Frontal hypometabolism in elderly breast cancer survivors determined by [¹⁸F]fluorodeoxyglucose (FDG) positron emission tomography (PET): a pilot study

Abstract

Purpose The term “chemobrain” is sometimes used to denote deficits in neuropsychological functioning that may occur as a result of cancer treatment. As breast cancer survivors now commonly reach late life, it is not known whether previous exposure to chemotherapy may affect long-term risk for cognitive impairment. To help address this concern, this study tested whether successfully surviving chemotherapy earlier in life was associated with later differences in brain metabolic function as an older adult compared to controls. This question was examined using PET measures of brain glucose metabolism in elderly women cancer survivors. Methods Breast cancer survivors (N=10), currently free of recurrent cancer and without a diagnosis of a cognitive disorder, were compared to matched healthy controls (N=10). All subjects were imaged at rest with [18F]fluorodeoxyglucose (FDG). Images were analyzed semi-quantitatively using the Alzheimer's Discrimination Tool (PMOD) and a VOI-based approach derived from co-registered MRIs. Results Relative FDG uptake (normalized to global) was significantly lower in the survivors compared to control subjects in bilateral orbital frontal regions, consistent with differences between the groups in cognition and executive function (i.e., TMT-B, MMSE) and despite no significant differences with respect to age, education, intelligence, or working memory. None of the survivors and only one control manifested a global PET score consistent with an Alzheimer's Disease (AD) metabolic pattern. Conclusion Breast cancer survivors treated with chemotherapy may manifest long-term changes in brain glucose metabolism indicative of subtle frontal hypometabolism, a finding consistent with results from neuropsychological testing and other imaging modalities.

Clinical characteristics, pathophysiology, and management of noncentral nervous system cancer‐related cognitive impairment in adults

“…These frontal regions were also noted to have decreased gray matter from prechemotherapy to postchemotherapy in a previous study by the same authors. 117,118 Findings from fMRI studies are supported by results from complementary techniques, including positron emission tomography, [134][135][136] arterial spin labeling, 137 and electroencephalography (EEG). [138][139][140][141] Magnetic resonance spectroscopy imaging has also provided further insight regarding certain pathophysiologic mechanisms, including inflammation and demyelination.…”

PET Evidence of the Effect of Donepezil on Cognitive Performance in an Animal Model of Chemobrain

“…Chiaravalloti's group reported that brain glucose metabolism in patients with Hodgkin disease was affected after diagnosis and during chemotherapy treatment [ 10 ]. Ponto's group reported that breast cancer survivors treated with chemotherapy may manifest long-term changes in brain glucose metabolism indicative of subtle frontal hypometabolism [ 11 ]. Simó's group reported a long-term decrease in gray matter and white matter volume in chemotherapy-treated patients [ 12 ].…”

Subject-specific computational modeling of DBS in the PPTg area

“…The PET images were analyzed with methods similar to those described previously (Ponto et al, 2014 ; Wyckhuys et al, 2014 ). Each non-contrast CT scan was transformed by rigid, manual co-registration (Jena et al, 2014 ) to align with a standard MRI template, INIA19 Macaca mulatta (Rohlfing et al, 2012 ), with the resultant transformation values individually applied to the PET image from the corresponding data acquisition session to align them to the normalized space.…”