Kölbel, Melanie; (2025) Exploring the relationship between sleep and neurocognitive functioning in children and adolescents with sickle cell disease. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Sleep, a fundamental physiological process, is universally experienced yet frequently undervalued. Its critical role in growth and development is well-established, primarily through research on healthy populations. However, a significant knowledge gap exists regarding sleep patterns and developmental consequences within vulnerable populations, such as children and young adolescents living with sickle cell disease. The aim of this thesis is to add to further understanding of sleep behaviour and sleep disorders in children and young adolescents living with sickle cell disease, using a multimodal research approach. Chapter 1 provides a general introduction of sleep behaviour and disorders in the general population and in individuals living with sickle cell disease. The field currently lacks robust case-control studies investigating sleep patterns in children and young adults living with sickle cell disease. Chapter 2 provides a systematic review of the literature and meta-analysis on sleep behaviour and sleep assessment in individuals living with sickle cell disease. Chapter 3 employs a longitudinal approach to investigate developmental trajectories of sleep patterns in children and young adolescents living with sickle cell disease. The analysis utilises polysomnography and questionnaire data collected at two distinct time points from participants enrolled in the Sleep Asthma Cohort (SAC 1 and 2). While existing sleep assessments reveal inconsistencies in 4 individual sleep profiles, the overall trend suggests a concerning pattern of reduced sleep quality and duration within this population. Chapter 4 employs a cross-sectional design to identify the presence of delayed or impaired developmental trajectories of cognitive function in participants from the Sleep Asthma Cohort (SAC 3) and the Prevention of Morbidity study in SCA 2B (POMS SB). This analysis is complemented by the inclusion of a community sample that I recruited, allowing for a broader investigation of these relationships within the general population. Analyses of the developmental trajectory suggest a potential delay, rather than an impairment, in cognitive development within this population. Haematological factors may be contributing influences on these observed developmental differences. Chapters 5 and 6 utilises the cohort of community participants. Chapter 5 focuses on elucidating the interrelationships between sleep patterns, cortisol profiles, and cognitive function. In children and young adults living with sickle cell disease, a flat cortisol profile and increased nocturnal movement may be associated with diminished perceptual reasoning skills. In contrast, Chapter 6 employs neuroimaging techniques to explore structural and functional brain characteristics in relation to sleep disturbances within this population. Evidence from structural and functional brain analysis shows difference in white matter microstructure and global efficiency, with cognitive consequences, in children and young adults living with sickle cell disease who experience nocturnal movement. Chapter 7 summarises key findings from the preceding chapters and provides a comprehensive discussion of findings for our understanding of sleep, cognition, and brain development in children and young adults living with sickle cell disease. Early interventions for children with sickle cell disease should prioritise promoting sufficient sleep behaviours. This is crucial because the cumulative effects of sleep disturbances are likely to have a multifaceted impact on early cognitive development, potentially leading to adverse disease outcomes.

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