Characterization of Non-Motor Fluctuations Using the Movement Disorder Society Non-Motor Rating Scale

Daniel Johannes van Wamelen; Silvia Rota; Anette Schrag; Alexandra Rizos; Pablo Martinez-Martin; Daniel Weintraub; Kallol Ray Chaudhuri

doi:10.1002/mdc3.13520

Characterization of Non-Motor Fluctuations Using the Movement Disorder Society Non-Motor Rating Scale

Daniel Johannes van Wamelen^*, Silvia Rota, Anette Schrag, Alexandra Rizos, Pablo Martinez-Martin, Daniel Weintraub, Kallol Ray Chaudhuri

^*Corresponding author for this work

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Abstract

Background: Non-motor fluctuations (NMF) in people with Parkinson's disease (PwP) are clinically important yet understudied. Objective: To study NMF in PwP using both the Movement Disorder Society Non-Motor Rating Scale (MDS-NMS) NMF subscale and wearable sensors. Methods: We evaluated differences in overall burden of NMF and of specific NMF across disease durations: <2 years (n = 33), 2–5 years (n = 35), 5–10 years (n = 33), and > 10 years (n = 31). In addition, wearable triaxial sensor output was used as an exploratory outcome for early morning “off” periods. Results: Significant between-group differences were observed for MDS-NMS NMF total scores (P < 0.001), and specifically for depression, anxiety, fatigue and cognition, with both NMF prevalence and burden increasing in those with longer disease duration. Whereas only 9.1% with a short disease duration had NMF (none of whom had dyskinesia), in PwP with a disease duration of >10 years this was 71.0% (P < 0.001). From a motor perspective, dyskinesia severity increased evenly with increasing disease duration, while NMF scores in affected individuals showed an initial increase with largest differences between 2–5 years disease duration (P < 0.001), with plateauing afterwards. Finally, we observed that the most common NMF symptoms in patients with sensor-confirmed early morning “off” periods were fluctuations in cognitive capabilities, restlessness, and excessive sweating. Conclusions: Non-motor fluctuations prevalence in PwP increases with disease duration, but in a pattern different from motor fluctuations. Moreover, NMF can occur in PwP without dyskinesia, and in those with NMF the severity of NMF increases most during years 2–5 after diagnosis.

Original language	English
Pages (from-to)	932-940
Number of pages	9
Journal	Movement Disorders Clinical Practice
Volume	9
Issue number	7
Early online date	5 Aug 2022
DOIs	https://doi.org/10.1002/mdc3.13520
Publication status	Published - Oct 2022

Keywords

fluctuations
non-motor fluctuations
non-motor symptoms
Parkinson's disease
progression
wearable sensor

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Characterization of Non-Motor_VAN WAMELEN_Publishedonline5August2022_GOLD VoR CC BYFinal published version, 298 KBLicence: CC BY

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@article{1dfe8607470642808de8317a2efe58d3,

title = "Characterization of Non-Motor Fluctuations Using the Movement Disorder Society Non-Motor Rating Scale",

abstract = "Background: Non-motor fluctuations (NMF) in people with Parkinson's disease (PwP) are clinically important yet understudied. Objective: To study NMF in PwP using both the Movement Disorder Society Non-Motor Rating Scale (MDS-NMS) NMF subscale and wearable sensors. Methods: We evaluated differences in overall burden of NMF and of specific NMF across disease durations: <2 years (n = 33), 2–5 years (n = 35), 5–10 years (n = 33), and > 10 years (n = 31). In addition, wearable triaxial sensor output was used as an exploratory outcome for early morning “off” periods. Results: Significant between-group differences were observed for MDS-NMS NMF total scores (P < 0.001), and specifically for depression, anxiety, fatigue and cognition, with both NMF prevalence and burden increasing in those with longer disease duration. Whereas only 9.1% with a short disease duration had NMF (none of whom had dyskinesia), in PwP with a disease duration of >10 years this was 71.0% (P < 0.001). From a motor perspective, dyskinesia severity increased evenly with increasing disease duration, while NMF scores in affected individuals showed an initial increase with largest differences between 2–5 years disease duration (P < 0.001), with plateauing afterwards. Finally, we observed that the most common NMF symptoms in patients with sensor-confirmed early morning “off” periods were fluctuations in cognitive capabilities, restlessness, and excessive sweating. Conclusions: Non-motor fluctuations prevalence in PwP increases with disease duration, but in a pattern different from motor fluctuations. Moreover, NMF can occur in PwP without dyskinesia, and in those with NMF the severity of NMF increases most during years 2–5 after diagnosis.",

keywords = "fluctuations, non-motor fluctuations, non-motor symptoms, Parkinson's disease, progression, wearable sensor",

author = "{van Wamelen}, {Daniel Johannes} and Silvia Rota and Anette Schrag and Alexandra Rizos and Pablo Martinez-Martin and Daniel Weintraub and {Ray Chaudhuri}, Kallol",

note = "Funding Information: The authors acknowledge grant support from the International Parkinson and Movement Disorder Society to plan, develop, and validate the English version of the MDS‐NMS in an international study from where the data for the current analyses were obtained. The authors acknowledge support from the NIHR Clinical Research Network and CRN‐supported staff for data collection in NHS clinics and of the UCL/H Biomedical Research Council. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health. Funding Information: In the past year D.v.W. has received speaker fees from Bial and Britannia pharmaceuticals, and research grants from NIHR BRC and CHDI; S.R. has nothing to disclose; A.S. has nothing to disclose; A.R. has received support from the National institute of Health Research (NIHR) Clinical Research Network (CRN) South London, Guy's Hospital, Great Maze Pond, London UK and International Parkinson and Movement Disorder Society (MDS); P.M.M. has nothing to disclose; In the past year D.W. has received research funding or support from Michael J. Fox Foundation for Parkinson's Research, Alzheimer's Therapeutic Research Initiative (ATRI), Alzheimer's Disease Cooperative Study (ADCS), International Parkinson and Movement Disorder Society (IPMDS), National Institute on Health (NIH), Parkinson's Foundation; U.S. Department of Veterans Affairs and Acadia Pharmaceuticals; honoraria for consultancy from Acadia Pharmaceuticals, Alkahest, Aptinyx, Cerevel Therapeutics, CHDI Foundation, Clexio, Clintrex LLC (Otsuka), EcoR1 Capital, Eisai, Ferring, Gray Matter Technologies, Great Lake Neurotechnologies, Intra‐Cellular Therapies, Janssen, Merck, Sage, Scion, Signant Health and Vanda; and license fee payments from the University of Pennsylvania for the QUIP and QUIP‐RS. K.R.C. reports advisory board for AbbVie, UCB, GKC, Bial, Cynapsus, Lobsor, Stada, Zambon, Profile Pharma, Synovion, Roche, and Therevance, Scion, as well as honoraria for lectures for AbbVie, Britannia, UCB, Zambon, Novartis, Boeringer Ingelheim, Bial, Kyowa Kirin, SK Pharma, and frants (Investigator Initiated) from Bial, EU Horizon 2020, Parkinson's UK, NIHR, Parkinson's Foundation, Wellcome Trust, and royalties or licenses (ongoing) from Oxford (book), Cambridge publishers (book), MAPI institute (KPPS, PDSS 2), and payment for expert testimony for the General Medical Council (UK). Publisher Copyright: {\textcopyright} 2022 The Authors. Movement Disorders Clinical Practice published by Wiley Periodicals LLC. on behalf of International Parkinson and Movement Disorder Society.",

year = "2022",

month = oct,

doi = "10.1002/mdc3.13520",

language = "English",

volume = "9",

pages = "932--940",

journal = "Movement Disorders Clinical Practice",

issn = "2330-1619",

publisher = "Wiley-Blackwell",

number = "7",

}

TY - JOUR

T1 - Characterization of Non-Motor Fluctuations Using the Movement Disorder Society Non-Motor Rating Scale

AU - van Wamelen, Daniel Johannes

AU - Rota, Silvia

AU - Schrag, Anette

AU - Rizos, Alexandra

AU - Martinez-Martin, Pablo

AU - Weintraub, Daniel

AU - Ray Chaudhuri, Kallol

N1 - Funding Information: The authors acknowledge grant support from the International Parkinson and Movement Disorder Society to plan, develop, and validate the English version of the MDS‐NMS in an international study from where the data for the current analyses were obtained. The authors acknowledge support from the NIHR Clinical Research Network and CRN‐supported staff for data collection in NHS clinics and of the UCL/H Biomedical Research Council. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health. Funding Information: In the past year D.v.W. has received speaker fees from Bial and Britannia pharmaceuticals, and research grants from NIHR BRC and CHDI; S.R. has nothing to disclose; A.S. has nothing to disclose; A.R. has received support from the National institute of Health Research (NIHR) Clinical Research Network (CRN) South London, Guy's Hospital, Great Maze Pond, London UK and International Parkinson and Movement Disorder Society (MDS); P.M.M. has nothing to disclose; In the past year D.W. has received research funding or support from Michael J. Fox Foundation for Parkinson's Research, Alzheimer's Therapeutic Research Initiative (ATRI), Alzheimer's Disease Cooperative Study (ADCS), International Parkinson and Movement Disorder Society (IPMDS), National Institute on Health (NIH), Parkinson's Foundation; U.S. Department of Veterans Affairs and Acadia Pharmaceuticals; honoraria for consultancy from Acadia Pharmaceuticals, Alkahest, Aptinyx, Cerevel Therapeutics, CHDI Foundation, Clexio, Clintrex LLC (Otsuka), EcoR1 Capital, Eisai, Ferring, Gray Matter Technologies, Great Lake Neurotechnologies, Intra‐Cellular Therapies, Janssen, Merck, Sage, Scion, Signant Health and Vanda; and license fee payments from the University of Pennsylvania for the QUIP and QUIP‐RS. K.R.C. reports advisory board for AbbVie, UCB, GKC, Bial, Cynapsus, Lobsor, Stada, Zambon, Profile Pharma, Synovion, Roche, and Therevance, Scion, as well as honoraria for lectures for AbbVie, Britannia, UCB, Zambon, Novartis, Boeringer Ingelheim, Bial, Kyowa Kirin, SK Pharma, and frants (Investigator Initiated) from Bial, EU Horizon 2020, Parkinson's UK, NIHR, Parkinson's Foundation, Wellcome Trust, and royalties or licenses (ongoing) from Oxford (book), Cambridge publishers (book), MAPI institute (KPPS, PDSS 2), and payment for expert testimony for the General Medical Council (UK). Publisher Copyright: © 2022 The Authors. Movement Disorders Clinical Practice published by Wiley Periodicals LLC. on behalf of International Parkinson and Movement Disorder Society.

PY - 2022/10

Y1 - 2022/10

N2 - Background: Non-motor fluctuations (NMF) in people with Parkinson's disease (PwP) are clinically important yet understudied. Objective: To study NMF in PwP using both the Movement Disorder Society Non-Motor Rating Scale (MDS-NMS) NMF subscale and wearable sensors. Methods: We evaluated differences in overall burden of NMF and of specific NMF across disease durations: <2 years (n = 33), 2–5 years (n = 35), 5–10 years (n = 33), and > 10 years (n = 31). In addition, wearable triaxial sensor output was used as an exploratory outcome for early morning “off” periods. Results: Significant between-group differences were observed for MDS-NMS NMF total scores (P < 0.001), and specifically for depression, anxiety, fatigue and cognition, with both NMF prevalence and burden increasing in those with longer disease duration. Whereas only 9.1% with a short disease duration had NMF (none of whom had dyskinesia), in PwP with a disease duration of >10 years this was 71.0% (P < 0.001). From a motor perspective, dyskinesia severity increased evenly with increasing disease duration, while NMF scores in affected individuals showed an initial increase with largest differences between 2–5 years disease duration (P < 0.001), with plateauing afterwards. Finally, we observed that the most common NMF symptoms in patients with sensor-confirmed early morning “off” periods were fluctuations in cognitive capabilities, restlessness, and excessive sweating. Conclusions: Non-motor fluctuations prevalence in PwP increases with disease duration, but in a pattern different from motor fluctuations. Moreover, NMF can occur in PwP without dyskinesia, and in those with NMF the severity of NMF increases most during years 2–5 after diagnosis.

AB - Background: Non-motor fluctuations (NMF) in people with Parkinson's disease (PwP) are clinically important yet understudied. Objective: To study NMF in PwP using both the Movement Disorder Society Non-Motor Rating Scale (MDS-NMS) NMF subscale and wearable sensors. Methods: We evaluated differences in overall burden of NMF and of specific NMF across disease durations: <2 years (n = 33), 2–5 years (n = 35), 5–10 years (n = 33), and > 10 years (n = 31). In addition, wearable triaxial sensor output was used as an exploratory outcome for early morning “off” periods. Results: Significant between-group differences were observed for MDS-NMS NMF total scores (P < 0.001), and specifically for depression, anxiety, fatigue and cognition, with both NMF prevalence and burden increasing in those with longer disease duration. Whereas only 9.1% with a short disease duration had NMF (none of whom had dyskinesia), in PwP with a disease duration of >10 years this was 71.0% (P < 0.001). From a motor perspective, dyskinesia severity increased evenly with increasing disease duration, while NMF scores in affected individuals showed an initial increase with largest differences between 2–5 years disease duration (P < 0.001), with plateauing afterwards. Finally, we observed that the most common NMF symptoms in patients with sensor-confirmed early morning “off” periods were fluctuations in cognitive capabilities, restlessness, and excessive sweating. Conclusions: Non-motor fluctuations prevalence in PwP increases with disease duration, but in a pattern different from motor fluctuations. Moreover, NMF can occur in PwP without dyskinesia, and in those with NMF the severity of NMF increases most during years 2–5 after diagnosis.

KW - fluctuations

KW - non-motor fluctuations

KW - non-motor symptoms

KW - Parkinson's disease

KW - progression

KW - wearable sensor

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U2 - 10.1002/mdc3.13520

DO - 10.1002/mdc3.13520

M3 - Article

AN - SCOPUS:85135407762

SN - 2330-1619

VL - 9

SP - 932

EP - 940

JO - Movement Disorders Clinical Practice

JF - Movement Disorders Clinical Practice

IS - 7

ER -

Characterization of Non-Motor Fluctuations Using the Movement Disorder Society Non-Motor Rating Scale

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