Periodic Reporting for period 4 - COGNAP (To nap or not to nap? Why napping habits interfere with cognitive fitness in ageing)
Période du rapport: 2022-07-01 au 2023-06-30
Identifying novel factors which associate with inter-individual variability in cognitive decline is a promising area in ageing research. Considering its strong implication in neuroprotective function, the proposal predicts that variability in circadian rhythmicity explains a significant part of the age-related changes in human cognition. Circadian rhythms -one of the most fundamental processes of living organisms- are present throughout the nervous system and act on cognitive brain function. Circadian rhythms shape the temporal organization of sleep and wakefulness to achieve human diurnality. Of prime importance is that the temporal organization of sleep and wakefulness evolves throughout the adult lifespan, leading to higher sleep-wake fragmentation with ageing. The increasing occurrence of daytime napping is the most visible manifestation of this fragmentation. Contrary to the common belief, napping stands as a health risk factor in seniors in epidemiological data. We posit that chronic napping in older people primarily reflects circadian disruption. We predict that this disruption will lead to lower cognitive fitness. We further hypothesize that a re-stabilization of circadian sleep-wake organization through a nap prevention intervention will reduce age-related cognitive decline. Characterizing the link between cognitive ageing and the temporal distribution of sleep and wakefulness will not only bring ground-breaking advances at the scientific level, but is also timely in the ageing society. Cognitive decline, as well as inadequately timed sleep, represent dominant determinants of the health span of our fast ageing population and easy implementable intervention programs are urgently needed
The work of the team over the past 5 years focused on the impact of sleep and sleep-wake cycle integrity on cognitive and brain ageing with a particular emphasis on the nap phenotype.Since 2018, we initiated the study with a cohort of 100 healthy retired individuals who underwent an extensive characterization of sleep parameters, brain functional and structural integrity, but also of cognitive fitness. The first year was mainly dedicated to the planning and organization of the proposed study. During the first half year, the team was recruited and the study procedure approved by the ethic committee. The next 6 months were devoted to pilot measurements. In parallel the first recruitment wave was launched (e.g. construction of an internet site for the project, presentation of the project at open public seminars). The entire study procedure was tested for its feasibility in a comprehensive pilot study in August 2018. We started the study with the first volunteer in September 2018. I The next three years were mainly dedicated to data acquisition. First results of the cross-sectional arm of the study were published in 2022 and go in line with our main assumption that the increasing occurrence of daytime napping in the aged reflects a visible manifestation of sleep-wake cycle fragmentation and underlying circadian disruption. We observed that increasing daytime rest is associated with alterations in circadian markers such as the 24-h profile of melatonin expression, but also with episodic memory performance (Reyt et al., 2022). Cross-sectional evidence further indicates that chronic napping in the aged is associated with altered circadian wake-promotion as indicated by a reduced circadian amplitude in electro-physiologically derived sleep efficiency as well as a reduced night-time melatonin expression (Deantoni*, Reyt*, et al., doi: https://doi.org/10.1101/2023.08.09.552270(s’ouvre dans une nouvelle fenêtre) for a preprint). Changes in rest-activity cycle integrity were further longitudinally followed-up using field actimetry monitored over a period of 1 year and a follow up 1 year later. First results point into this direction (reduced cognitive decline in response to the nap intervention), but are currently under more in-depth confirmatory analysis. We also observed that daytime rest is associated with reduced structural integrity of the wake-promoting postero-lateral hypothalamus which contributes to a mechanistic understanding of napping as a health risk factor in the aged. In the same vain, we observed that lab-derived indices of circadian sleep promotion, and more particularly circadian REM sleep modulation is associated with regional cortical gyrification, which has previously been shown to be age-sensitive (Deantoni et al., 2023). Finally, in order to share our point of view with the scientific community in a more general context, we wrote a review on the topic of sleep and structural brain ageing (Baillet & Schmidt, 2020). The team has also put particular effort over the past three years into building a comprehensive open-source analysis pipeline for actimetry data (pyActigraphy, Hammad et al., 2021) that allows for the extraction of circadian-related indices of rest–activity data collected in everyday life. These recent technical and conceptual developments represent a valuable tool to proceed to the next research steps. Our results were regularly submitted to the scientific audience through the organisation and/or participation to international congresses, including the Congress of the European Sleep Research Society (ESRS 2018, 2020, 2022), as well as the presentation of our findings during the Gordon Research Conference on Sleep regulation (Luca, Italy, 2022). We also shared our findings with the general public by organising seminars and interviews throughout the duration of the project and more recently through the invitation of our study participants to share and discuss the findings to which they contributed. Outputs were also exposed on a regular basis in the context of more technical workshops (e.g. for the use of the pyActigraphy toolbox) and a series of tutorials were elaborate to guide potential users.
We decided to include a modelling approach for WP01 by reasoning that fully grasping the modulatory potential of sleep phenotypes on cognitive aging needs a transition from mechanistic in-lab approaches to larger scale population-wide real life data acquisitions (field actimetry also acquired in the frame of the COGNAP project). To do so, we initiateed a collaboration with the Brain Dynamics Group of the University of Sydney (Dr Postnova) to bring new expertise. Dr. Postnova's key interest is in application of physics and mathematics methods to understanding how brain systems across different levels interact to produce the dynamics on the higher-level of functioning such as alertness, sleep and performance. The team developped a physiology-based model or arousal state dynamics are currently applied to the data collected in the context of the current project. We aim at assessing whether mathematical lab-proofed modelling of physiologically meaningful parameters of sleep-wake regulation can explain rest-activity phenotypes observed in daily life through actigraphy and whether actigraphy-derived sleep phenotypes have a predictive value for the individual’s cognitive and brain aging short-term trajectory. This collaboration was strenghtened by funds from both the Belgian (FNRS-FRS) and Australian (ARC) research funds.