Neurocognitive and psychosocial sequelae of cancer and cancer therapy

Christina A. Meyers, Ph.D.

Our clinical neuropsychology service provides objective assessments of a patient’s neurocognitive function, ability to perform activities of daily living and symptoms etiology, which are used for differential diagnosis, planning patient care, rehabilitation and other interventions, as well as research into the causes and treatment of neurocognitive symptoms. Research protocols are designed to include prospective assessments of cognition and quality of life in a number of different patient populations, development of functional neuroimaging techniques to improve neurosurgical planning and to better assess the effects of interventions on the brain, and development of intervention strategies to treat adverse cancer-related symptoms.

Clinical trials of new anti-cancer agents utilize neurocognitive and quality of life assessments to guard against unacceptable toxicities. In addition, these measures have been shown to be sensitive in detecting tumor progression. In a longitudinal study of patients with brain cancer, changes in cognitive function were measurable before MRI evidence of tumor progression.

Trials with interferon-alpha (IFN-alpha) have provided contradictory findings regarding cognitive side effects. In cooperation with the Psychiatry service, patients with chronic myelogenous leukemia were examined before and during treatment with IFN-alpha alone or IFN-alpha and chemotherapy. Increased depressive symptoms and declines in information processing and executive functions were observed, but depression alone could not account for cognitive dysfunction. Evidence suggested that exposure to chemotherapy and higher cumulative IFN-alpha dose may contribute to cognitive impairment.

Clinical and animal studies suggest that an altered cytokine profile is associated with cognitive impairment and fatigue. In a recent study (Cancer 2005), patients with acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) showed measurable cognitive impairment and fatigue before the initiation of their treatment. Levels of the circulating cytokines interleukin 1 (IL-1), IL-1 receptor antagonist (IL-1RA), IL-6, IL-8 and tumor necrosis factor-alpha (TNF-alpha) were elevated highly compared with normal controls. Higher IL-6 levels were associated with poorer executive function, whereas higher IL-8 levels were associated with better memory performance. IL-6, IL-1RA and TNF-alpha levels were related to measured fatigue. The results indicate a correlation between these symptoms and levels of circulating cytokines, suggesting the potential for targeted interventions for symptom control.

Selected Publications

Meyers CA, Albitar M, Estey E. Cognitive impairment, fatigue, and cytokine levels in patients with acute myelogenous leukemia or myelodysplastic syndrome. Cancer. 2005 Jun 22; [Epub ahead of print]

Scheibel RS, Valentine AD, O'Brien S, Meyers CA. Cognitive dysfunction and depression during treatment with interferon-alpha and chemotherapy. J Neuropsychiatry Clin Neurosci. 2004 Spring;16(2):185-91.

Wefel JS, Lenzi R, Theriault RL, Davis RN, Meyers CA. The cognitive sequelae of standard-dose adjuvant chemotherapy in women with breast carcinoma: results of a prospective, randomized, longitudinal trial. Cancer. 2004 Jun 1;100(11):2292-9.

Litofsky NS, Farace E, Anderson F Jr, Meyers CA, Huang W, Laws ER Jr. Glioma Outcomes Project Investigators. Depression in patients with high-grade glioma: results of the Glioma Outcomes Project. Neurosurgery. 2004 Feb;54(2):358-66; discussion 366-7.

Meyers CA, Hess KR. Multifaceted end points in brain tumor clinical trials: cognitive deterioration precedes MRI progression. Neuro-oncol. 2003 Apr;5(2):89-95.

Wefel JS, Lenzi R, Theriault R, Buzdar AU, Cruickshank S, Meyers CA. 'Chemobrain' in breast carcinoma?: a prologue. Cancer. 2004 Aug 1;101(3):466-75.

Wefel JS, Meyers CA. Cancer as a risk factor for dementia: a house built on shifting sand. J Natl Cancer Inst. 2005 Jun 1;97(11):788-9.

Lee BN, Dantzer R, Langley KE, Bennett GJ, Dougherty PM, Dunn AJ, Meyers CA, Miller AH, Payne R, Reuben JM, Wang XS, Cleeland CS. A cytokine-based neuroimmunologic mechanism of cancer-related symptoms. Neuroimmunomodulation. 2004;11(5):279-92. Review.