A B S T R AC TBackground: Melatonin may reduce REM-sleep behavior disorder (RBD) symptoms in Parkinson's disease (PD), though robust clinical trials are lacking. Objective: To assess the efficacy of prolonged-release (PR) melatonin for RBD in PD. Methods: Randomized, double-blind, placebocontrolled, parallel-group trial with an 8-week intervention and 4-week observation pre-and postintervention (ACTRN12613000648729). Thirty PD patients with rapid eye movement sleep behavior disorder were randomized to 4 mg of prolonged-release melatonin (Circadin) or matched placebo, ingested orally once-daily before bedtime. Primary outcome was the aggregate of rapid eye movement sleep behavior disorder incidents averaged over weeks 5 to 8 of treatment captured by a weekly diary. Data were included in a mixed-model analysis of variance (n = 15 per group). Results: No differences between groups at the primary endpoint (3.4 events/week melatonin vs. 3.6 placebo; difference, 0.2; 95% confidence interval = −3.2 to 3.6; P = 0.92). Adverse events included mild headaches, fatigue, and morning sleepiness (n = 4 melatonin; n = 5 placebo). Conclusion: Prolonged-release melatonin 4 mg did not reduce rapid eye movement sleep behavior disorder in PD.

Insomnia 100 sleep study: Australia New Zealand Clinical Trials Registry (ANZCTR) identification number 12612000049875. URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=347742.

Background Based on associations between sleep spindles, cognition, and sleep-dependent memory processing, here we evaluated potential relationships between levels of CSF Aβ 42 , P-tau, and T-tau with sleep spindle density and other biophysical properties of sleep spindles in a sample of cognitively normal elderly individuals. Methods One-night in-lab nocturnal polysomnography (NPSG) and morning to early afternoon CSF collection were performed to measure CSF Aβ 42 , P-tau and T-tau. Seven days of actigraphy were collected to assess habitual total sleep time. Results Spindle density during NREM stage 2 (N2) sleep was negatively correlated with CSF Aβ 42 , P-tau and T-tau. From the three, CSF T-tau was the most significantly associated with spindle density, after adjusting for age, sex and ApoE4. Spindle duration, count and fast spindle density were also negatively correlated with T-tau levels. Sleep duration and other measures of sleep quality were not correlated with spindle characteristics and did not modify the associations between sleep spindle characteristics and the CSF biomarkers of AD. Conclusions Reduced spindles during N2 sleep may represent an early dysfunction related to tau, possibly reflecting axonal damage or altered neuronal tau secretion, rendering it a potentially novel biomarker for early neuronal dysfunction. Given their putative role in memory consolidation and neuroplasticity, sleep spindles may represent a mechanism by which tau impairs memory consolidation, as well as a possible target for therapeutic interventions in cognitive decline. Electronic supplementary material The online version of this article (10.1186/s13024-019-0309-5) contains supplementary material, which is available to authorized users.