Gireesh, Aswathikutty; (2025) Social-to-Biological Pathways to Neurocognitive Disorders. Doctoral thesis (Ph.D), UCL (University College London).

Text Gireesh_A_Thesis.pdf - Accepted Version Access restricted to UCL open access staff until 1 October 2027. Download (14MB)

Abstract

Socioeconomic inequalities in neurocognitive health have been widely studied. Yet, much of the research focuses on general cognitive function or dementia, often neglecting the full spectrum of neurocognitive disorders (NCDs), from healthy cognitive states to advanced neurocognitive impairment in the context of population health in later life. Moreover, the neuroinflammatory and neuroendocrine mechanisms underlying the potential socioeconomic inequalities in NCDs remain poorly understood, creating significant gaps in addressing the broader dynamics underlying NCDs. Data from the English Longitudinal Study of Ageing (ELSA) were used to explore the associations between socioeconomic position (SEP) and NCDs and whether neuroinflammatory markers or glucocorticoids mediated this relationship. First, a measure of NCDs was operationalised based on objective and subjective cognitive measures available longitudinally in ELSA from wave 4 to wave 9. Multistate Markov Models tested the association between SEP and transitions between different neurocognitive states of NCDs. Mixed growth curve models tested the association between SEP and repeated measures of neuroinflammatory biomarkers: C-reactive protein (CRP), white blood cells (WBC), fibrinogen and insulin-like growth factor (IGF-1) before exploring the possible association between trajectories of these biomarkers and NCDs. Socioeconomic inequalities in glucocorticoids (hair cortisol and hair cortisone) and the association of these glucocorticoids with NCDs were explored using regression models. Finally, structural equation modelling was used to investigate the role of neuroinflammatory markers in the association between SEP and NCDs. Inequalities in NCDs were pronounced, with higher SEP facilitating reversions to a healthy cognitive state. Inequalities were observed for hair cortisone, alongside inequalities in baseline neuroinflammatory markers. A strong association was found between better wealth and declining levels of IGF. Changes in neuroinflammatory markers (CRP and fibrinogen) were linked to NCDs. A small mediation effect was observed, where inequalities influenced the NCDs partially through neuroinflammation. These findings provide new insights into how inequalities are embodied biologically and the potential utility of various biological markers in NCDs.

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