http://www.curetoday.com/publications/cure/2018/summer-2018/lifting-the-fog-on-chemo-brain
Lifting the Fog on 'Chemo Brain'

LEAH LAWRENCE

JUSTIN BIRCKBICHLER experienced chemo
brain after undergoing chemotherapy for
testicular cancer. - ERIN RAE PHOTOGRAPHY
JUSTIN BIRCKBICHLER experienced chemo brain after undergoing chemotherapy for testicular cancer. - ERIN RAE PHOTOGRAPHY
As a fourth-grade teacher, Justin Birckbichler, 26, was accustomed to asking his students to remember facts and ideas they had learned. But while undergoing chemotherapy to treat testicular cancer that was diagnosed in 2016, Birckbichler noticed that it was he who was having difficulty recalling information.

“I would compare it with attention deficit disorder or a general feeling of fogginess,” recalls Birckbichler, who writes a blog about his cancer experiences for curetoday.com.

This kind of cognitive impairment, sometimes referred to as chemo brain or chemo fog, can start before, during or just after cancer treatment and is associated with a variety of physical mechanisms and treatment modalities, not just chemotherapy. Common symptoms include forgetfulness, difficulty concentrating or recalling details or words, and trouble multitasking.

“Of the two biggest things I experienced, one was difficulty with word retrieval and the other was that I had a hard time focusing on anything,” Birckbichler says. “I wouldn’t even attempt to read a book, and some days even watching TV was too hard. I couldn’t focus for an extended period of time.”

Birckbichler had done research prior to starting chemotherapy and knew to expect some cognitive issues. When he experienced them, he discussed the symptoms with his physician, who offered just this advice: “Ride it out.”

GAINING RECOGNITION


Birckbichler is just one of many patients with cancer who report experiencing some kind of cognitive impairment. The exact number is hard to pin down and varies by treatment type, according to Fremonta Meyer, M.D., a clinical psychiatrist in the department of psychosocial oncology and palliative care at Dana-Farber Cancer Institute in Boston.

“There have been studies that suggested that up to 70 percent of patients notice cognitive ‘clouding’ during active chemotherapy,” Meyer says. “Of those patients, the majority will get better within six to nine months, but a subset may have longer-term effects.”

The chemotherapies Cytoxan (cyclophosphamide), Adriamycin (doxorubicin), Adrucil (5-FU) and Taxol (paclitaxel) are especially associated with chemo brain, as is any dose-dense chemotherapy, she says. Despite being known as chemo brain, cognitive complaints can occur following many cancer treatments besides chemotherapy, including radiation, surgery, hormonal therapy, immunotherapy and stem cell transplant; it is still unclear whether targeted therapies can contribute. In addition, the psychological stress of undergoing a cancer diagnosis and treatment, which many experts liken to post-traumatic stress disorder seen in war victims, can cause or worsen concentration and memory problems.

To treat his testicular cancer, Birckbichler had surgery to remove the affected testicle. Because the disease had spread to multiple lymph nodes, he also underwent 10 weeks of chemotherapy with Blenoxane (bleomycin), etoposide and Platinol (cisplatin). He cannot recall exactly when during his treatment he began to feel the cognitive effects, but knows they lasted well after the therapy ended.

Unfortunately, cases like Birckbichler’s are not rare, Meyer confirms. “There is only recently increasing awareness among oncologists and nurses about this phenomenon,” she says, “but there are data to support that it is real and not just in the patient’s head.”

In fact, the results of a 2016 study comparing cognitive function in patients with breast cancer with that of cancerfree people of the same age showed that patients with cancer had substantially more difficulties for as long as six months after treatment.


TRACKING THE CAUSES


Although often associated with breast cancer, cancer-related cognitive impairment can occur with any type of the disease, including prostate and colon cancer, and in patients undergoing stem cell transplant for leukemia or lymphoma. It may be seen more frequently in people who undergo multiple modes of treatment, according to Patricia Ganz, M.D., director of cancer prevention and control research at the Jonsson Comprehensive Cancer Center at UCLA.

In one small study of women treated for breast cancer, Ganz and colleagues found that patients who underwent chemotherapy had significantly worse cognitive functioning compared with those who had surgery alone, but women treated with both chemotherapy and hormone therapy had the greatest cognitive deficits.
 
Having experienced chemo brain,
BARBARA TAKO says more research
and treatments are needed to combat
the problem. - LAUREN B. PHOTOGRAPHY
Having experienced chemo brain, BARBARA TAKO says more research and treatments are needed to combat the problem. - LAUREN B. PHOTOGRAPHY
Barbara Tako, 54, underwent multiple types of treatment after receiving a diagnosis of stage 1 breast cancer at age 46. For Tako, an author and clutter-clearing expert who also blogs for curetoday.com about her cancer journey, the effects of treatment have persisted.

Because of certain characteristics of her cancer and her young age at diagnosis, Tako’s physicians treated her disease aggressively. She underwent a lumpectomy, several rounds of Cytoxan and Taxotere (docetaxel), local radiation to the chest, and hormone therapy with Arimidex (anastrozole).

She also had her ovaries removed — a prophylactic oophorectomy — which sent her into early menopause. “After chemotherapy you want to maybe get some degree of normal back in your life, but I was getting no sleep and could tell I was not as sharp as I had been before chemotherapy,” Tako says. “It was harder to retrieve words, and, as a writer, (I found) that was very difficult.”

Tako was frustrated by the lack of information available about what she was experiencing, she says. It was hard to know if her cognitive difficulties were due to cancer, treatment, menopause or the normal aging process.

“I felt like I was on my own,” Tako says. “It would have been great if they had done a baseline test, before chemotherapy, of my mental acuity so we could retest and evaluate the difference.”

However, evaluations like that are rare, Meyer says.

RESEARCHING CHEMO BRAIN


A huge amount of research is being devoted to looking at who is most at risk for cognitive impairment, according to Tim Ahles, Ph.D., a behavioral psychologist at Memorial Sloan Kettering Cancer Center in New York City. Age is definitely a risk factor, he says: An older brain is more vulnerable.

Researchers are also looking into the idea of cognitive reserve, or a kind of “knowledge bank” someone might acquire throughout life. “People with more education or professional jobs that are intellectually stimulating … tend to have higher levels of cognitive reserve and tend to be less vulnerable than people with lower levels of cognitive reserve,” Ahles says.

Genetic factors might also increase vulnerability. People who have genetic alterations that already make them susceptible to cognitive decline under normal circumstances may be at higher risk of cognitive impairment related to cancer, Ahles says. People with a form of the APOE gene called E4, which is associated with Alzheimer’s disease, and survivors of breast cancer who have a variant of the COMT gene, which influences how fast the brain metabolizes dopamine, seem to be at greater risk, he said. On the other hand, he says, a variant of the BDNF gene can protect against chemo brain.

When looking at chemotherapeutic agents associated with chemo brain, researchers have questioned why drugs that are able to cross a protective barrier within the body and affect the brain and spinal cord (the minority), as well as those that don’t, can stimulate the same side effect.

According to Ganz, inflammation might be a factor. “Our findings relate to the development of inflammation that occurs with tissue injury, such as what occurs with surgery, radiation or chemotherapy,” she says. “That inflammation travels through the whole body and passes into the brain, where it activates cells that can perpetuate inflammation. This is what we think may be one of the mechanisms by which fogginess or difficulties with organization, planning or concentration may occur.”

Inflammation may even set off chemo brain before treatment is given, according to a team of researchers who studied the issue in mice. In 2017, the journal Neuroscience published their findings, which demonstrated that cytokines released by the body to fight a tumor can inflame the brain’s nervous system, and also that chemotherapy limits production of memory cells. Combined, these dynamics led to shrinkage of areas of the brain responsible for learning and memory in mice, according to the researchers. Brain function problems could also be caused or worsened by sleep problems, depression, stress, anxiety, fatigue or other illness. Ahles is involved in research looking into how these disorders might affect cognitive function in patients with cancer.

For example, the 2016 study comparing cognitive function among women with and without breast cancer found that higher levels of anxiety and depressive symptoms before cancer treatment were associated with lower cognitive functioning scores.

Can scans of patients’ brains shed light on the causes or treatment of chemo brain? A small 2011 study of women with breast cancer used scans to show that patients who were treated with chemotherapy had less brain activity related to executive function tasks compared with those not given chemotherapy.

Brain imaging with PET and MRI scans is being employed today in a small, ongoing study of brain changes associated with chemo fog. However, more precise tools are needed to understand changes in the brain at a greater level of detail.

SEEKING TREATMENT


Both Birckbichler and Tako found that no treatments were available to help them combat the cognitive effects of cancer and its therapies. Despite an increased awareness of the issue in the medical community, treating cancerrelated cognitive impairment is not usually as easy as writing a prescription.

Medications are sometimes used to treat chemo brain: methylphenidate (Concerta, Ritalin and others), indicated for attention-deficit/hyperactivity disorder; Aricept (donepezil) and Namenda (memantine), both typically prescribed in people with Alzheimer’s; and Provigil (modafinil), used for certain sleep disorders. In study animals with imbalances or deficits in neurotransmitter activity that could contribute to chemo brain, the antidepressant Prozac (fluoxetine) has worked as a preventive before administering 5-FU, according to Ahles. However, he said, many of the medications tested produced disappointing results or worked in just a minority of patients.

Still, anyone who thinks he or she is dealing with chemo brain should visit a physician to discuss it, as well as to rule out or address other potential causes of cognitive deficits. “There is a whole list of other problems that can cause cognitive impairment,” Meyer says. Among them: depression, anxiety, vitamin D deficiency, sleep apnea, thyroid disease and anemia.

“You have to investigate each and every potential issue that could be treated,” she says. “Treating these other conditions might improve or alleviate the cognitive issues.” About a year after he finished his cancer treatment, Birckbichler was treated for depression. His fogginess had lifted by then, but he still wonders whether depression contributed to his chemo brain.

If other factors are eliminated, patients and survivors can take some recommended approaches, especially if symptoms have persisted for more than three to six months after treatment.

A good place to start is with an assessment by a neuropsychologist, who may identify certain areas of cognitive weakness, Ganz says. Then, compensation techniques can be learned through counseling.

There are standard cognitive-rehabilitation strategies available to address specific deficits. For example, Ganz says, if executive functioning is reduced, counseling can help people use calendars and other tactics to improve planning and organization. For a memory deficit, exercises can help promote mental nimbleness.

Some cognitive rehab programs can be done at home, and there is evidence that they help ease the symptoms of chemo brain, Meyer says. “I sometimes point patients to computerized training like Lumosity (lumosity.com) as a good way to keep the brain active and exercising,” she says, noting that she does not recommend these programs to patients who may find them upsetting. Several trials are formally assessing the impact of mental training programs used during and after chemotherapy, including an eight-week memory and thinking skills workshop in survivors of breast cancer.

Not to be overlooked, Meyer adds, is the impact of moving the body: “We are finding that physical exercise might be better than cognitive exercise in preventing new dementias and helping with chemo brain.”

REACHING OUT


Tako says her experience is proof that long-term problems with chemo brain exist. “If I had cancer 15 years ago rather than eight years ago, I think I would have felt a lot more isolated than I did,” she says. “At least now it is starting to be acknowledged, but I still don’t think enough is being done to figure it out. More should be done.”

Ganz agrees, adding that the issue has been minimized by clinicians. “On consent forms, we go into gory detail about things that might occur only rarely, but rarely speak to things that are more common,” she says. “If someone says they aren’t sleeping, a physician will send them for a sleep apnea evaluation or give them medication … likewise for pain issues.

But if someone tells you they are mentally foggy, it is not approached in the same way.”

Tako used, and continues to use, several coping mechanisms to deal with her cognitive symptoms, she says. For example, she plays mentally challenging games, such as sudoku, and incorporates lists and reminders into her daily life.

Most of all, she recommends seeking support from other people.

“Reach out to talk to a therapist. Let your doctors know what is going on,” Tako says. “Connect with fellow survivors, and do what you can to make sure you don’t feel like you are alone.”
Print | cure Printing...