‘Chemo Brain’:What We Know and What We Need to LearnRachel Isaksson Vogel, Ph.D.Assistant ProfessorDepartment of Obstetrics, Gynecology and Women’s HealthMasonic Cancer Center’s Women’s Health Scholar

My goal is to research survivorship issues during and after treatment for cancer

and test interventions to improve quality of life and outcomes.

Ice Breaker

What is “Chemo Brain”? How common is “Chemo Brain”? What can I do if I am experiencing “Chemo Brain”? What is currently being studied?

Questions for the Day…

What is “Chemo Brain”?

Changes in cognitive function associated with cancer diagnosis and treatment◦ Chemotherapy◦ Radiation◦ Surgery◦ Immunotherapy◦ Hormone therapy◦ Cancer/tumor itself

“Cancer-induced cognitive impairment” (CICI) or “Cancer-related cognitive impairment” (CRCI)

What is “Chemo Brain”?

Mental “fog” Memory deficits Slower processing speed Hard to maintain focus, concentration Difficulty multi-tasking Language concerns (word retrieval) Motor concerns (navigation, geographic memory)

Symptoms

Distress – unknown cause, duration Reactions from family and friends Job concerns Avoidance of social occasions Depression and anxiety

Impact on Quality of Life

Boykoff et al., J Cancer Surviv, 2009

“You have to fight to make yourself remember numbers, words, places that you go. Sometimes I would leave the house to go somewhere and I really couldn’t remember how to get there… it almost made me break down because of the fast that you think you’re losing your mind.”

“What I have to do sometimes if have my son come over and pay my bills. Can you imagine? It really makes me feel bad… I’ve been so independent and here I am at 55 years old and I can’t pay my bills. And the money’s there.”

Boykoff et al., J Cancer Surviv, 2009

One of the more commonly reported cancer-treatment related symptoms

Research estimates of “chemo brain” in cancer patients vary widelyfrom 0-75%

Some consensus that a SUBGROUP of patients experience “chemo brain”

How common is “Chemo Brain”?

Kohli et al., J Oncol Pract, 2007; Vardy et al., J Clin Oncol, 2015; Janelsins et al., J Clin Oncol, 2017

Results of large national study of breast cancer patients and age-matched controls ◦ 45% vs. 10% clinical significant changes in

cognitive function from baseline following chemotherapy◦ 37% vs. 14% 6 month follow-up

“Chemo brain” symptoms tends to improve over time for most people

Some (10-20%) may have long-term effects

How common is “Chemo Brain”?

Janelsins et al., J Clin Oncol, 2017

Controversy ◦ Many research studies have had some methodologic flaws No control group, no baseline measurements, inconsistent ways of measuring “chemo

brain”

Additional issues◦ Depression◦ Anxiety◦ Sleep deprivation◦ Fatigue

How common is “Chemo Brain”?

Functional neuroimaging findings (fMRI) or PET/CT

Neuropsychological tests◦ Ex. Processing speed◦ Issue: practice effects

Self-report (surveys)◦ Ex. “I have had trouble recalling the name of an object while

talking to someone.” Changes tend to be subtle or mild, hard to measure

Challenge: How to measure?

If patients notice cognitive changes and it is affecting their quality of life,

does the reason or mechanism matter?

Educate patients and families and acknowledge changes Regular exercise (yoga, aerobic + strength training) Social interactions Cognitive rehabilitation

Learn to work around deficits Brain training – ex. Luminosity, BrainHQ, puzzles Identify factors that make it worse – ex. limit multi-tasking Coping strategies – ex. daily planner, notes, following routine

What can I do if I am experiencing “Chemo Brain”?

Medications – still being studied, data mixed to date◦ Stimulants – help with fatigue and attention/concentration Methylphenidate (Ritalin) Dextroamphetamine (Adderall) Modafinil/armodafinil (Provigil/Nuvigil)

◦ Antidepressants◦ Anti-anxiety medications◦ Sleep medications

What can I do if I am experiencing “Chemo Brain”?

Tell your oncology team If you have any sleep problems, fatigue, depression or anxiety

symptoms, work with a psychologist/psychiatrist/Palliative Care If you are more than 6 months post-treatment and “chemo brain”

symptoms are still affecting your daily life, ask your oncologist for a referral to neuropsychologist for testing

What can I do if I am experiencing “Chemo Brain”?

Have you found anything to be particularly helpful for you?

Imaging studies Animal models Long-term follow-up studies in other cancers Testing of behavioral and medical interventions

Where is the research heading?

What exactly causes “chemo brain”? (mechanism) How do we best measure it? Who is at higher risk? What are the best ways to explain these possible effects to patients? What are the short- and long-term effects of “chemo brain” on quality

of life? What are the best interventions to alleviate symptoms and improve

quality of life? Can we prevent it?

Remaining questions…

What exactly causes “chemo brain”? (mechanism) How do we best measure it? Who is at higher risk? What are the best ways to explain these possible effects to patients? What are the short- and long-term effects of “chemo brain”

on quality of life? What are the best interventions to alleviate symptoms and improve

quality of life? Can we prevent it?

Remaining questions…

Some data suggest the following characteristics put individuals at risk, but none are firmly established◦ Females◦ Older Age◦ Lower Cognitive reserve◦ Menopausal status◦ Depression◦ Fatigue◦ Sleep dysfunction◦ Nausea/vomiting◦ Genetics

Who is at greater risk for “Chemo Brain”?

Recruit up to 50 post-menopausal women with newly diagnosed ovarian cancer prior to chemotherapy

Collect blood samples and cognitive functioning data at 4 time points:◦ Before chemotherapy, during chemotherapy, after chemotherapy, 6 months later

Explore Risk Factors:◦ Demographics◦ Co-morbidities ◦ Apolipoprotein-E4 (APOE4) allele◦ Vitamin B12

Risk Factors of ‘Chemo Brain’ among Women Treated for Ovarian Cancer

Funded by Masonic Cancer Center’s Women’s Health Scholar Award

20% of individuals in the US carry at least one APOE4 allele Carriers and non-carriers have demonstrated differences in several

cognitive domains APOE4 can directly affect cognitive decline, but it is hypothesized it

acts more frequently through indirect mechanisms, requiring a trigger by a secondary stressor.

Sparse research describing the relationship between APOE4 and the development of “chemo brain”

Apolipoprotein-E4 (APOE4) allele

Funded by Masonic Cancer Center’s Women’s Health Scholar Award

Vitamin B12 and folate are required to make normal red blood cells, repair tissues and cells, and synthesize DNA

B12 is also important for normal nerve cell function A deficiency in B12 can also result in varying degrees of nerve

damage and cognitive changes Vitamin B12 deficiency is relatively common later in life Postulated that chemotherapy may induce vitamin B12 deficiency Potentially modifiable risk factor

Vitamin B12

Funded by Masonic Cancer Center’s Women’s Health Scholar Award

Expected Outcomes◦ Identify a number of factors potentially associated with decline in cognitive

function◦ Provide preliminary data to begin testing prevention and/or intervention

options

Risk Factors of ‘Chemo Brain’ among Women Treated for Ovarian Cancer

Funded by Masonic Cancer Center’s Women’s Health Scholar Award

Phase II study of low-dose ibuprofen and exercise for cognitive impairment in colorectal cancer patients receiving chemotherapy

Efficacy of MBSR (meditation-based stress reduction) Treatment of Cognitive Impairment Among Breast Cancer Survivors

Phase 3 Randomized Placebo Controlled Clinical Trial of Donepezil (after chemotherapy for breast cancer)

Examples of ongoing national clinical trials…

Questions?

Advancing Knowledge, Enhancing Care