and forebrain in sleep testing procedures (Trzepacz, 1994). In as many as 75 percent of cases, the specific cause of cognitive impairment is unknown (Maddocks et al., 1996). Possible mechanisms of cognitive impairment include brain metastases, meningeal carcinomatosis, hypoxia, sepsis, metabolic abnormalities, hepatic and renal dysfunction, and increased drug levels in the brain or bloodstream (due to disruptions in the blood brain barrier and decreased drug metabolism). Research on cognitive impairment in patients with small cell lung cancer suggests that neuropsychological impairment may be caused by the disease process itself (Meyers et al., 1995; van Oosterhout et al., 1995). It has been hypothesized that long acting morphine metabolites are responsible for delirium (Maddocks et al., 1996; Bruera et al., 1995).

Cognitive impairment may also be caused or exacerbated by various anticancer treatments, including high-dose interferon alpha (INF-a) therapy, cranial irradiation, and high-dose chemotherapy. For example, patients treated with INF-a often exhibit a syndrome of mental slowing and memory impairment, accompanied by mood disturbances. These patients’ patterns of test responses suggest mild subcortical dementia (Valentine et al., 1998). Patients receiving recombinant IL-2 have also been noted to develop a severe dementia resembling dementia of the Alzheimer’s type (Walker et al., 1996). Therapy-induced cognitive impairment may be either acute or chronic. As discussed above, survivors of bone marrow transplantation may report cognitive impairment, physical symptoms, or emotional distress many years after the transplant (Andrykowski et al., 1995; McQuellon et al., 1996; Prieto et al., 1996).

Basic Research Needs

Major questions for basic research include the following:

  1. What are the underlying mechanisms of delirium and cognitive impairment?

  2. What is the role of the cancer disease process in producing cognitive impairment?

  3. What is the process through which biological therapies (e.g., IFN-a, IL-2) produce cognitive impairment?

  4. Are there biological markers for those patients most at risk for delirium and cognitive impairment?

Clinical Research Needs

Research in this area should focus on the understanding, prevention, and treatment of delirium, specifically



The National Academies | 500 Fifth St. N.W. | Washington, D.C. 20001
Copyright © National Academy of Sciences. All rights reserved.
Terms of Use and Privacy Statement