Long-term memory formation

What do you think of this article?

NYU scientists find that growth factors that build brains also build memories New York University "A team of New York University neuroscientists has determined how a pair of growth factor molecules contributes to long-term memory formation, a finding that appears in the journal Neuron. "These results give us a better understanding of memory's architecture and, specifically, how molecules act as a network in creating long-term memories," explains the paper's senior author, Thomas Carew, a professor in NYU's Center for Neural Science and dean of NYU's Faculty of Arts and Science. "More importantly, this marks another step toward elucidating the intricacies of memory function, which is vital in the development of cognitive therapies to address related afflictions." The importance of growth factor molecules (GFs) has long been known. They are critical in building brains beginning in utero and until adulthood. Moreover, over time, it's been established that GFs are "recycled" from brain builders to engineers of long-term memories. Less clear, however, is how the wide range of GF families, as well as different members within each family, act to help us create these memories. In working to address this question, the NYU research team, which also included graduate student Ashley Kopec, the study's lead author, and research scientist Gary Philips, focused on two GF families: TrkB and TGFβr-II, which represent two distinct classes of GFs that utilize different types of receptors to exert their actions in the brain. In their study, the researchers examined GFs in Aplysia californica, the California sea slug. Aplysia is a model organism that is quite powerful for this type of research because its neurons are 10 to 50 times larger than those of higher organisms, such as vertebrates, and it possesses a relatively small network of neurons--characteristics that readily allow for the examination of molecular signaling during memory formation. Specifically, to produce a form of "threat memory" called sensitization in a simple reflex system of Aplysia, the researchers presented the sea slugs with a pair of mild tail shocks delivered 45 minutes apart--the first to instill a "molecular context" in the neurons of the reflex and the second to use that context to drive molecular mechanisms that are required to form a long-term memory -- and then examined GF activity at both periods, Time 1 and Time 2. Their results showed differences in the role of these two GF families across two dimensions: time and space. At Time 1, when the context for the memory is first created, TrkB plays a critical role while TGFβr-II is irrelevant. However, at Time 2, when a long-term memory is actually formed, the roles are reversed: TGFβr-II is active, but TrkB is insignificant. In addition, the results showed spatial differences. In Aplysia, the simple neural circuit that mediates the reflex modified by learning is made up of unique sensory neurons and motor neurons. The sensory neurons' cell bodies live in one compartment of the brain while their companion synapses, which pass along signals to other cells, reside in another. In the Neuron study, the researchers found that the TrkB effects are exerted only at synapses while TGFβr-II functions only at the cell body. Overall the study provides new insights into how different GF families play unique roles both in time and in space, thus helping to elucidate the "when," "where," and "how" of memory formation." ### The research was supported by grants from the National Institute of Mental Health (RO1 MH 041083, F31 MH 100889). For more information on memory, please visit Aging and Long Term Care CE Course

Johns Hopkins research may improve early detection of dementia

Using scores obtained from cognitive tests, Johns Hopkins researchers think they have developed a model that could help determine whether memory loss in older adults is benign or a stop on the way to Alzheimer's disease. The risk of developing dementia increases markedly when a person is diagnosed with mild cognitive impairment, a noticeable and measurable decline in intellectual abilities that does not seriously interfere with daily life. But physicians have no reliable way to predict which people with mild cognitive impairment are likely to be in the 5 to 10 percent a year who progress to dementia. In a proof-of-concept study, the Johns Hopkins investigators analyzed records of 528 people age 60 and over, who were referred to the Johns Hopkins Medical Psychology Clinic for cognitive testing as part of a dementia work-up between 1996 and 2004. The results were compared to those of 135 healthy older adults who participated in a study of normal aging. Both groups completed tests of memory, language, attention, processing speed and drawing abilities from which 13 scores were recorded Nursing CEUs Since each person is naturally more skillful in some areas than in others, the scores of healthy adults showed a symmetrical, bell-shaped range: Most of their scores were high, a few were a bit lower, and a few were even lower. By grouping the patients into cohorts based on the severity of their dementia, the researchers found a trend in the test scores that is likely to mimic the deterioration of an individual's scores over time. At the outset, he says, Alzheimer's disease subtly disrupts some mental abilities, while leaving others intact. Thus, well before a person develops clear cognitive impairment, his or her performance declines slightly on a few measures. When shown on a graph, these changes cause the healthy symmetric, bell-shaped curve to shift and become asymmetrical. Regardless of how low a person's test scores were, the researchers determined that lopsidedness in their score distribution correlated with dementia. They predicted that people with low scores that were evenly distributed were not likely to develop dementia. But those with clearly lopsided test score distributions on the 13 measures administered were already experiencing varying levels of dementia. "Departures from the normal bell-shaped pattern of variability on cognitive tests might determine which people with low scores develop dementia," says David J. Schretlen, Ph.D., a professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine and leader of a study published online Nov. 12 in the journal Neuropsychology. Since these declines can be subtle, the researchers also increased the precision of cognitive testing by accounting for the effects of age, sex, race and education on test performance. The challenge for doctors, Schretlen explains, is that most normal, healthy people will produce a few low scores on cognitive testing. That makes it nearly impossible to know at the outset whether a patient who reports forgetfulness and produces one or two low scores has a benign form of mild cognitive impairment, or is in the earliest stage of dementia. As a result, doctors often tell such patients to return for follow-up testing in a year or two. But if future research confirms it, this new statistical model could help doctors get the prognosis right earlier in the disease, at the first visit, and start treating patients accordingly. Mostly, Schretlen says, doctors could use the new model to reassure patients who are not at risk of dementia, while fast-tracking interventions for those who are. Because there currently are no effective treatments for Alzheimer's disease, those likely headed that way could be counseled to take the good time they have to organize their affairs, and do things they have always wanted to do. They also could be fast-tracked into clinical trials of medications to slow the progression of dementia. "If we are going to have any hope of helping patients with Alzheimer's disease, we need to do it as early as possible," Schretlen says. "Once the brain deteriorates, there's no coming back." Recent failures of drugs in late-stage clinical trials for Alzheimer's disease have been a real blow, he adds, but new treatments are being developed. The new way of reading existing test scores follows a 2008 study by the same researchers showing that one of every six healthy adults scored poorly on two or more of 10 tests in a brief cognitive battery — even though there was nothing wrong with them. The main reason it is difficult to tell whether older people have benign mild cognitive impairment or not is because they are not routinely screened for cognitive impairment, he says. A visit to a specialist comes only after someone has noticed symptoms, and then cognitive testing is interpreted without the benefit of a baseline assessment. What would solve this problem, he says, would be for everyone over the age of 55 to get routine neurocognitive testing every five years. ### The study was supported by the Therapeutic Cognitive Neuroscience Fund; the Benjamin and Adith Miller Family Endowment on Aging, Alzheimer's and Autism; the William and Mary Ann Wockenfuss Research Fund Endowment; and the National Institutes of Health's National Institute of Mental Health (MH60504). Under an agreement with Psychological Assessment Resources, Inc., Schretlen is entitled to a share of royalties on sales of a test and software used in the study. The terms of this arrangement are being managed by The Johns Hopkins University in accordance with its conflict-of-interest policies. Other Johns Hopkins researchers involved in the study include Gila Z. Reckess, Ph.D.; Mark Varvaris, B.A.; and Barry Gordon, M.D., Ph.D. For more information about Schretlen, click here. Johns Hopkins Medicine (JHM), headquartered in Baltimore, Maryland, is a $6.7 billion integrated global health enterprise and one of the leading health care systems in the United States. JHM unites physicians and scientists of the Johns Hopkins University School of Medicine with the organizations, health professionals and facilities of The Johns Hopkins Hospital and Health System. JHM's vision, "Together, we will deliver the promise of medicine," is supported by its mission to improve the health of the community and the world by setting the standard of excellence in medical education, research and clinical care. Diverse and inclusive, JHM educates medical students, scientists, health care professionals and the public; conducts biomedical research; and provides patient-centered medicine to prevent, diagnose and treat human illness. JHM operates six academic and community hospitals, four suburban health care and surgery centers, and more than 30 primary health care outpatient sites. The Johns Hopkins Hospital, opened in 1889, was ranked number one in the nation for 21 years in a row by U.S. News & World Report. For more information about Johns Hopkins Medicine, its research, education and clinical programs, and for the latest health, science and research news, visit http://www.hopkinsmedicine.org Aging and Long Term Care CE Course Johns Hopkins Medicine Media Relations and Public Affairs

Paradox of aging: The older we get, the better we feel?

Presently, there are about 40 million Americans over the age of 65, with the fastest-growing segment of the population over 80 years old. Traditionally, aging has been viewed as a period of progressive decline in physical, cognitive and psychosocial functioning, and aging is viewed by many as the "number one public health problem" facing Americans today. But this negative view of aging contrasts with results of a comprehensive study of 1,006 older adults in San Diego by researchers from the University of California, San Diego School of Medicine and Stanford University. Results of the Successful Aging Evaluation (SAGE) study – comprising a 25-minute phone interview, followed by a comprehensive mail-in survey – will be published in the December 7 online issue of the American Journal of Psychiatry. "While there is a growing public health interest in understanding and promoting successful aging, until now little published research has combined measures of physical health with cognitive and psychological assessments, in a large and randomly selected sample," said principal investigator Dilip V. Jeste, MD, Estelle and Edgar Levi Chair in Aging, Distinguished Professor of Psychiatry and Neurosciences, and director of UC San Diego's Stein Institute for Research on Aging, and the current President of the American Psychiatric Association (which was not involved in this study). The SAGE study included adults between the ages of 50 and 99 years, with a mean age of just over 77 years. In addition to measures which assessed rates of chronic disease and disability, the survey looked at more subjective criteria such as social engagement and participants' self-assessment of their overall health. "Sometimes the most relevant outcomes are from the perspective of the subjects themselves," said Jeste. The study concludes that resilience and depression have significant bearing on how individuals self-rate successful aging, with effects that are comparable to that of physical health. "Even though older age was closely associated with worse physical and cognitive functioning, it was also related to better mental functioning," said co-author Colin Depp, PhD, associate professor of psychiatry at UC San Diego School of Medicine. After adjusting for age, a higher self-rating of successful aging was associated with higher education, better cognitive function, better perceived physical and mental health, less depression, and greater optimism and resilience. Participants were asked to rate the extent to which they thought they had "successfully aged," using a 10-point scale and using their own concept of the term. The study found that people with low physical functioning but high resilience, had self-ratings of successful aging similar to those of physical healthy people with low resilience. Likewise, the self-ratings of individuals with low physical functioning but no or minimal depression had scores comparable to those of physically healthy people with moderate to severe depression. "It was clear to us that, even in the midst of physical or cognitive decline, individuals in our study reported feeling that their well-being had improved with age," Jeste said. This counterintuitive increase in well-being with aging persisted even after accounting for variables like income, education and marriage. Jeste suggests there's a take-away message for clinicians, which is that an optimistic approach to the care of seniors may help reduce societal ageism. "There is considerable discussion In public forums about the financial drain on the society due to rising costs of healthcare for older adults – what some people disparagingly label the 'silver tsunami.' But, successfully aging older adults can be a great resource for younger generations," he said. The findings point to an important role for psychiatry in enhancing successful aging in older adults. "Perfect physical health is neither necessary nor sufficient," Jeste said. "There is potential for enhancing successful aging by fostering resilience and treating or preventing depression." Aging and Long Term Care (Abridged) CE Course (3 hours) ### Additional contributors to this study include Gauri N. Savla, PhD, Wesley K. Thompson, PhD, Ipsit V. Vahia, MD, Danielle K. Glorioso, MSW, A'verria Sirkin Martin, PhD, Barton W. Palmer, PhD, David Rock, BA, and Shahrokh Golshan, PhD, UC San Diego; and Helena C. Kraemer, PhD, professor of biostatistics in psychiatry at Stanford University. This work was supported, in part, by NIMH grants T32 MH-019934 and P30 MH-066248, by NIH National Center for Research Support grant UL1 RR-031980, by the John A. Hartford Foundation, and by the Sam and Rose Stein Institute for Research on Aging.

Guide Offers a Blueprint for End-of-Life Conversation With Youth

Enlisting the advice of adolescents and young adults with serious illness, researchers at the National Institutes of Health have developed a guide to help young people and their families address issues surrounding end-of-life care. Voicing My CHOICES is the first guide designed to help adolescents and young adults express how they would like to be comforted, supported, and cared for in the course of serious illness, and how they would like to be remembered if they do not survive. The guide is aimed at helping families and health professionals open difficult conversations, and was written using language and questions tailored to the particular needs and preferences of young people. A paper in the November 2012 issue of the journal Pediatrics reported on a study in which young people with serious illnesses read and commented on pages from two existing advance care planning guides. The study found that adolescents and young adults do want to be involved in end-of-life planning. Almost all of the 52 participants in the study felt that having such a guide was helpful and important. Their comments on specific questions shaped the content of Voicing My CHOICES. Lori Wiener, Ph.D., director of the pediatric psychosocial support and research program at the National Cancer Institute, is lead author of the Pediatrics study and developed the prototype for Voicing My CHOICES that the young participants evaluated. She collaborated with Maryland Pao, M.D., clinical director of the National Institute of Mental Health, whose staff provides psychiatric consultation at NIH’s research hospital for patients of all ages with serious illness. Developing Voicing My CHOICES began with focus groups in which young people with serious illness endorsed the need for an advance care planning guide for persons their age. Out of this came a study, reported in 2008, in which a group of 20 adolescents and young adults living with cancer or perinatally acquired HIV disease were asked to read and evaluate the publication Five Wishes, an advanced directive for adults, along with additional topics identified during the focus groups. The study team used their feedback to create a new guide for young people called My Thoughts, My Wishes, My Voice. In the current study, youth reviewed pages from this publication and Five Wishes. Their comments were incorporated in the final Voicing My CHOICES. “Adolescents and young adults often stay silent, not sharing their fears—as they do not want to further upset their parents,” said Wiener. “And parents don’t bring up end-of-life issues for the same reasons.” The research studies showed, however, that teens and young adults are interested in these issues and value the opportunity to express their preferences. The guide also serves a developmental purpose. “At a stage of life where they would normally be seeking identity and a way to leave their mark on the world, they are in a situation where they can’t make decisions,” said Pao. Youth are concerned, she said, with how they will be cared for and remembered and, true to their age, about peer relationships. They want to be heard. Voicing My CHOICES includes questions about making medical care decisions and the types of life support a young person would or would not want. In response to comments, changes were made to make the language in Voices My CHOICES less technical, and to offer both yes/no and open-ended questions. Participants in the study endorsed a section in which they can indicate whether they would like to donate their body to science or have an autopsy, which speaks powerfully, said Wiener, to their sense of altruism and the need to find meaning in their experience Aging and Long Term Care CE Course “Adolescents and young adults can feel very frightened and alone when their bodies are no longer responding to medical interventions and decisions are being made around them,” said Wiener. “Allowing them to be involved in decisions, and to document how they wish to be remembered, enhances the trust in parent and medical provider relationships and provides them with the opportunity to give meaning to their life.” The product of a collaboration between clinical research teams representing two different areas of focus within NIH’s research hospital—pediatric oncology and psychiatry—Voicing My CHOICES can be used to help patients, families, caregivers, and health care providers. Voicing My CHOICES is available from Aging With Dignity (www.agingwithdignity.org), a nonprofit that provides the advanced directive document for adults, Five Wishes. References Wiener L, Zadeh S, Battles H, Baird K, Ballard E, Osherow J, Pao M. Allowing adolescents and young adults to plan their end-of-life care. Pediatrics. 2012 Nov;130(5):897-905. doi: 10.1542/peds.2012-0663. Epub 2012 Oct 8. Wiener L, Ballard E, Brennan T, Battles H, Martinez P, Pao M. How I wish to be remembered: the use of an advance care planning document in adolescent and young adult populations. Journal of Palliative Medicine. 2008 Dec;11(10):1309-13.