Posts Tagged cognitive decline

[WEB SITE] The Brain Can Give Birth To New Cells Throughout Life, Study Finds

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Researchers used to think that after adolescence, people were pretty well stuck with the brain cells they’d already formed. No so anymore. Discoveries in recent years have shown that neurogenesis—the formation of new neurons—can occur much later than this, well into adulthood. And now, a new study from the University of Illinois at Chicago finds that brain cells can form into one’s nineties, even if one has cognitive decline and Alzheimer’s disease (though at a much decelerated rate). The question is how the late-in-life growth of new neurons fits into what’s already known about degenerative diseases.

The study was published last week in the journal Cell Stem Cell.

The researchers looked at the postmortem brains of people aged 79-99, some of whom had had cognitive decline or Alzheimer’s disease. They targeted markers for two kinds of burgeoning cells—neuroblasts (stem cells that would one day give rise to neurons), and immature neurons—in the hippocampus, the brain area that’s most affected in Alzheimer’s disease.

People who had died without cognitive problems had proliferation of both kinds of cells in their brains. People with cognitive decline and Alzheimer’s also had evidence of the cells, but in much lower numbers.

Lazarov, neurogenesis study

COURTESY, ORLY LAZAROV, ET AL.

“We found that there was active neurogenesis in the hippocampus of older adults well into their 90s,” said study author Orly Lazarov in a statement. “The interesting thing is that we also saw some new neurons in the brains of people with Alzheimer’s disease and cognitive impairment.”

What was interesting was the finding that people who had scored higher on tests of cognition during their later lives had more neuroblasts in their hippocampi, compared to those who’d scored lower—and this was independent of the level of degeneration that was visible in the brain.

“In brains from people with no cognitive decline who scored well on tests of cognitive function, these people tended to have higher levels of new neural development at the time of their death, regardless of their level of pathology,” Lazarov said. “The mix of the effects of pathology and neurogenesis is complex and we don’t understand exactly how the two interconnect, but there is clearly a lot of variation from individual to individual.”

The finding is intriguing since it’s long been known that a person’s level of brain “gunk” (the plaques and tangles associated with Alzheimer’s disease) doesn’t always correlate with their cognitive and behavioral symptoms. So it’s possible that these new findings helps explain why this disconnect exists—perhaps the level of neurogenesis matters as much or more than the amount of plaques and tangles that develop. If that’s true, then the big question would be how to harness this for therapeutic purposes.

“The fact that we found that neural stem cells and new neurons are present in the hippocampus of older adults means that if we can find a way to enhance neurogenesis, through a small molecule, for example, we may be able to slow or prevent cognitive decline in older adults, especially when it starts, which is when interventions can be most effective,” said Lazarov.

More research will obviously be needed to understand all of this, but preventing cognitive decline and dementia is probably the way to go, especially since medications to treat Alzheimer’s after the fact have fallen flat in recent years. In the meantime, the study is encouraging on another level: Certain lifestyle habits—most notably exercise—have consistently been shown to boost neurogenesis. The findings suggest we’d do well to pick up exercise, and other brain-healthy habits, and engage in them for as much of our lives as we can, as regularly as we’re able.

 

via The Brain Can Give Birth To New Cells Throughout Life, Study Finds

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[WEB SITE] Memory-enhancing drug reverses effects of traumatic brain injury in mice

The radial-arm water maze is a common test to assess working memory in rodents.

Whether caused by a car accident that slams your head into the dashboard or repeated blows to your cranium from high-contact sports, traumatic brain injury can be permanent. There are no drugs to reverse the cognitive decline and memory loss, and any surgical interventions must be carried out within hours to be effective, according to the current medical wisdom. But a compound previously used to enhance memory in mice may offer hope: Rodents who took it up to a month after a concussion had memory capabilities similar to those that had never been injured.

The study “offers a glimmer of hope for our traumatic brain injury patients,” says Cesario Borlongan, a neuroscientist who studies brain aging and repair at the University of South Florida in Tampa. Borlongan, who reviewed the new paper, notes that its findings are especially important in the clinic, where most rehabilitation focuses on improving motor—not cognitive—function.

Traumatic brain injuries, which cause cell death and inflammation in the brain, affect 2 million Americans each year. But the condition is difficult to study, in part because every fall, concussion, or blow to the head is different. Some result in bleeding and swelling, which must be treated immediately by drilling into the skull to relieve pressure. But under the microscope, even less severe cases appear to trigger an “integrated stress response,” which throws protein synthesis in neurons out of whack and may make long-term memory formation difficult.

In 2013, the lab of Peter Walter, a biochemist at the University of California, San Francisco (UCSF), discovered a compound—called ISRIB—that blocked the stress response in human cells in a dish. Surprisingly, when tested in healthy mice, ISRIB boosted their memory. Wondering whether the drug could also reverse memory impairment, Walter teamed up with UCSF neuroscientist Susanna Rosi to study mouse models of traumatic brain injury. First, they showed that the stress response remains active in the hippocampus, a brain region important for learning and memory, for at least 28 days in injured mice. And they wondered whether administering ISRIB would help.

Rosi and her team first used mechanical pistons to hit anesthetized mice in precise parts of their surgically exposed brains, resulting in contusive injuries, focused blows that can also result from car accidents or being hit with a heavy object. After 4 weeks of rest, Rosi trained the mice to swim through a water maze, where they used cues to remember the location of a hidden resting platform. Healthy mice got better with practice, but the injured ones didn’t improve. However, when the injured mice were given ISRIB 3 days in a row, they were able to solve the maze just as quickly as healthy mice up to a week later, the researchers report today in the Proceedings of the National Academy of Sciences.

“We kept replicating experiments, thinking maybe something went wrong,” Rosi says. So the team decided to study ISRIB in a second model of traumatic brain injury known as a closed head injury, which resembles a concussion from a fall. They again used a mechanical piston, but this time landed a broad blow to the back of the skull. Two weeks later, the mice were trained on a tougher maze, full of bright lights and loud noise. They had to scurry around a tabletop with 40 holes, looking for the one with an escape hatch. Again, while the uninjured mice improved at the task, the concussed mice never got the hang of it. But after four daily doses of ISRIB, the concussed mice performed as well as their healthy counterparts. “This is the most exciting piece of work I’ve ever done, no doubt,” Rosi says.

“Paradigm shift is not too strong a term to use,” says Ramon Diaz-Arrastia, neurologist and director of clinical traumatic brain injury research at the University of Pennsylvania. “This … shows for the first time that a therapy in the chronic period of traumatic brain injury can have pretty potent effects.” Walter agrees. “Normally you would give up on these mice and say nothing can be done here,” he says. “But ISRIB just magically brings the cognitive ability back.”

Still, Borlongan cautions that studies in animals often don’t pan out when tested in humans. He says that this drug has a leg up, though, because it was tested in two models and also readily crosses the blood-brain barrier, which prevents many drugs that look good on paper from entering the brain and having an effect.

If the therapy translates to humans, it could be a boon for soldiers returning from war, who sometimes wait weeks between leaving the battlefield and arriving home for treatment. Brian Head, a neurobiologist at the VA San Diego Healthcare System in California notes that traumatic brain injury is still hard to diagnose, especially with veterans that show up to the clinic long after the injury. “But right now nothing else is working, and giving a compound [that works] a month later is really impressive.”

In 2015, ISRIB was licensed to the secretive Google spinout company Calico, which studies the biology of aging and life span. Walter says his lab has a research agreement with Calico to pursue “basic mechanistic work” on ISRIB, but that the new study was not funded by Calico. Google declined to comment on the new research.

Although the protein target of ISRIB is known, the exact manner in which the drug restores memory is hazy. The team hypothesizes that ISRIB may work by allowing normal protein synthesis—essential for making new neuronal connections and thus forming new memories—to resume, which would otherwise be blunted by the integrated stress response. “Even if this drug doesn’t materialize, other ways of manipulating the integrated stress response may lead to an effective treatment in the future,” Walter says.

via Memory-enhancing drug reverses effects of traumatic brain injury in mice | Science | AAAS

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[BLOG POST] 20 Must-Know Facts To Harness Neuroplasticity And Improve Brain Health

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June is Alzheimer’s & Brain Awareness Month, so let me share these 20 Must-Know Facts to Harness Neuroplasticity & Improve Brain Health that come from the hundreds of scientific and medical studies we analyzed to prepare the book The SharpBrains Guide to Brain Fitness: How to Improve Brain Health and Performance at Any Age:

  1. There is more than one “It” in “Use It or Lose It” — our performance depends on a variety of brain functions and cognitive skills, not just one (be it “attention” or “memory” or any other).
  2. Genes do not determine the fate of our brains. Thanks to lifelong neuroplasticity, our lifestyles are as important as our genes-if not more- in how our brains grow and our minds evolve.
  3. We need to pay more attention to Randomized Controlled Trials (RCTs) to verify whether any intervention causes an effect, and under what specific circumstances.
  4. The largest recent RCT (the ongoing FINGER study) and a 2010 systematic review of all relevant RCTs provide useful guidance: First, they report a protective effect of social and cognitive engagement, physical exercise, and the Mediterranean diet. Second, the average benefits at the population level appear quite limited, so we need to have realistic expectations.
  5. Physical exercise and increased fitness promote brain functioning through a variety of mechanisms, including increased brain volume, blood supply and growth hormone levels.
  6. Cardiovascular exercise that gets the heart beating – from walking to skiing, tennis and basketball – seems to bring the greatest brain benefits; thirty to sixty minutes per day, three days a week, seems to be the best regimen.
  7. Mental stimulation strengthens the connections between neurons (synapses), improving neuron survival and cognitive functioning. Mental stimulation also helps build cognitive reserve, helping the brain better cope with potential AD pathology.
  8. Routine activities do not challenge the brain. Keeping up the challenge requires going to the next level of difficulty, or trying something new.
  9. The only leisure activity that has been associated with reduced cognitive function is watching television.
  10. Brain training can work, putting the “cells that fire together wire together” to good use, but available RCTs suggest some key conditions must be met to transfer to real-life benefits.
  11. The brain needs a lot of energy: It extracts approximately 50% of the oxygen and 10% of the glucose from arterial blood.
  12. The Mediterranean Diet, supplemented with olive oil and nuts, is associated with decreased risk of cognitive decline.
  13. Moderate doses of caffeine increase alertness but there is no clear sustained lifetime health benefit (or harm).
  14. Light-to-moderate alcohol consumption seems to lower the risk of dementia.
  15. Taking “brain supplements” of any kind does not seem to boost cognitive function or reduce risks of cognitive decline or dementia, unless directed to address an identified deficiency.
  16. The larger and the more complex a person’s social network is, the bigger the amygdala (which plays a major role in our behavior and motivation). There is no clear evidence to date on whether “online” relationships are fundamentally different from “offline” ones in this regard.
  17. Chronic stress reduces and can even inhibit neurogenesis. Memory and general mental flexibility are impaired by chronic stress.
  18. There is increasing evidence that meditation and biofeedback can successfully teach users to self-regulate physiological stress responses.
  19. We will not have a Magic Pill or General Solution to solve all our cognitive challenges any time soon, so a holistic multi-pronged approach is recommended, centered around nutrition, stress management, and both physical and mental exercise.
  20. Having said that, no size fits all, so it’s critical to understand and address individual needs, priorities and starting points.

Now, remember that what counts in terms of brain health is not reading this article, or any other, but practicing some healthy behaviors every day until small steps become internalized habits.

Revisit the fact above that really grabbed your attention…and make a decision to try something new this summer.

Source: 20 Must-Know Facts To Harness Neuroplasticity And Improve Brain Health | HuffPost

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[WEB SITE] UT Southwestern researchers find potential mechanism to prevent epileptic seizures following TBI.

UT Southwestern Medical Center researchers have found that halting production of new neurons in the brain following traumatic brain injury can help reduce resulting epileptic seizures, cognitive decline, and impaired memory.

Injury to the brain stimulates the production of new neurons, but these new cells are sometimes hyperexcitable, disrupting neural circuits and causing recurring seizures, researchers with UT Southwestern’s Texas Institute for Brain Injury and Repair reported in Nature Communications.

Effectively stopping the process in genetically modified mice resulted in fewer seizures. In addition, eliminating the development of new neurons – a process called neurogenesis ? appeared to reduce cognitive decline and impairment of memory, common effects of seizures.

“Understanding the mechanisms that promote aberrant neurogenesis caused by traumatic brain injury and subsequent seizures may open new therapeutic avenues to prevent epilepsy and associated memory problems caused by impact,” said senior author Dr. Jenny Hsieh, Associate Professor of Molecular Biology and a member of the UT Southwestern Hamon Center for Regenerative Science and Medicine.

Halting development of new neurons resulted in a roughly 40 percent reduction in seizure frequency in the mice, but did not alter the duration of individual seizures. However, the researchers found that stopping neurogenesis before the development of seizures had a long-lasting effect, suppressing chronic seizure frequency for nearly one year, even at a late stage of the disease.

An estimated 3 million Americans and 65 million people worldwide currently live with epilepsy, costing an estimated $15.5 billion annually, according to the Centers for Disease Control and Prevention. Traumatic brain injury accounts for 20 percent of epileptic seizures, but how or why recurring seizures develop after a severe brain injury has thus far been unclear. Some drugs can help control seizures, but there is no drug to prevent or cure epilepsy.

Degenerative diseases of the heart, brain, and other tissues represent the largest cause of death and disability in the world, affecting virtually everyone over the age of 40 and accounting for the lion’s share of health care costs. Regenerative medicine represents a new frontier in science, which seeks to understand the mechanistic basis of tissue aging, repair, and regeneration and to leverage this knowledge to improve human health.

UT Southwestern’s Hamon Center for Regenerative Science and Medicine, led by Molecular Biology Chair Dr. Eric Olson, was established in 2014 with a $10 million endowment gift from the Hamon Charitable Foundation. The Center’s goals are to understand the basic mechanisms underlying tissue and organ formation, and then to use this knowledge to regenerate, repair, and replace tissues damaged by aging and injury.

The Hsieh lab studies the cellular and molecular mechanisms of neurogenesis to understand how stem cells become mature, functioning nerve cells, and how aberrant neurogenesis contributes to seizure formation, an unwarranted side effect of neuroregenerative strategies.

Source: UT Southwestern researchers find potential mechanism to prevent epileptic seizures following TBI

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[ARTICLE] New Directions in Research and Therapies in Traumatic Brain Injury – Full Text HTML/PDF

Abstract:

Traumatic brain injury (TBI) is a significant cause of disability and death and its incidence is rising in some specific populations. TBI can result in various disabilities, cognitive problems and psychiatric disorders, depending on the location of the injury and premorbid patient conditions.

Effective pharmacological and surgical treatments, however, are currently limited. Most randomised clinical trials for TBI treatments carried out to date have failed to show significant benefits. Initiatives such as the TRACK-TBI have highlighted the large variability in TBI treatment quality at different hospitals and widely differing death rates. This stimulated the establishment of the International Initiative for TBI Research (InTIBR), which aims to improve disease characterisation and patient management.

The development of effective treatments for TBI and their evaluation requires an understanding of the complex neuroregenerative processes that follow an injury. In the case of haematoma in TBI, decompressive craniectomy can be a life-saving intervention but must be performed rapidly. The neurotrophic agent, Cerebrolysin®, acts by mimicking neurotrophic factors (NTFs) and by stimulating the endogenous production of NTF in brain tissue. Experimental models show that this drug increases neurogenesis following TBI but these findings need to be converted into clinical practice. The potential of Cerebrolysin in TBI was demonstrated in a large retrospective cohort trial in Romania (n=7,769 adults). Cerebrolysin significantly improved Glasgow Outcome Scores (GOS) and respiratory distress (RDS) in patients with moderate or severe TBI at 10 and 30 days compared with controls.

This and other experimental treatments have potential in TBI but, in developing such therapies, the design of clinical trials should closely reflect the reality of biological processes underlying natural recovery from brain injury.

Full Text HTML —>  New Directions in Research and Therapies in Traumatic Brain Injury | Touch Neurology | Independent Insight for Medical Specialists.

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[WEB SITE] Brain training games: No proof they prevent cognitive decline

cognitive testThe idea of playing a game to make you sharper seems like a no-brainer. That’s the thinking behind a billion-dollar industry selling brain training games and programs designed to boost cognitive ability.

But an investigation by CBC’s Marketplace reveals that brain training games such as Lumosity may not make your brain perform better in everyday life.

Brain training games, such as Lumosity, are a billion-dollar industry. Many people are worried about maintaining their brain health and want to prevent a decline in their mental abilities. (CBC)

Almost 15 per cent of Canadians over the age of 65 are affected by some kind of dementia. And many people of all ages are worried about maintaining their brain health and possibly preventing a decline in their mental abilities.

“I don’t think there’s anything to say that you can train your brain to be cognitively better in the way that we know that we can train our bodies to be physically better,” neuroscientist Adrian Owen told Marketplace co-host Tom Harrington.

  • CBC Marketplace: Mind Games
  • Dementia patients sold unproven ‘brainwave optimization’

To test how effective the games are at improving cognitive function, Marketplace partnered with Owen, who holds the Canada Excellence Research Chair in Cognitive Neuroscience and Imaging at the Brain and Mind Institute at Western University.

Continue —>  Brain training games: No proof they prevent cognitive decline – Health – CBC News.

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