Objective: We aimed to explore circadian disruption in iRBD and its association with the Diffusion Tensor Imaging- ALong the Perivascular Space (DTI-ALPS) index, a proxy of perivascular glymphatic dysfunction.

Background: Circadian disturbances have been described in patients with isolated REM sleep behavior disorder (iRBD), a prodromal stage of alpha-synucleinopathies[1,2]. Additionally, actigraphy-measured daytime acceleration, motion time during sleep and their ratio (A/T) have been used to objectively characterize sleep-wake alterations in Parkinson’s Disease[3]. Disturbed circadian rhythmicity has been proposed to impair glymphatic metabolic clearance, potentially contributing to alpha-synuclein accumulation and neurodegeneration[4].

Method: The study sample comprised 42 patients with video-polysomnography-confirmed iRBD recruited from the Sleep Center of the Hospital Clinic de Barcelona, Spain, and 27 healthy controls (HC). All participants underwent clinical examination and wore a circadian monitoring device for 7 days (KronowiseTM). Between-group differences in mean sleep probability, motor acceleration, motion time and the A/T index were analyzed. Actigraphy data were analyzed using repeated measures ANOVAs and FDR-correction for multiple comparisons. Diffusion-weighted imaging data was available for 41 iRBD and 23 HC, for which the DTI-ALPS index was calculated[5]. Correlations were performed between significant circadian metrics and the DTI-ALPS. A threshold of p<.05 was used in all the analyses.

Results: Patients with iRBD exhibited greater non-motor symptomology than HC [table1], lower mean motion time and decreased circadian function index of the motor rhythm [table2], as well as a decreased A/T ratio, reflective of decreased day/night activity contrast [table2b, figure3]. In repeated measures analyses, patients showed increased sleep probability, and decreased motor acceleration and motion time in specific periods of their circadian cycle [figure2). Patients showed a decreased DTI-ALPS index relative to HC, which positively correlated with the A/T index and mean motion time[figure3].

Conclusion: Patients with iRBD exhibit sleep-wake alterations which are associated with decreased perivascular glymphatic diffusivity, suggesting a link between circadian disruptions and impaired glymphatic clearance in early neurodegeneration.

Table 1

Table 2

Figure 1

Figure 2

Figure 3

References: 1. Winer, J. R. et al. Isolated REM sleep behavior disorder is associated with altered 24-h rest-activity measures. Front. Sleep 2, (2023).

2. Liguori, C. et al. Sleep−wake cycle dysregulation in idiopathic REM sleep behaviour disorder. Journal of Sleep Research 30, 1–6 (2021).

3. Madrid-Navarro, C. J. et al. Multidimensional circadian monitoring by wearable biosensors in Parkinson’s disease. Frontiers in Neurology 9, 1–14 (2018).

4. Buongiorno, M. et al. Altered sleep and neurovascular dysfunction in alpha-synucleinopathies: the perfect storm for glymphatic failure. Frontiers in aging neuroscience, 15 (2023)

5. Martín-Barceló, C.*, et al. DTI-ALPS index: evaluation of several approaches for automatic computation. Congress: ESMRMB (2024). Date: 2-5 October. Barcelona.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/sleep-wake-alterations-are-associated-with-a-decreased-dti-alps-a-marker-of-perivascular-glymphatic-functioning-in-patients-with-isolated-rem-sleep-behavior-disorder/