Comparison between four published definitions of hyposmia in Parkinson's disease

Sofia Kanavou; Vanessa Pitz; Michael A Lawton; Naveed Malek; Katherine A Grosset; Huw R Morris; Yoav Ben-Shlomo; Donald G Grosset

doi:10.1002/brb3.2258

Comparison between four published definitions of hyposmia in Parkinson's disease

Sofia Kanavou, Vanessa Pitz, Michael A Lawton, Naveed Malek, Katherine A Grosset, Huw R Morris, Yoav Ben-Shlomo, Donald G Grosset^*

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › peer-review

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Abstract

Objectives: Hyposmia is a common feature of Parkinson’s disease (PD), yet there is no standard method to define it. A comparison of 4 published methods was performed to explore and highlight differences. Materials & Methods: Olfactory testing was performed in 2,097 cases of early PD in 2 prospective studies. Olfaction was assessed using various cut-offs, usually corrected by age and/or gender. Control data were simulated based on the age and gender structure of the PD cases and published normal ranges. Association with age, gender and disease duration was explored by method and study cohort. Prevalence of hyposmia was compared with the age and gender-matched simulated controls. Between method agreement was measured using Cohen’s kappa and Gwet’s AC1. Results: Hyposmia was present in between 69.1% and 97.9% of cases in Tracking Parkinson’s cases, and between 62.2% and 90.8% of cases in the Parkinson’s Progression Marker Initiative, depending on the method. Between-method agreement varied (kappa 0.09-0.80, AC1 0.55-0.86). The absolute difference between PD cases and simulated controls was similar for men and women across methods. Age and male gender were positively associated with hyposmia (p<0.001, all methods). Odds of having hyposmia increased with advancing age (OR:1.06, 95% CI:1.03, 1.10, p<0.001). Longer disease duration had a negative impact on overall olfactory performance. Conclusions: Different definitions of hyposmia give different results using the same dataset. A standardised definition of hyposmia in PD is required, adjusting for age and gender, to account for the background decline in olfactory performance with ageing, especially in men.

Original language	English
Article number	e2258
Number of pages	9
Journal	Brain and Behavior
Volume	11
Issue number	8
Early online date	30 Jun 2021
DOIs	https://doi.org/10.1002/brb3.2258
Publication status	E-pub ahead of print - 30 Jun 2021

Bibliographical note

Funding Information:
PPMI – a public‐private partnership – is funded by the Michael J. Fox Foundation for Parkinson's Research and funding partners, including AbbVie, Allergan, AVid, Biogen, BioLegend, Bristol‐Myers Squibb, Celgene, Jenali, GE Healthcare, Genentech, GlaxoSmithKline, Lilly, Lundbeck, Merck, Meso Scale Discovery, Pfizer, Piramal, Prevail Therapeutics, Roche, Sanofi Genzyme, Servier, Takeda, Teva, UCB, Verily, Voyager Therapeutics.

Funding Information:
The research was funded by Parkinson's UK and supported by the National Institute for Health Research (NIHR) DeNDRoN network, the NIHR Newcastle Biomedical Research Unit based at Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University, and the NIHR funded Biomedical Research Centre in Cambridge. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. (Grant J‐1101)

Funding Information:
The research was funded by Parkinson's UK (Grant J-1101) and supported by the National Institute for Health Research (NIHR) DeNDRoN network, the NIHR Newcastle Biomedical Research Unit based at Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University, and the NIHR funded Biomedical Research Centre in Cambridge.?The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. Data used in the preparation of this article were also 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.

Funding Information:
HRM: Dr Morris is employed by UCL. In the last 24 months he reports paid consultancy from Biogen, UCB, Abbvie, Denali, Biohaven, Lundbeck; lecture fees/honoraria from Biogen, UCB, C4X Discovery, GE‐Healthcare, Wellcome Trust, Movement Disorders Society; Research Grants from Parkinson's UK, Cure Parkinson's Trust, PSP Association, CBD Solutions, Drake Foundation, Medical Research Council. Dr Morris is a co‐applicant on a patent application related to C9ORF72 ‐ Method for diagnosing a neurodegenerative disease (PCT/GB2012/052140).

Publisher Copyright:
© 2021 The Authors. Brain and Behavior published by Wiley Periodicals LLC

Keywords

hyposmia
Parkinson's disease
diagnosis
cut-off
olfactory impairment

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title = "Comparison between four published definitions of hyposmia in Parkinson's disease",

abstract = "Objectives: Hyposmia is a common feature of Parkinson{\textquoteright}s disease (PD), yet there is no standard method to define it. A comparison of 4 published methods was performed to explore and highlight differences. Materials & Methods: Olfactory testing was performed in 2,097 cases of early PD in 2 prospective studies. Olfaction was assessed using various cut-offs, usually corrected by age and/or gender. Control data were simulated based on the age and gender structure of the PD cases and published normal ranges. Association with age, gender and disease duration was explored by method and study cohort. Prevalence of hyposmia was compared with the age and gender-matched simulated controls. Between method agreement was measured using Cohen{\textquoteright}s kappa and Gwet{\textquoteright}s AC1. Results: Hyposmia was present in between 69.1% and 97.9% of cases in Tracking Parkinson{\textquoteright}s cases, and between 62.2% and 90.8% of cases in the Parkinson{\textquoteright}s Progression Marker Initiative, depending on the method. Between-method agreement varied (kappa 0.09-0.80, AC1 0.55-0.86). The absolute difference between PD cases and simulated controls was similar for men and women across methods. Age and male gender were positively associated with hyposmia (p<0.001, all methods). Odds of having hyposmia increased with advancing age (OR:1.06, 95% CI:1.03, 1.10, p<0.001). Longer disease duration had a negative impact on overall olfactory performance. Conclusions: Different definitions of hyposmia give different results using the same dataset. A standardised definition of hyposmia in PD is required, adjusting for age and gender, to account for the background decline in olfactory performance with ageing, especially in men.",

keywords = "hyposmia, Parkinson's disease, diagnosis, cut-off, olfactory impairment",

author = "Sofia Kanavou and Vanessa Pitz and Lawton, {Michael A} and Naveed Malek and Grosset, {Katherine A} and Morris, {Huw R} and Yoav Ben-Shlomo and Grosset, {Donald G}",

note = "Funding Information: PPMI – a public‐private partnership – is funded by the Michael J. Fox Foundation for Parkinson's Research and funding partners, including AbbVie, Allergan, AVid, Biogen, BioLegend, Bristol‐Myers Squibb, Celgene, Jenali, GE Healthcare, Genentech, GlaxoSmithKline, Lilly, Lundbeck, Merck, Meso Scale Discovery, Pfizer, Piramal, Prevail Therapeutics, Roche, Sanofi Genzyme, Servier, Takeda, Teva, UCB, Verily, Voyager Therapeutics. Funding Information: The research was funded by Parkinson's UK and supported by the National Institute for Health Research (NIHR) DeNDRoN network, the NIHR Newcastle Biomedical Research Unit based at Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University, and the NIHR funded Biomedical Research Centre in Cambridge. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. (Grant J‐1101) Funding Information: The research was funded by Parkinson's UK (Grant J-1101) and supported by the National Institute for Health Research (NIHR) DeNDRoN network, the NIHR Newcastle Biomedical Research Unit based at Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University, and the NIHR funded Biomedical Research Centre in Cambridge.?The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. Data used in the preparation of this article were also 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. Funding Information: HRM: Dr Morris is employed by UCL. In the last 24 months he reports paid consultancy from Biogen, UCB, Abbvie, Denali, Biohaven, Lundbeck; lecture fees/honoraria from Biogen, UCB, C4X Discovery, GE‐Healthcare, Wellcome Trust, Movement Disorders Society; Research Grants from Parkinson's UK, Cure Parkinson's Trust, PSP Association, CBD Solutions, Drake Foundation, Medical Research Council. Dr Morris is a co‐applicant on a patent application related to C9ORF72 ‐ Method for diagnosing a neurodegenerative disease (PCT/GB2012/052140). Publisher Copyright: {\textcopyright} 2021 The Authors. Brain and Behavior published by Wiley Periodicals LLC",

year = "2021",

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doi = "10.1002/brb3.2258",

language = "English",

volume = "11",

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TY - JOUR

T1 - Comparison between four published definitions of hyposmia in Parkinson's disease

AU - Kanavou, Sofia

AU - Pitz, Vanessa

AU - Lawton, Michael A

AU - Malek, Naveed

AU - Grosset, Katherine A

AU - Morris, Huw R

AU - Ben-Shlomo, Yoav

AU - Grosset, Donald G

N1 - Funding Information: PPMI – a public‐private partnership – is funded by the Michael J. Fox Foundation for Parkinson's Research and funding partners, including AbbVie, Allergan, AVid, Biogen, BioLegend, Bristol‐Myers Squibb, Celgene, Jenali, GE Healthcare, Genentech, GlaxoSmithKline, Lilly, Lundbeck, Merck, Meso Scale Discovery, Pfizer, Piramal, Prevail Therapeutics, Roche, Sanofi Genzyme, Servier, Takeda, Teva, UCB, Verily, Voyager Therapeutics. Funding Information: The research was funded by Parkinson's UK and supported by the National Institute for Health Research (NIHR) DeNDRoN network, the NIHR Newcastle Biomedical Research Unit based at Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University, and the NIHR funded Biomedical Research Centre in Cambridge. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. (Grant J‐1101) Funding Information: The research was funded by Parkinson's UK (Grant J-1101) and supported by the National Institute for Health Research (NIHR) DeNDRoN network, the NIHR Newcastle Biomedical Research Unit based at Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University, and the NIHR funded Biomedical Research Centre in Cambridge.?The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. Data used in the preparation of this article were also 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. Funding Information: HRM: Dr Morris is employed by UCL. In the last 24 months he reports paid consultancy from Biogen, UCB, Abbvie, Denali, Biohaven, Lundbeck; lecture fees/honoraria from Biogen, UCB, C4X Discovery, GE‐Healthcare, Wellcome Trust, Movement Disorders Society; Research Grants from Parkinson's UK, Cure Parkinson's Trust, PSP Association, CBD Solutions, Drake Foundation, Medical Research Council. Dr Morris is a co‐applicant on a patent application related to C9ORF72 ‐ Method for diagnosing a neurodegenerative disease (PCT/GB2012/052140). Publisher Copyright: © 2021 The Authors. Brain and Behavior published by Wiley Periodicals LLC

PY - 2021/6/30

Y1 - 2021/6/30

N2 - Objectives: Hyposmia is a common feature of Parkinson’s disease (PD), yet there is no standard method to define it. A comparison of 4 published methods was performed to explore and highlight differences. Materials & Methods: Olfactory testing was performed in 2,097 cases of early PD in 2 prospective studies. Olfaction was assessed using various cut-offs, usually corrected by age and/or gender. Control data were simulated based on the age and gender structure of the PD cases and published normal ranges. Association with age, gender and disease duration was explored by method and study cohort. Prevalence of hyposmia was compared with the age and gender-matched simulated controls. Between method agreement was measured using Cohen’s kappa and Gwet’s AC1. Results: Hyposmia was present in between 69.1% and 97.9% of cases in Tracking Parkinson’s cases, and between 62.2% and 90.8% of cases in the Parkinson’s Progression Marker Initiative, depending on the method. Between-method agreement varied (kappa 0.09-0.80, AC1 0.55-0.86). The absolute difference between PD cases and simulated controls was similar for men and women across methods. Age and male gender were positively associated with hyposmia (p<0.001, all methods). Odds of having hyposmia increased with advancing age (OR:1.06, 95% CI:1.03, 1.10, p<0.001). Longer disease duration had a negative impact on overall olfactory performance. Conclusions: Different definitions of hyposmia give different results using the same dataset. A standardised definition of hyposmia in PD is required, adjusting for age and gender, to account for the background decline in olfactory performance with ageing, especially in men.

AB - Objectives: Hyposmia is a common feature of Parkinson’s disease (PD), yet there is no standard method to define it. A comparison of 4 published methods was performed to explore and highlight differences. Materials & Methods: Olfactory testing was performed in 2,097 cases of early PD in 2 prospective studies. Olfaction was assessed using various cut-offs, usually corrected by age and/or gender. Control data were simulated based on the age and gender structure of the PD cases and published normal ranges. Association with age, gender and disease duration was explored by method and study cohort. Prevalence of hyposmia was compared with the age and gender-matched simulated controls. Between method agreement was measured using Cohen’s kappa and Gwet’s AC1. Results: Hyposmia was present in between 69.1% and 97.9% of cases in Tracking Parkinson’s cases, and between 62.2% and 90.8% of cases in the Parkinson’s Progression Marker Initiative, depending on the method. Between-method agreement varied (kappa 0.09-0.80, AC1 0.55-0.86). The absolute difference between PD cases and simulated controls was similar for men and women across methods. Age and male gender were positively associated with hyposmia (p<0.001, all methods). Odds of having hyposmia increased with advancing age (OR:1.06, 95% CI:1.03, 1.10, p<0.001). Longer disease duration had a negative impact on overall olfactory performance. Conclusions: Different definitions of hyposmia give different results using the same dataset. A standardised definition of hyposmia in PD is required, adjusting for age and gender, to account for the background decline in olfactory performance with ageing, especially in men.

KW - hyposmia

KW - Parkinson's disease

KW - diagnosis

KW - cut-off

KW - olfactory impairment

U2 - 10.1002/brb3.2258

DO - 10.1002/brb3.2258

M3 - Article (Academic Journal)

C2 - 34190430

VL - 11

JO - Brain and Behavior

JF - Brain and Behavior

SN - 2162-3279

IS - 8

M1 - e2258

ER -

Comparison between four published definitions of hyposmia in Parkinson's disease

Abstract

Bibliographical note

Keywords

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