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

被引：67

作者：

Joza, Stephen ^{[1
]}

Hu, Michele T. ^{[2
,3
]}

Jung, Ki-Young ^{[4
]}

Kunz, Dieter ^{[5
]}

Stefani, Ambra ^{[6
]}

Dusek, Petr ^{[7
,8
,9
]}

Terzaghi, Michele ^{[10
,11
]}

Arnaldi, Dario ^{[12
,13
]}

Videnovic, Aleksandar ^{[14
]}

Schiess, Mya C. ^{[15
]}

Hermann, Wiebke ^{[16
]}

Lee, Jee-Young ^{[17
]}

Ferini-Strambi, Luigi ^{[18
]}

Lewis, Simon J. G. ^{[19
]}

Leclair-Visonneau, Laurene ^{[20
,21
]}

Oertel, Wolfgang H. ^{[22
,23
,24
]}

Antelmi, Elena ^{[25
]}

Sixel-Doering, Friederike ^{[22
,23
,26
]}

De Cock, Valerie Cochen ^{[27
,28
]}

Liguori, Claudio ^{[29
,30
]}

Liu, Jun ^{[31
]}

Provini, Federica ^{[32
,33
]}

Puligheddu, Monica ^{[34
]}

Nicoletti, Alessandra ^{[35
]}

Bassetti, Claudio L. A. ^{[36
]}

Buskova, Jitka ^{[37
,38
]}

Dauvilliers, Yves ^{[39
]}

Ferri, Raffaele ^{[40
]}

Montplaisir, Jacques Y. ^{[41
,42
]}

Lawton, Michael ^{[43
]}

Kim, Han-Joon ^{[4
]}

Bes, Frederik ^{[5
]}

Hoegl, Birgit ^{[6
]}

Sonka, Karel ^{[7
,8
,9
]}

Fiamingo, Giuseppe ^{[10
,11
]}

Mattioli, Pietro ^{[12
]}

Lavadia, Maria Lorena ^{[14
]}

Suescun, Jessika ^{[15
]}

Woo, Kyung Ah ^{[17
]}

Marelli, Sara ^{[18
]}

Martens, Kaylena Ehgoetz ^{[44
]}

Janzen, Annette ^{[22
,23
]}

Plazzi, Giuseppe ^{[33
,45
]}

Mollenhauer, Brit ^{[26
,46
]}

Fernandes, Mariana ^{[29
]}

Li, Yuanyuan ^{[31
]}

Cortelli, Pietro ^{[32
,33
]}

Figorilli, Michela ^{[34
]}

Cicero, Calogero Edoardo ^{[35
]}

Schaefer, Carolin ^{[36
]}

机构：

[1] Montreal Neurol Inst, Dept Neurol, Montreal, PQ H3A 2B4, Canada

[2] Univ Oxford, Nuffield Dept Clin Neurosci, Div Neurol, Oxford OX3 9DU, England

[3] Univ Oxford, Oxford Parkinsons Dis Ctr, Oxford OX3 9DU, England

[4] Seoul Natl Univ, Seoul Natl Univ Hosp, Coll Med, Dept Neurol, Seoul 03080, South Korea

[5] St Hedwig Krankenhaus, Clin Sleep & Chronomed, D-10115 Berlin, Germany

[6] Med Univ Innsbruck, Dept Neurol, A-6020 Innsbruck, Austria

[7] Charles Univ Prague, Dept Neurol, Prague 11636, Czech Republic

[8] Charles Univ Prague, Fac Med 1, Ctr Clin Neurosci, Prague 11636, Czech Republic

[9] Gen Univ Hosp, Prague 11636, Czech Republic

[10] IRCCS Mondino Fdn, Sleep Med & Epilepsy Unit, I-27100 Pavia, Italy

[11] Univ Pavia, Dept Brain & Behav Sci, I-27100 Pavia, Italy

[12] Univ Genoa, Dept Neurosci Rehabil Ophthalmol Genet Maternal &, Clin Neurol, I-16132 Genoa, Italy

[13] IRCCS Osped Policlin San Martino, I-16132 Genoa, Italy

[14] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA

[15] Univ Texas Hlth Sci Ctr Houston, Dept Neurol, Houston, TX 77030 USA

[16] Univ Rostock, Dept Neurol, D-18147 Rostock, Germany

[17] Univ Vita Salute San Raffaele, Sleep Disorders Ctr, I-20132 Milan, Italy

[18] Seoul Natl Univ, Seoul Metropolitan Govt Seoul Natl Univ Boramae Me, Coll Med, Dept Neurol, Seoul 07061, South Korea

[19] Univ Sydney, Brain & Mind Ctr, Sch Med Sci, ForeFront Parkinsons Dis Res Clin, Sydney, NSW 2006, Australia

[20] CHU Nantes, Dept Clin Neurophysiol, F-44000 Nantes, France

[21] Nantes Univ, Inserm, TENS, Enter Nervous Syst Gut & Brain Dis, F-44000 Nantes, France

[22] Philipps Univ Marburg, Dept Neurol, D-35037 Marburg, Germany

[23] Philipps Univ Marburg, Sect Clin Neurosci, D-35037 Marburg, Germany

[24] Helmholtz Ctr Hlth & Environm, Inst Neurogenom, D-85764 Munich, Neuherberg, Germany

[25] Univ Verona, Dept Neurosci Biomed & Movement Sci, I-37121 Verona, Italy

[26] Ctr Movement Disorders, Paracelsus Elena Klin, D-34128 Kassel, Germany

[27] Univ Montpellier, EuroMov Digital Hlth Mot, IMT Mines Ales, F-34090 Montpellier, France

[28] Beau Soleil Clin, Dept Neurol & Sleep, F-34070 Montpellier, France

[29] Univ Roma Tor Vergata, Sleep Med Ctr, Dept Syst Med, I-00133 Rome, Italy

[30] Univ Hosp Rome Tor Vergata, Neurol Unit, I-00133 Rome, Italy

[31] Shanghai Jiao Tong Univ, Ruijin Hosp, Sch Med, Dept Neurol, Shanghai 200025, Peoples R China

[32] Univ Bologna, Dept Biomed & Neuromotor Sci, I-40127 Bologna, Italy

[33] IRCCS Ist Sci Neurol Bologna, I-40127 Bologna, Italy

[34] Univ Cagliari, Sleep Ctr, Dept Med Sci & Publ Hlth, I-09124 Cagliari, Italy

[35] Univ Catania, Dept Med Surg Sci & Adv Technol, GF Ingrassia, I-95124 Catania, Italy

[36] Univ Hosp Bern, Dept Neurol, Inselspital, CH-3010 Bern, Switzerland

[37] Natl Inst Mental Hlth, Klecany, Czech Republic

[38] Charles Univ Prague, Fac Med 3, Prague 11000, Czech Republic

[39] Hop Gui de Chauliac, Dept Neurol, Sleep Unit, F-34093 Montpellier 5, France

[40] IRCCS, Oasi Res Inst, Clin Neurophysiol Res Unit, I-94018 Troina, Italy

[41] Hop Sacre Coeur Montreal, Ctr Etud Avancees Med Sommeil, Montreal, PQ H4J 1C5, Canada

[42] Univ Quebec Montreal, Dept Psychol, Montreal, PQ H2L 2C4, Canada

[43] Univ Bristol, Sch Social & Community Med, Bristol Med Sch, Bristol BS8 1QU, England

[44] Univ Waterloo, Dept Kinesiol & Hlth Sci, Waterloo, ON N2L 3G1, Canada

[45] Univ Modena & Reggio Emilia, Dept Biomed Metab & Neural Sci, I-41121 Modena, Italy

[46] Univ Med Ctr Goettingen, Dept Neurosurg, D-37075 Gottingen, Germany

[47] Univ Catania, Dept Surg & Med Surg Specialties, I-95123 Catania, Italy

[48] Kangbuk Samsung Hosp, Dept Neurol, Seoul 04514, South Korea

[49] Montreal Neurol Inst, 3801 Univ Ave,Room NW107, Montreal, PQ H3A 2B4, Canada

来源：

BRAIN | 2023年 / 146卷 / 08期

基金：

新加坡国家研究基金会;

关键词：

REM sleep behaviour disorder; Parkinson's disease; dementia with Lewy bodies; prodromal stage; evolution; SLEEP BEHAVIOR DISORDER; SMELL IDENTIFICATION TEST; OLFACTORY FUNCTION; HOSPITAL ANXIETY; NORMATIVE DATA; RATING-SCALE; DEPRESSION; VALIDATION; INVENTORY; SCORES;

D O I：

10.1093/brain/awad072

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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 behaviour disorder 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 end points. In this study, we combined prospective follow-up data from 28 centres of the International REM Sleep Behavior Disorder Study Group representing 12 countries. Polysomnogram-confirmed REM sleep behaviour 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 to 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 multicentre study demonstrates the evolution of motor and non-motor manifestations in prodromal synucleinopathy. These findings provide optimized clinical end points and sample size estimates to inform future neuroprotective trials.

引用

页码：3258 / 3272

页数：15

共 53 条

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