Disentangling the PIGD classification for the prediction of cognitive impairment in de novo Parkinson’s disease

Daniele Urso; Valentina Leta; Lucia Batzu; Tayyabah Yousaf; Chloe Farrell; Daniel J. van Wamelen; K. Ray Chaudhuri

doi:10.1007/s00415-021-10730-3

Disentangling the PIGD classification for the prediction of cognitive impairment in de novo Parkinson’s disease

Daniele Urso^*, Valentina Leta, Lucia Batzu, Tayyabah Yousaf, Chloe Farrell, Daniel J. van Wamelen, K. Ray Chaudhuri

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

9 Citations (Scopus)

Abstract

Background: Postural Instability and Gait difficulties (PIGD) subtype has been associated with worse cognitive performance in Parkinson’s disease (PD). Objective: To investigate whether PIGD subtype classification or PIGD-related clinical features predict the development of cognitive decline in de novo PD patients. Methods: Data from 422 PD patients with de novo PD were obtained from the PPMI database. At follow-up (up to 6 years), patients were categorized as having cognitive impairment or not. Multivariate Cox survival analysis was carried out including motor subtype and individual MDS-UPDRS items defining PIGD phenotype as predictors. Previously validated clinical predictors of cognitive impairment were included in the model as covariates. Occurrence of cognitive impairment at follow-up was used as the time-to-event and Kaplan–Meier curve was generated. Results: At baseline, 76 patients were classified as PIGD, 299 tremor-dominant and 47 as indeterminate. Development of cognitive impairment was not associated with PIGD subtype (p = 0.252). When individual MDS-UPDRS items were interrogated in the model, postural instability proved to be an independent predictor of cognitive impairment (HR = 2.045; 95%CI: 1.068–3.918; p = 0.031), while gait difficulties were not associated with cognitive decline (p = 0.870). Conclusions: Our findings suggest that postural instability, as assessed by MDS-UPDRS III, may serve as a possible indicator of the risk of developing cognitive impairment in de novo PD patients rather than the PIGD phenotype.

Original language	English
Journal	Journal of Neurology
Volume	269
Issue number	3
Early online date	2 Aug 2021
DOIs	https://doi.org/10.1007/s00415-021-10730-3
Publication status	E-pub ahead of print - 2 Aug 2021

Keywords

Cognitive impairment
Parkinson’s disease
PIGD
Postural instability

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10.1007/s00415-021-10730-3

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@article{6edf6bdf26e8492e87757719f58cc1e5,

title = "Disentangling the PIGD classification for the prediction of cognitive impairment in de novo Parkinson{\textquoteright}s disease",

abstract = "Background: Postural Instability and Gait difficulties (PIGD) subtype has been associated with worse cognitive performance in Parkinson{\textquoteright}s disease (PD). Objective: To investigate whether PIGD subtype classification or PIGD-related clinical features predict the development of cognitive decline in de novo PD patients. Methods: Data from 422 PD patients with de novo PD were obtained from the PPMI database. At follow-up (up to 6 years), patients were categorized as having cognitive impairment or not. Multivariate Cox survival analysis was carried out including motor subtype and individual MDS-UPDRS items defining PIGD phenotype as predictors. Previously validated clinical predictors of cognitive impairment were included in the model as covariates. Occurrence of cognitive impairment at follow-up was used as the time-to-event and Kaplan–Meier curve was generated. Results: At baseline, 76 patients were classified as PIGD, 299 tremor-dominant and 47 as indeterminate. Development of cognitive impairment was not associated with PIGD subtype (p = 0.252). When individual MDS-UPDRS items were interrogated in the model, postural instability proved to be an independent predictor of cognitive impairment (HR = 2.045; 95%CI: 1.068–3.918; p = 0.031), while gait difficulties were not associated with cognitive decline (p = 0.870). Conclusions: Our findings suggest that postural instability, as assessed by MDS-UPDRS III, may serve as a possible indicator of the risk of developing cognitive impairment in de novo PD patients rather than the PIGD phenotype.",

keywords = "Cognitive impairment, Parkinson{\textquoteright}s disease, PIGD, Postural instability",

author = "Daniele Urso and Valentina Leta and Lucia Batzu and Tayyabah Yousaf and Chloe Farrell and {van Wamelen}, {Daniel J.} and {Ray Chaudhuri}, K.",

note = "Funding Information: Data used in the preparation of this article were obtained from the Parkinson{\textquoteright}s Progression Markers Initiative (PPMI) database ( www.ppmi-info.org/data ). For up-to-date information on the study, visit www.ppmi-info.org . PPMI (a public–private partnership) is funded by the Michael J Fox Foundation for Parkinson{\textquoteright}s Research and funding partners, including AbbVie, Avid, Biogen, Bristol-Myers Squibb, Covance, GE Healthcare, Genentech, GlaxoSmithKline, Lilly, Lundbeck, Merck, Meso Scale Discovery, Pfizer, Piramal, Roche, Servier, Teva, and UCB. The current data analysis was not supported by funding. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. The authors acknowledge the support of the NIHR London South Clinical Research Network and the NIHR Biomedical Research Centre. This article represents independent collaborative research part funded by the NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King{\textquoteright}s College London. The authors acknowledge the support of the NIHR London South Clinical Research Network and the NIHR Biomedical Research Centre. This article represents independent collaborative research part funded by the NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King{\textquoteright}s College London. Funding Information: DU, LB, TY, and CF have no disclosures. VL has received grants from BRC, Parkinson{\textquoteright}s UK, a travel and congress grant from Bial UK Ltd, speaker-related activities fees from Britannia pharmaceuticals, and consultancy fees from Invisio Pharmaceuticals, outside the submitted work. DvW reports grants, speaker fees, and honoraria from Britannia Pharmaceuticals Ltd, speaker fees from Abbvie UK Ltd, and honoraria from Invisio Pharmaceuticals, outside of the submitted work. KRC has received honoraria for Advisory board from AbbVie, UCB, GKC, Bial, Cynapsus, Novartis, Lobsor, Stada, Medtronic, Zambon, Profile, Sunovion, Roche, Therevance, Scion, Britannia; honoraria for lectures from AbbVie, Britannia, UCB, Mundipharma, Zambon, Novartis, Boeringer Ingelheim; Grants (Investigator Initiated) from Britannia Pharmaceuticals, AbbVie, UCB, GKC, Bial; Academic grants from EU, IMI EU, Horizon 2020, Parkinson's UK, NIHR, PDNMG, EU (Horizon 2020), Kirby Laing Foundation, NPF, MRC, Wellcome Trust, outside the submitted work. Publisher Copyright: {\textcopyright} 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2021",

month = aug,

day = "2",

doi = "10.1007/s00415-021-10730-3",

language = "English",

volume = "269",

journal = "Journal of Neurology",

issn = "0340-5354",

publisher = "Springer",

number = "3",

}

TY - JOUR

T1 - Disentangling the PIGD classification for the prediction of cognitive impairment in de novo Parkinson’s disease

AU - Urso, Daniele

AU - Leta, Valentina

AU - Batzu, Lucia

AU - Yousaf, Tayyabah

AU - Farrell, Chloe

AU - van Wamelen, Daniel J.

AU - Ray Chaudhuri, K.

N1 - Funding Information: Data used in the preparation of this article were obtained from the Parkinson’s Progression Markers Initiative (PPMI) database ( www.ppmi-info.org/data ). For up-to-date information on the study, visit www.ppmi-info.org . PPMI (a public–private partnership) is funded by the Michael J Fox Foundation for Parkinson’s Research and funding partners, including AbbVie, Avid, Biogen, Bristol-Myers Squibb, Covance, GE Healthcare, Genentech, GlaxoSmithKline, Lilly, Lundbeck, Merck, Meso Scale Discovery, Pfizer, Piramal, Roche, Servier, Teva, and UCB. The current data analysis was not supported by funding. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. The authors acknowledge the support of the NIHR London South Clinical Research Network and the NIHR Biomedical Research Centre. This article represents independent collaborative research part funded by the NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. The authors acknowledge the support of the NIHR London South Clinical Research Network and the NIHR Biomedical Research Centre. This article represents independent collaborative research part funded by the NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. Funding Information: DU, LB, TY, and CF have no disclosures. VL has received grants from BRC, Parkinson’s UK, a travel and congress grant from Bial UK Ltd, speaker-related activities fees from Britannia pharmaceuticals, and consultancy fees from Invisio Pharmaceuticals, outside the submitted work. DvW reports grants, speaker fees, and honoraria from Britannia Pharmaceuticals Ltd, speaker fees from Abbvie UK Ltd, and honoraria from Invisio Pharmaceuticals, outside of the submitted work. KRC has received honoraria for Advisory board from AbbVie, UCB, GKC, Bial, Cynapsus, Novartis, Lobsor, Stada, Medtronic, Zambon, Profile, Sunovion, Roche, Therevance, Scion, Britannia; honoraria for lectures from AbbVie, Britannia, UCB, Mundipharma, Zambon, Novartis, Boeringer Ingelheim; Grants (Investigator Initiated) from Britannia Pharmaceuticals, AbbVie, UCB, GKC, Bial; Academic grants from EU, IMI EU, Horizon 2020, Parkinson's UK, NIHR, PDNMG, EU (Horizon 2020), Kirby Laing Foundation, NPF, MRC, Wellcome Trust, outside the submitted work. Publisher Copyright: © 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/8/2

Y1 - 2021/8/2

N2 - Background: Postural Instability and Gait difficulties (PIGD) subtype has been associated with worse cognitive performance in Parkinson’s disease (PD). Objective: To investigate whether PIGD subtype classification or PIGD-related clinical features predict the development of cognitive decline in de novo PD patients. Methods: Data from 422 PD patients with de novo PD were obtained from the PPMI database. At follow-up (up to 6 years), patients were categorized as having cognitive impairment or not. Multivariate Cox survival analysis was carried out including motor subtype and individual MDS-UPDRS items defining PIGD phenotype as predictors. Previously validated clinical predictors of cognitive impairment were included in the model as covariates. Occurrence of cognitive impairment at follow-up was used as the time-to-event and Kaplan–Meier curve was generated. Results: At baseline, 76 patients were classified as PIGD, 299 tremor-dominant and 47 as indeterminate. Development of cognitive impairment was not associated with PIGD subtype (p = 0.252). When individual MDS-UPDRS items were interrogated in the model, postural instability proved to be an independent predictor of cognitive impairment (HR = 2.045; 95%CI: 1.068–3.918; p = 0.031), while gait difficulties were not associated with cognitive decline (p = 0.870). Conclusions: Our findings suggest that postural instability, as assessed by MDS-UPDRS III, may serve as a possible indicator of the risk of developing cognitive impairment in de novo PD patients rather than the PIGD phenotype.

AB - Background: Postural Instability and Gait difficulties (PIGD) subtype has been associated with worse cognitive performance in Parkinson’s disease (PD). Objective: To investigate whether PIGD subtype classification or PIGD-related clinical features predict the development of cognitive decline in de novo PD patients. Methods: Data from 422 PD patients with de novo PD were obtained from the PPMI database. At follow-up (up to 6 years), patients were categorized as having cognitive impairment or not. Multivariate Cox survival analysis was carried out including motor subtype and individual MDS-UPDRS items defining PIGD phenotype as predictors. Previously validated clinical predictors of cognitive impairment were included in the model as covariates. Occurrence of cognitive impairment at follow-up was used as the time-to-event and Kaplan–Meier curve was generated. Results: At baseline, 76 patients were classified as PIGD, 299 tremor-dominant and 47 as indeterminate. Development of cognitive impairment was not associated with PIGD subtype (p = 0.252). When individual MDS-UPDRS items were interrogated in the model, postural instability proved to be an independent predictor of cognitive impairment (HR = 2.045; 95%CI: 1.068–3.918; p = 0.031), while gait difficulties were not associated with cognitive decline (p = 0.870). Conclusions: Our findings suggest that postural instability, as assessed by MDS-UPDRS III, may serve as a possible indicator of the risk of developing cognitive impairment in de novo PD patients rather than the PIGD phenotype.

KW - Cognitive impairment

KW - Parkinson’s disease

KW - PIGD

KW - Postural instability

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U2 - 10.1007/s00415-021-10730-3

DO - 10.1007/s00415-021-10730-3

M3 - Article

AN - SCOPUS:85111845002

SN - 0340-5354

VL - 269

JO - Journal of Neurology

JF - Journal of Neurology

IS - 3

ER -

Disentangling the PIGD classification for the prediction of cognitive impairment in de novo Parkinson’s disease

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Keywords

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