Objective: To identify a cognitively intact enriched cohort of people with isolated rapid eye movement (iREM) sleep behaviour disorder (iRBD) and hyposmia, at risk of phenoconversion to Parkinson’s disease (PD). This cohort will be followed longitudinally to gain insights into disease mechanisms and epidemiology.

Background: Hyposmia^[i] and iRBD are biomarkers of prodromal α-synucleinopathies[ii] such as PD.

Method: Residents of Luxembourg aged 55-75 were invited to complete an online survey including the 1-item Mayo Sleep Questionnaire, 13-item RBD Screening Questionnaire (RBDSQ) and 16-item Short IQCODE. Individuals with RBDSQ≥7 underwent a structured telephone interview then, those qualifying, at-home olfactory tests (Short UPSIT) and a Parkinson’s Disease Screening Questionnaire. Finally, subjects with hyposmia but no signs of PD were invited for in-person cognitive screening and physical examination. Participants with clinically probable iRBD (pRBD) were referred for polysomnography (PSG) for RBD confirmation.

Results: 17,502 (13% of 134,098 invited) participated in the online survey; 1,987 had clinically pRBD. After telephone assessment, 666 qualified for home based olfactory testing. 592 (89%) completed; 204 had hyposmia (UPSIT≤8) and were invited for in-person visits (179 completed); 116 qualified for PSG. To date, 54 PSGs confirm 34 (62%) iRBD (28) or REM sleep without atonia (6); 8 obstructive sleep apnoea syndrome and 1 periodic limb movements.

Conclusion: This nationwide study is one of the most extensive pRBD prevalence surveys leading to an enriched cohort at-risk for PD. The systematic, stepwise screening process not only informs about population prevalence of pRBD, but also provides lessons for enrichment of a cohort of people at increased risk of PD.

References: [i] Barber TR, Lawton M, Rolinski M, Evetts S, Baig F, Ruffmann C, Gornall A, Klein JC, Lo C, Dennis G, Bandmann O, Quinnell T, Zaiwalla Z, Ben-Shlomo Y, Hu MTM. Prodromal Parkinsonism and Neurodegenerative Risk Stratification in REM Sleep Behavior Disorder. Sleep. 2017 Aug 1;40(8):zsx071. doi: 10.1093/sleep/zsx071. PMID: 28472425; PMCID: PMC5806544.
[ii] Postuma RB, Lang AE, Gagnon JF, Pelletier A, Montplaisir JY. How does parkinsonism start? Prodromal parkinsonism motor changes in idiopathic REM sleep behaviour disorder. Brain. 2012 Jun;135(Pt 6):1860-70. doi: 10.1093/brain/aws093. Epub 2012 May 4. PMID: 22561644.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/national-luxembourg-sleep-study-an-enriched-at-risk-prodromal-parkinsons-disease-cohort/