A pilot study of neuropsychological functions, APOE and amyloid imaging in patients with gliomas

Abstract

Brain tumor patients treated with radiotherapy (RT) often develop cognitive dysfunction, and recent studies suggest that the APOE ε-4 allele may influence cognitive outcome. The ε-4 allele is known to promote beta (β) amyloid deposition in the cortex, and preliminary evidence suggests that RT may be associated with this process. However, it is unknown whether β-amyloid accumulation contributes to treatment neurotoxicity. In this pilot study, we assessed neuropsychological functions and β-amyloid retention using ¹⁸F-florbetaben (FBB) PET in a subset of brain tumor patients who participated in our study of APOE polymorphisms and cognitive functions. Twenty glioma patients treated with conformal RT ± chemotherapy participated in the study: 6 were APOE ε-4 carriers and 14 were non-ε-4 carriers. Patients completed a neuropsychological re-evaluation (mean time interval = 5 years, SD = 0.83) and brain MRI and FBB PET scans. Wilcoxon signed-rank test comparisons between prior and current neuropsychological assessments showed a significant decline in 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/working memory (WAIS-III digits forward, p = 0.028 and digits backward, p = 0.032), with a decline among APOE ε-4 carriers. There were no significant differences in any of the FBB PET analyses between APOE ε-4 carriers and non-ε-4 carriers. The findings suggest that glioma patients may experience worsening in attention and executive functions several years after treatment, and that the APOE ε-4 allele may modulate cognitive decline, but independent of increased β-amyloid deposition.

Keywords: APOE; Amyloid; Brain tumors; Cognitive.

Figure 1

Regions of Interest (ROIs) drawn on axial FLAIR MRI scans and used to analyze the ¹⁸F-florbetaben PET images. ROIs were defined for each patient for the: a) cerebellar cortex; b) medial and lateral temporal cortex; c) occipital cortex; d) frontal cortex, caudate head, putamen, thalamus; e) parietal cortex and right frontal lesion; f) anterior and posterior cingulate cortex, white matter, and left frontal lesion.

Figure 2

¹⁸F-florbetaben PET images (top row) and PET images co-registered to the FLAIR images (bottom row) of: a) an APOE ε-4 carrier patient with a right frontal lesion; b) an APOE non-ε-4-carrier patient with a left frontal lesion. Radiotracer uptake was restricted to the white matter for both patients.