“This study shows that both systemic and inhaled glucocorticoids are associated with an apparently widespread reduction in white matter integrity,” wrote the lead study author, Merel van der Meulen of Leiden University Medical Center in the Netherlands, in research published August 30 in BMJ Open. White matter makes up about half of the tissue in the brain, and its main job is transmitting messages between the brain and the rest of the body. Reduced white matter volume has long been linked to cognitive decline — particularly when it comes to memory loss, processing information, and attention. Diminished white matter has also been tied to a variety of mental health issues including depression, anxiety, and bipolar disorder. Glucocorticoids have previously been linked to damaging changes in the brain, as well as cognitive decline and mood disorders. But much of this research has produced mixed results, often based on animal studies or human trials too small to support broad conclusions. For the new study, researchers examined data from the UK BioBank, which has collected detailed genetic and health information on half a million adults. The new analysis used data from brain scans, cognitive and psychological assessments, and prescription records for 222 patients who used oral glucocorticoids, 557 individuals who used inhaled glucocorticoids, and a control group of 24,106 people who didn’t use these drugs. None of the participants included in the analysis had a history of neurological, psychological, or hormonal disorders. And none of them took antidepressants or other medications for mood disorders. They all had brain magnetic resonance imaging (MRI) scans, completed cognitive testing, and answered questionnaires to identify any symptoms of mood disorders. Compared with people who never used glucocorticoids, those who did had significantly more damage to white matter in the brain, and greater reductions in white matter volume, the study found. The biggest damage was seen among oral glucocorticoid users who took these medicines over longer periods of time. Oral drugs are systemic medicines, meaning they travel through the whole body, and they often have more pronounced side effects than inhaled steroids that target the airways. Oral glucocorticoid users had significantly worse cognitive test scores in assessments of processing speed than people in the control group. Oral glucocorticoid users also reported significantly more psychological symptoms, such as depression and apathy. Inhaled glucocorticoids appeared to have a much lower impact on brain structure, cognitive performance, and psychological symptoms than oral versions of these drugs, the analysis found. Glucocorticoids are widely prescribed to treat a variety of medical conditions, including asthma, inflammatory bowel disease (IBD), rheumatoid arthritis, autoimmune diseases such as lupus, and certain cancers. So-called rescue inhalers for asthma don’t use glucocorticoids. These fast-acting inhalers contain medicines known as bronchodilators that help open airways and relax muscles in the lungs. Some patients with poorly controlled or severe asthma may use oral or inhaled glucocorticoids to manage the inflammation that can exacerbate symptoms. One limitation of the new study is that researchers lacked data on the exact dose of glucocorticoids prescribed, and another drawback is that prescription data doesn’t reveal how often people actually took medicines as directed. It also wasn’t a controlled experiment designed to prove whether or how glucocorticoids might directly cause damaging changes in the brain. “We can’t draw definitive conclusions about whether glucocorticoids caused the observed changes in brain structure and function that were seen in systemic and inhaled glucocorticoid users,” says Joanna Spencer-Segal, MD, PhD, a research assistant professor at the Michigan Neuroscience Institute in Ann Arbor, who wasn’t involved in the new study. That said, it’s plausible that the changes in the brain observed in the study were indeed due to glucocorticoids, Dr. Spencer-Segal says. “Systemic glucocorticoids are known to cause serious side effects, especially if taken for a long time,” she notes. In many cases, doctors may be able to treat patients without using these drugs. “People who take glucocorticoids should talk to their doctor about whether glucocorticoids might be decreased or discontinued,” Spencer-Segal says. “Do not stop taking glucocorticoids without consulting your doctor, since stopping them abruptly can be dangerous.” Asthma patients in particular need to prioritize managing their symptoms well, says Thomas Ritz, PhD, a professor and the director of the Psychobiology of Stress, Emotion, and Chronic Disease Research Program at Southern Methodist University in Dallas, who wasn’t involved in the new study. “We’ve known for a long time that we should avoid systemic corticosteroids as much as possible, as long as asthma is not severe,” Dr. Ritz says. “Inhaled corticosteroids have been the mainstay for regular ‘maintenance’ treatment of asthma for some time now. The key here is to find for patients the lowest possible dose that controls their asthma well.”
