Abstract
BACKGROUND
Many patients with brain tumors treated with radiotherapy (RT) and chemotherapy develop cognitive dysfunction, and recent studies suggest that the Apolipoprotein E (APOE) ε-4 allele may influence cognitive outcome in cancer patients. The APOE ε-4 allele is known to promote deposition of beta (β) amyloid in the cortex, and preliminary evidence suggests that RT may be associated with this process. However, it is unknown whether β-amyloid accumulation may contribute to treatment-related neurotoxicity. In this pilot study, we assessed neuropsychological functions and β-amyloid retention using 18F-florbetaben PET in a subset of brain tumor patients who participated in our study of APOE polymorphisms and cognitive functions.
METHODS
Twenty patients with gliomas treated with conformal RT ± chemotherapy participated in the study: 6 were APOE є-4 carriers and 14 were non-є-4 carriers. Patients completed a neuropsychological re-evaluation (mean time interval= 5 years, SD=0.83), and brain MRI and 18F-florbetaben PET scans.
RESULTS
The results of Wilcoxon rank sums test comparisons between prior and current assessments showed a significant decline in selective attention (Brief Test of Attention, p=0.018), and a near significant decline in verbal learning (Hopkins Verbal learning Test-Learning, p=0.07). Comparisons by APOE status showed significant differences over time in attention and working memory (WAIS-III digits forward, p=0.028 & digits backward, p=0.032), with a decline among APOE є-4 carriers. Comparisons of PET 18F-florbetaben regional standard uptake value ratios (SUVRs) showed near significance differences for the medial temporal cortex (p=0.069) and the putamen (p=0.069), with non-є-4 carriers having higher SUVRs.
CONCLUSION
The findings suggest that patients with gliomas may experience progressive worsening in attention and executive functions several years after treatment with conformal RT ± chemotherapy, and that the APOE є-4 allele may modulate cognitive decline.