Poster No:
230
Submission Type:
Abstract Submission
Authors:
Jack Anderson1, Ajay Konuri1, Lachlan Churchill1, Anna Ignatavicius1, Garry Cho2, Aaron Lam1, Ronald Grunstein3, Simon Lewis2, Elie Matar1
Institutions:
1University of Sydney, Sydney, New South Wales, 2Macquarie University, Sydney, New South Wales, 3The Woolcock Institute, Sydney, New South Wales
First Author:
Co-Author(s):
Garry Cho
Macquarie University
Sydney, New South Wales
Aaron Lam
University of Sydney
Sydney, New South Wales
Simon Lewis
Macquarie University
Sydney, New South Wales
Elie Matar
University of Sydney
Sydney, New South Wales
Introduction:
Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by the loss of muscle atonia during REM sleep, leading to dream enactment behaviors that may result in injury (Schneck & Mahowald, 2002). RBD is a strong clinical marker for α-synucleinopathies, including Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA) (Iranzo et al., 2016; Postuma and Trenkwalder, 2017; Li et al., 2017). Isolated RBD (iRBD) is recognised as a prodromal phase, with 75% of patients phenoconverting to one of these neurodegenerative conditions within 12 years (Postuma et al., 2019). Cholinergic degeneration plays a critical role in cognitive decline in these neurodegenerative conditions (Bohnen & Albin, 2011) and as the basal forebrain (BF) and its cholinergic neurons play an important role in REM sleep (Platt & Riedel, 2011), REM electroencephalographic (EEG) alterations may serve as a biomarker for early cholinergic dysfunction. This study aimed to investigate REM EEG slowing in iRBD and its association with changes in BF volume and Nucleus Basalis of Meyert (NBM) resting-state functional connectivity in this cohort.
Methods:
Sixty-five participants with polysomnography (PSG)-confirmed iRBD (mean age = 66.3 ± 8.6 years) and 58 age-matched controls (mean age = 66.3 ± 7.7 years) underwent comprehensive neuropsychological, medical, and psychiatric assessments, followed by T1-weighted and resting-state fMRI (3 Tesla) imaging and overnight PSG. Absolute spectral power for REM sleep was computed for the δ (0.5–4.5 Hz), θ (4.5–8 Hz), α (8–12 Hz), σ (12–15 Hz), and β (15–32 Hz) frequency bands. The weighted average spectral power within each frequency band was calculated across all REM sleep. BF volumes were extracted from T1 weighted images and standardised for total intracranial volume. Seed-based functional connectivity analysis was performed between the NBM and the whole brain, using a combined atlas of Schaefer 400 (Schaefer et al., 2018), Tian's subcortical regions (Tian et al., 2020), and probabilistic spatial mapping of NBM. Group differences in demographic, cognitive, and sleep variables were assessed using Mann-Whitney U tests, while general linear models adjusted for age and sex were used to compare REM PSA between groups with FDR correction applied for multiple comparisons. Spearman's correlations between REM EEG power, BF volumes, and NBM functional connectivity to the whole brain were examined in the iRBD group.
Results:
Compared to controls, the iRBD group exhibited significantly lower global cognition (MMSE; U=1146.0, p=0.04) and narrative episodic memory (Logical Memory Recall; U=1263.5 p=0.02). Sleep latency was shorter in iRBD participants (U=1348.5, p=0.04), but other macroarchitectural sleep variables, including sleep stage percentages, were not significantly different between groups. PSA revealed increased REM beta power across frontal, central, and occipital regions in iRBD, though these findings did not survive FDR correction. While BF volumes did not correlate with REM EEG power, greater REM delta frequency, a marker of EEG slowing, was negatively associated with NBM functional connectivity to the whole brain in central regions (rs=-0.530, p=0.03).
Conclusions:
EEG slowing during REM sleep in iRBD is associated with reduced NBM functional connectivity, independent of BF atrophy. This suggests that REM EEG slowing is related to early cholinergic dysfunction that precedes and is not explained by structural changes in the BF. As cholinergic dysfunction is a hallmark of dementia in α-synucleinopathies, REM EEG slowing may serve as a valuable early biomarker for tracking cholinergic network integrity and predicting phenoconversion in iRBD.
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) 1
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Anatomy and Functional Systems 2
Keywords:
Acetylcholine
Electroencephaolography (EEG)
Other - Idiopathic REM Sleep Behaviour Disorder (iRBD)
1|2Indicates the priority used for review
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Please indicate below if your study was a "resting state" or "task-activation” study.
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Healthy subjects only or patients (note that patient studies may also involve healthy subjects):
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Was this research conducted in the United States?
No
Were any human subjects research approved by the relevant Institutional Review Board or ethics panel?
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Functional MRI
EEG/ERP
Structural MRI
For human MRI, what field strength scanner do you use?
3.0T
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Free Surfer
Provide references using APA citation style.
Bohnen, N. I. (2011). The cholinergic system and Parkinson disease. Behavioural brain research, 221(2), 564-573.
Iranzo, A. (2016). Idiopathic rapid eye movement sleep behaviour disorder: diagnosis, management, and the need for neuroprotective interventions. The Lancet Neurology, 15(4), 405-419.
Li, Y., Kang, W. (2017). Predictive markers for early conversion of iRBD to neurodegenerative synucleinopathy diseases. Neurology, 88(16), 1493-1500.
Platt, B. (2011). The cholinergic system, EEG and sleep. Behavioural brain research, 221(2), 499-504.
Postuma, R. B. (2017). Neurodegeneration in REM sleep behavior disorder: stratification keeps improving. Neurology, 88(16), 1486-1487.
Postuma, R. B. (2019). Risk and predictors of dementia and parkinsonism in idiopathic REM sleep behaviour disorder: a multicentre study. Brain, 142(3), 744-759.
Schaefer, A. (2018). Local-Global Parcellation of the Human Cerebral Cortex from Intrinsic Functional Connectivity MRI. Cerebral Cortex, 28(9), 3095-3114.
Schenck, C. H. (2002). REM sleep behavior disorder: clinical, developmental, and neuroscience perspectives 16 years after its formal identification in SLEEP. Sleep, 25(2), 120-138.
Tian, Y. (2020). Topographic organization of the human subcortex unveiled with functional connectivity gradients. Nature Neuroscience, 23(11), 1421-1432.
No