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Chemobrain is a term used to describe the changes in cognitive abilities that some patients with cancer may experience, such as:

• Fogginess of thinking
• Trouble recalling recent events
• Feeling slower in their thought processes
• Mental tasks requiring more effort

It commonly affects patients undergoing chemotherapy and sometimes other types of cancer treatments, and it may impact their quality of life.

What we know ¡ª and don¡¯t know ¡ª about chemobrain

In previous studies looking at traditional systemic chemotherapy, around 33% to 50% of patients experienced chemobrain. ¡°However, in studies that ask patients about their cognitive concerns, that rate is much higher,¡± says neuropsychologist ¡°In general, at least 70% of patients feel like they're having cognitive changes during treatment.¡±

Although physicians know that the effects patients describe as chemobrain are actual, measurable changes in their cognitive function, the cause of those changes is not clear. ¡°Recently, there has been a dramatic increase in preclinical, translational research to reveal what some of the biological mechanisms underlying chemobrain might be,¡± Wefel says.

A possible cause of chemobrain

One such research effort was led by , an endocrinologist at MD Anderson, in collaboration with a team at Columbia University.

in cells called the ryanodine receptor type 2. Calcium channels are proteins that control the movement of calcium ions within and between cells to help maintain calcium gradients. Properly maintained calcium gradients are needed for a variety of biological functions, including muscle contraction and signaling between neurons.

Working in preclinical models, they used traditional chemotherapy to induce measurable cognitive dysfunction similar to what patients with chemobrain experience. In addition to the changes to cognitive function, they also saw increased levels of a protein called transforming growth factor beta (TGF-¦Â) in brain cells.

TGF-¦Â causes oxidative stress, which destabilizes the ryanodine receptor and causes it to ¡°leak¡± calcium ions. In muscle cells, ¡°leaky¡± calcium channels cause muscle weakness, so the team wondered if, in brain cells, they could be causing the cognitive dysfunction.

Fixing the ¡°leaky¡± calcium channels

¡°We found that we could prevent the cognitive dysfunction by using Rycals, a class of drugs that stabilize the ryanodine receptor, even under oxidative stress,¡± says Guise.

Rycals have already been in clinical trials for muscle and cardiac dysfunction with positive results and minimal side effects. One caveat is that they need to be given in a preventive way, before the calcium channels start to leak.

Implications for treatment

¡°This is an important study because we have identified a mechanism that can cause cognitive dysfunction,¡± Guise says, ¡°And we could potentially prevent it in the future by treating patients with this drug before they get chemotherapy.¡±

Currently, the only option to treat chemobrain is to identify co-occurring symptoms such as fatigue and sleep disturbances and to address them with behavioral plans or lifestyle changes. ¡°There's not a specific pharmaceutical therapy that will address this issue, and that's a gap that we're all hoping to close in the future,¡± says Wefel.

¡°We're trying to address this by understanding what causes chemobrain, so we can prevent it,¡± explains Guise. ¡°Because if we prevent things like cognitive dysfunction associated with therapy, patients are going to respond better to the therapy.¡±

Other chemobrain research directions

Historically, most chemobrain research has been in patients with breast cancer receiving chemotherapy. But as new therapies are developed and become standard of care, they also need to be studied for their cognitive effects. ¡°We know some of the emerging immunotherapies like CAR T cell therapy and immune checkpoint inhibitors may also have frequent cognitive dysfunction associated with them,¡± says Wefel.

¡°We¡¯ve also struggled to arrive at risk and resilience predictors for chemobrain,¡± he adds. Baseline measurements of cognitive function before treatment are needed to help measure the effect of the treatment and persistence after treatment ends. In general, larger data sets are also needed to help identify genetic risk factors.

At MD Anderson, a group of multidisciplinary clinicians and researchers created the NeuroHealth Initiative to establish a research-enabling clinic to help gather this data. Currently, the clinical research is only open to patients with ovarian cancer who are receiving chemotherapy. Patients can opt into a variety of types of research, including cognitive monitoring, patient-reported outcomes, brain imaging and blood draws.

In the meantime, patients should know that they can always bring up symptoms like chemobrain with their health care providers. ¡°It's really important for patients and caregivers to advocate for their care. We have a big neuropsychology group here at MD Anderson, but to get to us, you need to talk to your physicians,¡± Wefel says. ¡°It's worth bringing up, and there are people who can help you.¡±

Learn about research at MD Anderson.