Three or more concussions linked with worse brain function in later life

Experiencing three or more concussions is linked with worsened brain function in later life, according to major new research.

The study -- the largest of its kind -- also found having just one moderate-to-severe concussion, or traumatic brain injury (TBI), can have a long-term impact on brain function, including memory.

Led by teams at the University of Oxford and the University of Exeter, the research included data from more than 15,000 participants of the online PROTECT study, who were aged between 50 and 90 and based in the UK. They reported the severity and frequency of concussions they had experienced throughout their lives, and completed annual, computerised tests for brain function.

Published in the Journal of Neurotrauma, the paper found that people who reported three or more concussions had significantly worse cognitive function, which got successively worse with each subsequent concussion after that. Attention and completion of complex tasks were particularly affected.

Researchers say people who have had concussions should be warned of the dangers of continuing high-risk sport or work.

Lead investigator Dr Vanessa Raymont, from the University of Oxford, said: "We know that head injuries are a major risk factor for dementia, and this large-scale study gives the greatest detail to date on a stark finding -- the more times you injure your brain in life, the worse your brain function could be as you age.

"Our research indicates that people who have experienced three or more even mild episodes of concussion should be counselled on whether to continue high-risk activities. We should also encourage organisations operating in areas where head impact is more likely to consider how they can protect their athletes or employees."

The team found that participants who reported three episodes of even mild concussion throughout their lives had significantly worse attention and ability to complete complex tasks. Those who had four or more mild concussion episodes also showed worsened processing speed and working memory. Each additional reported concussion was linked to progressively worse cognitive function.

Furthermore, the researchers found that reporting even one moderate-to-severe concussion was associated with worsened attention, completion of complex tasks and processing speed capacity.

In the online PROTECT study, participants share detailed lifestyle information, and complete a suite of cognitive tests every year, for up to 25 years. This rich mine of data helps researchers understand how the brain ages, and the factors involved in maintaining a healthier brain in later life.

Dr Helen Brooker, a study co-author from the University of Exeter, said: "As our population ages, we urgently need new ways to empower people to live healthier lives in later life. This paper highlights the importance of detailed long-term studies like PROTECT in better understating head injuries and the impact to long term cognitive function, particularly as concussion has also been linked to dementia. We're learning that life events that might seem insignificant, life experiencing a mild concussion, can have an impact on the brain. Our findings indicate that cognitive rehabilitation should focus on key functions such as attention and completion of complex tasks, which we found to be susceptible to long-term damage."

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Rest isn't best: Getting kids back to school sooner after a concussion can mean a faster recovery

Contrary to popular belief, rest may not always be the best cure after a concussion, new study published in JAMA Network Open finds. In fact, an early return to school may be associated with a lower symptom burden after suffering a concussion and, ultimately, faster recovery.

"We know that absence from school can be detrimental to youth in many ways and for many reasons," says Christopher Vaughan, Psy.D., neuropsychologist at Children's National Hospital and the study's lead author. "The results of this study found that, in general, an earlier return to school after a concussion was associated with better outcomes. This helps us feel reassured that returning to some normal activities after a concussion -- like going to school -- is ultimately beneficial."

In this cohort study, data from over 1,600 youth aged 5 to 18 were collected across nine pediatric emergency departments in Canada. Because of the large sample size, many factors associated with greater symptom burden and prolonged recovery were first accounted for through the complex statistical approach used to examine the data. The authors found that an early return to school was associated with a lower symptom burden 14 days post-injury in the 8 to 12 and 13 to 18-year-old age groups.

"Clinicians can now confidently inform families that missing at least some school after a concussion is common, often between 2 and 5 days, with older kids typically missing more school," Dr. Vaughan says. "But the earlier a child can return to school with good symptom management strategies and with appropriate academic supports, the better that we think that their recovery will be."

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'Resetting' the injured brain offers clues for concussion treatment

New research in mice raises the prospects for development of post-concussion therapies that could ward off cognitive decline and depression, two common conditions among people who have experienced a moderate traumatic brain injury.

The study in mice clarified the role of specific immune cells in the brain that contribute to chronic inflammation. Using a technique called forced cell turnover, researchers eliminated these cells in the injured brains of mice for a week and then let them repopulate for two weeks.

"It's almost like hitting the reset button," said senior study author Jonathan Godbout, professor of neuroscience in The Ohio State University College of Medicine.

Compared to brain-injured mice recovering naturally, mice that were given the intervention showed less inflammation in the brain and fewer signs of thinking problems 30 days after the injury.

Though temporarily clearing away these cells, called microglia, in humans isn't feasible, the findings shed light on pathways to target that could lower the brain's overall inflammatory profile after a concussion, potentially reducing the risk for behavioral and cognitive problems long after the injury.

"In a moderate brain injury, if the CT scan doesn't show damage, patients go home with a concussion protocol. Sometimes people come back weeks, months later with neuropsychiatric issues. It's a huge problem affecting millions of people," said Godbout, faculty director of Ohio State's Chronic Brain Injury Program and assistant director of basic science in the Institute for Behavioral Medicine Research.

"How do you treat that? At least in mice, by turning over the microglia in the brain we had a very positive effect on their behavior, cognitive status and level of inflammation in the brain. Now we can focus on cellular pathways that generate chronic inflammation as a target."

The research is published online in the Journal of Neuroscience.

About 85% of traumatic brain injuries are similar to the type of concussion examined in this study, involving dispersed impact to the head that causes brain tissue to bump against the skull. Previous research suggests that at least 75% of people who experience a moderate brain injury have long-term mental health and cognitive complications.

Godbout's lab previously linked depressive symptoms in mice to microglia's sustained "high alert" status after a head injury, which causes the cells to overreact to later challenges to the immune system and become excessively inflammatory. In a more recent study in mice, his team showed that forced turnover of microglia before a head injury could reduce later neuropsychiatric complications.

"That was a proof of principle to show that a lot of the inflammation, especially in the long term, is mediated by microglia," he said. "But there is an acute phase of inflammation -- you want to initiate that repair process. There's a positive to that early inflammatory response in the brain or spinal cord. If it lasts a long time and doesn't fully resolve, that's when it's dangerous."

In this new study, researchers waited for seven days after the brain injury to force the turnover of microglia, giving the cells time to carry out their work promoting initial healing. An experimental drug that inhibits a protein that microglia in mice need for survival was added to their food for a week, resulting in depletion of over 95% of microglia in their brains.

After allowing 16 days for the microglia to repopulate, researchers compared the intervention mice to injured mice that recovered without the cell turnover treatment. The intervention mice performed better than control mice on tasks testing their memory and depressive symptoms.

Further analyses of injured brain tissue suggested the cell turnover reversed some injury-related damage to neurons, lowered overall inflammation and improved the brain's ability to adapt to change. Researchers also injected mice with a molecule that triggers an immune response to mimic an infection, and found that sickness behavior was lower in the intervention mice.

Godbout said these combined findings suggest that the repopulating microglia returned in a less "primed" state of readiness, lowering chances for a lifetime of exaggerated inflammatory responses in the brain to any challenge to the immune system -- that brain inflammation being the likely culprit behind the neuropsychiatric complications that follow a head injury.

"If microglia in the human brain don't return to normal and chronic inflammation persists after a head injury, it's not just a secondary brain injury that causes problems. Even getting a viral infection after concussion recovery can progress into a cognitive or behavioral issue or amplify some other part of behavior, like depression," Godbout said. "There is a real connection between a head injury and mental health, and the risk doesn't go away.

"Now we're looking more closely at the pathways that cause changes in microglia, and targeting something specific in that pathway. That is a way forward."

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How long does it really take to recover from concussion?

A new study suggests that people with mild traumatic brain injuries may be more likely to have cognitive impairment, cognitive decline or both one year later, compared to people who were not injured. The research is published in the February 16, 2022, online issue of Neurology®, the medical journal of the American Academy of Neurology. People with poor cognitive outcomes were also more likely to have other symptoms like anxiety and lower satisfaction with life.

"Our results suggest that clinically meaningful poor cognitive outcomes, which we defined as cognitive impairment, cognitive decline or both, one year after a concussion may be more common than previously thought," said study author Raquel Gardner, MD, of the University of California San Francisco. "They also highlight the need to better understand the mechanisms underlying poor cognitive outcome, even after relatively mild brain injuries, to improve therapy for recovery."

The study looked at 656 people who had been admitted to trauma center emergency rooms with concussions and 156 healthy people without head injuries. Their average age was 40. Participants were given up to three neurological evaluations after their injury, at two weeks, six months and one year. Each of those evaluations provided five scores from three tests of recall, language skills and other cognitive domains.

Poor cognitive outcome was defined as satisfying the criteria for cognitive impairment, cognitive decline or both. Cognitive impairment was defined as lower-than-expected performance on at least two cognitive tests such as one memory test and one processing speed test. Cognitive decline was defined as clinically meaningful decline on at least two cognitive tests.

Researchers found that 86 out of 656 people with mild brain injuries, or 14%, had poor cognitive outcomes one year later. Of those, 10% had cognitive impairment only, 2% had cognitive decline only and 2% had both. That's compared to eight out of 156 people without concussions, or 5%, who had poor cognitive outcomes one year later. Of those healthy people, 3% had cognitive impairment, none had cognitive decline only, and 1% had both.

Researchers also found that people who had depression before their injury, had no health insurance, or had a high school education or less were more likely to have a poor cognitive outcome than those who were not depressed before the injury, or had insurance or had more than a high school education.

Researchers found that people who had good cognitive outcomes were more likely to have higher life satisfaction one year after their concussion. The life satisfaction test given to participants ranges in score from five to 35, with lower scores indicating lower life satisfaction. The people with good cognitive outcomes scored an average of 26 on the test, compared to people with poor cognitive outcomes, who scored an average of 21.

The study does not prove that people with concussions will have worse cognitive outcomes one year later, but it shows an association.

"Previous studies of people with moderate to severe brain injuries show that early, intensive rehabilitation can improve people's cognitive outcomes over time. More research is needed to find out the role of cognitive rehabilitation on people with more mild brain injuries who are also at risk for poor cognitive outcomes, and how to predict who falls into this risk category," Gardner said.

A limitation of the study is that people were enrolled at the time of their concussion and their cognitive health before injury was not known.

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