Circadian sleep regulation and brain tissue microstructure in cognitively unimpaired older adults

Abstract

AbstractBackgroundCircadian 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.MethodEighty‐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.ResultsWhole‐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).ConclusionOur 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.