Influences of Endogenous and Exogenous Melatonin in Older Adults at Risk of Dementia

Abstract

Dementia develops through multiple pathways decades prior to the onset of clinical symptoms. Circadian disturbances are one such and have been touted as a potential risk factor. This thesis aims to assess possible factors linked with heightened risk of circadian disturbance and consequently, dementia development. Chapter 2 aims to investigate if light exposure, the primary synchroniser of the circadian system, could predict cognition in older adults with varying risks of dementia at 2-year follow-up. The findings were mixed and revealed that additional research is needed. Chapter 3 investigates easily collected demographic, clinical, and rest/wake variables associated with Dim-Light Melatonin Onset (DLMO), to identify older adults at risk of dementia. Morning and evening light exposure, combined with chronotype were identified. Chapters 4 and 5 aim to investigate the feasibility and safety of high-dose melatonin as a potential prophylactic medication. Chapter 4 presents a systematic review and meta-analysis demonstrating that based on the limited existing research, high-dose melatonin appears to have a favourable safety profile in adults and older adults for a variety of indications including dementia. The clinical trial in Chapter 5 demonstrates the feasibility, acceptability, and tolerability of investigating high dose melatonin in older adults with MCI delivered chiefly via a remote protocol. It demonstrates that participants were able to keep up with the requirements of an online trial and continue with their designated intervention. Together, this thesis contains a body of research using multidisciplinary approaches investigating the associations between light exposure, circadian misalignment, melatonin, and cognitive decline. Overall, these studies enhance the literature and indicate that circadian disruption and preventative therapeutics should be further investigated with regards to dementia.