Posts tagged cognitive impairment
Articles and news from the latest research reports.
Alzheimer’s Muddles Memory of How Things Work
Which is bigger, a key or an ant? That question might be easy for you to answer quickly, but it could be a little more confusing for a person with Alzheimer’s.
The most obvious trait of the mind-ruining disease is memory loss, with patients forgetting once-familiar people, places and experiences. New research shows how this mental deterioration extends to semantic memory, which has more to do with remembering facts and concepts and underlies a basic understanding of how things works.
For their study, researchers recruited 70 cognitively healthy people, 27 patients with Alzheimer’s 25 patients with mild cognitive impairment (MCI), often considered a precursor to dementia. All were tested on their ability to make size judgments about two pictures shown to them — the premise being that the bigger the difference in size between two objects, the faster a person would be able to answer the question.
"If you ask someone what is bigger, a key or an ant, they would be slower in their response than if you asked them what is bigger, a key or a house," researcher Terry Goldberg, of the Hofstra North Shore-LIJ School of Medicine, said in a statement.
This held true in the experiments, but the MCI and Alzheimer’s patients had much more trouble when asked to respond to a task with small size differences.
The experiment was then tweaked so that the participants were shown pictures of a small ant and a big house or a big ant and a small house. The MCI and Alzheimer’s patients did not have a problem making judgments about the small ant and big house, but had trouble with the more incongruent set. They were confused about which object was actually larger when shown a big ant and a small house, and were more likely to answer incorrectly or take longer to arrive at a response, the researchers said.
Goldberg said the findings indicate “that something is slowing down the patient and it is not episodic memory but semantic memory.”
The team will continue to study these patients over time to see if these semantic problems get worse as the disease advances.
Study Details Brain Damage Triggered by Mini-Strokes
A new study appearing today in the Journal of Neuroscience details for the first time how “mini-strokes” cause prolonged periods of brain damage and result in cognitive impairment. These strokes, which are often imperceptible, are common in older adults and are believed to contribute to dementia.
“Our research indicates that neurons are being lost as a result of delayed processes following a mini-strokes that may differ fundamentally from those of acute ischemic events,” said Maiken Nedergaard, M.D., D.M.Sc., the lead author of the study and professor of Neurosurgery at the University of Rochester Medical Center (URMC). “This observation suggests that the therapeutic window to protect cells after these tiny strokes may extend to days and weeks after the initial injury.”
The prevalence of mini-strokes, or microinfarcts, has only been recently appreciated because common imaging techniques, such as MRI, are typically not sensitive enough to detect these microscopic injuries.
Similar to severe ischemic strokes, mini-strokes are caused when blood flow is blocked to a small area of the brain, usually by particle that travelled there from another part of the body. But unlike acute ischemic strokes – which bring about immediate symptoms such as numbness, blurry vision, and slurred speech – mini-strokes usually pass without notice. However, it is increasingly appreciated that these smaller strokes have a lasting impact on neurological function.
Microinfarcts are far more common than previously understood; it is believed that about 50 percent of individuals over the age of 60 have experienced at least one mini-stroke. Studies have also correlated the presence of mini-strokes with the symptoms of dementia. An estimated 55 percent of individuals with mild dementia and upwards of 70 percent of individuals with more severe symptoms show evidence of past mini-strokes. This association has led researchers to believe that these mini-strokes may be key contributors to age-related cognitive decline and dementia.
Nedergaard and her colleagues were the first to develop an animal model in which the complex progression and, ultimately, the cognitive impact of mini-strokes could be observed. Her team found that, in most instances, these strokes result in a prolonged period of damage to the brain.
Research shows diabetes drug improves memory
An FDA-approved drug initially used to treat insulin resistance in diabetics has shown promise as a way to improve cognitive performance in some people with Alzheimer’s disease.
Working with genetically engineered mice designed to serve as models for Alzheimer’s, University of Texas Medical Branch at Galveston researchers found that treatment with the anti-insulin-resistance drug rosiglitazone enhanced learning and memory as well as normalized insulin resistance. The scientists believe that the drug produced the response by reducing the negative influence of Alzheimer’s on the behavior of a key brain-signaling molecule.
The molecule, called extracellular signal-regulated kinase (ERK), becomes hyperactive both in the brains of Alzheimer’s patients and in the mice at a disease stage corresponding to mild cognitive impairment in human Alzheimer’s. This excessive activity leads to improper synaptic transmission between neurons, interfering with learning and memory.
Rosiglitazone brings ERK back into line by activating what’s known as the peroxisome proliferator-activated receptor gamma (PPARγ) pathway, which interacts with genes that respond to both PPARγ and ERK.
“Using this drug appears to restore the neuronal signaling required for proper cognitive function,” said UTMB professor Larry Denner, the lead author of a paper describing this work now online (posted Nov. 21) in the Journal of Neuroscience. “It gives us an opportunity to test several FDA-approved drugs to normalize insulin resistance in Alzheimer’s patients and possibly also enhance memory, and it also gives us a remarkable tool to use in animal models to understand the molecular mechanisms that underlie cognitive issues in Alzheimer’s.”
Experimental Drug Improves Memory in Mice with Multiple Sclerosis
Johns Hopkins researchers report the successful use of a form of MRI to identify what appears to be a key biochemical marker for cognitive impairment in the brains of people with multiple sclerosis (MS). In follow-up experiments on mice with a rodent form of MS, researchers were able to use an experimental compound to manipulate that same marker and dramatically improve learning and memory.
Half of people with MS experience learning and memory problems, for which there is no approved treatment, along with movement abnormalities that characterize the debilitating autoimmune disorder.
"We have a potentially novel treatment for cognitive impairment in MS, a devastating condition on the rise that affects at least 400,000 people in the United States," says study leader Adam I. Kaplin, M.D., Ph.D., an assistant professor of psychiatry and behavioral sciences and neurology at the Johns Hopkins University School of Medicine.
Kaplin cautions that the treatment has so far been used only in mouse models of MS and is years away from clinical trials in people.
Nevertheless, he says, the research, described in the Proceedings of the National Academy of Sciences published online on Nov. 19, has the potential to speed development of new drugs to treat cognitive impairment not only in MS patients, but also in patients with Alzheimer’s disease and other neurological conditions.
Virtual Reality Could Spot Real-World Impairments
A virtual reality test being developed at UTSC might do a better job than pencil-and-paper tests of predicting whether a cognitive impairment will have real-world consequences.
The test developed by Konstantine Zakzanis, associate professor of psychology, and colleagues, uses a computer-game-like virtual world and asks volunteers to navigate their ways through tasks such as delivering packages or running errands around town.
“If we’re being asked to tell if people could do things like work, houseclean, and take care of their kids, we need to show that our tests predict performance in the real world,” says Zakzanis.
But standard tests don’t do that very well, he says. Although tests that ask people to do things like solve math problems, sort cards, remember names, or judge the relative positions of lines in visual two dimensional space, can detect cognitive impairments caused by circumscribed lesions following a stroke or head injury, they’re not very good at predicting who will be able to function in the real world and who won’t.
That’s a problem for cognitively impaired people who might be denied insurance benefits or workers compensation based on tests that are insensitive to demonstrating their impairment. It is akin to having a broken arm with no x-ray to prove it.
Reduced Cardiac Vagal Modulation Impacts on Cognitive Performance in Chronic Fatigue Syndrome
Background: Cognitive difficulties and autonomic dysfunction have been reported separately in patients with chronic fatigue syndrome (CFS). A role for heart rate variability (HRV) in cognitive flexibility has been demonstrated in healthy individuals, but this relationship has not as yet been examined in CFS. The objective of this study was to examine the relationship between HRV and cognitive performance in patients with CFS.
Methods: Participants were 30 patients with CFS and 40 healthy controls; the groups were matched for age, sex, education, body mass index, and hours of moderate exercise/week. Questionnaires were used to obtain relevant medical and demographic information, and assess current symptoms and functional impairment. Electrocardiograms, perceived fatigue/effort and performance data were recorded during cognitive tasks. Between–group differences in autonomic reactivity and associations with cognitive performance were analysed.
Results: Patients with CFS showed no deficits in performance accuracy, but were significantly slower than healthy controls. CFS was further characterized by low and unresponsive HRV; greater heart rate (HR) reactivity and prolonged HR-recovery after cognitive challenge. Fatigue levels, perceived effort and distress did not affect cognitive performance. HRV was consistently associated with performance indices and significantly predicted variance in cognitive outcomes.
Conclusions: These findings reveal for the first time an association between reduced cardiac vagal tone and cognitive impairment in CFS and confirm previous reports of diminished vagal activity.
Hunting neuron killers in Alzheimer’s and TBI
Sanford-Burnham researchers discovered that the protein appoptosin prompts neurons to commit suicide in several neurological conditions—giving them a new therapeutic target for Alzheimer’s disease and traumatic brain injury.
Dying neurons lead to cognitive impairment and memory loss in patients with neurodegenerative disorders–conditions like Alzheimer’s disease and traumatic brain injury. To better diagnose and treat these neurological conditions, scientists first need to better understand the underlying causes of neuronal death.
Enter Huaxi Xu, Ph.D., professor in Sanford-Burnham’s Del E. Webb Neuroscience, Aging, and Stem Cell Research Center. He and his team have been studying the protein appoptosin and its role in neurodegenerative disorders for the past several years. Appoptosin levels in the brain skyrocket in conditions like Alzheimer’s and stroke, and especially following traumatic brain injury.
Appoptosin is known for its role in helping the body make heme, the molecule that carries iron in our blood (think “hemoglobin,” which makes blood red). But what does heme have to do with dying brain cells? As Xu and his group explain in a paper they published recently in the Journal of Neuroscience, excess heme leads to the overproduction of reactive oxygen species, which include cell-damaging free radicals and peroxides, and triggers apoptosis, the carefully regulated process of cellular suicide. This means that more appoptosin and more heme cause neurons to die.
Not only did Xu and his team unravel this whole appoptosin-heme-neurodegeneration mechanism, but when they inhibited appoptosin in laboratory cell cultures, they noticed that the cells didn’t die. This finding suggests that appoptosin might make an interesting new therapeutic target for neurodegenerative disorders.
What’s next? Xu and colleagues are now probing appoptosin’s function in mouse models. They’re also looking for new therapies that target the protein.
“Since the upregulation of appoptosin is important for cell death in diseases such as Alzheimer’s, we’re now searching for small molecules that modulate appoptosin expression or activity. We’ll then determine whether these compounds may be potential drugs for Alzheimer’s or other neurodegenerative diseases,” Xu explains.
Putting a stop to runaway appoptosin won’t be easy, though. That’s because we still need the heme-building protein to operate at normal levels for our blood to carry iron. In a previous study, researchers found that a mutation in the gene that encodes appoptosin causes anemia. “Too much of anything is bad, but so is too little,” Xu says.
New therapies that target neurodegenerative disorders and traumatic brain injury are sorely needed. According to the CDC, approximately 1.7 million people sustain a traumatic brain injury each year. It’s an acute injury, but one that can also lead to long-term problems, causing epilepsy and increasing a person’s risk for Alzheimer’s and Parkinson’s diseases. Not only has traumatic brain injury become a worrisome problem in youth and professional sports in recent years, the Department of Defense calls traumatic brain injury “one of the signature injuries of troops wounded in Afghanistan and Iraq.”
(Source: beaker.sanfordburnham.org)
Inflammation and Cognition in Schizophrenia
There are a growing number of clues that immune and inflammatory mechanisms are important for the biology of schizophrenia. In a new study in Biological Psychiatry, Dr. Mar Fatjó-Vilas and colleagues explored the impact of the interleukin-1β gene (IL1β) on brain function alterations associated with schizophrenia.
Fatjó-Vilas said that “this study is a contribution to the relatively new field of ‘functional imaging genetics’ which appears to be potentially powerful for the study of schizophrenia, where genetic factors are of established importance and cognitive impairment – affecting particularly executive function and long-term memory – is increasingly recognized as a core feature of the disorder.”
To conduct this study, they recruited patients with schizophrenia and healthy volunteers, all of whom completed a working memory task while undergoing a functional magnetic resonance imaging scan in the laboratory. This allowed the researchers to determine which areas of the brain became activated during the task. Each participant was also genotyped to determine which allelic combination of the -511C/T polymorphism at the promoter region of the IL1β gene they carry: CC, TT, or CT.
Patients who were homozygous for the C allele (CC) showed reduced prefrontal cortex activation associated with working memory than patients who had at least one copy of the T allele. Among the healthy volunteers, frontal brain activation did not differ according to genotype.
“The analyzed genetic variant exerts an influence on prefrontal cortex function and this influence is different in healthy subjects and patients with schizophrenia,” summarized Fatjó-Vilas.
An important issue is that the -511C/T seems to have a role in regulating the levels of IL1B expression, in which case it would influence neuronal activity dependent on the protein availability. This means that the T allele has been reported to be more active than the C allele, suggesting that a tendency for greater expression of IL1β is associated with greater compromise of frontal cortical functions underlying cognition.
Interleukin-1β is released in the blood under stressful conditions and its release is one of the ways that stress promotes inflammation. IL-1β levels in the blood are altered, for example, in patients with depression and other neuropsychiatric disorders.
Apart from having a role in the immune system, interleukins are also involved in a variety of developmental and functioning processes of the central nervous system. Thus, this study provides further clues for identifying specific biological mechanisms of the disorder associated with both neurodevelopmental processes and immunological and stress response functions.
Dr. John Krystal, Editor of Biological Psychiatry, commented, “We are just beginning to explore the functional impact of inflammatory mechanisms in schizophrenia and the current findings increase our curiosity about these novel mechanisms.”
(Source: alphagalileo.org)
Caffeine may block inflammation linked to mild cognitive impairment
(Image credit: chichacha)
Recent studies have linked caffeine consumption to a reduced risk of Alzheimer’s disease, and a new University of Illinois study may be able to explain how this happens.
“We have discovered a novel signal that activates the brain-based inflammation associated with neurodegenerative diseases, and caffeine appears to block its activity. This discovery may eventually lead to drugs that could reverse or inhibit mild cognitive impairment,” said Gregory Freund, a professor in the U of I’s College of Medicine and a member of the U of I’s Division of Nutritional Sciences.
Freund’s team examined the effects of caffeine on memory formation in two groups of mice—one group given caffeine, the other receiving none. The two groups were then exposed to hypoxia, simulating what happens in the brain during an interruption of breathing or blood flow, and then allowed to recover.
The caffeine-treated mice recovered their ability to form a new memory 33 percent faster than the non-caffeine-treated mice. In fact, caffeine had the same anti-inflammatory effect as blocking IL-1 signaling. IL-1 is a critical player in the inflammation associated with many neurodegenerative diseases, he said.
“It’s not surprising that the insult to the brain that the mice experienced would cause learning memory to be impaired. But how does that occur?” he wondered.
The scientists noted that the hypoxic episode triggered the release of adenosine by brain cells.
“Your cells are little powerhouses, and they run on a fuel called ATP that’s made up of molecules of adenosine. When there’s damage to a cell, adenosine is released,” he said.
Just as gasoline leaking out of a tank poses a danger to everything around it, adenosine leaking out of a cell poses a danger to its environment, he noted.
The extracellular adenosine activates the enzyme caspase-1, which triggers production of the cytokine IL-1β, a critical player in inflammation, he said.
“But caffeine blocks all the activity of adenosine and inhibits caspase-1 and the inflammation that comes with it, limiting damage to the brain and protecting it from further injury,” he added.
Caffeine’s ability to block adenosine receptors has been linked to cognitive improvement in certain neurodegenerative diseases and as a protectant against Alzheimer’s disease, he said.
“We feel that our foot is in the door now, and this research may lead to a way to reverse early cognitive impairment in the brain. We already have drugs that target certain adenosine receptors. Our work now is to determine which receptor is the most important and use a specific antagonist to that receptor,” he said.
The study appears in the Journal of Neuroscience and can be viewed online at http://www.jneurosci.org/content/32/40/13945.full
(Source: news.aces.illinois.edu)
The party drug mephedrone can cause lasting damage to the brain, according to new research led by the University of Sydney.
"Mephedrone is highly addictive in the worst possible way. Users tend to binge on massive doses of the drug over short time spans," said Craig Motbey, a PhD candidate in the University’s School of Psychology and lead author of the research published in PLOS ONE, the Public Library of Science journal, today.
"Combined with the fact mephedrone is skyrocketing in popularity worldwide, with Australia following that trend, our finding that high doses can cause ongoing cognitive impairment spells a significant risk for users."
Also known as ‘meow meow’ and ‘MCAT’, mephedrone’s immediate effect on the brain is similar to a combination of ecstasy and methamphetamine.
"You get the euphoria and touchy-feeliness of ecstasy together with the intense addictiveness of methamphetamine or cocaine," said Motbey.
The current results, based upon experiments with laboratory rats, provide evidence of mephedrone’s ability to damage memory.