APOS PSYCHOSOCIAL
POCKET GUIDE

Cancer-related cognitive impairment (CRCI) consists of changes in cognition experienced by patients as a side-effect of cancer and cancer therapy. It is one of the most burdensome survivorship experiences and can have a negative impact on social, occupational, and economic well-being. CRCI usually manifests as mild to moderate decline in neuropsychological domains of verbal recall, attention, working memory, and processing speed, and can persist for years following treatment. Estimates of the prevalence of cognitive impairment vary widely in clinical research ranging from 15-75%, but this may be due to differences in time of testing (e.g., during active treatment vs. post-treatment) or differences in neuropsychological measures used. Research suggests about half of survivors can experience long-term CRCI.^1,2

Decades ago, CRCI research was limited to brain tumors, brain metastasis, or neurosurgical effects. However, over the last 4 decades, popular terms such as “chemo brain” or “chemo fog” have been used to describe cognitive sequelae of cancer therapy for non-central nervous system (CNS) tumors. The body of evidence suggests that CRCI has multiple mechanisms of causality such as neurotoxic effects of chemotherapy or estrogen reduction through endocrine therapy. Cancer itself can exert cognitive change through enhanced proinflammatory cytokine response, diminished brain-derived neurotrophic factor (BDNF), and a host of genetic polymorphisms that have been associated with vulnerability to CRCI. While causes remain under investigation, this chapter outlines evidence-based strategies for the clinician to evaluate and remediate CRCI among cancer survivors.

Screening/Risk Factors

Self-report measures can guide the need for additional testing and/or facilitate treatment planning.

Questionnaires for Cognitive Screening:

• Functional Assessment of Cancer Therapy – Cognitive Scale (FACT-Cog): FACT-Cog (facit.org)
• European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30): EORTC Quality of Life Website – EORTC – Quality of Life : EORTC – Quality of Life
• S. National Institute of Health (NIH) Patient-Reported Outcomes Measurement Information Systems (PROMIS): PROMIS (healthmeasures.net)

If a patient has abnormal screening, at a minimum, a brief discussion with the patient pertaining to the nature and onset of cognitive problems, functional status, and ability to perform instrumental activities of daily living (IADLs) is recommended. Further evaluation/testing with a neuropsychologist may be needed for:

• Patients seeking disability benefits
• Patients making return-to-work decisions
• Those requiring documentation of cognitive abilities and potential impairments

Click here to view table as PDF

Table 1. Risk Factors Associated with CRCI Evaluation & Diagnosis

Assessment

A comprehensive evaluation of cognitive function among people with cancer includes an integrated assessment of patient-reported cognition and emotional well-being combined with testing by a neuropsychologist. Patient distress, such as anxiety or depressive symptoms associated with the high stress of cancer, can complicate the clinical presentation.

1) Timing

Evaluation of cognition should ideally occur prior to initiating treatment, after completion of chemotherapy (short-term), and 1-2 years, post-treatment. However, this is not always feasible or indicated in all cases. Early evaluation after cancer treatment completion is a feasible alternative.

2) Cognitive Domains to Evaluate and Appropriate Neuropsychological Tests

Attention/Working Memory: Paced Auditory Serial Addition Test*, Wechsler Adult Intelligence Scale – Fourth Edition Digit Span, Flanker Inhibitory Control and Attention Test^

Processing Speed: Trail Making Test – A*, Symbol Digit Modality Test, Pattern Comparison Processing Speed Test^

Verbal Learning and Memory: Hopkins Verbal Learning Test – Revised*, California Verbal Learning Test – Third Edition, Rey Auditory Verbal Learning Test

Executive Function: Trail Making Test – B*, Controlled Oral Word Association of the Multilingual Aphasia Examination*, Delis-Kaplan Executive Function System Color Word Interference Test

*Tests recommended by the International Cognition and Cancer Task Force ([ICCTR], Wefel et al., 2011)

^Tests in the NIH Toolbox Cognition Battery

3) Quality of Assessment

Sound validity and reliability; Sensitivity to mild impairment; Brief due to fatigue effects; Repeatable tests with reliable change indices (RCI’s) or alternate forms to minimize effects of practice.

4) Cultural Considerations in Neuropsychological Testing

Neuropsychological tests must be normed and validated on populations representative of the individual patient. Culturally and linguistically diverse individuals are underrepresented in studies on neuropsychological tests and CRCI, which may limit the accuracy of these tests for detecting cognitive impairment in minority populations.⁴

5) Differential Diagnosis

Consider patient cognitive self-report, functional status as well as neuropsychological testing outcomes together; Also consider the co-existence of, or distinction from, a neurodegenerative disease or psychiatric disorder

6) Evidence of Cognitive Impairment

There are two primary approaches to measuring the presence of cognitive change for an individual patient: nomothetic or idiographic.

Nomothetic approach compares the patient’s data to established normative data and is helpful when pre-treatment testing is not available. However, this approach does not consider the individual strengths and weaknesses of the patient.

One research standard that has been proposed as a working definition the presence of cognitive impairment has been proposed by ICCTF. A patient with two or more test scores at or below -1.5 standard deviations (SDs) the normative mean, or at least one test score at or below -2.0 SDs the normative mean meets criteria for cognitive impairment.³

Idiographic approach involves comparison of patient’s own data over time to monitor for change.

7) Severity of Cognitive Impairment

CRCI impairments are usually mild to moderate in severity. The level of cognitive impairment should be determined by the degree of estimated change from baseline and the patient’s ability to uphold functional responsibilities. A diagnosis of mild cognitive impairment is generally reserved for individuals who exhibit cognitive impairment, but it is not interfering with IADL’s.

Treatment

Treatment of CRCI has undergone increased research and development in the last two decades. Two broad categories of CRCI treatment have included pharmacologic and non-pharmacologic interventions. This chapter is focused on non-pharmacologic approaches. To date, CRCI treatment research has been limited in scope with small studies and short-duration follow-up. However, quality of research is improving greatly with treatments having to been shown to be generally safe and helpful.⁵

While there is no single definitive non-pharmacologic CRCI treatment, there are a variety of approaches with moderate clinical efficacy. Table 2 below details some of the specific treatments, what they entail and how they are delivered.

Table 2. Non-Pharmacologic Management of CRCI

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Before implementing CRCI treatment, the following points are important to consider:

• CRCI treatments developed and researched to date are primarily designed to mitigate mild to moderate memory impairments.
• While depression, anxiety, fatigue, and sleep disturbance all influence cognition, most CRCI research has controlled for these factors. They are not sole causes of CRCI. However, in the clinical setting, when assessing individuals with CRCI, it is good practice to evaluate the influence of mood or anxiety disorders, persistent fatigue, or sleep disturbance and treat those problems when they are present. In some cases, this may improve cognitive symptoms. It is important to not dismiss the report of cognitive complaints and attribute them solely to stress-related disorders or normal aging.
• It is likely individuals with CNS disease may benefit from some of the treatments listed in this pocket guide, so long as they do not have severe cognitive impairment (e.g., requires supervision to remain safe or assistance to initiate and carryout IADL’s).
• A cultural consideration for some of these treatments is that many have not been translated to non-English languages. This is an ongoing topic of research and development.
• Telehealth treatment delivery has been used in long-term survivorship care for many survivorship problems prior to the COVID-19 pandemic. This was to increase access to services for cancer survivors who could no longer afford to miss any more work or engage in long-distance travel to cancer centers. Consider if the CRCI treatment is either designed for or is readily adaptable to telehealth for improved care access.
• Check if the CRCI treatment is reimbursable by insurance payors or is otherwise affordable.

Bottom Line

Although the exact prevalence of CRCI is unknown, it can have profound negative quality of life effects for a large proportion of cancer survivors. At present, there are approximately 17 million individuals in the United States today who have had a cancer diagnosis in their lifetime. Owing to great advances in early screening, detection and precision treatment, this number is anticipated to reach 22.2 million by 2030.⁶ The bottom line is, a lot of people in the future will go through cancer and cancer treatment and experience mild to moderate memory problems. While more research on the causes of CRCI and how best treat it is needed, non-pharmacologic treatment research is beginning bear fruit for better clinical management now.

References

1. Wefel JS, Kesler SR, Noll KR, Schagen SB. Clinical characteristics, pathophysiology, and management of noncentral nervous system cancer‐related cognitive impairment in adults. CA: a cancer journal for clinicians. 2015;65(2):123-138.
2. Országhová Z, Mego M, Chovanec M. Long-Term Cognitive Dysfunction in Cancer Survivors. Frontiers in Molecular Biosciences. 2021;8
3. Wefel J, Vardy, J, Ahles, T, Schagen, Sanne B. International Cognition and Cancer Task Force recommendations to harmonise studies of cognitive function in patients with cancer. The Lancet Oncology. 2011;12(7):703-708.
4. Rivera Mindt, M., Byrd, D., Saez, P., & Manly, J. Increasing culturally competent neuropsychological services for ethnic minority populations: A call to action. The Clinical Neuropsychologist, 2010; 24(3), 429-453.
5. Von Ah D, Crouch A. Cognitive rehabilitation for cognitive dysfunction after cancer and cancer treatment: implications for nursing practice. Elsevier; 2020:150977.
6. Miller KD, Nogueira L, Mariotto AB, et al. Cancer treatment and survivorship statistics, 2019. CA: a cancer journal for clinicians. 2019;69(5):363-385.