Urate and Homocysteine: Predicting Motor and Cognitive Changes in Newly Diagnosed Parkinson's Disease

Isobel Sleeman, Rachael A Lawson* (Corresponding Author), Alison J. Yarnall, Gordon W. Duncan, Fionnuala Johnston, Tien K. Khoo, David J. Burn

*Corresponding author for this work

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

BACKGROUND: Urate and homocysteine are potential biomarkers for disease progression in Parkinson's disease (PD). Baseline serum urate concentration has been shown to predict motor but not cognitive decline. The relationship between serum homocysteine concentration and cognitive and motor impairment is unknown.

OBJECTIVES: The aim of this study was to examine the association between baseline serum urate and homocysteine, and prospective measures of disease progression and cognition over 54 months in early PD.

METHODS: 154 newly diagnosed PD participants and 99 age-matched controls completed a schedule of assessments at baseline, 18, 36 and 54 months. The Movement Disorders Society Unified Parkinson's Disease Scale Part III (MDS-UPDRS III) was used to assess motor severity. The Montreal Cognitive Assessment (MoCA) was used to assess global cognition. Serum samples drawn at baseline were analysed for urate, homocysteine, red cell folate and vitamin B12 concentrations.

RESULTS: Baseline urate was 331.4±83.8 and 302.7±78.0μmol/L for control and PD participants, respectively (p = 0.015). Baseline homocysteine was 9.6±3.3 and 11.1±3.8μmol/L for controls and PD participants, respectively (p < 0.01). Linear mixed effects modelling showed that lower baseline urate (β= 0.02, p < 0.001) and higher homocysteine (β= 0.29, p < 0.05) predicted decline in motor function. Only higher homocysteine concentrations at baseline, however, predicted declining MoCA scores over 54 months (β= 0.11, p < 0.01).

CONCLUSIONS: Lower serum urate concentration is associated with worsening motor function; while higher homocysteine concentration is associated with change in motor function and cognitive decline. Therefore, urate and homocysteine may be suitable biomarkers for predicting motor and cognitive decline in early PD.

Original languageEnglish
Pages (from-to)351-359
Number of pages9
Journal Journal of Parkinson's Disease
Volume9
Issue number2
DOIs
Publication statusPublished - 23 May 2019

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Homocysteine
Uric Acid
Parkinson Disease
Serum
Cognition
Disease Progression
Biomarkers
Movement Disorders
Vitamin B 12
Folic Acid
Appointments and Schedules
Cognitive Dysfunction

Keywords

  • Parkinson's disease
  • disease progression
  • homocysteine
  • prospective study
  • urate
  • DEMENTIA
  • CARDIOVASCULAR-DISEASE
  • RISK FACTOR
  • PLASMA HOMOCYSTEINE
  • PROGRESSION
  • ACCURACY
  • IMPAIRMENT

ASJC Scopus subject areas

  • Clinical Neurology
  • Cellular and Molecular Neuroscience

Cite this

Urate and Homocysteine : Predicting Motor and Cognitive Changes in Newly Diagnosed Parkinson's Disease. / Sleeman, Isobel; Lawson, Rachael A (Corresponding Author); Yarnall, Alison J.; Duncan, Gordon W.; Johnston, Fionnuala; Khoo, Tien K.; Burn, David J.

In: Journal of Parkinson's Disease, Vol. 9, No. 2, 23.05.2019, p. 351-359.

Research output: Contribution to journalArticle

Sleeman, Isobel ; Lawson, Rachael A ; Yarnall, Alison J. ; Duncan, Gordon W. ; Johnston, Fionnuala ; Khoo, Tien K. ; Burn, David J. / Urate and Homocysteine : Predicting Motor and Cognitive Changes in Newly Diagnosed Parkinson's Disease. In: Journal of Parkinson's Disease. 2019 ; Vol. 9, No. 2. pp. 351-359.
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abstract = "BACKGROUND: Urate and homocysteine are potential biomarkers for disease progression in Parkinson's disease (PD). Baseline serum urate concentration has been shown to predict motor but not cognitive decline. The relationship between serum homocysteine concentration and cognitive and motor impairment is unknown.OBJECTIVES: The aim of this study was to examine the association between baseline serum urate and homocysteine, and prospective measures of disease progression and cognition over 54 months in early PD.METHODS: 154 newly diagnosed PD participants and 99 age-matched controls completed a schedule of assessments at baseline, 18, 36 and 54 months. The Movement Disorders Society Unified Parkinson's Disease Scale Part III (MDS-UPDRS III) was used to assess motor severity. The Montreal Cognitive Assessment (MoCA) was used to assess global cognition. Serum samples drawn at baseline were analysed for urate, homocysteine, red cell folate and vitamin B12 concentrations.RESULTS: Baseline urate was 331.4±83.8 and 302.7±78.0μmol/L for control and PD participants, respectively (p = 0.015). Baseline homocysteine was 9.6±3.3 and 11.1±3.8μmol/L for controls and PD participants, respectively (p < 0.01). Linear mixed effects modelling showed that lower baseline urate (β= 0.02, p < 0.001) and higher homocysteine (β= 0.29, p < 0.05) predicted decline in motor function. Only higher homocysteine concentrations at baseline, however, predicted declining MoCA scores over 54 months (β= 0.11, p < 0.01).CONCLUSIONS: Lower serum urate concentration is associated with worsening motor function; while higher homocysteine concentration is associated with change in motor function and cognitive decline. Therefore, urate and homocysteine may be suitable biomarkers for predicting motor and cognitive decline in early PD.",
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author = "Isobel Sleeman and Lawson, {Rachael A} and Yarnall, {Alison J.} and Duncan, {Gordon W.} and Fionnuala Johnston and Khoo, {Tien K.} and Burn, {David J.}",
note = "ACKNOWLEDGMENTS The ICICLE-PD study group would like to thank all participants for their contribution towards the study. The research was funded by Parkinson’s UK (J-0802, G-1507) and supported by the Lockhart Parkinson’s Disease Research Fund, the National Institute for Health Research (NIHR) Newcastle Biomedical Research Centre in Ageing and Chronic Disease and Biomedical Research Unit in Lewy Body Dementia based at Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University and the NIHR Biomedical Research Centre award to the University of Cambridge/Addenbrooke's Hospital. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.",
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T2 - Predicting Motor and Cognitive Changes in Newly Diagnosed Parkinson's Disease

AU - Sleeman, Isobel

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AU - Yarnall, Alison J.

AU - Duncan, Gordon W.

AU - Johnston, Fionnuala

AU - Khoo, Tien K.

AU - Burn, David J.

N1 - ACKNOWLEDGMENTS The ICICLE-PD study group would like to thank all participants for their contribution towards the study. The research was funded by Parkinson’s UK (J-0802, G-1507) and supported by the Lockhart Parkinson’s Disease Research Fund, the National Institute for Health Research (NIHR) Newcastle Biomedical Research Centre in Ageing and Chronic Disease and Biomedical Research Unit in Lewy Body Dementia based at Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University and the NIHR Biomedical Research Centre award to the University of Cambridge/Addenbrooke's Hospital. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.

PY - 2019/5/23

Y1 - 2019/5/23

N2 - BACKGROUND: Urate and homocysteine are potential biomarkers for disease progression in Parkinson's disease (PD). Baseline serum urate concentration has been shown to predict motor but not cognitive decline. The relationship between serum homocysteine concentration and cognitive and motor impairment is unknown.OBJECTIVES: The aim of this study was to examine the association between baseline serum urate and homocysteine, and prospective measures of disease progression and cognition over 54 months in early PD.METHODS: 154 newly diagnosed PD participants and 99 age-matched controls completed a schedule of assessments at baseline, 18, 36 and 54 months. The Movement Disorders Society Unified Parkinson's Disease Scale Part III (MDS-UPDRS III) was used to assess motor severity. The Montreal Cognitive Assessment (MoCA) was used to assess global cognition. Serum samples drawn at baseline were analysed for urate, homocysteine, red cell folate and vitamin B12 concentrations.RESULTS: Baseline urate was 331.4±83.8 and 302.7±78.0μmol/L for control and PD participants, respectively (p = 0.015). Baseline homocysteine was 9.6±3.3 and 11.1±3.8μmol/L for controls and PD participants, respectively (p < 0.01). Linear mixed effects modelling showed that lower baseline urate (β= 0.02, p < 0.001) and higher homocysteine (β= 0.29, p < 0.05) predicted decline in motor function. Only higher homocysteine concentrations at baseline, however, predicted declining MoCA scores over 54 months (β= 0.11, p < 0.01).CONCLUSIONS: Lower serum urate concentration is associated with worsening motor function; while higher homocysteine concentration is associated with change in motor function and cognitive decline. Therefore, urate and homocysteine may be suitable biomarkers for predicting motor and cognitive decline in early PD.

AB - BACKGROUND: Urate and homocysteine are potential biomarkers for disease progression in Parkinson's disease (PD). Baseline serum urate concentration has been shown to predict motor but not cognitive decline. The relationship between serum homocysteine concentration and cognitive and motor impairment is unknown.OBJECTIVES: The aim of this study was to examine the association between baseline serum urate and homocysteine, and prospective measures of disease progression and cognition over 54 months in early PD.METHODS: 154 newly diagnosed PD participants and 99 age-matched controls completed a schedule of assessments at baseline, 18, 36 and 54 months. The Movement Disorders Society Unified Parkinson's Disease Scale Part III (MDS-UPDRS III) was used to assess motor severity. The Montreal Cognitive Assessment (MoCA) was used to assess global cognition. Serum samples drawn at baseline were analysed for urate, homocysteine, red cell folate and vitamin B12 concentrations.RESULTS: Baseline urate was 331.4±83.8 and 302.7±78.0μmol/L for control and PD participants, respectively (p = 0.015). Baseline homocysteine was 9.6±3.3 and 11.1±3.8μmol/L for controls and PD participants, respectively (p < 0.01). Linear mixed effects modelling showed that lower baseline urate (β= 0.02, p < 0.001) and higher homocysteine (β= 0.29, p < 0.05) predicted decline in motor function. Only higher homocysteine concentrations at baseline, however, predicted declining MoCA scores over 54 months (β= 0.11, p < 0.01).CONCLUSIONS: Lower serum urate concentration is associated with worsening motor function; while higher homocysteine concentration is associated with change in motor function and cognitive decline. Therefore, urate and homocysteine may be suitable biomarkers for predicting motor and cognitive decline in early PD.

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KW - disease progression

KW - homocysteine

KW - prospective study

KW - urate

KW - DEMENTIA

KW - CARDIOVASCULAR-DISEASE

KW - RISK FACTOR

KW - PLASMA HOMOCYSTEINE

KW - PROGRESSION

KW - ACCURACY

KW - IMPAIRMENT

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