COPD patients have a higher risk of brain problems, possibly due to inflammation

Patients with chronic obstructive pulmonary disease (COPD) have a higher chance of suffering from brain-related problems such as anxiety, depression and memory problems. PhD candidate Charlotte Pelgrim discovered that inflammation in the brain and a less protective barrier of the blood vessels in the brain may play a role. She also showed that anti-inflammatory nutrients in the diet could have a positive effect on the psychological well-being of COPD patients. Pelgrim will defend her dissertation today.

COPD is a chronic lung disease that is usually caused by smoking. Patients with COPD suffer from bronchitis, inflammation of the lower airways, and pulmonary emphysema, damaged air sacs. As a result, they have difficulty breathing and tire easily. COPD patients may experience ’lung attacks’, periods during which the COPD symptoms worsen. Bacterial or viral infections are usually the cause of these attacks.

Often also brain problems

People with COPD have a relatively high risk of having brain problems, Pelgrim concludes based on prescription data from 800 Dutch pharmacists. Her research shows that about 15 percent of Dutch people who receive medication for COPD, also receive medication for depression and/or anxiety disorders. This is high, even compared to other chronic diseases. Of the Dutch people who have none of the chronic diseases studied, only 2 to 3 percent receive medication against these brain disorders.

Experiments

The exact cause of the higher occurrence of brain problems in COPD patients is not known. Pelgrim: "A lot of factors are at play. Patients are, for example, short of breath, which makes them more anxious. Thanks to studies with mice, we know that disease processes in the lungs can also play a role."

There are currently no animal-free models to investigate how disease in the lungs can lead to problems in the brain. To gain more insight into the interaction between the lungs and the brain in COPD, Pelgrim induced COPD symptoms in mice. She also mimicked a lung attack in the mice by inducing inflammation in the lungs. Pelgrim: "Lung attacks can worsen brain problems in COPD patients. Therefore, we also wanted to gain insight into the effect of these attacks."

Memory problems and changed behavior

By comparing the learning ability of mice with pulmonary emphysema to that of healthy mice, Pelgrim and her colleagues showed that mice with damaged air sacs have memory problems. She also found that mice with COPD symptoms ànd a mimicked lung attack showed different behavior than healthy mice: depending on exactly how the COPD was induced, they were either less active, or they actually moved more and explored their environment more actively.

Inflammation in the brain

Pelgrim and her colleagues believe that inflammatory processes may play an important role in the link between brain problems and COPD. Pelgrim: "Mice with induced COPD function worse cognitively. This is partly due to a lack of oxygen, but a weaker blood-brain barrier and inflammation in the brain probably also play a role."

The walls of blood vessels in the brain form a barrier that keeps harmful substances from entering the brain. Pelgrim found that this barrier was less robust in mice with COPD symptoms. Certain proteins in the walls were present in lower quantities than in healthy mice, likely due to inflammatory processes in the bloodstream. Pelgrim’s results also suggest that the mice with COPD symptoms had inflammation in a part of the brain that plays a role in cognitive function.

A healthy lifestyle is a relatively easy way to positively influence the symptoms in the lungs, as well as the consequences of COPD outside the lungs.

Nutrition may help

Pelgrim also investigated at the role of nutrition in all this. Some of the mice with induced COPD were given food rich in four anti-inflammatory substances: Omega-3 fatty acids, prebiotics, tryptophan and vitamin D. Pelgrim: "We found evidence that this diet improves the behavior of the mice, as it seems to make them somewhat less anxious. And we saw that the barrier of blood vessels in the brain recovered slightly thanks to the diet." By examining immune cells in the mice’s spleens, she also showed that diet can have a positive effect on the immune system.

The effects on behavior and the blood-brain barrier that Pelgrim and colleagues observed were not very large. Pelgrim therefore emphasizes that additional research is needed to shed more light on the potential role of nutrition. But according to the PhD candidate, eating healthy is important for COPD patients in any case. Pelgrim: "There are definitely gains to be made there. Some COPD patients do not get enough nutrients through their diet, such as dietary fibers. A healthy lifestyle is a relatively easy way to positively influence the symptoms in the lungs, as well as the consequences of COPD outside the lungs."