"This study shows that both systemic and inhaled glucocorticoids are associated with an apparently widespread reduction in white matter integrity," wrote study author Merel van der Meulen, a postdoctoral student at Leiden University Medical Center in the Netherlands, in the study published Tuesday in the journal BMJ Open.
White matter is the tissue that forms connections between brain cells and the rest of the nervous system. Having less white matter can slow the brain's ability to process information, pay attention and remember. Lower levels of white matter have also been connected to psychiatric issues such as depression, anxiety and irritability.
"This new study is particularly interesting in showing the extent to which white matter, which is required for neurons to connect with each other, is affected by medication use," said Thomas Ritz, a professor of psychology at Southern Methodist University who has researched the impact of steroids on people with asthma. He was not involved in the study.
However, "there's no reason for alarm," said neuroimmunologist Dr. Avindra Nath, the clinical director of the National Institute of Neurological Disorders and Stroke, who was also not involved in the study. Doctors have long known that, if you give patients steroids, "the brain does shrink, but when you take them off the steroids, it comes back," Nath said.
Due to brain plasticity - the ability of the brain to reorganize its structure, functions or connections - "these could be temporary effects," he said. "They don't necessarily have to be permanent. White matter can repair itself."
Glucocorticoids are some of the most frequently prescribed anti-inflammatory medications due to their widespread use in a number of conditions, experts say.
In addition to asthma, both oral and inhaled glucocorticoids can be used to treat allergies, chronic obstructive pulmonary disease (COPD), Crohn's disease and other types of inflammatory bowel disease, eczema and other skin conditions, lupus, tendinitis, multiple sclerosis, osteoarthritis, and rheumatoid arthritis.
However, glucocorticoid inhalers should not be confused with quick-relief inhalers used to stop an asthma attack. Quick-relief inhalers contain non-steroid medications that relax the muscles in the lungs, such as albuterol, levalbuterol and pirbuterol, which can open airways in minutes. Inhaled corticosteroids do not work in emergencies - they are prescribed for longer-term control of inflammatory conditions.
Prior research has linked the long-term use of oral glucocorticoids to structural brain abnormalities and shrinkage of certain areas of the brain, as well as mental health issues such as anxiety, depression, confusion and disorientation. Studies have also shown that people who have lived with asthma have higher rates of cognitive and memory impairment later in life than people without the condition.
But much prior research has been small in scale, and at times, inconclusive, experts say.
The new study used data from the UK BioBank, a large biomedical research center that followed 500,000 residents of the United Kingdom from 2006 to 2010. From that database, the researchers were able to find 222 oral glucocorticoid users and 557 users of inhaled glucocorticoids who did not have a previous diagnosis of any neurological, hormonal or mental health disorder.
Those people underwent cognitive and mental health testing and received a diffusion MRI of the brain. Researchers pulled that data and compared those MRI and cognitive findings to over 24,000 people in the database who did not use steroids.
"To the best of our knowledge, this is the largest study to date assessing the association between glucocorticoid use and brain structure, and the first to investigate these associations in inhaled glucocorticoid users," wrote the study authors.
The study found the greatest amount of white matter damage in people who use oral steroids regularly over long periods of time. The mental processing speed of chronic oral steroid users tested lower than non-users. People on oral steroids also had more apathy, depression, fatigue and restlessness than non-users of steroids.
The smallest impact on white matter occurred in people who use inhaled steroids, the study found.
That fits with what doctors see in clinical practice, said pulmonologist Dr. Raj Dasgupta, an assistant professor of clinical medicine at the Keck School of Medicine at the University of Southern California. He was not involved in the study.
"We don't see side effects as often with the inhaled form of glucocorticoids," he said. "And of course, mainstay of therapy for allergies and asthma is always going to be avoiding the triggers and making lifestyle modifications."
Pulmonologists and rheumatologists are cautious about prescribing the smallest dose of steroids needed to control symptoms, Dasgupta said, due to the large number of side effects from steroid use that can also impact health, including brain health.
"As a clinician, the minute you start a person on these medications, you're immediately thinking, 'How do I safely take that person off in a timely fashion?' Steroids cause weight gain, and weight gain is always going to be a risk for developing diabetes and high blood pressure,d" Dasgupta said.
"When you give steroids to people with diabetes, their blood sugar can go up," he added. "When you take steroids acutely, you could definitely have insomnia and trouble sleeping, and when you're on long-term steroids, it puts you at a high risk for infections because they are an immunosuppressant."
The new study had limitations. For one, it was not able to determine steroid dose or track adherence, Ritz said.
"We know that only about 50% of patients with asthma take their medication as prescribed, and potential overreporting of intake is also an issue," Ritz said. "You should take your inhaled corticosteroids, which reduce the inflammation locally, as regularly as possible, albeit at the lowest possible dose that allows you to control you asthma.
"This study gives us another reason to keep the dosages low," he added.
Another limitation was that it was unable to differentiate between people who take steroid tablets and those who use infusions, according to study authors.
"The study mainly confirms what we know for a long time in asthma management: Take as few systemic (oral) corticosteroids as possible, as long as you are not a patient with severe asthma. Stick to inhaled steroids and discuss with your treating physician plans to step down medication regimens during good times," Ritz said.
"It's a very well done study," Nath said. "But the findings demand another study to be done to see how long these effects last and how they can be reversed."
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