221 Discussion to assess cognitive functioning in a heterogeneous population, should aim to encompass the entire spectrum of potential cognitive disorders. An example is the cognitive domain of social cognition. Social cognition encompasses the cognitive processes involved in the perception, interpretation and understanding of social information. In patients with traumatic brain injury, impairment of social cognition has shown to negatively impact patient QoL and was associated with higher caregiver burden.51 While highly relevant for daily functioning, social cognition has long been overlooked in both research and clinical practice.52 The limited available research in patients with intracranial tumors suggest impairments in social cognition, specifically emotion recognition, occur in a substantial proportion of patients with primary brain tumors53,54, especially when tumors were located in proximity of the insula and anterior temporal lobe54,55. I observed emotion recognition impairment in almost one third of patients with BMs already prior to radiotherapy (Chapter 3). This stresses the importance of the incorporation of at least one social cognition measure in routine NCA in both clinical practice and research. Brain heterogeneity Cognitive deterioration after cranial radiotherapy cannot yet be predicted at an individual level, and the underlying mechanisms for this so-called radiationinduced cognitive decline are still not fully comprehended. Previous research has illustrated post-radiotherapy changes in white matter microstructure56–63, as well as in functional brain networks64–68. These changes bear similarities to agerelated cognitive decline in healthy individuals, which is associated with structural shrinkage, white matter lesions, and altered functional connectivity.69–74 Notably, a recent study demonstrated that patients with gliomas who underwent radiotherapy exhibited brain tissue atrophy at a rate approximately three times faster than normal aging.14 In healthy individuals, age-related brain changes extend to changes in hemodynamics. For example, age-related changes in hemodynamics, including reduced whole-brain oxygen metabolism and lower CVR, have been observed in healthy individuals.75,76 Moreover, some studies have indicated a relationship between age-related CVR changes and cognitive changes in healthy individuals.77,78 Consequently, investigating hemodynamic changes following cranial radiotherapy could offer valuable insights into the mechanisms underlying radiation-induced cognitive decline. The brain relies on a steady supply of oxygen and glucose for proper functioning, which are delivered through arterial blood. To guarantee healthy functioning, cerebral blood flow (CBF) to the brain must remain relatively constant in response to changes in perfusion pressure or other hemodynamic events. The cerebral 9
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