Chemo Brain : What We Know and What We Need to Learn

Chemo Brain : What We Know and What We Need to Learn Rachel Isaksson Vogel, Ph.D. Assistant Professor Department of Obstetrics, Gynecology and Women s Health Masonic 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

Questions for the Day What is Chemo Brain? How common is Chemo Brain? What can I do if I am experiencing Chemo Brain? What is currently being studied?

What is Chemo Brain?

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)

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

Impact on Quality of Life Distress unknown cause, duration Reactions from family and friends Job concerns Avoidance of social occasions Depression and anxiety 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

How common is Chemo Brain? One of the more commonly reported cancer-treatment related symptoms Research estimates of chemo brain in cancer patients vary widely from 0-75% Some consensus that a SUBGROUP of patients experience chemo brain Kohli et al., J Oncol Pract, 2007; Vardy et al., J Clin Oncol, 2015; Janelsins et al., J Clin Oncol, 2017

How common is Chemo Brain? 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 Janelsins et al., J Clin Oncol, 2017

How common is Chemo Brain? 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

Challenge: How to measure? 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

If patients notice cognitive changes and it is affecting their quality of life, does the reason or mechanism matter?

What can I do if I am experiencing Chemo Brain? 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

Have you found anything to be particularly helpful for you?

Where is the research heading? Imaging studies Animal models Long-term follow-up studies in other cancers Testing of behavioral and medical interventions

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 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?

Who is at greater risk for Chemo Brain? 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

Risk Factors of Chemo Brain among Women Treated for Ovarian Cancer 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 Funded by Masonic Cancer Center s Women s Health Scholar Award

Apolipoprotein-E4 (APOE4) allele 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 Funded by Masonic Cancer Center s Women s Health Scholar Award

Vitamin B12 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 Funded by Masonic Cancer Center s Women s Health Scholar Award

Risk Factors of Chemo Brain among Women Treated for Ovarian Cancer 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 Funded by Masonic Cancer Center s Women s Health Scholar Award

Examples of ongoing national clinical trials 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)

Questions?

Advancing Knowledge, Enhancing Care