1. Exercising can protect the brain from Alzheimer’s disease

    May 26, 2017 by Ashley

    From the University of British Columbia Okanagan campus press release:

    The evidence is clear. Physical activity is associated with a reduced risk of Alzheimer’s disease, says a panel of researchers and not-for-profit leaders, led by UBC’s Okanagan campus.

    The researchers also confirmed that regular physical activity may improve the performance of daily activities for people afflicted with Alzheimer’s. Their conclusions may have significant implications for the 1.1 million Canadians affected directly or indirectly by dementia.

    “As there is no current cure for Alzheimer’s, there is an urgent need for interventions to reduce the risk of developing it and to help manage the symptoms,” says study first author Kathleen Martin Ginis, professor in UBC Okanagan’s School of Health and Exercise Sciences. “After evaluating all the research available, our panel agrees that physical activity is a practical, economical and accessible intervention for both the prevention and management of Alzheimer’s disease and other dementias.”

    Martin Ginis and her cohort reviewed data from more than 150 research articles about the impact of physical activity on people with Alzheimer’s. Some of the work explored how physical activity improves the patient’s quality of life and the others examined the risk of developing Alzheimer’s based on the amount of activity in which an individual participated.

    The panel concluded that regular physical activity improves activities of daily living and mobility in in older adults with Alzheimer’s and may improve general cognition and balance. They also established that older adults not diagnosed with Alzheimer’s who are physically active, were significantly less likely to develop the disease compared to people who were inactive.

    “This is exciting work,” says Martin Ginis. “From here we were able to prepare a consensus statement and messaging which not only has community backing, but is also evidence-based. Now we have the tool to promote the protective benefit of physical activity to older adults. I’m hopeful this will move the needle on this major health concern.”

    Alzheimer’s disease is the most common form of dementia, characterized by progressive neurodegeneration that results in severe cognitive impairment, compromised physical ability and loss of independence. The number of worldwide cases is expected to increase from 30.8 million in 2010 to more than 106 million in 2050.


  2. Spread of tau protein measured in brains of Alzheimer’s patients

    May 25, 2017 by Ashley

    From the Karolinska Institutet press release:

    In a new study presented in Molecular Psychiatry, researchers at Karolinska Institutet have measured how deposits of the pathological protein tau spread through the brain over the course of Alzheimer’s disease. Their results show that the size of the deposit and the speed of its spread differ from one individual to the next, and that large amounts of tau in the brain can be linked to episodic memory impairment.

    Already in a very early phase of Alzheimer’s disease there is an accumulation of tau in the brain cells, where its adverse effect on cell function causes memory impairment. It is therefore an attractive target for vaccine researchers. For the present study, Professor Agneta Nordberg at Karolinska Institutet’s Department of Neurobiology, Care Sciences and Society and her doctoral student Konstantinos Chiotis along with the rest of her team used PET brain imaging to measure the spread of tau deposits as well as the amyloid plaque associated with Alzheimer’s disease, and charted the energy metabolism of the brain cells. They then examined how these three parameters changed over the course of the disease.

    “There’s been an international race to measure tau spread, and we probably got there first,” says Professor Nordberg. “There are no previous reports on how tau deposits spread after 17 months into the disease. Our results can improve understanding of tau accumulation in Alzheimer’s disease, help ongoing research to quantify the effect of tau vaccines, and enable early diagnosis.”

    The study included 16 patients at different stages of Alzheimer’s disease from the memory unit at Karolinska Hospital in Huddinge. The patients were given a series of neurological memory tests and underwent PET scans at 17-month intervals. While all 16 participants had abundant amyloid plaque deposition in the brain, the size and speed of spread of their tau deposits differed significantly between individuals.

    “We also saw a strong direct correlation between size of deposit and episodic memory impairment,” continues Professor Nordberg. “This could explain why the disease progresses at such a varying rate from one patient to the other. That said, tau doesn’t seem to have much of an effect on the global general memory, which is more reasonably related to brain metabolism.”

    The study was conducted in collaboration with Uppsala University, where the PET scans were performed.


  3. Study measures communication in couples affected by dementia

    May 20, 2017 by Ashley

    From the Florida Atlantic University press release:

    In marriage, good communication is key to a fulfilling and enduring relationship. For people with dementia, communicating needs, emotions and interacting with others becomes increasingly difficult as communication deteriorates as dementia progresses. Problems in communicating lead to misinterpretations and misunderstandings, which often cause considerable stress for family members, especially the spouse caregivers as well as the patient.

    But all is not lost according to the first study to look at and measure communication outcomes in both the caregiver spouse and the patient with dementia. In fact, researchers from Florida Atlantic University have found that “practice makes perfect” with the right intervention and a tool that can accurately measure couples’ communication. Results from the study are published in the journal Issues in Mental Health Nursing.

    “There has been very little focus on the patient with dementia’s role in maintaining spousal relationships through conversation,” said Christine L. Williams, DNSc, principal investigator of the study and a professor and director of the Ph.D. in Nursing Program in FAU’s Christine E. Lynn College of Nursing, who designed the intervention program and developed the first tool that measures couples’ communication. “Maybe it’s because researchers assume that the patient can’t have a positive influence on communication because of dementia. We wanted to explore this issue further, especially for couples with a history of special memories shared over decades of marriage.”

    For the study, Williams videotaped and later analyzed and measured 118 conversations between 15 patients with varying degrees of dementia and their spouses — married an average of 45 years — to evaluate the effects of a 10-week communication-enhancement intervention on participant’s communication and mental health.

    Caregivers were taught to communicate in a manner that was clear, succinct and respectful, and to avoid testing memory and arguing. Spouses with dementia were given the opportunity to practice their conversation skills with a member of the research team who was trained in communication deficits associated with dementia as well as the intervention. Conversations were recorded at the couples’ homes. After setting up the video camera, Williams conducted the intervention and then left the room for 10 minutes. Couples were instructed to converse on a topic of their choice for 10 minutes.

    “There are very few studies that have looked at actual communication between couples in these circumstances and tried to analyze it,” said Williams. “For instance, I’ve seen studies where they have taught communication strategies to caregivers, but then what they measure is the caregivers’ knowledge about communication, which doesn’t tell you anything about whether or not they were able to communicate.”

    Unlike other measures of patient communication, the Verbal and Nonverbal Interaction Scale-CR (VNIS-CR) tool developed by Williams takes into account nonverbal behaviors, which account for more than 70 percent of communication, as well as verbal behaviors. VNIS-CR delineates social and unsociable behaviors, characterizes patient behaviors (not through the lens of a caregiver), and is targeted to spousal relationships in the home. Consisting of 13 social and 13 unsociable communication behaviors with both verbal and nonverbal items, the tool helps to describe sociable and unsociable communication in patients with dementia as they engage in conversations with their spouses.

    Nonverbal, non-sociable items in the tool included aloofness, staring into space and being nonresponsive; nonverbal, sociable items included looking or gazing at the spouse, being affectionate and joking. Social verbal behaviors included using coherent conversation, responding to questions, and addressing their partner by name or endearment. Unsociable verbal behaviors included shouting, cursing and unintelligible communication. The 13-item scores were summed up to obtain the final score.

    “Using this new tool, I was able to confirm that the intervention I used actually worked and that communication improved in both the spouse caregiver and the patient over time,” said Williams. “I was ecstatic because I originally thought that maybe the caregiver’s communication would improve and that would be great. However, to have positive changes in a person who is continuing to decline over 10 weeks, which is a long time, was something I really did not expect. This intervention worked for both the caregiver and the patient and we now have a tool to demonstrate it.”

    Globally, Alzheimer’s disease (AD) and related dementias affected 35.6 million individuals in 2010 and it is expected to grow to 115.4 million by 2050. The prevalence of dementia will increase as longevity increases and future family caregivers are likely to be predominantly spouses. In the United States, most people with dementia are cared for by their spouses.

    “As patients progress with dementia, couples don’t have to lose everything especially if they are engaged, if they can still relate to one another and if they focus on the here and now,” said Williams.

    The VNIS-CR could be used in clinical practice to describe changes in social communication abilities over time, as well as to educate spousal caregivers about the importance of encouraging sociable communication. Knowledge gained from using this tool could better guide the development of interventions to support intimate relationships and ultimately measure changes following those interventions.


  4. PTSD, certain prescriptions for PTSD may raise risk for dementia

    May 15, 2017 by Ashley

    From the American Geriatrics Society press release:

    Researchers are discovering that post-traumatic stress disorder (PTSD) is a significant risk factor in developing dementia. Dementia is a memory problem that affects a person’s ability to carry out usual tasks. Dementia is a leading cause of serious illness, disability, and death. It often requires care in a nursing home or other long-term care facility for people aged 65 and older.

    Until now, researchers didn’t know whether the kinds of medications used for people with PTSD could increase risks for dementia. (These medications include including antidepressants, antipsychotics, sedatives, or tranquilizers.) A new study, published in the Journal of the American Geriatrics Society, examined this connection.

    In their study, researchers examined information from 3,139,780 veterans aged 56 and older. At the beginning of the study, in 2003, the veterans were receiving health care from a Veterans Health Administration facility. Almost all the veterans were male and 82% were white.

    Of the veterans in the study, 5.4% had been diagnosed with PTSD. As the researchers looked at the data over the study’s nine-year follow-up period, they also included veterans who were diagnosed with dementia.

    Research has previously shown that veterans with PTSD are more likely to have health problems linked to a higher risk for dementia. These include traumatic brain injury, diabetes, chronic obstructive pulmonary disease (COPD), psychiatric disorders, substance abuse, and other health issues.

    In this study, researchers discovered that taking certain antidepressants, tranquilizers, sedatives, or antipsychotic medications significantly increased veterans’ risks for developing dementia compared to the risks for veterans who didn’t take such medications.

    Medicines that significantly increased dementia risk included:

    • Selective serotonin reuptake inhibitors (SSRIs)
    • Novel antidepressants
    • Atypical antipsychotics

    The increase in the risk of dementia for veterans taking the drugs was the same whether or not they were diagnosed with PTSD. (This is compared to veterans who weren’t taking these drugs.)

    What’s more, veterans who used three classes of medications were also more likely to be diagnosed with dementia whether or not they had PTSD. These medicines include:

    • Novel antidepressants
    • Serotonin-norepinephrine reuptake inhibitors (SNRIs)
    • Benzodiazepines

    The researchers noted that an interaction among these “psychoactive” drugs could potentially affect how PTSD impacts a person’s risk for developing dementia. The researchers concluded that further research should be conducted to learn more about PTSD and psychoactive drugs, including dosage, how long to take the medications, and which people could most benefit from them.


  5. Study suggests cannabis reverses aging processes in the brain

    May 13, 2017 by Ashley

    From the University of Bonn press release:

    Memory performance decreases with increasing age. Cannabis can reverse these ageing processes in the brain. This was shown in mice by scientists at the University of Bonn with their colleagues at The Hebrew University of Jerusalem (Israel). Old animals were able to regress to the state of two-month-old mice with a prolonged low-dose treatment with a cannabis active ingredient. This opens up new options, for instance, when it comes to treating dementia. The results are now presented in the journal Nature Medicine.

    Like any other organ, our brain ages. As a result, cognitive ability also decreases with increasing age. This can be noticed, for instance, in that it becomes more difficult to learn new things or devote attention to several things at the same time. This process is normal, but can also promote dementia. Researchers have long been looking for ways to slow down or even reverse this process.

    Scientists at the University of Bonn and The Hebrew University of Jerusalem (Israel) have now achieved this in mice. These animals have a relatively short life expectancy in nature and display pronounced cognitive deficits even at twelve months of age. The researchers administered a small quantity of THC, the active ingredient in the hemp plant (cannabis), to mice aged two, twelve and 18 months over a period of four weeks.

    Afterwards, they tested learning capacity and memory performance in the animals — including, for instance, orientation skills and the recognition of other mice. Mice who were only given a placebo displayed natural age-dependent learning and memory losses. In contrast, the cognitive functions of the animals treated with cannabis were just as good as the two-month-old control animals. “The treatment completely reversed the loss of performance in the old animals,” reported Prof. Andreas Zimmer from the Institute of Molecular Psychiatry at the University of Bonn and member of the Cluster of Excellence ImmunoSensation.

    Years of meticulous research

    This treatment success is the result of years of meticulous research. First of all, the scientists discovered that the brain ages much faster when mice do not possess any functional receptors for THC. These cannabinoid 1 (CB1) receptors are proteins to which the substances dock and thus trigger a signal chain. CB1 is also the reason for the intoxicating effect of THC in cannabis products, such as hashish or marihuana, which accumulate at the receptor. THC imitates the effect of cannabinoids produced naturally in the body, which fulfil important functions in the brain. “With increasing age, the quantity of the cannabinoids naturally formed in the brain reduces,” says Prof. Zimmer. “When the activity of the cannabinoid system declines, we find rapid ageing in the brain.”

    To discover precisely what effect the THC treatment has in old mice, the researchers examined the brain tissue and gene activity of the treated mice. The findings were surprising: the molecular signature no longer corresponded to that of old animals, but was instead very similar to that of young animals. The number of links between the nerve cells in the brain also increased again, which is an important prerequisite for learning ability. “It looked as though the THC treatment turned back the molecular clock,” says Zimmer.

    Next step: clinical trial on humans

    A low dose of the administered THC was chosen so that there was no intoxicating effect in the mice. Cannabis products are already permitted as medications, for instance as pain relief. As a next step, the researchers want to conduct a clinical trial to investigate whether THC also reverses ageing processes in the brain in humans and can increase cognitive ability.

    The North Rhine-Westphalia science minister Svenja Schulze appeared thrilled by the study: “The promotion of knowledge-led research is indispensable, as it is the breeding ground for all matters relating to application. Although there is a long path from mice to humans, I feel extremely positive about the prospect that THC could be used to treat dementia, for instance.”


  6. Better quality relationships associated with reduced dementia risk

    May 11, 2017 by Ashley

    From the University of East Anglia press release:

    Positive social support from adult children is associated with reduced risk of developing dementia, according to a new research published today.

    Conversely, negative social support is linked with increased risk, according to the 10-year follow-up study carried out by a team of researchers from the University of East Anglia (UEA), University College London (UCL), London Metropolitan University and the University of Nottingham.

    The study was based on data from the English Longitudinal Study of Ageing (ELSA) and conducted by Dr Mizanur Khondoker at UEA, Professors Andrew Steptoe and Stephen Morris at UCL, Dr Snorri Rafnsson at London Metropolitan and Prof Martin Orrell at Nottingham. The research was part of the Promoting Independence in Dementia (PRIDE) programme and is published today in the Journal of Alzheimer’s Disease.

    The researchers analysed a decade of data that followed 10,055 core participants from ELSA who were dementia-free at the start of the study in 2002-2003. Participants were interviewed every two years during 2004-2012 and incidence of dementia was identified from self-reports by participants or information given by nominated informants.

    Measures of positive and negative experiences of social support were calculated at baseline (2002) using a set of six items within the ‘Health and lifestyle of people aged 50 and over’ questionnaire of ELSA. The scale ranged from 1-4 with higher values indicating more of positive or negative support.

    An increase of one point in the positive social support score led to up to a 17 per cent reduction in the instantaneous risk of developing dementia, the findings showed. Positive support was characterised by having a reliable, approachable and understanding relationship with spouses or partners, children and other immediate family.

    But negative support scores showed stronger effects — an increase of one point in the negative support score led to up to 31 per cent rise in the risk. Negative support was characterised by experiences of critical, unreliable and annoying behaviours from spouses or partners, children and other immediate family.

    Of the 5,475 men and 4,580 women the study followed, 3.4 per cent were recorded as developing some form of dementia during 2004 — 2012.

    Dr Mizanur Khondoker, a senior lecturer in medical statistics at UEA’s Norwich Medical School, said: “It is well known that having a rich network of close relationships, including being married and having adult children, is related to a reduced risk of cognitive decline and developing dementia.

    “However, a relationship or social connection that does not work well can be a source of intense interpersonal stress, which may have a negative impact on both physical and mental health of older adults. It is not only the quantity of social connections, but the quality of those connections may be an important factor affecting older people’s cognitive health.

    “This work is a step toward better understanding of the impact of social relationships on dementia risk, but further research is needed to better establish any potential causal mechanisms that may drive these associations.”

    UCL Prof Andrew Steptoe said: “Our findings add to the growing evidence of the relevance of social relationships for cognitive health in older age. Specifically for health and social care practice, the research highlights the value of thinking about social relationship issues in individuals vulnerable to dementia, while pointing toward specific ways of potentially modifying risk.

    “Our results will add to the impetus underlying local and national efforts to help strengthen the social relationships of older people, many of whom are isolated and lonely.”


  7. Retirement associated with lower stress, but only if you were in a top job

    May 10, 2017 by Ashley

    From the Oxford University Press USA press release:

    A new paper published in the Journal of Gerontology suggests that the period around retirement may widen socio-economic inequalities in stress and health.

    Poorer people, or people in low status occupations, often have poorer health and higher biological stress response levels. The socio-economic-health gradient peaks around retirement in the United States and a number of European countries. This widening in health inequalities could be a reflection of the accumulation of socio-economic disadvantages over a lifetime, with early life inequalities in health becoming magnified over the life cycle.

    Retirement, however, could potentially moderate this pattern of widening health inequalities if changes in biological stress levels during retirement differ between socioeconomic groups. Higher stress levels associated with lower status work could be mitigated by retirement.

    Cortisol is a stress hormone that follows a diurnal profile, peaking around 30 minutes after awakening, and returning to very low levels by bedtime. Stressors disrupt the diurnal profile of cortisol, resulting in elevated levels of cortisol and a flatter diurnal slope from the awakening response to bedtime. Flatter diurnal cortisol slopes are thus a key biomarker associated with higher levels of stress.

    Flatter diurnal cortisol slopes are also associated with cardiovascular mortality — a one standard deviation increase in cortisol at bedtime was associated with a doubling of the relative risk of cardiovascular mortality within 6-8 years.

    This study investigated whether workers who had recently retired had lower biological stress levels as indicated by steeper (more advantageous) diurnal cortisol slopes compared to those still working in later life.

    Data from the London based Whitehall II civil servants study were analysed. 1,143 respondents who were employed with an average age of 60 were measured from five samples collected across the day. Civil service employment grade was used to categorise people into high, middle or low grades.

    Retirement was associated with lower stress levels- those who had recently retired had steeper diurnal slopes compared to those who remained in work. But on further investigation, this apparent benefit of retirement on lowering biological stress response levels was only confined to those in high status jobs. Workers in the lowest status jobs had flatter diurnal cortisol slopes compared to those in the top jobs. And retirement increased, rather than decreased these differences in biological stress levels.

    This study has shown that British civil servants employed in the lowest status jobs had the highest levels of stress as indicated by flatter (more adverse) diurnal cortisol slopes compared to those in the highest status jobs. Socio-economic differences in cortisol levels increase, rather than decrease, around the retirement period. These biological differences associated with transitions into retirement for different occupational groups may partly explain the pattern of widening social inequalities in health in early old age.

    “It may seem counter-intuitive that stopping low status work which may be stressful does not reduce biological levels of stress, said the study’s lead author, Tarani Chandola. “This may be because workers who retire from low status jobs often face financial and other pressures in retirement. This study suggests that people’s stress levels are not just determined by immediate circumstances, but by long run factors over the course of their lives.


  8. Brain’s power to adapt offers short-term gains, long-term strains

    May 9, 2017 by Ashley

    From the Penn State press release:

    Like air-traffic controllers scrambling to reconnect flights when a major hub goes down, the brain has a remarkable ability to rewire itself after suffering an injury. However, maintaining these new connections between brain regions can strain the brain’s resources, which can lead to serious problems later, including Alzheimer’s Disease, according to researchers.

    After a head injury, the brain can show enhanced connectivity by using alternative routes between two previously connected regions of the brain that need to communicate, as well as make stronger connections, said Frank G. Hillary, associate professor of psychology, Penn State. These new connections between damaged areas are often referred to as hyperconnections, he added.

    Hyperconnectivity has been called a compensatory reaction to brain injury and it’s a little counterintuitive because it implies that the brain can increase its functional response when you take away physical resources,” said Hillary. “If the axon — the physical connection — between brain areas is removed, the brain can retain that connection functionally by using alternative routes. So what we’re seeing is there are all sorts of ways in which the brain can adapt and one way is to heighten the response, but the question is what does that do for you in the short term and what are the potential secondary consequences in the long term.”

    Because neural networks are typically designed to communicate as efficiently as possible, disruptions may mean that new networks are less efficient and use more energy, said Hillary, who worked with Jordan H. Grafman, director, brain injury research at Shirley Ryan Abilitylab and professor of physical medicine and rehabilitation, neurology and psychiatry and behavioral sciences at the Northwestern University in Chicago.

    It’s costly metabolically and it’s costly with respect to how quickly you think,” said Hillary. “One of the primary cognitive deficits in all neurological disorders — multiple sclerosis, traumatic brain injury, schizophrenia — is impairments in how quickly you can think, called processing speed. In neurological disorders, processing speed diminishes and it can be related to a decrease in brain efficiency.”

    Over time, these chronic inefficiencies may cascade into serious brain disorders, according to the researchers, who report their findings in the current issue of Trends in Cognitive Science.

    “If we know which patients would be susceptible to pathological hyperconnectivity following a traumatic brain injury, we might be able to develop new interventions to alter the course of that process,” said Grafman. Prior research has suggested a connection between brain injury and Alzheimer’s Disease, according to the researchers.

    “We know that brain injury is a risk factor for Alzheimer’s Disease later in life and the long-term effect of hyperconnections may be a link to how it happens,” said Hillary, who also is a faculty member at Penn State College of Medicine.

    Just as inefficient motors tend to pollute more, inefficient neural connections may build up harmful deposits that can further impair the brain. Although other factors, such as genetics, are likely involved, the researchers noted that higher deposits of amyloid beta — a marker of Alzheimer’s Disease — are often located at sites where there is the highest connectivity.

    “Where there’s a lot of activity going on, it increases metabolic byproducts and if you don’t clear them, they collect,” said Hillary. “Heavy activation, heavy connectivity can put pressure on network hubs and that’s why those hubs are some of the first to go in Alzheimer’s.”

    While more research is needed and possible treatment targets for Alzheimer’s or other neurological conditions remain uncertain, Hillary said the findings underscore the need to take precautions against brain injury.

    “What I always tell my students is be good to your brain,” said Hillary. “You only get one brain and while it can adapt to some injuries over your life, there is probably a cost for those adjustments.”


  9. Brain stimulation during training boosts performance

    by Ashley

    From the DOE/Sandia National Laboratories press release:

    Your Saturday Salsa club or Introductory Italian class might be even better for you than you thought.

    According to Sandia National Laboratories cognitive scientist Mike Trumbo, learning a language or an instrument or going dancing is the best way to keep your brain keen despite the ravages of time. Not only do you enhance your cognition but you also learn a skill and have fun.

    Several commercial enterprises have claimed you can get cognitive benefits from brain training games intended to enhance working memory. Working memory is the amount of information you can hold and manipulate in your mind at one time, said cognitive scientist Laura Matzen. However, a burgeoning body of research shows working memory training games don’t provide the benefits claimed. A study by Trumbo, Matzen and six colleagues published in Memory and Cognition shows evidence that working memory training actually impairs other kinds of memory.

    On the other hand, studies have shown that learning another language can help school-age children do better in math and can delay the onset of dementia in older adults. Also going dancing regularly is the best protection against dementia compared to 16 different leisure activities, such as doing crossword puzzles and bicycling. Playing board games and practicing a musical instrument are the next best activities for keeping the mind sharp. Dancing is probably so effective because it combines cognitive exertion, physical exercise and social interaction, said Trumbo.

    New research from Sandia published in Neuropsychologia shows that working memory training combined with a kind of noninvasive brain stimulation can lead to cognitive improvement under certain conditions. Improving working memory or cognitive strategies could be very valuable for training people faster and more efficiently.

    “The idea for why brain stimulation might work when training falls short is because you’re directly influencing brain plasticity in the regions that are relevant to working memory task performance. If you’re improving connectivity in a brain region involved in working memory, then you should get transfer to other tasks to the extent that they rely on that same brain region,” said Trumbo. “Whereas when you’re having people do tasks in the absence of brain stimulation, it’s not clear if you’re getting this general improvement in working memory brain areas. You might be getting very selective, task kind of improvements.”

    Matzen cautioned that research using transcranial direct current stimulation (tDCS) to improve cognitive performance is relatively new, and the field has produced mixed results. More research is needed to understand how best to use this technology.

    Neurons that fire together wire together

    Using more than 70 volunteers divided into six groups, the researchers used different combinations of working memory training with transcranial direct current stimulation. Then they assessed the volunteers’ performance on working memory tests and a test of problem-solving ability.

    Using electrodes placed on the scalp and powered by a 9-volt battery, a tDCS unit delivers weak constant current through the skull to the brain tissue below. According to Trumbo, most people feel some mild tingling, itching or heat under the electrode for the first few minutes. There are well-established safety guidelines for tDCS research, ensuring that the procedure is safe and comfortable for participants and this research was approved by Sandia’s Human Studies Board and the University of New Mexico’s Institutional Review Board. There are commercial tDCS devices already on the market.

    Researchers think tDCS makes neurons a little bit more likely to fire, which can help speed up the formation of neuronal connections and thus learning, said Matzen. Though the exact mechanisms aren’t well understood, its potential is. According to studies, tDCS can help volunteers remember people’s names, is better than caffeine at keeping Air Force personnel awake and may even help fight depression.

    Brain stimulation and brain training: better together?

    In the Sandia-led study, the volunteers played verbal or spatial memory training games for 30 minutes while receiving stimulation to the left or right forehead. That part of the brain is called the dorsolateral prefrontal cortex and is involved in working memory and reasoning. Since the right hemisphere is involved in spatial tasks and the left hemisphere is involved in verbal tasks, the researchers thought volunteers who received stimulation on the right side while training on spatial tasks would improve on spatial tests and those who received stimulation on the left side while training on verbal tasks would improve on verbal tests.

    The verbal task involved remembering if a letter had appeared three letters back in a string of letters, for instance A-C-B-A-D. The spatial task was similar but involved remembering the sequence that blocks appear in a grid.

    As expected, the spatial/right group got better at the spatial test but not verbal or reasoning tests. The spatial/left group performed about the same as the volunteers that received mock stimulation. The verbal/left group got better at the verbal test but not spatial or reasoning tests.

    However, the results from the verbal/right group were surprising, said Trumbo. This group got better at the trained task — remembering strings of letters — as well as the closely related task — remembering the sequence of boxes in a grid. They also improved on a reasoning test. The sample size was small, with only 12 volunteers, but the improvements were statistically significant, said Matzen.

    One explanation Trumbo offered is that the right dorsolateral prefrontal cortex is particularly involved in strategy use during tasks. By stimulating the right side during the verbal task, the volunteers might get better at using a strategy. The tDCS improves the connections of these neurons, which leads to enhanced ability to use this strategy, even on other tasks.

    He added, “We did not explicitly collect data related to strategy use, so it is kind of an open question. I’d really like to do some follow-up work.”

    If tDCS can reliably enhance working memory or cognitive strategies, it could be very useful for training people faster and more efficiently. Matzen said, “This could benefit many mission areas at Sandia where people must learn complex tools and systems. Reducing training time and improving cognitive performance would have substantial benefits to overall system performance.”


  10. Low levels of ‘memory protein’ linked to cognitive decline in Alzheimer’s disease

    May 7, 2017 by Ashley

    From the Johns Hopkins Medicine press release:

    Working with human brain tissue samples and genetically engineered mice, Johns Hopkins Medicine researchers together with colleagues at the National Institutes of Health, the University of California San Diego Shiley-Marcos Alzheimer’s Disease Research Center, Columbia University, and the Institute for Basic Research in Staten Island say that consequences of low levels of the protein NPTX2 in the brains of people with Alzheimer’s disease (AD) may change the pattern of neural activity in ways that lead to the learning and memory loss that are hallmarks of the disease.

    This discovery, described online in the April 25 edition of eLife, will lead to important research and may one day help experts develop new and better therapies for Alzheimer’s and other forms of cognitive decline.

    AD currently affects more than five million Americans.

    Clumps of proteins called amyloid plaques, long seen in the brains of people with AD, are often blamed for the mental decline associated with the disease. But autopsies and brain imaging studies reveal that people can have high levels of amyloid without displaying symptoms of AD, calling into question a direct link between amyloid and dementia.

    This new study shows that when the protein NPTX2 is “turned down” at the same time that amyloid is accumulating in the brain, circuit adaptations that are essential for neurons to “speak in unison” are disrupted, resulting in a failure of memory.

    “These findings represent something extraordinarily interesting about how cognition fails in human Alzheimer’s disease,” says Paul Worley, M.D., a neuroscientist at the Johns Hopkins University School of Medicine and the paper’s senior author. “The key point here is that it’s the combination of amyloid and low NPTX2 that leads to cognitive failure.”

    Since the 1990s, Worley’s group has been studying a set of genes known as “immediate early genes,” so called because they’re activated almost instantly in brain cells when people and other animals have an experience that results in a new memory.

    The gene NPTX2 is one of these immediate early genes that gets activated and makes a protein that neurons use to strengthen “circuits” in the brain.

    “Those connections are essential for the brain to establish synchronized groups of ‘circuits’ in response to experiences,” says Worley. “Without them, neuronal activation cannot be effectively synchronized and the brain cannot process information.”

    Worley says he was intrigued by previous studies indicating altered patterns of activity in brains of individuals with Alzheimer’s. Worley’s group wondered whether altered activity was linked to changes in immediate early gene function.

    To get answers, the researchers first turned to a library of 144 archived human brain tissue samples to measure levels of the protein encoded by the NPTX2 gene. NPTX2 protein levels, they discovered, were reduced by as much as 90 percent in brain samples from people with AD compared with age-matched brain samples without AD. By contrast, people with amyloid plaques who had never shown signs of AD had normal levels of NPTX2. This was an initial suggestion of a link between NPTX2 and cognition.

    Prior studies had shown NPTX2 to play an essential role for developmental brain wiring and for resistance to experimental epilepsy. To study how lower-than-normal levels of NPTX2 might be related to the cognitive dysfunction of AD, Worley and his collaborators examined mice bred without the rodent equivalent of the NPTX2 gene.

    Tests showed that a lack of NPTX2 alone wasn’t enough to affect cell function as tested in brain slices. But then the researchers added to mice a gene that increases amyloid generation in their brain. In brain slices from mice with both amyloid and no NPTX2, fast-spiking interneurons could not control brain “rhythms” important for making new memories. Moreover, a glutamate receptor that is normally expressed in interneurons and essential for interneuron function was down-regulated as a consequence of amyloid and NPTX2 deletion in mouse and similarly reduced in human AD brain.

    Worley says that results suggest that the increased activity seen in the brains of AD patients is due to low NPTX2, combined with amyloid plaques, with consequent disruption of interneuron function. And if the effect of NPTX2 and amyloid is synergistic — one depending on the other for the effect — it would explain why not all people with high levels of brain amyloid show signs of AD.

    The team then examined NPTX2 protein in the cerebrospinal fluid (CSF) of 60 living AD patients and 72 people without AD. Lower scores of memory and cognition on standard AD tests, they found, were associated with lower levels of NPTX2 in the CSF. Moreover, NPTX2 correlated with measures of the size of the hippocampus, a brain region essential for memory that shrinks in AD. In this patient population, NPTX2 levels were more closely correlated with cognitive performance than current best biomarkers — including tau, a biomarker of neurodegenerative diseases, and a biomarker known as A-beta-42, which has long been associated with AD. Overall, NPTX2 levels in the CSF of AD patients were 36 to 70 percent lower than in people without AD.

    “Perhaps the most important aspect of the discovery is that NPTX2 reduction appears to be independent of the mechanism that generates amyloid plaques. This means that NPTX2 represents a new mechanism, which is strongly founded in basic science research, and that has not previously been studied in animal models or in the context of human disease. This creates many new opportunities,” says Worley.

    “One immediate application may be to determine whether measures of NPTX2 can be helpful as a way of sorting patients and identifying a subset that are most responsive to emerging therapies.” Worley says. For instance, drugs that disrupt amyloid may be more effective in patients with relatively high NPTX2. His group is now providing reagents to companies to assess development of a commercial test that measures NPTX2 levels.

    More work is needed, Worley adds, to understand why NPTX2 levels become low in AD and how that process could be prevented or slowed.