neurosciencestuff:

Mental Rest and Reflection Boost Learning

A new study, which may have implications for approaches to education, finds that brain mechanisms engaged when people allow their minds to rest and reflect on things they’ve learned before may boost later learning.

Scientists have already established that resting the mind, as in daydreaming, helps strengthen memories of events and retention of information. In a new twist, researchers at The University of Texas at Austin have shown that the right kind of mental rest, which strengthens and consolidates memories from recent learning tasks, helps boost future learning.

The results appear online this week in the journal Proceedings of the National Academy of Sciences.

Margaret Schlichting, a graduate student researcher, and Alison Preston, an associate professor of psychology and neuroscience, gave participants in the study two learning tasks in which participants were asked to memorize different series of associated photo pairs. Between the tasks, participants rested and could think about anything they chose, but brain scans found that the ones who used that time to reflect on what they had learned earlier in the day fared better on tests pertaining to what they learned later, especially where small threads of information between the two tasks overlapped. Participants seemed to be making connections that helped them absorb information later on, even if it was only loosely related to something they learned before.

"We’ve shown for the first time that how the brain processes information during rest can improve future learning," says Preston. "We think replaying memories during rest makes those earlier memories stronger, not just impacting the original content, but impacting the memories to come.

Until now, many scientists assumed that prior memories are more likely to interfere with new learning. This new study shows that at least in some situations, the opposite is true.

"Nothing happens in isolation," says Preston. "When you are learning something new, you bring to mind all of the things you know that are related to that new information. In doing so, you embed the new information into your existing knowledge."

Preston described how this new understanding might help teachers design more effective ways of teaching. Imagine a college professor is teaching students about how neurons communicate in the human brain, a process that shares some common features with an electric power grid. The professor might first cue the students to remember things they learned in a high school physics class about how electricity is conducted by wires.

"A professor might first get them thinking about the properties of electricity," says Preston. "Not necessarily in lecture form, but by asking questions to get students to recall what they already know. Then, the professor might begin the lecture on neuronal communication. By prompting them beforehand, the professor might help them reactivate relevant knowledge and make the new material more digestible for them."

This research was conducted with adult participants. The researchers will next study whether a similar dynamic is at work with children.

A Discourse on Institutional Review Boards

In 2012, Dyck and Allen suggested that Institutional Review Boards (IRB), instead of approving and enforcing onerous rules, should “provide guidance and feedback on submitted projects.” They argue that, while the role of IRBs is undisputed, researchers should ultimately be responsible for ethical conduct in research. Dyck and Allen’s proposal arises out of a frustration with the IRB process as applied to low-risk research unrelated to past instances of unethical treatment of people in medical research. While their suggestion has understandable merits, I consider their proposal harmful in that it greatly weakens the ability of IRBs to prevent abuse and could potentially put IRBs on the path to ineffective irrelevance.

Researchers’ criticisms of IRBs have been well documented, especially for research outside of medicine. It is understandable that researchers want more freedom in conducting minimal-risk research, especially for purely public, anonymous, and observational research. Public policy is starting to incorporate this feedback: In 2010, the Canadian National Research Council has incorporated this feedback into their TCPS2 statement on ethical research. However, Dyck and Allen’s criticism of IRB’s disrespect for researchers exemplifies a much more systemic problem with the people who make up IRBS, one that requires much more effort to remedy.

Dyck and Allen’s suggest that the systemic problem could be solved by shifting responsibility for ethical conduct to researchers. A clear consequence of this change is to shift the ethical conversation from a largely deontological perspective to a relativist perspective. The relativist ethical perspective eschews the notion of universal ethics and instead focuses on maintaining good relationships with other people. Unintended consequences of the shift include systemic corruption, blindness to negative consequences to people outside of the researcher’s social network, and harm to future generations. For example, consider the case in which government whistleblowers have no ability to effect change after revealing corruption. Like IRBs in a relativist role, government employees would be greatly disincentivized from preventing abuse without the ability to change behaviour.

On the other hand, if Dyck and Allen’s suggestion is adopted, members of IRBs could become exasperated that they cannot stop unethical behaviour, just as researchers are currently frustrated that IRBs sometimes block or delay what they consider minimal-risk research. The IRB members would then become disincentivized from providing further feedback for lack of effectiveness and disband IRBs altogether. The role of IRBs, wether to provide guidance and feedback and/or to prevent harm, then becomes moot in the face of dissolution.

In any case, Dyck and Allen suggest that their proposal mirrors the ethical model in medicine in that doctors are trusted to upload a code of ethics and intervention is necessary only when misbehaviour is suspect. Unfortunately, this view does not address the fact that doctors generally carry out well-understood procedures while researchers explore as-yet not understood phenomena that sometimes require creative, untried methods. IRBs in advisory roles would be ineffective in reviewing the ethics of these novel methods.

Clearly, the potential consequences of shifting the role of IRBs to advisory boards are severe enough that it would be very unwise to adopt Dyck and Allen’s suggestion unilaterally. IRBs, as Dyck and Allen have indicated, have the clear and well-understood purpose of preventing ethical abuse in research. Instead of effectively abolishing IRBs, I believe that the role of IRBs can and should change to incorporate critical feedback from the research community, as in the case of IRBs in Canada.

Engaging with the World: An Epistemological Perspective

Growing up in a generally secular school environment, with little mention of religion or God, and a strong emphasis on science and mathematics, it was no surprise that I adopted the objectivist epistemology early in life. When I went to the University of Washington, however, I joined an intellectually diverse group of students as part of the University Honours Program. In the program, I experienced the social constructionist viewpoint through both courses and an immersive experience in Berlin. In the years after graduation, I relied heavily on social constructionism to make sense of a world that, to my mind, was chaotic, disordered, and unpredictablebefore eventually reintegrating objectivism for triangulation.

Before university, I had been predominantly taught the objectivist view that there is a single Truth to the world and that there was a single right way to do things. The social constructionist approach, on the other hand, taught me that people create and reaffirm meaning, and that my role in society is not only constructed, but also highly malleable. My involvement with Gay Rights groups on campus exemplified social constructionism and taught me how to challenge social hegemony, as well as challenge my own preconceptions about the world.

Unfortunately, after earning my Bachelor’s degree, reality became unpredictable. Finding work I enjoyed seemed like an insurmountable obstacle. The behaviours I learned as part of the Gay Rights movement positioned every relationship as hegemonic or adversarial, social life became wholly unstructured, and my support network disappeared almost overnight. During this time of turmoil, I read Victor Frankl’s Man’s Search for Meaning and began to search for meaning in my own lifeI continued on to read the works of Andrew Zolli, Carol Dweck, and David Brooks. From these researchers, I learned about resilience thinking, the growth mindset, and how culture and social interaction influence our sense of self and how we relate to one another. These and many other thought curators ignited a period of enlightenment in my life and taught me how to learn to think creatively, strategically, and wisely.

To better learn from past mistakes, I decided to engage, in my personal life,strategies I learned from volunteering with the startup community in Seattle. The most instrumental strategy was the fast pivot, described in Lean Startupa book and strategy by Eric Ries. The strategy required me to develop appropriate metrics to continually assessthe effectiveness of my activities and behaviours towards meeting an end goal, an approach very similar to objectivism and post-positivism. However, rather than having the notion that there is a right solution, there is instead the concept of a most appropriatesolution that meets the requirements, as indicated by the metrics. In addition, I also engaged in the 4 Actions Frameworkfrom the Blue Ocean Strategy, described by W. Chan Kim and Renée Mauborgne in a book of the same name, as a way to systematicallydefine appropriate metrics and targets.

While the research that led to the strategies I previously described engaged in social constructionism, much of the research also engaged in objectivism as well. As Danel Kahneman and other psychologists have discovered, the human mind is vulnerable to a number of cognitive fallacies, including groupthink, overestimation of improbable events, and personal bias. Objectivism offers a way to counter these fallacies, and hence the reason for my heavy emphasis on developing appropriate metrics. I use the metrics to engage in the Russian proverb to “Trust, but verify”, both to validate my own work and to provide constructive feedback for others, without relying solely on opinion or majority beliefs.

These developments have led to the current triangulation strategy in which I now engage. I use social constructionism to study and verbalize tacit knowledge and wisdom, and objectivism to validate the findings and hedge against cognitive fallacies. The strategy has proven effective thus far and I humbly thank the many wonderful people in my life, many of whom I have only met through their writing, who have taught me how to engage with the world. I could not have done it without their wisdom and generosity.

neurosciencestuff:

Study suggests neurobiological basis of human-pet relationship

It has become common for people who have pets to refer to themselves as  “pet parents,” but how closely does the relationship between people and their non-human companions mirror the parent-child relationship? A small study from a group of Massachusetts General Hospital (MGH) researchers makes a contribution to answering this complex question by investigating differences in how important brain structures are activated when women view images of their children and of their own dogs. Their report is being published in the open-access journal PLOS ONE.

“Pets hold a special place in many people’s hearts and lives, and there is compelling evidence from clinical and laboratory studies that interacting with pets can be beneficial to the physical, social and emotional wellbeing of humans,” says Lori Palley, DVM, of the MGH Center for Comparative Medicine, co-lead author of the report.  “Several previous studies have found that levels of neurohormones like oxytocin – which is involved in pair-bonding and maternal attachment – rise after interaction with pets, and new brain imaging technologies are helping us begin to understand the neurobiological basis of the relationship, which is exciting.”

In order to compare patterns of brain activation involved with the human-pet bond with those elicited by the maternal-child bond, the study enrolled a group of women with at least one child aged 2 to 10 years old and one pet dog that had been in the household for two years or longer. Participation consisted of two sessions, the first being a home visit during which participants completed several questionnaires, including ones regarding their relationships with both their child and pet dog. The participants’ dog and child were also photographed in each participants’ home.

The second session took place at the Athinoula A. Martinos Center for Biomedical Imaging at MGH, where functional magnetic resonance imaging (fMRI) – which indicates levels of activation in specific brain structures by detecting changes in blood flow and oxygen levels – was performed as participants lay in a scanner and viewed a series of photographs. The photos included images of each participant’s own child and own dog alternating with those of an unfamiliar child and dog belonging to another study participant. After the scanning session, each participant completed additional assessments, including an image recognition test to confirm she had paid close attention to photos presented during scanning, and rated several images from each category shown during the session on factors relating to pleasantness and excitement.

Of 16 women originally enrolled, complete information and MR data was available for 14 participants. The imaging studies revealed both similarities and differences in the way important brain regions reacted to images of a woman’s own child and own dog. Areas previously reported as important for functions such as emotion, reward, affiliation, visual processing and social interaction all showed increased activity when participants viewed either their own child or their own dog. A region known to be important to bond formation – the substantia nigra/ventral tegmental area (SNi/VTA) – was activated only in response to images of a participant’s own child. The fusiform gyrus, which is involved in facial recognition and other visual processing functions, actually showed greater response to own-dog images than own-child images.

“Although this is a small study that may not apply to other individuals, the results suggest there is a common brain network important for pair-bond formation and maintenance that is activated when mothers viewed images of either their child or their dog,” says Luke Stoeckel, PhD, MGH Department of Psychiatry, co-lead author of the PLOS One report. “We also observed differences in activation of some regions that may reflect variance in the evolutionary course and function of these relationships. For example, like the SNi/VTA, the nucleus accumbens has been reported to have an important role in pair-bonding in both human and animal studies. But that region showed greater deactivation when mothers viewed their own-dog images instead of greater activation in response to own-child images, as one might expect. We think the greater response of the fusiform gyrus to images of participants’ dogs may reflect the increased reliance on visual than verbal cues in human-animal communications.”

Co-author Randy Gollub, MD, PhD, of MGH Psychiatry adds, “Since fMRI is an indirect measure of neural activity and can only correlate brain activity with an individual’s experience, it will be interesting to see if future studies can directly test whether these patterns of brain activity are explained by the specific cognitive and emotional functions involved in human-animal relationships. Further, the similarities and differences in brain activity revealed by functional neuroimaging may help to generate hypotheses that eventually provide an explanation for the complexities underlying human-animal relationships.”

The investigators note that further research is needed to replicate these findings in a larger sample and to see if they are seen in other populations – such as women without children, fathers and parents of adopted children – and in relationships with other animal species. Combining fMRI studies with additional behavioral and physiological measures could obtain evidence to support a direct relationship between the observed brain activity and the purported functions.

(Image: Fotolia)

neurosciencestuff:

How curiosity changes the brain to enhance learning
The more curious we are about a topic, the easier it is to learn information about that topic. New research publishing online October 2 in the Cell Press journal Neuron provides insights into what happens in our brains when curiosity is piqued. The findings could help scientists find ways to enhance overall learning and memory in both healthy individuals and those with neurological conditions.
"Our findings potentially have far-reaching implications for the public because they reveal insights into how a form of intrinsic motivation—curiosity—affects memory. These findings suggest ways to enhance learning in the classroom and other settings," says lead author Dr. Matthias Gruber, of University of California at Davis.
For the study, participants rated their curiosity to learn the answers to a series of trivia questions. When they were later presented with a selected trivia question, there was a 14 second delay before the answer was provided, during which time the participants were shown a picture of a neutral, unrelated face. Afterwards, participants performed a surprise recognition memory test for the faces that were presented, followed by a memory test for the answers to the trivia questions. During certain parts of the study, participants had their brains scanned via functional magnetic resonance imaging.
The study revealed three major findings. First, as expected, when people were highly curious to find out the answer to a question, they were better at learning that information. More surprising, however, was that once their curiosity was aroused, they showed better learning of entirely unrelated information (face recognition) that they encountered but were not necessarily curious about. People were also better able to retain the information learned during a curious state across a 24-hour delay. “Curiosity may put the brain in a state that allows it to learn and retain any kind of information, like a vortex that sucks in what you are motivated to learn, and also everything around it,” explains Dr. Gruber.
Second, the investigators found that when curiosity is stimulated, there is increased activity in the brain circuit related to reward. “We showed that intrinsic motivation actually recruits the very same brain areas that are heavily involved in tangible, extrinsic motivation,” says Dr. Gruber. This reward circuit relies on dopamine, a chemical messenger that relays messages between neurons.
Third, the team discovered that when curiosity motivated learning, there was increased activity in the hippocampus, a brain region that is important for forming new memories, as well as increased interactions between the hippocampus and the reward circuit. “So curiosity recruits the reward system, and interactions between the reward system and the hippocampus seem to put the brain in a state in which you are more likely to learn and retain information, even if that information is not of particular interest or importance,” explains principal investigator Dr. Charan Ranganath, also of UC Davis.
The findings could have implications for medicine and beyond. For example, the brain circuits that rely on dopamine tend to decline in function as people get older, or sooner in people with neurological conditions. Understanding the relationship between motivation and memory could therefore stimulate new efforts to improve memory in the healthy elderly and to develop new approaches for treating patients with disorders that affect memory. And in the classroom or workplace, learning what might be considered boring material could be enhanced if teachers or managers are able to harness the power of students’ and workers’ curiosity about something they are naturally motivated to learn.

neurosciencestuff:

How curiosity changes the brain to enhance learning

The more curious we are about a topic, the easier it is to learn information about that topic. New research publishing online October 2 in the Cell Press journal Neuron provides insights into what happens in our brains when curiosity is piqued. The findings could help scientists find ways to enhance overall learning and memory in both healthy individuals and those with neurological conditions.

"Our findings potentially have far-reaching implications for the public because they reveal insights into how a form of intrinsic motivation—curiosity—affects memory. These findings suggest ways to enhance learning in the classroom and other settings," says lead author Dr. Matthias Gruber, of University of California at Davis.

For the study, participants rated their curiosity to learn the answers to a series of trivia questions. When they were later presented with a selected trivia question, there was a 14 second delay before the answer was provided, during which time the participants were shown a picture of a neutral, unrelated face. Afterwards, participants performed a surprise recognition memory test for the faces that were presented, followed by a memory test for the answers to the trivia questions. During certain parts of the study, participants had their brains scanned via functional magnetic resonance imaging.

The study revealed three major findings. First, as expected, when people were highly curious to find out the answer to a question, they were better at learning that information. More surprising, however, was that once their curiosity was aroused, they showed better learning of entirely unrelated information (face recognition) that they encountered but were not necessarily curious about. People were also better able to retain the information learned during a curious state across a 24-hour delay. “Curiosity may put the brain in a state that allows it to learn and retain any kind of information, like a vortex that sucks in what you are motivated to learn, and also everything around it,” explains Dr. Gruber.

Second, the investigators found that when curiosity is stimulated, there is increased activity in the brain circuit related to reward. “We showed that intrinsic motivation actually recruits the very same brain areas that are heavily involved in tangible, extrinsic motivation,” says Dr. Gruber. This reward circuit relies on dopamine, a chemical messenger that relays messages between neurons.

Third, the team discovered that when curiosity motivated learning, there was increased activity in the hippocampus, a brain region that is important for forming new memories, as well as increased interactions between the hippocampus and the reward circuit. “So curiosity recruits the reward system, and interactions between the reward system and the hippocampus seem to put the brain in a state in which you are more likely to learn and retain information, even if that information is not of particular interest or importance,” explains principal investigator Dr. Charan Ranganath, also of UC Davis.

The findings could have implications for medicine and beyond. For example, the brain circuits that rely on dopamine tend to decline in function as people get older, or sooner in people with neurological conditions. Understanding the relationship between motivation and memory could therefore stimulate new efforts to improve memory in the healthy elderly and to develop new approaches for treating patients with disorders that affect memory. And in the classroom or workplace, learning what might be considered boring material could be enhanced if teachers or managers are able to harness the power of students’ and workers’ curiosity about something they are naturally motivated to learn.

neurosciencestuff:

Why Wet Feels Wet: Understanding the Illusion of Wetness

Human sensitivity to wetness plays a role in many aspects of daily life. Whether feeling humidity, sweat or a damp towel, we often encounter stimuli that feel wet. Though it seems simple, feeling that something is wet is quite a feat because our skin does not have receptors that sense wetness. The concept of wetness, in fact, may be more of a “perceptual illusion” that our brain evokes based on our prior experiences with stimuli that we have learned are wet.

So how would a person know if he has sat on a wet seat or walked through a puddle? Researchers at Loughborough University and Oxylane Research proposed that wetness perception is intertwined with our ability to sense cold temperature and tactile sensations such as pressure and texture. They also observed the role of A-nerve fibers—sensory nerves that carry temperature and tactile information from the skin to the brain—and the effect of reduced nerve activity on wetness perception. Lastly, they hypothesized that because hairy skin is more sensitive to thermal stimuli, it would be more perceptive to wetness than glabrous skin (e.g., palms of the hands, soles of the feet), which is more sensitive to tactile stimuli.

Davide Filingeri et al. exposed 13 healthy male college students to warm, neutral and cold wet stimuli. They tested sites on the subjects’ forearms (hairy skin) and fingertips (glabrous skin). The researchers also performed the wet stimulus test with and without a nerve block. The nerve block was achieved by using an inflatable compression (blood pressure) cuff to attain enough pressure to dampen A-nerve sensitivity.

They found that wet perception increased as temperature decreased, meaning subjects were much more likely to sense cold wet stimuli than warm or neutral wet stimuli. The research team also found that the subjects were less sensitive to wetness when the A-nerve activity was blocked and that hairy skin is more sensitive to wetness than glabrous skin. These results contribute to the understanding of how humans interpret wetness and present a new model for how the brain processes this sensation.

“Based on a concept of perceptual learning and Bayesian perceptual inference, we developed the first neurophysiological model of cutaneous wetness sensitivity centered on the multisensory integration of cold-sensitive and mechanosensitive skin afferents,” the research team wrote. “Our results provide evidence for the existence of a specific information processing model that underpins the neural representation of a typical wet stimulus.”

The article “Why wet feels wet? A neurophysiological model of human cutaneous wetness sensitivity” is published in the Journal of Neurophysiology.

(Image credit)

neurosciencestuff:

Memory loss associated with Alzheimer’s reversed for first time
Since its first description over 100 years ago, Alzheimer’s disease has been without effective treatment. That may finally be about to change: in the first, small study of a novel, personalized and comprehensive program to reverse memory loss, nine of 10 participants, including the ones above, displayed subjective or objective improvement in their memories beginning within 3-to-6 months after the program’s start. Of the six patients who had to discontinue working or were struggling with their jobs at the time they joined the study, all were able to return to work or continue working with improved performance. Improvements have been sustained, and as of this writing the longest patient follow-up is two and one-half years from initial treatment. These first ten included patients with memory loss associated with Alzheimer’s disease (AD), amnestic mild cognitive impairment (aMCI), or subjective cognitive impairment (SCI; when a patient reports cognitive problems). One patient, diagnosed with late stage Alzheimer’s, did not improve.
The study, which comes jointly from the UCLA Mary S. Easton Center for Alzheimer’s Disease Research and the Buck Institute for Research on Aging, is the first to suggest that memory loss in patients may be reversed, and improvement sustained, using a complex, 36-point therapeutic 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.
The findings, published in the current online edition of the journal Aging, “are very encouraging. However, at the current time the results are anecdotal, and therefore a more extensive, controlled clinical trial is warranted,” said Dale Bredesen, the Augustus Rose Professor of Neurology and Director of the Easton Center at UCLA, a professor at the Buck Institute, and the author of the paper.
In the case of Alzheimer’s disease, Bredesen notes, there is not one drug that has been developed that stops or even slows the disease’s progression, and drugs have only had modest effects on symptoms. “In the past decade alone, hundreds of clinical trials have been conducted for Alzheimer’s at an aggregate cost of over a billion dollars, without success,” he said.
Other chronic illnesses such as cardiovascular disease, cancer, and HIV, have been improved through the use of combination therapies, he noted. Yet in the case of Alzheimer’s and other memory disorders, comprehensive combination therapies have not been explored. Yet over the past few decades, genetic and biochemical research has revealed an extensive network of molecular interactions involved in AD pathogenesis. “That suggested that a broader-based therapeutics approach, rather than a single drug that aims at a single target, may be feasible and potentially more effective for the treatment of cognitive decline due to Alzheimer’s,” said Bredesen.
While extensive preclinical studies from numerous laboratories have identified single pathogenetic targets for potential intervention, in human studies, such single target therapeutic approaches have not borne out. But, said Bredesen, it’s possible addressing multiple targets within the network underlying AD may be successful even when each target is affected in a relatively modest way. “In other words,” he said, “the effects of the various targets may be additive, or even synergistic.”
The uniform failure of drug trials in Alzheimer’s influenced Bredesen’s research to get a better understanding of the fundamental nature of the disease. His laboratory has found evidence that Alzheimer’s disease stems from an imbalance in nerve cell signaling: in the normal brain, specific signals foster nerve connections and memory making, while balancing signals support memory loss, allowing irrelevant information to be forgotten. But in Alzheimer’s disease, the balance of these opposing signals is disturbed, nerve connections are suppressed, and memories are lost.
The model of multiple targets and an imbalance in signaling runs contrary to the popular dogma that Alzheimer’s is a disease of toxicity, caused by the accumulation of sticky plaques in the brain. Bredesen believes the amyloid beta peptide, the source of the plaques, has a normal function in the brain – as part of a larger set of molecules that promotes signals that cause nerve connections to lapse. Thus the increase in the peptide that occurs in Alzheimer’s disease shifts the memory-making vs. memory-breaking balance in favor of memory loss.
Given all this, Bredesen thought that rather than a single targeted agent, the solution might be a systems type approach, the kind that is in line with the approach taken with other chronic illnesses—a multiple-component system.
“The existing Alzheimer’s drugs affect a single target, but Alzheimer’s disease is more complex. 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’s approach is personalized to the patient, based on extensive testing to determine what is affecting the plasticity signaling network of the brain. As one example, in the case of the patient with the demanding job who was forgetting her way home, her therapeutic program consisted of some, but not all of the components involved with Bredesen’s therapeutic program, and included:
(1) eliminating all simple carbohydrates, leading to a weight loss of 20 pounds; (2) eliminating gluten and processed food from her diet, with increased vegetables, fruits, and non-farmed fish; (3) to reduce stress, she began yoga; (4) as a second measure to reduce the stress of her job, she began to meditate for 20 minutes twice per day; (5) she took melatonin each night; (6) she increased her sleep from 4-5 hours per night to 7-8 hours per night; (7) she took methylcobalamin each day; (8) she took vitamin D3 each day; (9) fish oil each day; (10) CoQ10 each day; (11) she optimized her oral hygiene using an electric flosser and electric toothbrush; (12) following discussion with her primary care provider, she reinstated hormone replacement therapy that had been discontinued; (13) she fasted for a minimum of 12 hours between dinner and breakfast, and for a minimum of three hours between dinner and bedtime; (14) she exercised for a minimum of 30 minutes, 4-6 days per week.
The results for nine of the 10 patients reported in the paper suggest that memory loss may be reversed, and improvement sustained with this therapeutic program, said Bredesen. “This is the first successful demonstration,” he noted, but he cautioned that the results are anecdotal, and therefore a more extensive, controlled clinical trial is needed.
The downside to this program is its complexity. It is not easy to follow, with the burden falling on the patients and caregivers, and none of the patients were able to stick to the entire protocol. The significant diet and lifestyle changes, and multiple pills required each day, were the two most common complaints. The good news, though, said Bredesen, are the side effects: “It is noteworthy that the major side effect of this therapeutic system is improved health and an optimal body mass index, a stark contrast to the side effects of many drugs.”
The results for nine of the 10 patients reported in the paper suggest that memory loss may be reversed, and improvement sustained with this therapeutic program, said Bredesen. “This is the first successful demonstration,” he noted, but he cautioned that the results need to be replicated. “The current, anecdotal results require a larger trial, not only to confirm or refute the results reported here, but also to address key questions raised, such as the degree of improvement that can be achieved routinely, how late in the course of cognitive decline reversal can be effected, whether such an approach may be effective in patients with familial Alzheimer’s disease, and last, how long improvement can be sustained,” he said.
Cognitive decline is a major concern of the aging population. 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.
(Image: Corbis)

neurosciencestuff:

Memory loss associated with Alzheimer’s reversed for first time

Since its first description over 100 years ago, Alzheimer’s disease has been without effective treatment. That may finally be about to change: in the first, small study of a novel, personalized and comprehensive program to reverse memory loss, nine of 10 participants, including the ones above, displayed subjective or objective improvement in their memories beginning within 3-to-6 months after the program’s start. Of the six patients who had to discontinue working or were struggling with their jobs at the time they joined the study, all were able to return to work or continue working with improved performance. Improvements have been sustained, and as of this writing the longest patient follow-up is two and one-half years from initial treatment. These first ten included patients with memory loss associated with Alzheimer’s disease (AD), amnestic mild cognitive impairment (aMCI), or subjective cognitive impairment (SCI; when a patient reports cognitive problems). One patient, diagnosed with late stage Alzheimer’s, did not improve.

The study, which comes jointly from the UCLA Mary S. Easton Center for Alzheimer’s Disease Research and the Buck Institute for Research on Aging, is the first to suggest that memory loss in patients may be reversed, and improvement sustained, using a complex, 36-point therapeutic 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.

The findings, published in the current online edition of the journal Aging, “are very encouraging. However, at the current time the results are anecdotal, and therefore a more extensive, controlled clinical trial is warranted,” said Dale Bredesen, the Augustus Rose Professor of Neurology and Director of the Easton Center at UCLA, a professor at the Buck Institute, and the author of the paper.

In the case of Alzheimer’s disease, Bredesen notes, there is not one drug that has been developed that stops or even slows the disease’s progression, and drugs have only had modest effects on symptoms. “In the past decade alone, hundreds of clinical trials have been conducted for Alzheimer’s at an aggregate cost of over a billion dollars, without success,” he said.

Other chronic illnesses such as cardiovascular disease, cancer, and HIV, have been improved through the use of combination therapies, he noted. Yet in the case of Alzheimer’s and other memory disorders, comprehensive combination therapies have not been explored. Yet over the past few decades, genetic and biochemical research has revealed an extensive network of molecular interactions involved in AD pathogenesis. “That suggested that a broader-based therapeutics approach, rather than a single drug that aims at a single target, may be feasible and potentially more effective for the treatment of cognitive decline due to Alzheimer’s,” said Bredesen.

While extensive preclinical studies from numerous laboratories have identified single pathogenetic targets for potential intervention, in human studies, such single target therapeutic approaches have not borne out. But, said Bredesen, it’s possible addressing multiple targets within the network underlying AD may be successful even when each target is affected in a relatively modest way. “In other words,” he said, “the effects of the various targets may be additive, or even synergistic.”

The uniform failure of drug trials in Alzheimer’s influenced Bredesen’s research to get a better understanding of the fundamental nature of the disease. His laboratory has found evidence that Alzheimer’s disease stems from an imbalance in nerve cell signaling: in the normal brain, specific signals foster nerve connections and memory making, while balancing signals support memory loss, allowing irrelevant information to be forgotten. But in Alzheimer’s disease, the balance of these opposing signals is disturbed, nerve connections are suppressed, and memories are lost.

The model of multiple targets and an imbalance in signaling runs contrary to the popular dogma that Alzheimer’s is a disease of toxicity, caused by the accumulation of sticky plaques in the brain. Bredesen believes the amyloid beta peptide, the source of the plaques, has a normal function in the brain – as part of a larger set of molecules that promotes signals that cause nerve connections to lapse. Thus the increase in the peptide that occurs in Alzheimer’s disease shifts the memory-making vs. memory-breaking balance in favor of memory loss.

Given all this, Bredesen thought that rather than a single targeted agent, the solution might be a systems type approach, the kind that is in line with the approach taken with other chronic illnesses—a multiple-component system.

“The existing Alzheimer’s drugs affect a single target, but Alzheimer’s disease is more complex. 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’s approach is personalized to the patient, based on extensive testing to determine what is affecting the plasticity signaling network of the brain. As one example, in the case of the patient with the demanding job who was forgetting her way home, her therapeutic program consisted of some, but not all of the components involved with Bredesen’s therapeutic program, and included:

(1) eliminating all simple carbohydrates, leading to a weight loss of 20 pounds; (2) eliminating gluten and processed food from her diet, with increased vegetables, fruits, and non-farmed fish; (3) to reduce stress, she began yoga; (4) as a second measure to reduce the stress of her job, she began to meditate for 20 minutes twice per day; (5) she took melatonin each night; (6) she increased her sleep from 4-5 hours per night to 7-8 hours per night; (7) she took methylcobalamin each day; (8) she took vitamin D3 each day; (9) fish oil each day; (10) CoQ10 each day; (11) she optimized her oral hygiene using an electric flosser and electric toothbrush; (12) following discussion with her primary care provider, she reinstated hormone replacement therapy that had been discontinued; (13) she fasted for a minimum of 12 hours between dinner and breakfast, and for a minimum of three hours between dinner and bedtime; (14) she exercised for a minimum of 30 minutes, 4-6 days per week.

The results for nine of the 10 patients reported in the paper suggest that memory loss may be reversed, and improvement sustained with this therapeutic program, said Bredesen. “This is the first successful demonstration,” he noted, but he cautioned that the results are anecdotal, and therefore a more extensive, controlled clinical trial is needed.

The downside to this program is its complexity. It is not easy to follow, with the burden falling on the patients and caregivers, and none of the patients were able to stick to the entire protocol. The significant diet and lifestyle changes, and multiple pills required each day, were the two most common complaints. The good news, though, said Bredesen, are the side effects: “It is noteworthy that the major side effect of this therapeutic system is improved health and an optimal body mass index, a stark contrast to the side effects of many drugs.”

The results for nine of the 10 patients reported in the paper suggest that memory loss may be reversed, and improvement sustained with this therapeutic program, said Bredesen. “This is the first successful demonstration,” he noted, but he cautioned that the results need to be replicated. “The current, anecdotal results require a larger trial, not only to confirm or refute the results reported here, but also to address key questions raised, such as the degree of improvement that can be achieved routinely, how late in the course of cognitive decline reversal can be effected, whether such an approach may be effective in patients with familial Alzheimer’s disease, and last, how long improvement can be sustained,” he said.

Cognitive decline is a major concern of the aging population. 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.

(Image: Corbis)