Improvements in the treatment of brain tumors have been shown to prolong patients' survival considerably. However, a substantial number of patients who have their underlying malignancy controlled, develop cognitive deficits as a consequence of their treatment. These patients often experience progressive cognitive impairment that disrupt their ability to perform at premorbid levels at work and at home. The risk of developing neurocognitive impairment as a result of radiation or chemoradiation treatment has been recognized in several studies, but its incidence is not well understood. The proposed study will examine neurocognitive functioning and quality of life prospectively in a large group of newly diagnosed patients with low-grade or anaplastic gliomas and primary central nervous system lymphoma (PCNSL). Neuropsychological measures reported to be particularly sensitive to the delayed effects of radiation and a quality of life questionnaire will be administered prior to treatment and at 6-month intervals subsequently. The proposed study will also apply advanced neuro-imaging techniques, such as 1H- magnetic resonance spectroscopy (1H-MRSI) and diffusion tensor imaging (DTI), to quantitatively assess metabolic and diffusion changes in the white matter that may be associated with the delayed effects of radiation or chemotherapy. Serial 1HMRSI and DTI studies will be performed prior to and after treatment, at intervals that coincide with the neurocognitive evaluations. This study will also explore the possibility that the possession of the apolipoprotein E (APOE) e-4 allele correlates with the development of cognitive impairment after radiation or chemoradiation treatments. The findings of this study will provide valuable information regarding the incidence and extent of cognitive deficits in this population, and the specific areas that should be addressed in the development of strategies for cognitive rehabilitation. The investigation of white matter metabolic and diffusion abnormalities, and possible genetic susceptibility for the development of treatment-induced cognitive impairment will be instrumental for defining parameters and prevention strategies that may alter treatment practice.
