RESUMO
Sleep is a potential early, modifiable risk factor for cognitive decline and dementia. Impaired slow wave sleep (SWS) is pronounced in individuals with cognitive impairment (CI). Cognitive decline and impairments of SWS are bi-directionally linked in a vicious cycle. SWS can be enhanced non-invasively using phase-locked acoustic stimulation (PLAS), potentially breaking this vicious cycle. Eighteen healthy older adults (HC, agemean±sd, 68.3 ± 5.1) and 16 older adults (agemean±sd, 71.9 ± 3.9) with CI (Montreal Cognitive Assessment ≤ 25) underwent one baseline (sham-PLAS) night and three consecutive stimulation nights (real-PLAS). EEG responses and blood-plasma amyloid beta Aß42/Aß40 ratio were measured pre- and post-intervention, as was episodic memory. The latter was again evaluated 1 week and 3 months after the intervention. In both groups, PLAS induced a significant electrophysiological response in both voltage- and time-frequency analyses, and memory performance improved in association with the magnitude of this response. In the CI group, both electrophysiological and associated memory effects were delayed compared to the healthy group. After 3 intervention nights, electrophysiological response to PLAS was no longer different between CI and HC groups. Only in the CI sample, stronger electrophysiological responses were significantly associated with improving post-intervention Aß42/Aß40 ratios. PLAS seems to improve SWS electrophysiology, memory, and amyloid dynamics in older adults with CI. However, effects on memory require more time to unfold compared to healthy older adults. This indicates that PLAS may become a potential tool to ameliorate cognitive decline, but longer interventions are necessary to compensate for declining brain integrity. This study was pre-registered (clinicaltrials.gov: NCT04277104).
RESUMO
Dementia is the seventh leading cause of mortality, and a major source of disability and dependency in older individuals globally. Cognitive decline (and, to a lesser extent, normal ageing) are associated with sleep fragmentation and loss of slow-wave sleep. Evidence suggests a bidirectional causal link between these losses. Phase-locked auditory stimulation has emerged as a promising non-invasive tool to enhance slow-wave sleep, potentially ameliorating cognitive decline. In laboratory settings, auditory stimulation is usually supervised by trained experts. Different algorithms (simple amplitude thresholds, topographic correlation, sine-wave fitting, phase-locked loop, and phase vocoder) are used to precisely target auditory stimulation to a desired phase of the slow wave. While all algorithms work well in younger adults, the altered sleep physiology of older adults and particularly those with neurodegenerative disorders requires a tailored approach that can adapt to older adults' fragmented sleep and reduced amplitudes of slow waves. Moreover, older adults might require a continuous intervention that is not feasible in laboratory settings. Recently, several auditory stimulation-capable portable devices ('Dreem®', 'SmartSleep®' and 'SleepLoop®') have been developed. We discuss these three devices regarding their potential as tools for science, and as clinical remote-intervention tools to combat cognitive decline. Currently, SleepLoop® shows the most promise for scientific research in older adults due to high transparency and customizability but is not commercially available. Studies evaluating down-stream effects on cognitive abilities, especially in patient populations, are required before a portable auditory stimulation device can be recommended as a clinical preventative remote-intervention tool.
