Cognitive Alterations in a Growing Population of Cancer Survivors

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Cognitive Profile and Putative Mechanisms of Cancer Therapy-Associated Cognitive Changes: A Primer for Mental Health Professionals

Chemotherapy-associated cognitive changes can interfere with cancer treatment and adversely affect daily functioning, quality of life, and long-term survival.
Chemotherapy-associated cognitive changes can interfere with cancer treatment and adversely affect daily functioning, quality of life, and long-term survival.

In 2014, nearly 14.5 million children and adults in the United States were living with a history of cancer.1 By January 1, 2016, the number of cancer survivors increased to 15.5 million, according to a new report published in CA: A Cancer Journal for Clinicians.2

Currently more than 3.5 million women and more than 3.3 million men report a history of breast or prostate cancer, respectively, and nearly 50% of survivors diagnosed with any cancer are 70 years of age and older.2 Despite overall declining cancer rates, the size of this population is projected to reach more than 20 million within the next decade due to advances in early detection and improved efficacy of cancer therapy.2

Given the trajectory of survivorship, and considering the great psychological and emotional stress associated with cancer diagnosis and treatment, mental health professionals will be faced with and will need to address unique short-term and long-term needs of individuals with cancer or living with a history of cancer.3

A subgroup of survivors is vulnerable to persistent posttreatment adverse effects of neurotoxic cancer therapies such as fatigue, depression, chronic pain, sleep disturbance, and dysfunction across several cognitive domains. Neurocognitive complications vary in onset, duration, and severity and are associated with radiation treatment and most chemotherapeutic agents.4,5 Cognitive adverse effects not only affect daily functioning and quality of life, but also influence patient survival by affecting dosage regimen and compromising adherence to treatment.6

Chemotherapy-associated cognitive impairments were first reported almost half a century ago, and while candidate mechanisms have been identified, they have not been fully elucidated.7,8 It is becoming evident that a mechanistic link exists between cancer therapy-induced and neurodegenerative disease-associated cognitive changes.9 Likely causal pathways include genetic susceptibility, DNA damage and compromised DNA repair, dysregulated immune response and chronic inflammation, altered hormonal milieu, diminished neurogenesis, and disrupted functional brain connectivity.10 Clinical cognitive profiles also reflect overlapping symptoms shared by cancer survivors and neurodegenerative disease patients, including deficits in working and modality-specific memory, executive function, information-processing speed, and attention and concentration.6

Strategies aimed at preventing or minimizing cognitive deficits resulting from cancer therapy-associated neurodegeneration include pharmacologic and cognitive-behavioral approaches with varying degrees of efficacy and no recognized treatment.11 Taken together, the available evidence indicates that chemoradiation-induced adverse effects such as cognitive difficulties, neuropathy, and fatigue may persist indefinitely (even long after treatment cessation); this can cause great distress for the patient and may thus interfere with cancer treatment, daily functioning, overall quality of life, and ultimately, long-term survival.12,13 Continued engagement of mental health professionals, and consideration of the entire clinical spectrum associated with psychosocial health, will help to prevent or minimize distress and promote well-being in cancer survivors.


1. DeSantis CE, Lin CC, Mariotto AB, et al. Cancer treatment and survivorship statistics, 2014. CA Cancer J Clin. 2014;64:252-271.

2. Miller KD, Siegel RL, Lin CC, et al. Cancer treatment and survivorship statistics, 2016. CA Cancer J Clin. 2016. doi: 10.3322/caac.21349.

3. Naughton MJ, Weaver KE. Physical and mental health among cancer survivors. N C Med J. 2014;75:283-286.

4. Dizon DS, Krilov L, Cohen E, et al. Clinical cancer advances 2016: annual report on progress against cancer from the American Society of Clinical Oncology. J Clin Oncol. 2016;34:987-1011.

5. Janelsins MC, Kesler SR, Ahles TA, Morrow GR. Prevalence, mechanisms, and management of cancer-related cognitive impairment. Int Rev Psychiatry. 2014;26:102-113.

6. Wefel JS, Vardy J, Ahles T, Schagen SB. International Cognition and Cancer Task Force recommendations to harmonise studies of cognitive function in patients with cancer. Lancet Oncol. 2011;12:703-708.

7. Silberfab, PM. Chemotherapy and cognitive defects in cancer patients. Annu Rev Med. 1983;34:35-46.

8. Kaiser J, Bledowski C, Dietrich J. Neural correlates of chemotherapy-related cognitive impairment. Cortex. 2014;54:33-50.

9. Ahles TA, Saykin AJ. Candidate mechanisms for chemotherapy-induced cognitive changes. Nat Rev Cancer. 2007;7:192-201.

10. Seigers R, Schagen SB, Van Tellingen O, Dietrich J. Chemotherapy-related cognitive dysfunction: current animal studies and future directions. Brain Imaging Behav. 2013;7:453-459.

11. Fardell JE, Vardy J, Johnston IN, Winocur G. Chemotherapy and cognitive impairment: treatment options. Clin Pharmacol Ther. 2011;90:366-376.

12. Bower JE, Ganz PA. Symptoms: fatigue and cognitive dysfunction. Adv Exp Med Biol. 2015;862:53-75.

13. Fisch MJ, Chang VT. Striving for safe, effective, affordable care for cancer survivors with chronic pain: another kind of moonshot. JAMA Oncol. 2016. doi: 10.1001/jamaoncol.2016.0854. [Epub ahead of print]

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