Study Objectives: Daytime napping is frequently reported among the older population and has attracted increasing attention due to its association with multiple health conditions. Here, we tested whether napping in the aged is associated with altered circadian regulation of sleep, sleepiness, and vigilance performance. Methods: Sixty healthy older individuals (mean age: 69 years, 39 women) were recruited with respect to their napping habits (30 nappers, 30 non-nappers). All participants underwent an in-lab 40-hour multiple nap protocol (10 cycles of 80 minutes of sleep opportunity alternating with 160 minutes of wakefulness), preceded and followed by a baseline and recovery sleep period. Saliva samples for melatonin assessment, sleepiness, and vigilance performance were collected during wakefulness and electrophysiological data were recorded to derive sleep parameters during scheduled sleep opportunities. Results: The circadian amplitude of melatonin secretion was reduced in nappers, compared to non-nappers. Furthermore, nappers were characterized by higher sleep efficiencies and REM sleep proportion during day- compared to nighttime naps. The nap group also presented altered modulation in sleepiness and vigilance performance at specific circadian phases. Discussion: Our data indicate that napping is associated with an altered circadian sleep–wake propensity rhythm. They thereby contribute to the understanding of the biological correlates underlying napping and/or sleep–wake cycle fragmentation during healthy aging. Altered circadian sleep–wake promotion can lead to a less distinct allocation of sleep into nighttime and/or a reduced wakefulness drive during the day, thereby potentially triggering the need to sleep at adverse circadian phase.

The circadian system orchestrates sleep timing and structure and is altered with increasing age. Sleep propensity, and particularly REM sleep is under strong circadian control and has been suggested to play an important role in brain plasticity. In this exploratory study, we assessed whether surface-based brain morphometry indices are associated with circadian sleep regulation and whether this link changes with age. Twenty-nine healthy older (55–82 years; 16 men) and 28 young participants (20–32 years; 13 men) underwent both structural magnetic resonance imaging and a 40-h multiple nap protocol to extract sleep parameters over day and night time. Cortical thickness and gyrification indices were estimated from T1-weighted images acquired during a classical waking day. We observed that REM sleep was significantly modulated over the 24-h cycle in both age groups, with older adults exhibiting an overall reduction in REM sleep modulation compared to young individuals. Interestingly, when taking into account the observed overall age-related reduction in REM sleep throughout the circadian cycle, higher day–night differences in REM sleep were associated with increased cortical gyrification in the right inferior frontal and paracentral regions in older adults. Our results suggest that a more distinctive allocation of REM sleep over the 24-h cycle is associated with regional cortical gyrification in aging, and thereby point towards a protective role of circadian REM sleep regulation for age-related changes in brain organization.

Rapid eye movement sleep (REMS) is increasingly suggested as a discriminant sleep state for subtle signs of age-related neurodegeneration. While REMS expression is under strong circadian control and circadian dysregulation increases with age, the association between brain aging and circadian REMS regulation has not yet been assessed. Here, we measure the circadian amplitude of REMS through a 40-h in-lab multiple nap protocol in controlled laboratory conditions, and brain microstructural integrity with quantitative multi-parameter mapping (MPM) imaging in 86 older individuals. We show that reduced circadian REMS amplitude is related to lower magnetization transfer saturation (MTsat), longitudinal relaxation rate (R1) and effective transverse relaxation rate (R2*) values in several white matter regions mostly located around the lateral ventricles, and with lower R1 values in grey matter clusters encompassing the hippocampus, parahippocampus, thalamus and hypothalamus. Our results further highlight the importance of considering circadian regulation for understanding the association between sleep and brain structure in older individuals.

Fixed sleep schedules with an 8 h time in bed (TIB) are used to ensure participants are well-rested before laboratory studies. However, such schedules may lead to cumulative excess wakefulness in young individuals. Effects on older individuals are unknown. We combine modelling and experimental data to quantify the effects of sleep debt on sleep propensity in healthy younger and older participants. A model of arousal dynamics was fitted to sleep data from 22 young (20–31 y.o.) and 26 older (61–82 y.o.) individuals (25 male) undertaking 10 short sleep–wake cycles during a 40 h napping protocol, following >1 week of fixed 8 h TIB schedules. Homeostatic sleep drive at the study start was varied systematically to identify best fits between observed and predicted sleep profiles for individuals and group averages. Daytime sleep duration was the same on the two days of the protocol within the groups but different between the groups (young: 3.14 ± 0.98 h vs. 3.06 ± 0.75 h, older: 2.60 ± 0.98 h vs. 2.37 ± 0.64 h). The model predicted an initial homeostatic drive of 11.2 ± 3.5% (young) and 10.1 ± 3.5% (older) above well-rested. Individual variability in first-day, but not second-day, sleep patterns was explained by the differences in the initial homeostatic drive for both age groups. Our study suggests that both younger and older participants arrive at the laboratory with cumulative sleep debt, despite 8 h TiB schedules, which dissipates after the first four sleep opportunities on the protocol. This has implications for protocol design and the interpretation of laboratory studies.

Background: Circadian dysfunction increases with age, leading to changes in the circadian regulation of physiological and biological rhythms, including sleep. Actigraphy studies demonstrated that altered 24‐h rest‐activity patterns, an estimate of circadian sleep‐wake regulation, is related to cognitive decline and tightly linked to Alzheimer’s disease progression. Here, we assessed whether circadian sleep regulation, measured during a multiple naps protocol, is related to brain microstructural integrity in a group of cognitively unimpaired older adults.Method: Eighty‐six retired older individuals (mean age [SD] = 69.9 ± 5.2 y.o., 32 females, Table 1) with no major sleep disorders or medical condition, underwent an in‐lab 40‐h multiple naps protocol and brain structural magnetic resonance imaging. As rapid eye movement (REM) sleep is under strong circadian control, circadian REM sleep amplitude was computed by fitting a Gaussian curve on REM sleep duration (% of total sleep time) measured for each nap opportunity. The multiparametric mapping protocol was used to derive indices of brain tissue microstructure using magnetization transfer saturation (MTsat), R1 and R2* maps (hMRI toolbox v0.2.2). Statistical models were adjusted for age, sex, education, and for additional covariates related to sleep architecture and its circadian modulation, including mean REM% and sleep efficiency (SE), the accumulation of REM sleep and sleep need (slope of a fitted first‐order polynomial curve), and circadian SE amplitude.Results: Whole‐brain voxel‐based quantification analysis revealed that low circadian REM amplitude was related to low MTsat, R1 and R2* values in several white matter regions mostly located around the lateral ventricles (Figure 1A). In addition, a significant association was observed between low circadian REM amplitude and low R1 values in two grey matter clusters encompassing the hippocampus, entorhinal cortex, thalamus and hypothalamus (Figure 1B).Conclusion: Our findings provide first evidence that changes in circadian sleep regulation is associated with microstructural changes in key brain regions sensitive to the aging process and involved in sleep‐wake regulation. These results further emphasize the relevance of monitoring circadian sleep regulation for the early detection of individuals at risk for neurodegeneration and cognitive decline.