Posts tagged memory
Articles and news from the latest research reports.
Statin Use Not Linked to a Decline in Cognitive Function
Based on the largest comprehensive systematic review to date, researchers at the Perelman School of Medicine at the University of Pennsylvania concluded that available evidence does not support an association between statins and memory loss or dementia. The new study, a collaborative effort between faculty in Penn Medicine’s Preventive Cardiovascular Program, the Penn Memory Center, and the Penn Center for Evidence-Based Practice, will be published in Annals of Internal Medicine.
“Statins are prescribed to approximately 30 million people in the United States, and these numbers may increase as a result of the national cholesterol guidelines recently released,” said senior study author Emil deGoma, MD, assistant professor of Medicine and medical director of the Preventive Cardiovascular Program at Penn. “A wealth of data supports a benefit of these cholesterol-lowering medications among individuals at risk for cardiovascular disease in terms of a reduction in the risk of heart attack and stroke; however, potential side effects of statins are less well understood. In February 2012, largely based on anecdotal reports, the U.S. Food and Drug Administration (FDA) issued a safety statement warning patients of possible adverse cognitive effects associated with statin use. Many concerned patients have asked if there is a relationship between statins and memory problems. Their concerns, along with the FDA statement, prompted us to pursue a rigorous analysis of all available evidence to better answer the question – are statins associated with changes in cognition?”
The research team conducted a systematic review of the published literature and identified 57 statin studies reporting measures of cognitive function. Dr. deGoma and colleagues found no evidence of an increased risk of dementia with statin therapy. In fact, in cohort studies, statin users had a 13 percent lower risk of dementia, a 21 percent lower risk of Alzheimer’s disease, and a 34 percent lower risk of mild cognitive impairment compared to people who did not take statins.
Most importantly, cognitive test scores were not adversely affected by statin treatment in randomized controlled trials. In these trials, roughly half of the study participants received statins and the other half received placebo. All study participants underwent formal testing of memory and other cognitive domains through tests such as the ability to recall a set of numbers. The analysis of 155 cognitive tests spanning eight categories of cognitive function, including 26 tests of memory, revealed no differences between study participants treated with statins and those provided placebo.
The research team additionally performed an analysis of the FDA post-marketing surveillance databases and found no difference in the frequency of cognitive adverse event reports between statins and two commonly prescribed cardiovascular medications that have not been associated with cognitive impairment, namely, clopidogrel and losartan.
“Overall, these findings are quite reassuring. I wouldn’t let concerns about adverse effects on cognition influence the decision to start a statin in patients suffering from atherosclerotic disease or at risk for cardiovascular disease. I also wouldn’t jump to the conclusion that statins are the culprit when an individual who is taking a statin describes forgetfulness. We may be doing more harm than good if we withhold or stop statins – medications proven to reduce the risk of heart attack and stroke – due to fears that statins might possibly cause memory loss,” said Dr. deGoma.
The team acknowledges that while their analysis is reassuring, large, high-quality randomized controlled trials are needed to confirm their findings.
“For many of the cognitive outcomes that we examined, the identified studies were small, were at risk for bias, used varying diagnostic tests to assess cognitive domains, and did not include patients on high-dose statins, which is important given the increasing use of high-dose statins for secondary prevention,” noted study co-author Craig Umscheid, MD, MSCE, assistant professor of Medicine and Epidemiology and director of the Penn Center for Evidence-based Practice. “Thus, additional trials addressing these limitations would strengthen our conclusions. Despite this, the totality of the evidence does reassure us that there’s unlikely to be a significant link between statins and cognitive impairment.”
Stress makes snails forgetful
New research on pond snails has revealed that high levels of stress can block memory processes. Researchers from the University of Exeter and the University of Calgary trained snails and found that when they were exposed to multiple stressful events they were unable remember what they had learned.
Previous research has shown that stress also affects human ability to remember. This study, published in the journal PLOS ONE, found that experiencing multiple stressful events simultaneously has a cumulative detrimental effect on memory.
Dr Sarah Dalesman, a Leverhulme Trust Early Career Fellow, from Biosciences at the University of Exeter, formally at the University of Calgary, said: “It’s really important to study how different forms of stress interact as this is what animals, including people, frequently experience in real life. By training snails, and then observing their behaviour and brain activity following exposure to stressful situations, we found that a single stressful event resulted in some impairment of memory but multiple stressful events prevented any memories from being formed.”
The pond snail, Lymnaea stagnalis, has easily observable behaviours linked to memory and large neurons in the brain, both useful benefits when studying memory processes. They also respond to stressful events in a similar way to mammals, making them a useful model species to study learning and memory.
In the study, the pond snails were trained to reduce how often they breathed outside water. Usually pond snails breathe underwater and absorb oxygen through their skin. In water with low oxygen levels the snails emerge and inhale air using a basic lung opened to the air via a breathing hole.
To train the snails not to breathe air they were placed in poorly oxygenated water and their breathing holes were gently poked every time they emerged to breathe. Snail memory was tested by observing how many times the snails attempted to breathe air after they had received their training. Memory was considered to be present if there was a reduction in the number of times they opened their breathing holes. The researchers also assessed memory by monitoring neural activity in the brain.
Immediately before training, the snails were exposed to two different stressful experiences, low calcium - which is stressful as calcium is necessary for healthy shells - and overcrowding by other pond snails.
When faced with the stressors individually, the pond snails had reduced ability to form long term memory, but were still able to learn and form short and intermediate term memory lasting from a few minutes to hours. However, when both stressors were experienced at the same time, results showed that they had additive effects on the snails’ ability to form memory and all learning and memory processes were blocked.
Future work will focus on the effects of stress on different populations of pond snail.
(Source: exeter.ac.uk)
New Study Decodes Brain’s Process for Decision Making
When faced with a choice, the brain retrieves specific traces of memories, rather than a generalized overview of past experiences, from its mental Rolodex, according to new brain-imaging research from The University of Texas at Austin.
Led by Michael Mack, a postdoctoral researcher in the departments of psychology and neuroscience, the study is the first to combine computer simulations with brain-imaging data to compare two different types of decision-making models.
In one model — exemplar — a decision is framed around concrete traces of memories, while in the other model — prototype — the decision is based on a generalized overview of all memories lumped into a specific category.
Whether one model drives decisions more than the other has remained a matter of debate among scientists for more than three decades. But according to the findings, the exemplar model is more consistent with decision-making behavior.
The study was published this month in Current Biology. The authors include Alison Preston, associate professor in the Department of Psychology and the Center for Learning and Memory; and Bradley Love, a professor at University College London.
In the study, 20 respondents were asked to sort various shapes into two categories. During the task their brain activity was observed using functional magnetic resonance imaging (fMRI), allowing researchers to see how the respondents associate shapes with past memories.
According to the findings, behavioral research alone cannot determine whether a subject uses the exemplar or prototype model to make decisions. With brain-imaging analysis, researchers found that the exemplar model accounted for the majority of participants’ decisions. The results show three different regions associated with the exemplar model were activated during the learning task: occipital (visual perception), parietal (sensory) and frontal cortex (attention).
While processing new information, the brain stores concrete traces of experiences, allowing it to make different kinds of decisions, such as categorization information (is that a dog?), identification (is that John’s dog?) and recall (when did I last see John’s dog?).
To illustrate, Mack says: Imagine having a conversation with a friend about buying a new car. When you think of the category “car,” you’re likely to think of an abstract concept of a car, but not specific details. However, abstract categories are composed of memories from individual experiences. So when you imagine “car,” the abstract mental picture is actually derived from experiences, such as your friend’s white sedan or the red sports car you saw on the morning commute.
“We flexibly memorize our experiences, and this allows us to use these memories for different kinds of decisions,” Mack says. “By storing concrete traces of our experiences, we can make decisions about different types of cars and even specific past experiences in our life with the same memories.”
Mack says this new approach to model-based cognitive neuroscience could lead to discoveries in cognitive research.
“The field has struggled with linking theories of how we behave and act to the activation measures we see in the brain,” Mack says. “Our work offers a method to move beyond simply looking at blobs of brain activation. Instead, we use patterns of brain activation to decode the algorithms underlying cognitive behaviors like decision making.”
(Source: utexas.edu)
Learning and memory: How neurons activate PP1
A study in The Journal of Cell Biology describes how neurons activate the protein PP1, providing key insights into the biology of learning and memory.
PP1 is known to be a key regulator of synaptic plasticity, the phenomenon in which neurons remodel their synaptic connections in order to store and relay information—the foundation of learning and memory. But how PP1 is controlled has been unclear. Now, a team led by researchers from the LSU Health Science Center describes several mechanisms for PP1 regulation that close some major gaps in our understanding of its role in neuronal signaling.
Among the novel findings, the researchers describe how the neurotransmitter NMDA leads to activation of PP1. They show that, when NMDA activates neuronal synapses, it switches off an enzyme, Cdk5, that would otherwise inhibit PP1. This allows PP1 to activate itself and promote synaptic remodeling. In addition, the researchers suggest that, despite its name, a regulatory protein called inhibitor-2 helps promote PP1 activity in neurons. Together, these findings significantly extend our understanding of how PP1 is regulated in the context of synaptic plasticity.
(Source: eurekalert.org)
Kessler researchers find aerobic exercise benefits memory in persons with MS
Kessler researchers find aerobic exercise benefits memory in persons with multiple sclerosis
A research study headed by Victoria Leavitt, Ph.D. and James Sumowski, Ph.D., of Kessler Foundation, provides the first evidence for beneficial effects of aerobic exercise on brain and memory in individuals with multiple sclerosis (MS). The article, “Aerobic exercise increases hippocampal volume and improves memory in multiple sclerosis: Preliminary findings,” was released as an epub ahead of print on October 4 by Neurocase: The Neural Basis of Cognition. The study was funded by Kessler Foundation.
Hippocampal atrophy seen in MS is linked to the memory deficits that affect approximately 50% of individuals with MS. Despite the prevalence of this disabling symptom, there are no effective pharmacological or behavioral treatments. “Aerobic exercise may be the first effective treatment for MS patients with memory problems,” noted Dr. Leavitt, research scientist in Neuropsychology & Neuroscience Research at Kessler Foundation. “Moreover, aerobic exercise has the advantages of being readily available, low cost, self-administered, and lacking in side effects.” No beneficial effects were seen with non-aerobic exercise. Dr. Leavitt noted that the positive effects of aerobic exercise were specific to memory; other cognitive functions such as executive functioning and processing speed were unaffected.
The study’s participants were two MS patients with memory deficits who were randomized to non-aerobic (stretching) and aerobic (stationary cycling) conditions. Baseline and follow-up measurements were recorded before and after the treatment protocol of 30-minute exercise sessions 3 times per week for 3 months. Data were collected by high-resolution MRI (neuroanatomical volumes), fMRI (functional connectivity), and memory assessment. Aerobic exercise resulted in a 16.5% increase in hippocampal volume, a 53.7% increase in memory, and increased hippocampal resting-state functional connectivity. Non-aerobic exercise resulted in minimal change in hippocampal volume and no changes in memory or functional connectivity.
“These findings clearly warrant large-scale clinical trials of aerobic exercise for the treatment of memory deficits in the MS population,” said James Sumowski„ Ph.D., research scientist in Neuropsychology & Neuroscience Research at Kessler Foundation.
(Source: kesslerfoundation.org)
Babies can learn their first lullabies in the womb
An infant can recognise a lullaby heard in the womb for several months after birth, potentially supporting later speech development. This is indicated in a new study at the University of Helsinki.
The study focused on 24 women during the final trimester of their pregnancies. Half of the women played the melody of Twinkle Twinkle Little Star to their fetuses five days a week for the final stages of their pregnancies. The brains of the babies who heard the melody in utero reacted more strongly to the familiar melody both immediately and four months after birth when compared with the control group. These results show that fetuses can recognise and remember sounds from the outside world.
This is significant for the early rehabilitation, since rehabilitation aims at long-term changes in the brain.
“Even though our earlier research indicated that fetuses could learn minor details of speech, we did not know how long they could retain the information. These results show that babies are capable of learning at a very young age, and that the effects of the learning remain apparent in the brain for a long time,” expounds Eino Partanen, who is currently finishing his dissertation at the Cognitive Brain Research Unit.
“This is the first study to track how long fetal memories remain in the brain. The results are significant, as studying the responses in the brain let us focus on the foundations of fetal memory. The early mechanisms of memory are currently unknown,” points out Dr Minna Huotilainen, principal investigator.
The researchers believe that song and speech are most beneficial for the fetus in terms of speech development. According to the current understanding, the processing of singing and speech in the babies brains are partly based on shared mechanisms, and so hearing a song can support a baby’s speech development. However, little is known about the possible detrimental effects that noise in the workplace can cause to a fetus during the final trimester. An extensive research project on this topic is underway at the Finnish Institute of Occupational Health.
NIH-supported study identifies 11 new Alzheimer’s disease risk genes
An international group of researchers has identified 11 new genes that offer important new insights into the disease pathways involved in Alzheimer’s disease. The highly collaborative effort involved scanning the DNA of over 74,000 volunteers—the largest genetic analysis yet conducted in Alzheimer’s research—to discover new genetic risk factors linked to late-onset Alzheimer’s disease, the most common form of the disorder.
By confirming or suggesting new processes that may influence Alzheimer’s disease development—such as inflammation and synaptic function—the findings point to possible targets for the development of drugs aimed directly at prevention or delaying disease progression.
Supported in part by the National Institute on Aging (NIA) and other components of the National Institutes of Health, the International Genomic Alzheimer’s Project (IGAP) reported its findings online in Nature Genetics on Oct. 27, 2013. IGAP is comprised of four consortia in the United States and Europe which have been working together since 2011 on genome-wide association studies (GWAS) involving thousands of DNA samples and shared datasets. GWAS are aimed at detecting the subtle gene variants involved in Alzheimer’s and defining how the molecular mechanisms influence disease onset and progression.
"Collaboration among researchers is key to discerning the genetic factors contributing to the risk of developing Alzheimer’s disease," said Richard J. Hodes, M.D., director of the NIA. "We are tremendously encouraged by the speed and scientific rigor with which IGAP and other genetic consortia are advancing our understanding."
The search for late-onset Alzheimer’s risk factor genes had taken considerable time, until the development of GWAS and other techniques. Until 2009, only one gene variant, Apolipoprotein E-e4 (APOE-e4), had been identified as a known risk factor. Since then, prior to today’s discovery, the list of known gene risk factors had grown to include other players—PICALM, CLU, CR1, BIN1, MS4A, CD2AP, EPHA1, ABCA7, SORL1 and TREM2.
IGAP’s discovery reported today of 11 new genes strengthens evidence about the involvement of certain pathways in the disease, such as the role of the SORL1 gene in the abnormal accumulation of amyloid protein in the brain, , a hallmark of Alzheimer’s disease. It also offers new gene risk factors that may influence several cell functions, to include the ability of microglial cells to respond to inflammation.
The researchers identified the new genes by analyzing previously studied and newly collected DNA data from 74,076 older volunteers with Alzheimer’s and those free of the disorder from 15 countries. The new genes (HLA-DRB5/HLA0DRB1, PTK2B, SLC24A4-0RING3, DSG2, INPP5D, MEF2C, NME8, ZCWPW1, CELF1, FERMT2 and CASS4) add to a growing list of gene variants associated with onset and progression of late-onset Alzheimer’s. Researchers will continue to explore the roles played by these genes, to include:
- How SORL1 and CASS4 influence amyloid, and how CASS4 and FERMT2 affect tau, another protein hallmark of Alzheimer’s disease
- How inflammation is influenced by HLA-DRB5/DRB1, INPP5D, MEF2C, CR1 and TREM2
- How SORL1affects lipid transport and endocytosis (or protein sorting within cells)
- How MEF2C and PTK2B influence synaptic function in the hippocampus, a brain region important to learning and memory
- How CASS4, CELF1, NME8 and INPP5 affect brain cell function
The study also brought to light another 13 variants that merit further analysis.
"Interestingly, we found that several of these newly identified genes are implicated in a number of pathways," said Gerard Schellenberg, Ph.D., University of Pennsylvania School of Medicine, Philadelphia, who directs one of the major IGAP consortia. "Alzheimer’s is a complex disorder, and more study is needed to determine the relative role each of these genetic factors may play. I look forward to our continued collaboration to find out more about these—and perhaps other—genes."
(Image: National Institute on Aging)
A Trace of Memory: Researchers Watch Neurons in the Brain During Learning and Memory Recall
A team of neurobiologists led by Simon Rumpel at the Research Institute of Molecular Pathology (IMP) in Vienna succeeded in tracking single neurons in the brain of mice over extended periods of time. Advanced imaging techniques allowed them to establish the processes during memory formation and recall. The results of their observations are published this week in PNAS Early Edition.
Most of our behavior – and thus our personality – is shaped by previous experience. To store the memory of these experiences and to be able to retrieve the information at will is therefore considered one of the most basic and important functions of the brain. The current model in neuroscience poses that memory is stored as long-lasting anatomical changes in synapses, the specialized structures by which nerve cells connect and signal to each other.
At the Research Institute of Molecular Pathology (IMP) in Vienna, Simon Rumpel and Kaja Moczulska used mice to study the effects of learning and memorizing on the architecture of synapses. They employed an advanced microscopic technique called in vivo two-photon imaging that allows the analysis of structures as small as a thousandth of a millimetre in the living brain.
Using this technology, the neurobiologists tracked individual neurons over the course of several weeks and analysed them repeatedly. They focussed their attention on dendritic spines that decorate the neuronal processes and correspond to excitatory synapses. The analyses were combined with behavioral experiments in which the animals underwent classic auditory conditioning. The results showed that the learning experience triggered the formation of new synaptic connections in the auditory cortex. Several of these new structures persisted over time, suggesting a long-lasting trace of memory and confirming an important prediction of the current model.
Apart from the changes during memory formation, the IMP-scientists were interested in the act of remembering. Earlier studies had shown that memory recall is associated with molecular processes similar to the initial formation of memory. These similarities have been suggested to reflect remodelling of memory traces during recall.
To test this hypothesis, previously trained mice were exposed to the auditory cue a week after conditioning while tracking dendritic spines in the auditory cortex. The results showed that although some molecular processes indeed resembled those during memory formation, the anatomical structure of the synapses did not change. These findings suggest that memory retrieval does not lead to a modification of the memory trace per se. Instead, the molecular processes triggered by memory formation and recall could reflect the stabilization of previously altered or recently retrieved synaptic connections.
The primary goal of elucidating the processes during memory formation and recall is to increase our basic knowledge. Insights gained from these studies might however help us to understand diseases of the nervous system that affect memory. They may also, in the future, provide the basis for treatments that offer relief to traumatized patients.
A step towards early Alzheimer’s diagnosis
If Alzheimer’s disease is to be treated in the future it requires an early diagnosis, which is not yet possible. Now researchers at higher education institutions such as Linköping University have identified six proteins in spinal fluid that can be used as markers for the illness.
Alzheimer’s causes great suffering and has a one hundred percent fatality rate. The breakdown of brain cells has been in progress for ten years or more by the time symptoms begin to appear. Currently there is no treatment that can stop the process.
(Image: Human neuroblastoma with cell nucleus in blue; beta amyloid as red aggregates within green-tinted lysosomes. Photo: Lotta Agholme.)
Most researchers now agree that one cause of the illness is toxic accumulations – plaques – of the beta amyloid protein. In a healthy brain, the cells are cleansed of such surplus products through lysosomes, the cells’ “waste disposal facilities” (green in the picture).
“In victims of Alzheimer’s, something happens to the lysosomes so that they can’t manage to take care of the surplus of beta amyloid. They fill up with junk that normally is broken down into its component parts and recycled,” says Katarina Kågedal, reader in Experimental Pathology at Linköping University. She led the study that is now being published in Neuromolecular Medicine.
The researchers’ hypothesis was that these changes in the brain’s lysosomal network could be reflected in the spinal fluid, which surrounds the brain’s various parts and drains down into the spinal column. They studied samples of spinal marrow from 20 Alzheimer’s patients and an equal number of healthy control subjects. The screening was aimed at 35 proteins that are associated with the lysosomal network.
“Six of these had clearly increased in the patients; none of them were previously known as markers for Alzheimer’s,” says Kågedal.
Her hope is that the group’s discovery will contribute to early diagnoses of the illness, which is necessary in the first stage in order to be able to begin reliable clinical tests of candidates for drugs. But perhaps the six lysosomal proteins could also be “drug targets” – targets for developing drugs.
“It may be a question of strengthening protection against plaque formation or reactivating the lysosomes so that they manage to break down the plaque,” Kågedal says.
The study was conducted on 20 anonymised, archived spinal marrow samples and the results were confirmed afterwards on an independent range of samples of equal size. All samples were provided by the Laboratory for Clinical Chemistry at Sahlgrenska University Hospital.
(Source: liu.se)
Learning New Skills Keeps an Aging Mind Sharp
Older adults are often encouraged to stay active and engaged to keep their minds sharp, that they have to “use it or lose it.” But new research indicates that only certain activities — learning a mentally demanding skill like photography, for instance — are likely to improve cognitive functioning.
These findings, forthcoming in Psychological Science, a journal of the Association for Psychological Science, reveal that less demanding activities, such as listening to classical music or completing word puzzles, probably won’t bring noticeable benefits to an aging mind.
“It seems it is not enough just to get out and do something—it is important to get out and do something that is unfamiliar and mentally challenging, and that provides broad stimulation mentally and socially,” says psychological scientist and lead researcher Denise Park of the University of Texas at Dallas. “When you are inside your comfort zone you may be outside of the enhancement zone.”
The new findings provide much-needed insight into the components of everyday activities that contribute to cognitive vitality as we age.
“We need, as a society, to learn how to maintain a healthy mind, just like we know how to maintain vascular health with diet and exercise,” says Park. “We know so little right now.”
For their study, Park and colleagues randomly assigned 221 adults, ages 60 to 90, to engage in a particular type of activity for 15 hours a week over the course of three months.
Some participants were assigned to learn a new skill — digital photography, quilting, or both — which required active engagement and tapped working memory, long-term memory and other high-level cognitive processes.
Other participants were instructed to engage in more familiar activities at home, such as listening to classical music and completing word puzzles. And, to account for the possible influence of social contact, some participants were assigned to a social group that included social interactions, field trips, and entertainment.
At the end of three months, Park and colleagues found that the adults who were productively engaged in learning new skills showed improvements in memory compared to those who engaged in social activities or non-demanding mental activities at home.
“The findings suggest that engagement alone is not enough,” says Park. “The three learning groups were pushed very hard to keep learning more and mastering more tasks and skills. Only the groups that were confronted with continuous and prolonged mental challenge improved.”
The study is particularly noteworthy given that the researchers were able to systematically intervene in people’s lives, putting them in new environments and providing them with skills and relationships:
“Our participants essentially agreed to be assigned randomly to different lifestyles for three months so that we could compare how different social and learning environments affected the mind,” says Park. “People built relationships and learned new skills — we hope these are gifts that keep on giving, and continue to be a source of engagement and stimulation even after they finished the study.”
Park and colleagues are planning on following up with the participants one year and five years down the road to see if the effects remain over the long term. They believe that the research has the potential to be profoundly important and relevant, especially as the number of seniors continues to rise:
“This is speculation, but what if challenging mental activity slows the rate at which the brain ages?” asks Park. “Every year that you save could be an added year of high quality life and independence.”