Objective: To assess for cognitive impairment and features of prodromal Lewy body dementia (LBD) in persons with isolated REM sleep behavior disorder (iRBD) and neuronal α-synuclein disease (NSD).
Background: The NSD biological definition and Integrated Staging System (NSD-ISS) provides a research framework to identify individuals with underlying Lewy body pathology (based on α-synuclein seed amplification assay [SAA] and dopamine transporter scan [DaTscan]) and stage them based on underlying biology and increasing degree of functional impairment1. Stage 2 (Stage 2A is SAA+/DaTscan-; Stages 2B and 3-6 are SAA+/DaTscan+)1.
Method: Using Parkinson’s Progression Markers Initiative (PPMI) baseline data2, the cohorts were (1) persons with PSG-confirmed iRBD, a positive CSF neuronal α-synuclein SAA test, and no neurodegenerative disease diagnosis, and (2) an internal robust healthy control (HC) group. Cognitive performance was assessed globally with a recently-developed cognitive summary z-score (CSS) developed from a multi-cognitive domain battery using HC data3. In addition, we assessed key criteria for prodromal LBD, including mild cognitive impairment (MCI; based on MoCA score ≤25), fluctuating cognition, parkinsonism, and hallucinations4. Performance was compared between HCs and participants classified as Stage 2A or 2B and above, and percentage of iRBD meeting criteria for prodromal LBD was calculated.
Results: The cohorts were robust HC (N=136) and iRBD with NSD (N=197; Stage 2A [N=101], Stage 2B and above [N=96]). For participants with iRBD, 32% (N=63) had an MCI diagnosis MCI, the essential criterion for a diagnosis of prodromal LBD. The database is being finalized, and analyses will be completed in time to present results at the IPMDS annual meeting in October 2025.
Conclusion: Findings from these analyses will demonstrate whether or not persons with iRBD and neuronal synuclein disease, but not a diagnosed neurodegenerative disease, have cognitive deficits and other features of prodromal Lewy body dementia. The results will help inform the design of clinical trials in early synuclein disease.
References: 1. Simuni T, Chahine LM, Poston K, et al. A biological definition of neuronal alpha-synuclein disease: towards an integrated staging system for research. Lancet Neurol. Feb 2024;23(2):178-190. doi:10.1016/S1474-4422(23)00405-2
2. Marek K, Chowdhury S, Siderowf A, et al. The Parkinson’s progression markers initiative (PPMI) – establishing a PD biomarker cohort. Ann Clin Transl Neurol. Dec 2018;5(12):1460-1477. doi:10.1002/acn3.644
3. Weintraub D, Brumm MC, Kurth R, York MK, Parkinson’s Progression Markers I. Use of robust norming to create a sensitive cognitive summary score in de novo Parkinson’s disease: an illustrative example. Mov Disord. Jan 6 2025;doi:10.1002/mds.30111
4. McKeith IG, Ferman TJ, Thomas AJ, et al. Research criteria for the diagnosis of prodromal dementia with Lewy bodies. Neurology. Apr 28 2020;94(17):743-755. doi:10.1212/WNL.0000000000009323
To cite this abstract in AMA style:
D. Weintraub. Prodromal Lewy body dementia features in isolated REM sleep behavior disorder with neuronal synuclein disease [abstract]. Mov Disord. 2025; 40 (suppl 1). https://www.mdsabstracts.org/abstract/prodromal-lewy-body-dementia-features-in-isolated-rem-sleep-behavior-disorder-with-neuronal-synuclein-disease/. Accessed October 5, 2025.« Back to 2025 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/prodromal-lewy-body-dementia-features-in-isolated-rem-sleep-behavior-disorder-with-neuronal-synuclein-disease/