RT dose to the hippocampus increases memory decline in patients with brain tumors; hippocampal avoidance (mean dose<9 Gy and max dose <16 Gy) reduces risk of cognitive decline.  As older adults may be more vulnerable to RT toxicity, we compared the impact of standard hippocampal dose constraints in older and younger patients to evaluate for differential effects on cognitive function.

Forty-three patients with brain tumors receiving partial brain RT were prospectively enrolled. HVLTR was completed pre-RT and 3 mo post-RT . Maximum and mean RT dose to bilateral hippocampi were calculated. Hippocampal mean dose>9 Gy or maximum dose>16 Gy were considered ‘high’. A nonlinear mixed model was used to evaluate impact of age (>=65 vs <65 years), WRAT4 score (cognitive reserve), PHQ2 (depression), gender, and high hippocampal dose on decline on the HVLTR.

Decline on HVLTR was observed in 27% of patients <65 and 50% of patients >=65. High hippocampal dose (p=0.04) and age>=65 (p=0.04) predicted decline on HVLTR. For patients <65, high hippocampal doses were associated with HVLTR decline (p=0.04). For patients >=65, high hippocampal doses were not associated with HVLTR decline; all older patients who declined on HVLTR did not have doses to the hippocampi that exceeded standard dose constraints.

Both age>65 and hippocampal doses exceeding standard dose constraints were predictive of decline. While exceeding standard hippocampal dose was predictive of cognitive toxicity in younger adults, this was not true in older adults. Nearly twice as many older vs. younger adults developed cognitive toxicity following RT, despite lower hippocampal RT doses. Future research should identify factors including lower hippocampal RT doses that predispose older adults to cognitive decline.