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Joza, S.* ; Hu, M.T.* ; Jung, K.Y.* ; Kunz, D.* ; Stefani, A.* ; Dušek, P.* ; Terzaghi, M.* ; Arnaldi, D.* ; Videnovic, A.* ; Schiess, M.C.* ; Hermann, W.* ; Lee, J.Y.* ; Ferini-Strambi, L.* ; Lewis, S.J.G.* ; Leclair-Visonneau, L.* ; Oertel, W.H. ; Antelmi, E.* ; Sixel-Döring, F.* ; Cochen De Cock, V.* ; Liguori, C.* ; Liu, J.* ; Provini, F.* ; Puligheddu, M.* ; Nicoletti, A.* ; Bassetti, C.L.A.* ; Bušková, J.* ; Dauvilliers, Y.* ; Ferri, R.* ; Montplaisir, J.Y.* ; Lawton, M.* ; Kim, H.J.* ; Bes, F.* ; Högl, B.* ; Sonka, K.* ; Fiamingo, G.* ; Pietro, M.* ; Lavadia, M.L.* ; Suescun, J.* ; Woo, K.A.* ; Marelli, S.* ; Ehgoetz Martens, K.* ; Janzen, A.* ; Plazzi, G.* ; Mollenhauer, B.* ; Fernandes, M.* ; Li, Y.* ; Cortelli, P.* ; Figorilli, M.* ; Cicero, C.E.* ; Schaefer, C.* ; Guiraud, L.* ; Lanza, G.* ; Gagnon, J.F.* ; Sunwoo, J.S.* ; Ibrahim, A.* ; Girtler, N.* ; Trenkwalder, C.* ; Baldelli, L.* ; Pelletier, A.* ; Postuma, R.B.*

Progression of clinical markers in prodromal Parkinson's disease and dementia with Lewy bodies: a multicentre study.

Brain 146, 3258-3272 (2023)
DOI PMC
The neurodegenerative synucleinopathies, including Parkinson's disease and dementia with Lewy bodies, are characterized by a typically lengthy prodromal period of progressive subclinical motor and non-motor manifestations. Among these, idiopathic REM sleep behavior disorder (iRBD) is a powerful early predictor of eventual phenoconversion, and therefore represents a critical opportunity to intervene with neuroprotective therapy. To inform the design of randomized trials, it is essential to study the natural progression of clinical markers during the prodromal stages of disease in order to establish optimal clinical endpoints. In this study, we combined prospective follow-up data from 28 centers of the International REM Sleep Behavior Disorder Study Group representing 12 countries. Polysomnogram-confirmed REM sleep behavior disorder subjects were assessed for prodromal Parkinson's disease using the Movement Disorder Society criteria and underwent periodic structured sleep, motor, cognitive, autonomic and olfactory testing. We used linear mixed-effect modelling to estimate annual rates of clinical marker progression stratified by disease subtype, including prodromal Parkinson's disease and prodromal dementia with Lewy bodies. In addition, we calculated sample size requirements to demonstrate slowing of progression under different anticipated treatment effects. Overall, 1160 subjects were followed over an average of 3.3 ± 2.2 years. Among clinical variables assessed continuously, motor variables tended to progress faster and required the lowest sample sizes, ranging from 151-560 per group (at 50% drug efficacy and 2-year follow-up). By contrast, cognitive, olfactory, and autonomic variables showed modest progression with higher variability, resulting in high sample sizes. The most efficient design was a time-to-event analysis using combined milestones of motor and cognitive decline, estimating 117 per group at 50% drug efficacy and 2-year trial duration. Finally, while phenoconverters showed overall greater progression than non-converters in motor, olfactory, cognitive, and certain autonomic markers, the only robust difference in progression between Parkinson's disease and dementia with Lewy bodies phenoconverters was in cognitive testing. This large multicenter study demonstrates the evolution of motor and non-motor manifestations in prodromal synucleinopathy. These findings provide optimized clinical endpoints and sample size estimates to inform future neuroprotective trials.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Parkinson’s Disease ; Rem Sleep Behavior Disorder ; Dementia With Lewy Bodies ; Evolution ; Prodromal Stage; Sleep Behavior Disorder; Smell Identification Test; Olfactory Function; Hospital Anxiety; Normative Data; Rating-scale; Depression; Validation; Inventory; Scores
ISSN (print) / ISBN 0006-8950
e-ISSN 1460-2156
Zeitschrift Brain: A Journal of Neurology
Quellenangaben Band: 146, Heft: 8, Seiten: 3258-3272 Artikelnummer: , Supplement: ,
Verlag Oxford University Press
Verlagsort Great Clarendon St, Oxford Ox2 6dp, England
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Neurogenomics (ING)
Förderungen Canada Research Chair in Cognitive Decline in Pathological Aging
CIHR
ParkinsonFonds Deutschland
Charitable Hertie Foundation, Frankfurt/Main, Germany
National Research Foundation of Korea (NRF) - Ministry of Science, ICT and Future Planning (MSIP)
Parkinson's UK and the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC), UK