Kirkman, Matthew Anthony; (2024) Exploring predictors of cognitive outcome variability in individuals with low-grade glioma including educational attainment, socioeconomic factors, clinicodemographic variables, estimated premorbid intelligence, neuroimaging characteristics, and genetic factors. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Low-grade gliomas are a group of primary brain tumours that commonly (>80%) result in cognitive impairment due to the disease and/or the associated treatments. However, the variability in cognitive function between individuals and across domains is marked. A number of factors have been studied as putative influences on cognition in this population, but study findings to date have been conflicting and the identified influences do not fully account for the variability seen in clinical practice. To this end, the first aim of this body of work was to perform and describe a systematic review of the literature in order to fully understand the scope of putative influences on cognition in patients with brain tumours and to identify any corresponding gaps. A second systematic review was performed to evaluate interventional studies attempting to prevent or ameliorate cognitive dysfunction in patients with brain tumours, in order to shed light on possible pathophysiological mechanisms. The first review confirmed the aforementioned conflicting findings in the literature, but indicated a number of relatively neglected potential influences on cognition; this laid the foundation for an empirical study in 21 patients with WHO grade II diffuse low-grade glioma (mean 57.5 [standard deviation 24.8] months following diagnosis) that evaluated a broad range of educational, socioeconomic, clinical, demographic, imaging, and genetic variables, as well as estimated premorbid intelligence, as potential influences on cognitive variability. The findings provide further evidence to support previously suggested influences on cognition in patients with brain tumours. The work also highlights the complexity of the underlying mechanisms as well as some of the challenges of performing studies in this clinical population, and provides recommendations for future work in the field.

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