Actigraphic and melatonin alignment in older adults with varying dementia risk

ABSTRACT

Circadian rhythms alter with ageing and may be aetiologically linked to neurodegeneration. This study explored the association between clinical markers and 1) dim light melatonin onset (DLMO) time and 2) phase angle derived from sleep midpoint, in older adults with varying dementia risks. Participants completed 14 days of actigraphy followed by in-lab measurement of salivary melatonin, from which DLMO time and phase angle were computed. Eighty participants (age = 65.5, SD = 9.6), 44 males (55%), MMSE (28.6, SD = 1.5) were included in the analysis. Sex (t = 2.15, p = .04), sleep onset (r = 0.49, p < .001) and midpoint (r = 0.44, p < .001) also correlated with DLMO time. Multiple linear regression showed chronotype, average actigraphy-derived light exposure during the DLMO window (window 2 h prior to DLMO to 2 h post), early biological day (6–10 h post DLMO time) and late biological day (10–14 h post DLMO time) were predictive of DLMO time (adjusted R² = 0.75). Sleep offset, depression severity, average light exposure during the early biological night and early and late biological day were shown to be predictive variables in the estimation of phase angle (adjusted R² = 0.78). The current study highlights the potential use of clinical variables, such as actigraphy-derived light, as circadian markers in ageing which could be easily implemented into existing clinical practice and could yield potential targets focusing on chronotherapeutic interventions.

KEYWORDS:

• Circadian
• dim light melatonin onset
• actigraphy
• dementia
• light
• sleep

Acknowledgements

The authors wish to thank the participants for their involvement in the study and Prof David Kennaway for his expertise with melatonin assays.

Disclosure statement

Professor Ian Hickie is the Co–Director, Health and Policy at the Brain and Mind Centre (BMC) University of Sydney, Australia. The BMC operates an early–intervention youth services at Camperdown under contract to headspace. He has led projects for health professionals and the community supported by governmental, community agency and pharmaceutical industry partners (Wyeth, Eli Lily, Servier, Pfizer, AstraZeneca) for the identification and management of depression and anxiety. He has received honoraria for presentations of his own work at educational seminars supported by a number of non–government organisations and the pharmaceutical industry (including Pfizer, Servier and Astra Zeneca). He has led an investigator–initiated study of the effects of agomelatine on circadian parameters (supported in part by Servier but also by other NHMRC funding) and a Servier–supported study of major depression and sleep disturbance in primary care settings. He is the Chief Scientific Advisor to, and a 5% equity shareholder in, InnoWell Pty Ltd. InnoWell was formed by the University of Sydney (45% equity) and PwC (Australia; 45% equity) to deliver the $30 M Australian Government–funded Project Synergy (2017–20) and to lead transformation of mental health services internationally through the use of innovative technologies. No other authors have competing interests to declare.

Ethics approval and consent to participate

This research was approved by the Human Research Ethics Committee of The University of Sydney and was conducted in accordance with the latest version of the Declaration of Helsinki. Written informed consent was obtained from all participants.

Consent for publication

No individual participant data or any identifiable data are being published so no specific consent has been given. Participants were informed in the information statement that the de-identifiable data would be published.

Availability of data and materials

The datasets used and/or analysed during the current study are available from the corresponding author at the discretion of the investigators.

Authors’ contributions

SN, NLR and SL conceived the idea for the original study and obtained funding. All authors were involved in the conception and design of the current analysis. CH and SN oversaw all aspects of the current study. JRP and JEP assisted with actigraphy and coding. JM consulted on light analysis techniques. IH, NR, SJG, and ZT assisted with the formation and running of the original study on which these data were taken. ZMS was responsible for data cleaning, data processing, and data analysis. ZMS prepared the manuscript and all authors contributed to the interpretation of results and the planning, editing and revising of the manuscript.

Data Availability Statement

Data is available on request from authors with permission.

Additional information

Funding

This work was supported by the NHMRC under grant NHMRC, No. 632689. Dr Camilla Hoyos and Professor Simon Lewis were funded by NHMRC-ARC Dementia Research Development Fellowships (APP1104003 and APP1110414 respectively). Dr Hoyos was also funded by a National Heart Foundation Future Leader Fellowship and Professor Sharon Naismith was funded by a NHMRC Boosting Dementia Leadership Fellowship. Zoe Menczel Schrire is funded by a scholarship from the NHMRC Centre of Research Excellence to Optimise Sleep in Brain Ageing and Neurodegeneration (CogSleep CRE) (SC2984);National Health and Medical Research Council [632689, APP1104003, APP1110414];National Heart Foundation of Australia