylon cinnamon.

"Although both types of cinnamon are metabolized into sodium benzoate, we have seen that Ceylon cinnamon is much more pure than Chinese cinnamon, as the latter contains coumarin, a hepatotoxic (liver damaging) molecule," Pahan said.

The study of cinnamon and learning ability was supported by grants from National Institutes of Health, the U.S. Department of Veterans Affairs and the Alzheimer's Association.
Science Daily/SOURCE :https://www.sciencedaily.com/releases/2016/07/160712214659.htm

Middle-age memory decline a matter of changing focus

Research sheds new light on what constitutes healthy aging of the brain

July 12, 2016
Science Daily/McGill University
The inability to remember details, such as the location of objects, begins in early midlife (the 40s) and may be the result of a change in what information the brain focuses on during memory formation and retrieval, rather than a decline in brain function.

https://images.sciencedaily.com/2016/07/160712110724_1_540x360.jpg
When middle-aged and older adults were shown a series of faces, red regions of the brain were more active; these include an area in the medial prefrontal cortex that is associated with self-referential thinking. In young adults, by contrast, blue regions -- which include areas important for memory and attention -- were more active during this task.
Credit: N. Rajah, McGill University

Senior author Natasha Rajah, Director of the Brain Imaging Centre at McGill University's Douglas Institute and Associate Professor in McGill's Department of Psychiatry, says this reorientation could impact daily life. "This change in memory strategy with age may have detrimental effects on day-to-day functions that place emphasis on memory for details such as where you parked your car or when you took your prescriptions."

Brain changes associated with dementia are now thought to arise decades before the onset of symptoms. So a key question in current memory research concerns which changes to the aging brain are normal and which are not. But Dr. Rajah says most of the work on aging and memory has concentrated on understanding brain changes later in life. "So we know little about what happens at midlife in healthy aging and how this relates to findings in late life. Our research was aimed at addressing this issue."

In this study, published in the journal, NeuroImage, 112 healthy adults ranging in age from 19 to 76 years were shown a series of faces. Participants were then asked to recall where a particular face appeared on the screen (left or right) and when it appeared (least or most recently). The researchers used functional MRI to analyze which parts of brain were activated during recall of these details.

Rajah and colleagues found that young adults activated their visual cortex while successfully performing this task. As she explains, "They are really paying attention to the perceptual details in order to make that decision." On the other hand, middle-aged and older adults didn't show the same level of visual cortex activation when they recalled the information. Instead, their medial prefrontal cortex was activated. That's a part of the brain known to be involved with information having to do with one's own life and introspection.

Even though middle-aged and older participants didn't perform as well as younger ones in this experiment, Rajah says it may be wrong to regard the response of the middle-aged and older brains as impairment. "This may not be a 'deficit' in brain function per se, but reflects changes in what adults deem 'important information' as they age." In other words, the middle-aged and older participants were simply focusing on different aspects of the event compared to those in the younger group.

Rajah says that middle-aged and older adults might improve their recall abilities by learning to focus on external rather than internal information. "That may be why some research has suggested that mindfulness meditation is related to better cognitive aging."

Rajah is currently analyzing data from a similar study to discern if there are any gender differences in middle-aged brain function as it relates to memory. "At mid-life women are going through a lot of hormonal change. So we're wondering how much of these results is driven by post-menopausal women."

Science Daily/SOURCE :https://www.sciencedaily.com/releases/2016/07/160712110724.htm

Working memory in aging adults becomes increasingly affected by alcohol

July 15, 2016
Science Daily/Research Society on Alcoholism
Working memory can be thought of as short-term memory, temporarily holding ideas and recent events in the mind for quick recall. Working memory often declines with age; it may also be susceptible to interactions between age and alcohol use. Frontal theta power (FTP) and posterior alpha power (PAP) are electrophysiological measures of brain activity associated with cognitive effort and maintenance of visual information. A new study looks at alcohol effects on FTP and PAP during a working memory task in younger and older social drinkers.

Researchers recruited two groups of participants for this study: 51 older (55-70 years of age; 29 women, 22 men), and 70 younger (25-35 years of age; 39 women, 31 men) moderate drinkers living in the community. Participants were given either a placebo or an active dose designed to produce a breath alcohol concentration of 0.04 or 0.065 g/dL. Following absorption, participants completed a visual working-memory task in which they were required to remember briefly-shown images during a nine-second delay period. FTP and PAP were recorded during this delay.

During working memory maintenance, PAP was lower in the older than the younger adults. In addition, active alcohol doses increased PAP in younger adults but decreased PAP in older adults. These results support a small but growing body of evidence that older adults are more sensitive than younger adults to the neurobehavioral effects of moderate alcohol use, and further demonstrate that PAP activity may help to identify alcohol's negative effects on working-memory efficiency in older adults.
Science Daily/SOURCE :https://www.sciencedaily.com/releases/2016/07/160715181713.htm

Mental, physical exercises produce distinct brain benefits

July 18, 2016
Science Daily/Center for BrainHealth
Cognitive brain training improves executive function whereas aerobic activity improves memory, according to new research.

The study, published in Frontiers in Human Neuroscience, found that healthy adults who participated in cognitive training demonstrated positive changes in executive brain function as well as a 7.9 percent increase in global brain flow compared to study counterparts who participated in an aerobic exercise program. The aerobic exercise group showed increases in immediate and delayed memory performance that were not seen in the cognitive training group. The randomized trial is the first to compare cerebral blood flow and cerebrovascular reactivity data obtained via MRI.

"Many adults without dementia experience slow, continuous and significant age-related changes in the brain, specifically in the areas of memory and executive function, such as planning and problem-solving," said Dr. Sandra Bond Chapman, study lead author, founder and chief director of the Center for BrainHealth, and Dee Wyly Distinguished University Professor. "We can lose 1-2 percent in global brain blood flow every decade, starting in our 20s. To see almost an 8 percent increase in brain blood flow in the cognitive training group may be seen as regaining decades of brain health since blood flow is linked to neural health."

For the study, 36 sedentary adults ages 56-75 years were randomized into either a cognitive training or a physical training group. Each group took part in training three hours per week over 12 weeks. Neurocognitive, physiological, and MRI data were taken before, during and after training. The cognitive group received Strategic Memory Advanced Reasoning Training (SMART), a manualized brain training developed at the Center for BrainHealth. The strategy-based training focuses on three executive functions: strategic attention (prioritizing brain resources); integrative reasoning (synthesizing information at a deeper level); and innovation (encouraging fluid thinking, diverse perspective-taking, and problem solving). The physical training group completed three, 60-minute sessions per week that included five minutes of warmup and cool down with 50 minutes of either walking on a treadmill or cycling on a stationary bike while maintaining 50-75 percent of maximum heart rate.

"Most people tell me that they want a better memory and notice memory changes as they get older," said Dr. Mark D'Esposito, study co-author and professor of neuroscience and psychology, and director of the Henry H. Wheeler Jr. Brain Imaging Center at the Helen Wills Neuroscience Institute at the University of California, Berkeley. "While memory is important, executive functions such as decision-making and the ability to synthesize information are equally, if not more so, but we often take them for granted. The takeaway: Aerobic activity and reasoning training are both valuable tools that give your brain a boost in different ways."

The research team attributes the global cerebral blood flow gains to concerted mental effort during the reasoning training.

"We believe the reasoning training triggered neural plasticity by engaging the brain networks involved in staying focused on a goal, such as writing a brief business proposal, while continuously adapting to new information, such as feedback from a collaborator," Chapman said.

The aerobic exercise group did not show significant global blood flow gains, however the exercisers with improved memory performance showed higher cerebral blood flow in the bilateral hippocampi, an area underlying memory function and particularly vulnerable to aging and dementia.

"Our research has shown that all brain training protocols do not return equal benefits. When targeting the brain functions that give us a mental edge in daily life, strategy-based programs prevail," Chapman said. "This study highlights the potential to accelerate brain health in healthy adults by adopting lifestyle habits that exercise the mind and body. Future trials are needed to further develop and test neuroprotective programs that unite physical and cognitive training protocols for the highest health returns starting early and continuing into late life."

Dr. Laura DeFina, chief executive officer of The Cooper Institute in Dallas and collaborator on the study, says the findings are encouraging.

"We know that physical activity can lead to improved fitness levels. In our Cooper Center Longitudinal Study population, higher fitness has been shown to result in less all-cause dementia with aging," DeFina said. "The current study highlights the benefit of training both the body and the brain, as both produce observable benefits. The initial findings are encouraging and underscore the need for a multifaceted approach when it comes to brain health."
Science Daily/SOURCE :https://www.sciencedaily.com/releases/2016/07/160718110942.htm

Deep brain stimulation continues to show promise for patients with mild Alzheimer’s disease

July 19, 2016
Science Daily/University Health Network (UHN)
New research findings have provided further insight into the effects of Deep Brain Stimulation (DBS) in the treatment of Alzheimer’s disease.

Forty-two patients with mild Alzheimer's disease were enrolled in a randomized, double-blind multicentre phase II clinical trial and implanted with DBS electrodes directed at the fornix -- a bundle of nerve fibres in the brain that carry signals from the hippocampus. To better measure the impact of electrical stimulation in the brain, patients were then randomly assigned to either the "on" or "off" stimulation group and monitored for the 12 months following their procedure. Once the trial follow up was complete, all patients then had their electrodes turned on.

Results from the trial showed that DBS stimulation of the fornix (DBS-f) continues to be safe and that, although overall there were no differences in cognitive outcomes between the "on" and "off" study participants, those 65 years of age and older appeared to experience slower cognitive decline as a result of the treatment.

Another finding of interest was that the brain's ability to metabolize glucose increased over the year-long study period in patients receiving electrical stimulation, indicating that the brain networks made dysfunctional by Alzheimer's improved in some ways.

"We are encouraged by these findings as they indicate we are headed in the right direction with our research on DBS as a treatment for Alzheimer's disease," says Dr. Andres Lozano, neurosurgeon and the lead author of the study. "We now have a better idea of which patients will benefit most from this treatment and how the stimulation might slow the progression of Alzheimer's."

"The next phase of our research will focus on determining what stimulation dosage will have the most impact against this disease," adds Lozano who is also University Professor and Chairman, Department of Neurosurgery, University of Toronto.

The findings were published in the Journal of Alzheimer's Disease and will be used for the recruitment of a phase III clinical trial to refine the patient criteria.
Science Daily/SOURCE :https://www.sciencedaily.com/releases/2016/07/160719144831.htm

Specific brain training reduces dementia risk across 10 years

August 4, 2016
Science Daily/American Psychological Association
While many companies have long promised that their brain-training products can sharpen aging minds, only one type of computerized brain training so far has been shown to improve people's mental quickness and significantly reduce the risk of dementia, according to new research.

"The mistake some people make is thinking that all brain training is the same," said presenter Jerri Edwards, PhD, of the University of South Florida. "Lumping all brain training together is like trying to determine the effectiveness of antibiotics by looking at the universe of all pills, and including sugar pills and dietary supplements in that analysis. You'll find that some work and some do not. To then conclude that brain training does not work -- or is not yet proven -- is based on flawed analysis."

Because of this lack of targeted analysis, Edwards looked at studies focused on the effectiveness of a specific brain training exercise called speed of processing training -- also known as useful field of view training. Edwards and her team completed a systematic review and meta-analysis of more than 50 peer-reviewed research papers examining speed of processing training.

In addition to this meta-analysis, Edwards and her team released findings from their ACTIVE study, which stands for Advanced Cognitive Training for Independent and Vital Elderly. This study, which was presented last week, found that older adults' risk for dementia was reduced by 48 percent over 10 years when they completed 11 or mores sessions of this brain-training technique. Specifically, the risk of dementia was reduced by 8 percent for each session of speed of processing training completed, Edwards said.

"This highly specific exercise is designed to improve the speed and accuracy of visual attention or someone's mental quickness," Edwards said. For example, during one task, a person must identify an object (e.g., a car or truck) at the center of a screen while locating a target, such as another car, in his or her peripheral vision. As people practice the task, the time it takes them to locate the peripheral object gets shorter and shorter even as the objects become harder to distinguish. In more difficult tasks, the peripheral target is surrounded by distracting objects, forcing the person to work harder to stay focused, she said.

Participants who completed the speed of processing training experienced improved performance across standard cognitive (attention), behavioral (depressive symptoms, feelings of control), functional (health-related quality of life, functional performance) and real world measures (driving, predicted health care costs).

Edwards pointed to the speed of processing research around driving as a concrete example of how this training generalizes to everyday activities. Studies have shown that speed of processing training resulted in improvement in reaction time, yielding another 22 feet of stopping distance at 55 mph and a 36 percent decrease in dangerous maneuvers. In addition, 40 percent fewer people stopped driving altogether and there was a 48 percent reduction in at-fault crashes, she said.

"Some brain training does work, but not all of it," Edwards concluded. "People should seek out training backed by multiple peer-reviewed studies. The meta-analysis of this particular speed of processing training shows it can improve how people function in their everyday lives."

The ACTIVE study consisted of 2,832 participants, ages 65 to 94. The sample was 74 percent white and 26 percent African-American and 76 percent women. While Edwards acknowledged the sample is not representative of the entire U.S. population, this study is the first large-scale, randomized trial to test the long-term outcomes of brain training effects on prevention of cognitive impairment in daily lives, she said.

The UFOV exercise was developed by Karlene Ball, PhD, and Daniel Roenker, PhD, at the University of Alabama Birmingham and Western Kentucky University and is exclusively licensed to Posit Science Inc. It is marketed under the name "Double Decision" at BrainHQ.com. While Edwards worked as a consultant to Posit Science Inc. in 2008, she no longer has any financial interest in the speed of processing training or UFOV.
Science Daily/SOURCE :https://www.sciencedaily.com/releases/2016/08/160804135857.htm

Want a better memory? Try eating a Mediterranean diet

Eating a Mediterranean diet can slow down cognitive decline

August 9, 2016
Science Daily/Frontiers
The Mediterranean diet can improve your mind, as well your heart, shows a new study

The Mediterranean diet can improve your mind, as well your heart, shows a study published in the open-access journal Frontiers in Nutrition.

By sticking to the Mediterranean diet the study showed that people had slowed rates of cognitive decline, reduced conversion to Alzheimer's, and improved cognitive function.

The main foods in the Mediterranean diet (MedDiet) include plant foods, such as leafy greens, fresh fruit and vegetables, cereals, beans, seeds, nuts, and legumes. The MedDiet is also low in dairy, has minimal red meat, and uses olive oil as its major source of fat.

Leading author Roy Hardman from the Centre for Human Psychopharmacology Swinburne University of Technology Melbourne Australia and his colleagues evaluated all the available papers between 2000-2015 that investigated if and how a MedDiet may impact cognitive processes over time. In total, 18 out of the 135 articles met their strict inclusion criteria.

"The most surprising result was that the positive effects were found in countries around the whole world. So regardless of being located outside of what is considered the Mediterranean region, the positive cognitive effects of a higher adherence to a MedDiet were similar in all evaluated papers;" he said.

Attention, memory, and language improved. Memory, in particular, was positively affected by the MedDiet including improvements in: delayed recognition, long-term, and working memory, executive function, and visual constructs.

"Why is a higher adherence to the MedDiet related to slowing down the rate of cognitive decline? The MedDiet offers the opportunity to change some of the modifiable risk factors," he explained.

"These include reducing inflammatory responses, increasing micronutrients, improving vitamin and mineral imbalances, changing lipid profiles by using olive oils as the main source of dietary fats, maintaining weight and potentially reducing obesity, improving polyphenols in the blood, improving cellular energy metabolism and maybe changing the gut micro-biota, although this has not been examined to a larger extent yet."

Moreover, the benefits to cognition afforded by the MedDiet were not exclusive to older individuals. Two of the included studies focused on younger adults and they both found improvements in cognition using computerized assessments.

The researchers stress that research in this area is important due to the expected extensive population aging over the next 20-30 years. They envision that the utilization of a dietary pattern, such as the MedDiet, will be an essential tool to maintain quality of life and reduce the potential social and economic burdens of manifested cognitive declines like dementia.

"I would therefore recommend people to try to adhere or switch to a MedDiet, even at an older age," Hardman added.

Like many researchers, Hardman takes his research home: "I follow the diet patterns and do not eat any red meats, chicken or pork. I have fish two-three times per week and adhere to a Mediterranean style of eating."
Science Daily/SOURCE :https://www.sciencedaily.com/releases/2016/08/160809145258.htm

Similar brain connectivity during rest, tasks linked to better mental performance

August 16, 2016
Science Daily/Society for Neuroscience
A brain on task differs from a brain at rest. But, how much it differs could depend on the cognitive ability of the person whose brain is being studied. New research suggests greater similarity between brain connectivity at rest and on task may be associated with better mental performance.

The study suggests that general cognitive ability may be the result of well-tuned brain network updates, said study author Michael Cole of Rutgers University. "The results also suggest that if we can figure out how to better tune these networks, we can possibly influence cognitive ability generally."

Different types of cognitive tasks spur activity in various regions of the brain, as indicated by studies using functional magnetic resonance imaging (fMRI). The regions activated depend on the specific task, and scientists believe regions active at the same time work together as a network. Even when our brains are at rest, collections of regions remain active in "resting-state networks." However, Cole and study author Douglas Schultz previously found the resting and on-task networks were highly similar. This led the researchers to propose that the brain has an intrinsic network that reconfigures itself when we switch from resting to performing a task, and they hypothesized the reconfiguration of this intrinsic network relates to how well we perform a given task.

To test this, Schultz and Cole analyzed brain imaging data obtained by researchers at Washington University in St. Louis and the University of Minnesota as part of the Human Connectome Project. One hundred healthy adults had their brains scanned with fMRI while they rested quietly and while they performed various cognitive tests. To study brain network reconfiguration, the Rutgers scientists compared participants' resting-state networks to the networks active during language, reasoning, and memory tasks and computed how similar each task-related network was to the resting-state network.

When they compared these similarity ratings to the participants' performance on each task, they found individuals who performed better had more similar resting and task networks. The researchers also compared the networks active during each of the three cognitive tasks and created a composite generalized task network pattern. They found that the more similar this generalized task network pattern was to the resting-state network pattern, the better the participant performed on each task, suggesting individuals who performed well had resting-state networks optimized to switch to any of a variety of new tasks. In other words, high performers appeared to use their brains more efficiently, only needing to make small changes when switching tasks.

The results of the study suggest that "people's performance on various cognitive tasks is better the fewer changes they have to their brain connectivity," said John Dylan Haynes, a neuroscientist at the Bernstein Center for Computational Neuroscience in Berlin who studies cognition and was not involved in the study. "The efficiency with which a brain engages in a task might be a predictor of intelligence."

The researchers are planning additional studies to examine how training may improve cognitive abilities by influencing the brain's intrinsic network and its reconfiguration during different tasks.
Science Daily/SOURCE :https://www.sciencedaily.com/releases/2016/08/160816182615.htm

Diet and exercise can reduce protein build-ups linked to Alzheimer's

August 16, 2016
Science Daily/University of California - Los Angeles
A healthy diet, regular physical activity and a normal body mass index can reduce the incidence of protein build-ups that are associated with the onset of Alzheimer's disease, research shows.

In the study, 44 adults ranging in age from 40 to 85 (mean age: 62.6) with mild memory changes but no dementia underwent an experimental type of PET scan to measure the level of plaque and tangles in the brain. Researchers also collected information on participants' body mass index, levels of physical activity, diet and other lifestyle factors. Plaque, deposits of a toxic protein called beta-amyloid in the spaces between nerve cells in the brain; and tangles, knotted threads of the tau protein found within brain cells, are considered the key indicators of Alzheimer's.

The study found that each one of several lifestyle factors -- a healthy body mass index, physical activity and a Mediterranean diet -- were linked to lower levels of plaques and tangles on the brain scans. (The Mediterranean diet is rich in fruits, vegetables, legumes, cereals and fish and low in meat and dairy, and characterized by a high ratio of monounsaturated to saturated fats, and mild to moderate alcohol consumption.)

"The fact that we could detect this influence of lifestyle at a molecular level before the beginning of serious memory problems surprised us," said Dr. David Merrill, the lead author of the study, which appears in the September issue of the American Journal of Geriatric Psychiatry.

Earlier studies have linked a healthy lifestyle to delays in the onset of Alzheimer's. However, the new study is the first to demonstrate how lifestyle factors directly influence abnormal proteins in people with subtle memory loss who have not yet been diagnosed with dementia, Merrill said. Healthy lifestyle factors also have been shown to be related to reduced shrinking of the brain and lower rates of atrophy in people with Alzheimer's.

Older age is the No. 1 non-modifiable risk factor for Alzheimer's disease, which affects an estimated 5.2 million people in the United States and results in more than $200 billion in health care costs annually.

"The study reinforces the importance of living a healthy life to prevent Alzheimer's, even before the development of clinically significant dementia," Merrill said. "This work lends key insight not only into the ability of patients to prevent Alzheimer's disease, but also physicians' ability to detect and image these changes."

The next step in the research will be to combine imaging with intervention studies of diet, exercise and other modifiable lifestyle factors, such as stress and cognitive health, Merrill said.
Science Daily/SOURCE :https://www.sciencedaily.com/releases/2016/08/160816084740.htm

From pollution to caffeine intake: Researcher reveals dementia risks

August 19, 2016
Science Daily/Imperial College London
Dementia strikes 47 million people worldwide. Yet scientists are still urgently trying to find why the disease affects some but not others. Among the findings from the latest research are that eating a large amount of fatty foods and living in a polluted area may increase dementia risk, whereas taking regular exercise and keeping cholesterol at healthy levels may lower risk.

Dr Ruth Peters, a neuropsychologist from Imperial College London, is one such scientist. Her research involves trying to pinpoint the risk factors for dementia. Dr Peters, from the School of Public Health at Imperial, is particularly focused on the factors that are in our power to change -- such as weight, blood pressure and alcohol intake.

Using the latest information from clinical trials and studies into dementia, she has created an infographic that shows what factors do -- and don't -- reduce the risk of dementia. She has compiled this in conjunction with Professor Kaarin J Anstey, Director of the Centre for Research on Ageing at Australian National University.

Among the findings from the latest research, represented in the infographic, are that eating a large amount of fatty foods and living in a polluted area may increase dementia risk, whereas taking regular exercise and keeping cholesterol at healthy levels may lower risk.

Dr Peters explained: "The evidence is increasingly suggesting that keeping a healthy blood circulation throughout the body is crucial for lowering dementia risk -- in other words, what is good for your heart is good for your brain."

A healthy heart, arteries and veins ensures the brain receives an adequate supply of oxygen and nutrients, which keeps our neurons functioning properly.

Dr Peters' current work is investigating whether any particular blood pressure medications seem to improve cognitive function. Her most recent research, published this week in the journal Current Hypertensive Reports, found no type of medicine seems to work better than another.

"Previous work has suggested a type of blood pressure medication called calcium channel blockers may improve cognitive function, though the latest findings don't suggest this," said Dr Peters. "There are still large gaps in our knowledge when it comes to dementia risk, which scientists are working hard to fill -- but in the meantime keeping yourself fit, active and healthy will keep your brain -- and body -- in good shape."

Professor Anstey added: "Keeping healthy in middle age is important for brain aging and reducing risk of dementia in old age -- but it's never too early or too late to take steps to reduce your risk"
Science Daily/SOURCE :https://www.sciencedaily.com/releases/2016/08/160819123603.htm

Sleep makes relearning faster and longer-lasting

August 22, 2016
Science Daily/Association for Psychological Science
Getting some sleep in between study sessions may make it easier to recall what you studied and relearn what you've forgotten, even six months later, according to new findings.
https://images.sciencedaily.com/2016/08/160822083446_1_540x360.jpg
Sleeping in between learning sessions can result in learning in less time and with less effort.
Credit: © Kar Tr / Fotolia

"Our results suggest that interleaving sleep between practice sessions leads to a twofold advantage, reducing the time spent relearning and ensuring a much better long-term retention than practice alone," explains psychological scientist Stephanie Mazza of the University of Lyon. "Previous research suggested that sleeping after learning is definitely a good strategy, but now we show that sleeping between two learning sessions greatly improves such a strategy."

While studies have shown that both repeated practice and sleep can help improve memory, there is little research investigating how repetition and sleep influence memory when they are combined. Mazza and colleagues hypothesized that sleeping in between study sessions might make the relearning process more efficient, reducing the effort needed to commit information to memory.

A total of 40 French adults were randomly assigned to either a "sleep" group or a "wake" group. At the first session, all participants were presented with 16 French-Swahili word pairs in random order. After studying a pair for 7 seconds, the Swahili word appeared and participants were prompted to type the French translation. The correct word pair was then shown for 4 seconds. Any words that were not correctly translated were presented again, until each word pair had been correctly translated.

Twelve hours after the initial session, the participants completed the recall task again, practicing the whole list of words until all 16 words were correctly translated.

Importantly, some participants completed the first session in the morning and the second session in the evening of the same day ("wake" group); others completed the first session in the evening, slept, and completed the second session the following morning ("sleep" group).

In the first session, the two groups showed no difference in how many words they could initially recall or in the number of trials they needed to be able to remember all 16 word pairs.

But after 12 hours, the data told another story: Participants who had slept between sessions recalled about 10 of the 16 words, on average, while those who hadn't slept recalled only about 7.5 words. And when it came to relearning, those who had slept needed only about 3 trials to be able to recall all 16 words, while those who had stayed awake needed about 6 trials.

Ultimately, both groups were able to learn all 16 word pairs, but sleeping in between sessions seemed to allow participants to do so in less time and with less effort.

"Memories that were not explicitly accessible at the beginning of relearning appeared to have been transformed by sleep in some way," says Mazza. "Such transformation allowed subjects to re-encode information faster and to save time during the relearning session."

The memory boost that participants got from sleeping between sessions seemed to last over time. Follow-up data showed that participants in the sleep group outperformed their peers on the recall test 1 week later. The sleep group showed very little forgetting, recalling about 15 word pairs, compared to the wake group, who were able to recall about 11 word pairs. This benefit was still noticeable 6 months later.

The benefits of sleep could not be ascribed to participants' sleep quality or sleepiness, or to their short-term or long-term memory capacity, as the two groups showed no differences on these measures.

The results suggest that alternating study sessions with sleep might be an easy and effective way to remember information over longer periods of time with less study, Mazza and colleagues conclude.
Science Daily/SOURCE :https://www.sciencedaily.com/releases/2016/08/160822083446.htm

How sleep deprivation harms memory

August 23, 2016
Science Daily/eLife
Researchers have discovered a piece in the puzzle of how sleep deprivation negatively affects memory.

For the first time, a study in mice, to be published in the journal eLife, shows that five hours of sleep deprivation leads to a loss of connectivity between neurons in the hippocampus, a region of the brain associated with learning and memory.

"It's clear that sleep plays an important role in memory -- we know that taking naps helps us retain important memories. But how sleep deprivation impairs hippocampal function and memory is less obvious," says first author Robbert Havekes, PhD, Assistant Professor at the Groningen Institute for Evolutionary Life Sciences.

It has been proposed that changes in the connectivity between synapses -- structures that allow neurons to pass signals to each other -- can affect memory. To study this further, the researchers examined the impact of brief periods of sleep loss on the structure of dendrites, the branching extensions of nerve cells along which impulses are received from other synaptic cells, in the mouse brain.

They first used the Golgi silver-staining method to visualize the length of dendrites and number of dendritic spines in the mouse hippocampus following five hours of sleep deprivation, a period of sleep loss that is known to impair memory consolidation. Their analyses indicated that sleep deprivation significantly reduces the length and spine density of the dendrites belonging to the neurons in the CA1 region of the hippocampus.

They repeated the sleep-loss experiment, but left the mice to sleep undisturbed for three hours afterwards. This period was chosen based on the scientists' previous work showing that three hours is sufficient to restore deficits caused by lack of sleep. The effects of the five-hour sleep deprivation in the mice were reversed so that their dendritic structures were similar to those observed in the mice that had slept.

The researchers then investigated what was happening during sleep deprivation at the molecular level. "We were curious about whether the structural changes in the hippocampus might be related to increased activity of the protein cofilin, since this can cause shrinkage and loss of dendritic spines," Havekes says.

"Our further studies revealed that the molecular mechanisms underlying the negative effects of sleep loss do in fact target cofilin. Blocking this protein in hippocampal neurons of sleep-deprived mice not only prevented the loss of neuronal connectivity, but also made the memory processes resilient to sleep loss. The sleep-deprived mice learned as well as non-sleep deprived subjects."

Ted Abel, PhD, Brush Family Professor of Biology at the University of Pennsylvania and senior author of the study, explains: "Lack of sleep is a common problem in our 24/7 modern society and it has severe consequences for health, overall wellbeing, and brain function.

"Despite decades of research, the reasons why sleep loss negatively impacts brain function have remained unknown. Our novel description of a pathway through which sleep deprivation impacts memory consolidation highlights the importance of the neuronal cell network's ability to adapt to sleep loss. What is perhaps most striking is that these neuronal connections are restored with several hours of recovery sleep. Thus, when subjects have a chance to catch up on much-needed sleep, they are rapidly remodeling their brain."
Science Daily/SOURCE :https://www.sciencedaily.com/releases/2016/08/160823125219.htm

Study strengthens evidence that cognitive activity can reduce dementia risk

Bias analysis shows any confounding factors not enough to account for benefits found in previous studies

August 24, 2016
Science Daily/Massachusetts General Hospital
A formal bias analysis of previous studies finding that cognitive activities can reduce the risk of Alzheimer's disease and other dementias concluded that any confounding factors in the earlier studies probably do not totally account for any associations between cognitive activity and dementia risk.

Are there any ways of preventing or delaying the development of Alzheimer's disease or other forms of age-associated dementia? While several previously published studies have suggested a protective effect for cognitive activities such as reading, playing games or attending cultural events, questions have been raised about whether these studies reveal a real cause-and-effect relationship or if the associations could result from unmeasured factors. To address this question, a Boston-based research team conducted a formal bias analysis and concluded that, while potentially confounding factors might have affected previous studies' results, it is doubtful that such factors totally account for observed associations between cognitive activities and a reduced risk of dementia.

"Our paper lends support to a potential role for late-in-life cognitive activity in prevention of Alzheimer's disease," says Deborah Blacker MD, ScD, director of the Gerontology Research Unit in the Massachusetts General Hospital Department of Psychiatry and senior author of the report in the September issue of the journal Epidemiology. "While it is possible that socioeconomic factors such as educational level might contribute to the association between cognitive activity and reduced risk, any bias introduced by such factors is probably not strong enough to fully account for the observed association."

Blacker and her colleagues from Harvard T.H. Chan School of Public Health maintain a database on the Alzheimer's Research Forum website cataloging evidence from observational studies and some clinical trials about known and proposed risk and protective factors for the devastating neurologic disorder. The current paper was developed from the database's systematic review of studies examining the impact of cognitive activity, conducted by lead author Guatam Sajeev, ScD, as part of his Harvard Chan school dissertation.

The research team analyzed 12 peer-reviewed epidemiologic studies that examined the relationship between late-in-life cognitive activities and the incidence of Alzheimer's disease or other forms of dementia. The studies were selected on the basis of prespecified criteria for the AlzRisk database, included almost 14,000 individual participants and consistently showed a benefit, sometimes substantial, for cognitive activity.

Since any observational studies are likely to be confounded by unmeasured factors -- such as participants' socioeconomic level or the presence of conditions like depression -- the researchers also conducted a bias analysis designed to evaluate how much such factors might influence reported associations between the amount of cognitive activity and dementia risk. This analysis indicated that bias due to unmeasured factors was unlikely to account for all of the association because the impact of such factors is likely to be considerably smaller than the observed effect.

The group also investigated the possible role of reverse causation -- whether a reduction in cognitive activity among those already in the long phase of cognitive decline that precedes Alzheimer's dementia might have led to an apparent rather than a real causal relationship. The findings of that analysis could not rule out the possibility that reverse causation contributed substantially to the observed associations, but analyses restricted to studies with longer term follow-up might be better able to address this question, the authors note.

"Ultimately, clinical trials with long-term follow-up are the surest way to definitively address reverse causation," says co-author and AlzRisk co-director Jennifer Weuve, MPH, ScD, of Boston University School of Public Health. "Trials could also confront the vexing question of whether training to improve specific cognitive skills has benefits that extend into everyday functions. But not every question about cognitive activity is well-suited for a trial. To fill those gaps, innovations in epidemiology, such as the analytic techniques used in this study, should help us get even greater insights from available observational data."

Blacker adds, "Cognitive activity looks like it may offer some modest protection, and based on our bias analysis, I am somewhat less skeptical than I was previously. But remember that any impact will be relative, not absolute. I typically advise people to engage in cognitive activities that they find interesting and enjoyable for their own sake. There is no evidence that one kind of activity is better than another, so I would advise against spending money on programs claiming to protect against dementia."
Science Daily/SOURCE :https://www.sciencedaily.com/releases/2016/08/160824144019.htm

Western diet increases Alzheimer's risk

August 25, 2016
Science Daily/Taylor & Francis
Globally, about 42 million people now have dementia, with Alzheimer’s disease as the most common type of dementia. Rates of Alzheimer’s disease are rising worldwide. The most important risk factors seem to be linked to diet, especially the consumption of meat, sweets, and high-fat dairy products that characterize a Western Diet. The evidence of these risk factors, which come from ecological and observational studies, also shows that fruits, vegetables, grains, low-fat dairy products, legumes, and fish are associated with reduced risk.

In addition to reviewing the journal literature, a new ecological study was conducted using Alzheimer's disease prevalence from 10 countries (Brazil, Chile, Cuba, Egypt, India, Mongolia, Nigeria, Republic of Korea, Sri Lanka, and the United States) along with dietary supply data 5, 10, and 15 years before the prevalence data. Dietary supply of meat or animal products (minus milk) 5 years before Alzheimer's disease prevalence had the highest correlations with Alzheimer's disease prevalence in this study. The study discussed the specific risk each country and region faces for developing Alzheimer's disease based on their associated dietary habits.

Residents of the United States seem to be at particular risk, with each person in the U.S. having about a 4% chance of developing Alzheimer's disease, likely due in part to the Western dietary pattern, which tends to include a large amount of meat consumption. The author, William B. Grant, states, "reducing meat consumption could significantly reduce the risk of Alzheimer's disease as well as of several cancers, diabetes mellitus type 2, stroke, and, likely, chronic kidney disease."

He concludes, "Mounting evidence from ecological and observational studies, as well as studies of mechanisms, indicates that the Western dietary pattern -- especially the large amount of meat in that diet -- is strongly associated with risk of developing Alzheimer's disease and several other chronic diseases. Although the traditional Mediterranean diet is associated with about half the risk for Alzheimer's disease of the Western diet, the traditional diets of countries such as India, Japan, and Nigeria, with very low meat consumption, are associated with an additional 50% reduction in risk of Alzheimer's disease."
Science Daily/SOURCE :https://www.sciencedaily.com/releases/2016/08/160825102121.htm

Scientists shed new light on the role of calcium in learning, memory

August 26, 2016
Science Daily/The Scripps Research Institute
While calcium's importance for our bones and teeth is well known, its role in neurons -- in particular, its effects on processes such as learning and memory -- has been less well defined. A new study offers insights into how calcium in mitochondria -- the powerhouse of all cells -- can impact the development of the brain and adult cognition.

In particular, the team showed in fruit flies, a widely used model system, that blocking a channel that brings calcium to the mitochondria, called "mitochondrial calcium uniporter," causes memory impairment but does not alter learning capacity.

"When we knocked down the activity of the uniporter, we found that flies have a deficit memory," said Ron Davis, chair of the TSRI's Department of Neuroscience. "Intact uniporter function is necessary for full and complete memory in the adult fly. What surprised us is that they were still able to learn -- albeit with a fleeting memory. But we thought they wouldn't be able to learn at all."

The mitochondrial calcium uniporter protein, first identified in 2011, allows calcium ions to move from the cell's interior into mitochondria -- like coal moving through a shoot into a furnace room. It is regulated by other proteins known as MICU1, MICU2 and EMRE. Davis noted that human patients with mutations in MICU1 can exhibit learning disabilities.

"The new study's conclusion is that mitochondrial calcium entry during development is necessary to establish the neuronal competency for supporting adult memory," said TSRI Research Associate Ilaria Drago, the first author of the study.

Drago noted the team found evidence that inhibiting mitochondrial calcium uniporter function led to a decrease in the content of synaptic vesicles (miniscule sacs within the cell where various neurotransmitters are stored) and an increase in the length of axons (the slender filaments of neurons).

While these structural problems were clearly observed, she added, what they mean in terms of neuronal development remains tantalizingly unclear.

"The discovery of a developmental role for the mitochondrial calcium uniporter complex in regulating memory in adult flies is especially intriguing and deserves more exploration," said Davis.

https://www.sciencedaily.com/releases/2016/08/160826083948.htm

Caffeine and its analogues counteract memory deficits by normalizing stress responses in the brain

August 30, 2016
Science Daily/INSERM (Institut national de la santé et de la recherche médicale)
A new study describes the mechanism by which caffeine counteracts age-related cognitive deficits in animals. The study shows that the abnormal expression of a particular receptor -- adenosine A2A, a target for caffeine -- in the brain of rats induces an aging-like profile: namely, memory impairments linked to the loss of stress controlling mechanisms.

The study coordinated by Portuguese researchers from Instituto de Medicina Molecular (iMM Lisboa) and collaborators from Inserm in Lille, France, along with teams from Germany and United States, showed that the abnormal expression of a particular receptor -- adenosine A2A, a target for caffeine -- in the brain of rats induces an aging-like profile: namely, memory impairments linked to the loss of stress controlling mechanisms.

"This is part of a larger study initiated 4 years ago in which we identified the role of this receptor in stress, but we did not know whether its activation would be sufficient to trigger all the changes. We now found that by altering the amount of this receptor alone in neurons from hippocampus and cortex -- memory related areas -- is sufficient to induce a profile that we designate as 'early-aging' combining the memory loss and an increase in stress hormones in plasma (cortisol)," explains Luisa Lopes, Group Leader at iMM Lisboa and the coordinator of the study.

When the same animals were treated with a caffeine analogue, which blocks the action of adenosine A2A receptors, both memory and stress related deficits were normalized.

David Blum, from Inserm research director, adds: "In elderly people, we know there is an increase of stress hormones that have an impact on memory. Our work supports the view that the procognitive effects of A2AR antagonists, namely caffeine, observed in Alzheimer's and age-related cognitive impairments may rely on this ability to counteract the loss of stress controlling mechanisms that occurs upon aging."

"This is important not only to understand the fundamental changes that occur upon aging, but it also identifies the dysfunctions of the adenosine A2A receptor as a key player in triggering these changes. And a very appealing therapeutic target," concludes Luisa Lopes.
Science Daily/SOURCE :https://www.sciencedaily.com/releases/2016/08/160830113749.htm