Radiotherapeutic effects on brain function: Double dissociation of memory systems

Objective: The neurocognitive sequelae of therapeutic cranial irradiation a re not well characterized in adults with primary brain tumors. To address t his problem, we prospectively examined neuropsychological findings during t wo phases of radiation effects. Background: Investigations of radiation eff ects have revealed variable outcomes that range from no radiation-associate d morbidity to severe cognitive impairment, but have relied on case reports or retrospective studies of late-delayed changes in white matter or in cog nition. No reliable radiographic or neurocognitive tools exist to describe the multiple phases of radiation effects, Method: Twenty adult patients (me dian age, 39 years) from a university hospital were treated with radiothera py (RT) for low-grade primary brain tumors. Prospective longitudinal neurop sychological studies were compared at baseline (after surgery and before ir radiation) and at 3, 6, and 12 months after RT to examine early-delayed eff ects, including verbal memory changes in 20 patients and visual memory chan ges in 11 patients. We also examined cognitive changes during the late-dela yed phase for up to 3 years after RT and determined whether early-delayed m emory deficit predicted late-delayed memory deficit in a small subset of pa tients. A comprehensive neuropsychological battery was used,including verba l and visual memory tests designed to compare learning. storage, and retrie val. Results: Patients demonstrated normal verbal memory at baseline, decre ment, and then rebound in verbal retrieval. Deficit at baseline and recover y up to I year after RT defined visual memory. Together, these observations constitute a double dissociation of memory functions. No changes over time were observed in other neurocognitive tests or in fatigue or mood measures . Time-dependent patterns of each long-term memory test were examined in re lation to lesion site in individual patients. Conclusions: The double disso ciation of memory functions after RT may provide markers for the damaging a nd facilitative early-delayed effects of RT. Late-delayed effects were not predicted based on early-delayed changes in a small sample.