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Background: The nonmotor symptom spectrum of Parkinson’s disease (PD) includes progressive cognitive decline mainly in late stages of the disease. The aim of this study was to map the patterns of altered structural connectivity of patients with PD with different cognitive profiles ranging from cognitively unimpaired to PD-associated dementia.
Methods: Diffusion tensor imaging and neuropsychological data from the observational multicentre LANDSCAPE study were analyzed. A total of 134 patients with PD with normal cognitive function (56 PD-N), mild cognitive impairment (67 PD-MCI), and dementia (11 PD-D) as well as 72 healthy controls were subjected to whole-brain-based fractional anisotropy mapping and covariance analysis with cognitive performance measures.
Results: Structural data indicated subtle changes in the corpus callosum and thalamic radiation in PD-N, whereas severe white matter impairment was observed in both PD-MCI and PD-D patients including anterior and inferior fronto-occipital, uncinate, insular cortices, superior longitudinal fasciculi, corona radiata, and the body of the corpus callosum. These regional alterations were demonstrated for PD-MCI and were more pronounced in PD-D. The pattern of involved regions was significantly correlated with the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) total score.
Conclusions: The findings in PD-N suggest impaired cross-hemispherical white matter connectivity that can apparently be compensated for. More pronounced involvement of the corpus callosum as demonstrated for PD-MCI together with affection of fronto-parieto-temporal structural connectivity seems to lead to gradual disruption of cognition-related cortico-cortical networks and to be associated with the onset of overt cognitive deficits. The increase of regional white matter damage appears to be associated with the development of PD-associated dementia.
Brain metastases are the most common intracranial tumor in adults and are associated with poor patient prognosis and median survival of only a few months. Treatment options for brain metastasis patients remain limited and largely depend on surgical resection, radio- and/or chemotherapy. The development and pre-clinical testing of novel therapeutic strategies require reliable experimental models and diagnostic tools that closely mimic technologies that are used in the clinic and reflect histopathological and biochemical changes that distinguish tumor progression from therapeutic response. In this study, we sought to test the applicability of magnetic resonance (MR) spectroscopy in combination with MR imaging to closely monitor therapeutic efficacy in a breast-to-brain metastasis model. Given the importance of radiotherapy as the standard of care for the majority of brain metastases patients, we chose to monitor the post-irradiation response by magnetic resonance spectroscopy (MRS) in combination with MR imaging (MRI) using a 7 Tesla small animal scanner. Radiation was applied as whole brain radiotherapy (WBRT) using the image-guided Small Animal Radiation Research Platform (SARRP). Here we describe alterations in different metabolites, including creatine and N-acetylaspartate, that are characteristic for brain metastases progression and lactate, which indicates hypoxia, while choline levels remained stable. Radiotherapy resulted in normalization of metabolite levels indicating tumor stasis or regression in response to treatment. Our data indicate that the use of MR spectroscopy in addition to MRI represents a valuable tool to closely monitor not only volumetrical but also metabolic changes during tumor progression and to evaluate therapeutic efficacy of intervention strategies. Adapting the analytical technology in brain metastasis models to those used in clinical settings will increase the translational significance of experimental evaluation and thus contribute to the advancement of pre-clinical assessment of novel therapeutic strategies to improve treatment options for brain metastases patients.