Objective: In this study, we aimed to investigate the relationship between regional [18F]florbetaben PET binding to amyloid-β (Aβ) and REM sleep behavior disorder (RBD) in a cohort of Parkinson’s disease (PD) patients.

Background: Amyloid pathology in PD is a primary risk factor for cognitive impairment and dementia [1]. Moreover, recent studies suggest a possible role of amyloid pathology in other non-motor symptoms of PD such as anxiety, depression [2] and sleep disorders (3). However, the relationship between amyloid deposition and RBD in PD patients remains unclear.

Method: We selected PD patients from the Parkinson’s Progression Markers Initiative (PPMI) cohort who underwent 18F-florbetaben positron emission topography (FBB-PET). Amyloid burden was quantified as the uptake of FBB referenced to the cerebellar cortex in a set of cortical and subcortical regions. Clinical features, including demographic characteristics, cerebrospinal fluid (CSF) biomarkers, montreal cognitive assessment (MOCA), and RBD-screening questionnaire (RBDSQ), were extracted. Patients were divided in RBD and non-RBD groups using  a cut‐off score of 1 for question 6 of the RBDSQ [4]. Non-parametric Wilcoxon rank sum tests were used to assess differences in FBB uptake between groups, also estimating Cohen’s d to report effect sizes. Partial correlation analysis was performed to explore the relationship between FBB uptake and clinical features, including age and disease duration as covariates

Results: This study included a cohort of 59 PD patients (mean age = 66 years, SD = 9; 71% male), with an average disease duration of 4 years and a mean MOCA score of 26.5 (SD = 2.6). Twenty-four PD patients were classified as RBD. We found increased FBB uptake for the non-RBD group in most regions, with the highest effects in the orbitofrontal, frontal, and parietal cortices (Figure A). Higher FBB uptake in frontotemporal and striatal regions was associated with lower scores on the RBDSQ (p < 0.05) (Figure B). Furthermore, higher FBB uptake in temporoparietal and striatal regions was associated with worse cognitive function and with higher CSF-tau.

Conclusion: Our findings suggest a complex role for amyloid accumulation in the pathogenesis of RBD symptoms in PD, indicating that amyloid pathology may be protective against the development of this sleep disorder. Further studies are necessary to investigate the underlying mechanisms of these relationships.

References: 1- Fiorenzato, E., Biundo, R., Cecchin, D., Frigo, A. C., Kim, J., Weis, L., Strafella, A. P., & Antonini, A. (2018). Brain Amyloid Contribution to Cognitive Dysfunction in Early-Stage Parkinson’s Disease: The PPMI Dataset. Journal of Alzheimer’s disease : JAD, 66(1), 229–237. https://doi.org/10.3233/JAD-180390\
2- Krell-Roesch, J., Rakusa, M., Syrjanen, J. A., van Harten, A. C., Lowe, V. J., Jack, C. R., Jr, Kremers, W. K., Knopman, D. S., Stokin, G. B., Petersen, R. C., Vassilaki, M., & Geda, Y. E. (2022). Association between CSF biomarkers of Alzheimer’s disease and neuropsychiatric symptoms: Mayo Clinic Study of Aging. Alzheimer’s & dementia : the journal of the Alzheimer’s Association, 10.1002/alz.12557. Advance online publication. https://doi.org/10.1002/alz.12557
3- Insel PS, Mohlenhoff BS, Neylan TC, Krystal AD, Mackin RS. Association of Sleep and β-Amyloid Pathology Among Older Cognitively Unimpaired Adults. JAMA Netw Open. 2021;4(7):e2117573. Published 2021 Jul 1. doi:10.1001/jamanetworkopen.2021.17573
4- Halsband C, Zapf A, Sixel-Döring F, Trenkwalder C, Mollenhauer B. The REM Sleep Behavior Disorder Screening Questionnaire is not Valid in De Novo Parkinson’s Disease. Mov Disord Clin Pract. 2018;5(2):171-176. Published 2018 Mar 1. doi:10.1002/mdc3.12591

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MDS Abstracts - https://www.mdsabstracts.org/abstract/relevance-of-amyloid-deposition-for-rem-sleep-behavior-disorder-in-parkinsons-disease/