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Purpose: To investigate the short-term cerebral metabolic effects of intravenous chemotherapy and their association with long-term fatigue/cognitive complaints. Experimental design: Using [18F]-FDG-PET/CT whole-body scans, we retrospectively quantified relative cerebral glucose metabolism before and after neoadjuvant chemotherapy in a cohort of patients treated for non-metastatic breast cancer (2009-2019). Self-report of cognitive complaints and fatigue were prospectively assessed 7 ± 3 years after therapy. Metabolic changes were estimated with i) robust mixed-effects modelling in regions-of-interest (frontal, parietal, temporal, occipital, and insular cortex) and ii) general-linear modelling of whole-brain voxel-wise outcomes. iii) The association between metabolic changes and self-reported outcomes was evaluated using linear regression-analysis. Results: Of the 667 screened patients, 263 underwent PET/CT before and after chemotherapy and 183 (48 ± 9 years) met the inclusion criteria. After chemotherapy, decreased frontal and increased parietal and insular metabolism were observed (|ß|>0.273, pFDR <0.008). Separately, additional increased occipital metabolism after epiribucin+ cyclophosphamide (EC) and temporal metabolism after EC+ fluorouracil chemotherapy were observed (ß>0.244, pFDR ≤0.048). Voxel-based analysis (pcluster-FWE <0.001) showed decreased metabolism in the paracingulate gyrus (-3.2 ± 3.9%) and putamen (3.1 ± 4.1%) and increased metabolism in the lateral cortex (L=2.9 ± 3.1%) and pericentral gyri (3.0 ± 4.4%). Except for the central sulcus, the same regions showed changes in EC, but not in FEC patients. Of the 97 self-reported responders, 23% and 27% experienced extreme fatigue and long-term cognitive complaints, respectively, which were not associated with metabolic changes. Conclusion: Both hyper- and hypometabolism were observed after chemotherapy for breast cancer. Combined with earlier findings, this study could support inflammatory mechanisms resulting in relative hypermetabolism, mainly in the parietal/occipital cortices. As early metabolic changes did not precede long-term complaints, further research is necessary to identify vulnerable patients.
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Late-life depression (LLD) is associated with a risk of developing Alzheimer's disease (AD). However, the role of AD-pathophysiology in LLD, and its association with clinical symptoms and cognitive function are elusive. In this study, one hundred subjects underwent amyloid positron emission tomography (PET) imaging with [18F]-flutemetamol and structural MRI: 48 severely depressed elderly subjects (age 74.1 ± 7.5 years, 33 female) and 52 age-/gender-matched healthy controls (72.4 ± 6.4 years, 37 female). The Geriatric Depression Scale (GDS) and Rey Auditory Verbal Learning Test (RAVLT) were used to assess the severity of depressive symptoms and episodic memory function respectively. Amyloid deposition was quantified using the standardized uptake value ratio. Whole-brain voxel-wise comparisons of amyloid deposition and gray matter volume (GMV) between LLD and controls were performed. Multivariate analysis of covariance was conducted to investigate the association of regional differences in amyloid deposition and GMV with clinical factors, including GDS and RAVLT. As a result, there were no significant group differences in amyloid deposition. In contrast, LLD showed significant lower GMV in the left temporal and parietal region. GMV reduction in the left temporal region was associated with episodic memory dysfunction, but not with depression severity. Regional GMV reduction was not associated with amyloid deposition. LLD is associated with lower GMV in regions that overlap with AD-pathophysiology, and which are associated with episodic memory function. The lack of corresponding associations with amyloid suggests that lower GMV driven by non-amyloid pathology may play a central role in the neurobiology of LLD presenting as a psychiatric disorder.Trial registration: European Union Drug Regulating Authorities Clinical Trials identifier: EudraCT 2009-018064-95.