The relationship between systemic inflammation and neurocognitive performance in adult Chinese

Abstract

Age-related neurocognitive decline, manifesting across multiple domains, significantly contributes to the loss of independence and compromises the quality of life for individuals. Systemic inflammation is a significant mechanism underlying neurocognitive ageing. In Chapter 1, we introduced age-associated immune changes, delineated the complex relationship between inflammation and age-related neurocognitive changes, and critically reviewed its neurobiological mechanisms as well as several physiological and psychological factors modulating this multi-level relationship. In Chapter 2, we investigated the effect of systemic inflammation on neurocognitive performance in a cohort of 252 healthy middle-aged to older adults. Our findings revealed that better neurocognitive performance, as reflected by the Hong Kong Montreal Cognitive Assessment, was associated with lower IL-18 levels (p = 0.046) and better sleep quality measured by the Pittsburgh Sleep Quality Index (p = 0.006). Using moderated mediation analysis, we further demonstrated that better subjective sleep quality mediated the association between higher IL-18 levels and better neurocognitive performance when IL-12 levels were low (bootstrapping 95% CI: [- 0.0824, - 0.0018]). On the contrary, poor subjective sleep quality mediated the association between higher IL-18 levels and poorer neurocognitive performance when IL-12 levels were elevated (bootstrapping 95% CI: [0.0004, 0.0608]). These results indicate that systemic inflammation, characterised by activation of interleukin-12/ interleukin-18 axis, is associated with neurocognitive performance based on sleep-dependent mechanisms. In Chapter 3, we discussed the theoretical implications of our study in understanding the psychoneuroimmunological basis of neurocognitive ageing. Furthermore, we explored the translational implications for utilising inflammatory markers for early-stage disease detection and the development of tailored preventive and intervention strategies targeting sleep health and controlling inflammation levels to mitigate neurocognitive impairments. We also proposed future research directions that are worth in-depth investigation. Finally, Chapter 4 concludes the thesis, summarising the key findings and contributions of our study.