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October 24, 2017; 89 (17) Article

Caffeine as symptomatic treatment for Parkinson disease (Café-PD)

A randomized trial

Ronald B. Postuma, Julius Anang, Amelie Pelletier, Lawrence Joseph, Mariana Moscovich, David Grimes, Sarah Furtado, Renato P. Munhoz, Silke Appel-Cresswell, Adriana Moro, Andrew Borys, Douglas Hobson, Anthony E. Lang
First published September 27, 2017, DOI: https://doi.org/10.1212/WNL.0000000000004568
Ronald B. Postuma
From the Department of Neurology, Montreal General Hospital (R.B.P., A.P.), and Department of Epidemiology and Biostatistics (L.J.), McGill University, Montreal; Department of Neurology (J.A., A.B., D.H.), University of Manitoba, Winnipeg, Canada; Pontifical Catholic University of Parana (M.M., A.M.), Curitiba, Brazil; Department of Neurology (D.G.), Ottawa Hospital, University of Ottawa Brain and Mind Research Institute; Department of Neurology (S.F.), University of Calgary; Division of Neurology (R.P.M., A.E.L.), Toronto Western Hospital; and Department of Medicine, Division of Neurology, Djavad Mowafaghian Centre for Brain Health, and Pacific Parkinson's Research Centre (S.A.-C.), University of British Columbia, Vancouver, Canada.
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Julius Anang
From the Department of Neurology, Montreal General Hospital (R.B.P., A.P.), and Department of Epidemiology and Biostatistics (L.J.), McGill University, Montreal; Department of Neurology (J.A., A.B., D.H.), University of Manitoba, Winnipeg, Canada; Pontifical Catholic University of Parana (M.M., A.M.), Curitiba, Brazil; Department of Neurology (D.G.), Ottawa Hospital, University of Ottawa Brain and Mind Research Institute; Department of Neurology (S.F.), University of Calgary; Division of Neurology (R.P.M., A.E.L.), Toronto Western Hospital; and Department of Medicine, Division of Neurology, Djavad Mowafaghian Centre for Brain Health, and Pacific Parkinson's Research Centre (S.A.-C.), University of British Columbia, Vancouver, Canada.
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Amelie Pelletier
From the Department of Neurology, Montreal General Hospital (R.B.P., A.P.), and Department of Epidemiology and Biostatistics (L.J.), McGill University, Montreal; Department of Neurology (J.A., A.B., D.H.), University of Manitoba, Winnipeg, Canada; Pontifical Catholic University of Parana (M.M., A.M.), Curitiba, Brazil; Department of Neurology (D.G.), Ottawa Hospital, University of Ottawa Brain and Mind Research Institute; Department of Neurology (S.F.), University of Calgary; Division of Neurology (R.P.M., A.E.L.), Toronto Western Hospital; and Department of Medicine, Division of Neurology, Djavad Mowafaghian Centre for Brain Health, and Pacific Parkinson's Research Centre (S.A.-C.), University of British Columbia, Vancouver, Canada.
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Lawrence Joseph
From the Department of Neurology, Montreal General Hospital (R.B.P., A.P.), and Department of Epidemiology and Biostatistics (L.J.), McGill University, Montreal; Department of Neurology (J.A., A.B., D.H.), University of Manitoba, Winnipeg, Canada; Pontifical Catholic University of Parana (M.M., A.M.), Curitiba, Brazil; Department of Neurology (D.G.), Ottawa Hospital, University of Ottawa Brain and Mind Research Institute; Department of Neurology (S.F.), University of Calgary; Division of Neurology (R.P.M., A.E.L.), Toronto Western Hospital; and Department of Medicine, Division of Neurology, Djavad Mowafaghian Centre for Brain Health, and Pacific Parkinson's Research Centre (S.A.-C.), University of British Columbia, Vancouver, Canada.
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Mariana Moscovich
From the Department of Neurology, Montreal General Hospital (R.B.P., A.P.), and Department of Epidemiology and Biostatistics (L.J.), McGill University, Montreal; Department of Neurology (J.A., A.B., D.H.), University of Manitoba, Winnipeg, Canada; Pontifical Catholic University of Parana (M.M., A.M.), Curitiba, Brazil; Department of Neurology (D.G.), Ottawa Hospital, University of Ottawa Brain and Mind Research Institute; Department of Neurology (S.F.), University of Calgary; Division of Neurology (R.P.M., A.E.L.), Toronto Western Hospital; and Department of Medicine, Division of Neurology, Djavad Mowafaghian Centre for Brain Health, and Pacific Parkinson's Research Centre (S.A.-C.), University of British Columbia, Vancouver, Canada.
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David Grimes
From the Department of Neurology, Montreal General Hospital (R.B.P., A.P.), and Department of Epidemiology and Biostatistics (L.J.), McGill University, Montreal; Department of Neurology (J.A., A.B., D.H.), University of Manitoba, Winnipeg, Canada; Pontifical Catholic University of Parana (M.M., A.M.), Curitiba, Brazil; Department of Neurology (D.G.), Ottawa Hospital, University of Ottawa Brain and Mind Research Institute; Department of Neurology (S.F.), University of Calgary; Division of Neurology (R.P.M., A.E.L.), Toronto Western Hospital; and Department of Medicine, Division of Neurology, Djavad Mowafaghian Centre for Brain Health, and Pacific Parkinson's Research Centre (S.A.-C.), University of British Columbia, Vancouver, Canada.
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Sarah Furtado
From the Department of Neurology, Montreal General Hospital (R.B.P., A.P.), and Department of Epidemiology and Biostatistics (L.J.), McGill University, Montreal; Department of Neurology (J.A., A.B., D.H.), University of Manitoba, Winnipeg, Canada; Pontifical Catholic University of Parana (M.M., A.M.), Curitiba, Brazil; Department of Neurology (D.G.), Ottawa Hospital, University of Ottawa Brain and Mind Research Institute; Department of Neurology (S.F.), University of Calgary; Division of Neurology (R.P.M., A.E.L.), Toronto Western Hospital; and Department of Medicine, Division of Neurology, Djavad Mowafaghian Centre for Brain Health, and Pacific Parkinson's Research Centre (S.A.-C.), University of British Columbia, Vancouver, Canada.
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Renato P. Munhoz
From the Department of Neurology, Montreal General Hospital (R.B.P., A.P.), and Department of Epidemiology and Biostatistics (L.J.), McGill University, Montreal; Department of Neurology (J.A., A.B., D.H.), University of Manitoba, Winnipeg, Canada; Pontifical Catholic University of Parana (M.M., A.M.), Curitiba, Brazil; Department of Neurology (D.G.), Ottawa Hospital, University of Ottawa Brain and Mind Research Institute; Department of Neurology (S.F.), University of Calgary; Division of Neurology (R.P.M., A.E.L.), Toronto Western Hospital; and Department of Medicine, Division of Neurology, Djavad Mowafaghian Centre for Brain Health, and Pacific Parkinson's Research Centre (S.A.-C.), University of British Columbia, Vancouver, Canada.
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Silke Appel-Cresswell
From the Department of Neurology, Montreal General Hospital (R.B.P., A.P.), and Department of Epidemiology and Biostatistics (L.J.), McGill University, Montreal; Department of Neurology (J.A., A.B., D.H.), University of Manitoba, Winnipeg, Canada; Pontifical Catholic University of Parana (M.M., A.M.), Curitiba, Brazil; Department of Neurology (D.G.), Ottawa Hospital, University of Ottawa Brain and Mind Research Institute; Department of Neurology (S.F.), University of Calgary; Division of Neurology (R.P.M., A.E.L.), Toronto Western Hospital; and Department of Medicine, Division of Neurology, Djavad Mowafaghian Centre for Brain Health, and Pacific Parkinson's Research Centre (S.A.-C.), University of British Columbia, Vancouver, Canada.
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Adriana Moro
From the Department of Neurology, Montreal General Hospital (R.B.P., A.P.), and Department of Epidemiology and Biostatistics (L.J.), McGill University, Montreal; Department of Neurology (J.A., A.B., D.H.), University of Manitoba, Winnipeg, Canada; Pontifical Catholic University of Parana (M.M., A.M.), Curitiba, Brazil; Department of Neurology (D.G.), Ottawa Hospital, University of Ottawa Brain and Mind Research Institute; Department of Neurology (S.F.), University of Calgary; Division of Neurology (R.P.M., A.E.L.), Toronto Western Hospital; and Department of Medicine, Division of Neurology, Djavad Mowafaghian Centre for Brain Health, and Pacific Parkinson's Research Centre (S.A.-C.), University of British Columbia, Vancouver, Canada.
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Andrew Borys
From the Department of Neurology, Montreal General Hospital (R.B.P., A.P.), and Department of Epidemiology and Biostatistics (L.J.), McGill University, Montreal; Department of Neurology (J.A., A.B., D.H.), University of Manitoba, Winnipeg, Canada; Pontifical Catholic University of Parana (M.M., A.M.), Curitiba, Brazil; Department of Neurology (D.G.), Ottawa Hospital, University of Ottawa Brain and Mind Research Institute; Department of Neurology (S.F.), University of Calgary; Division of Neurology (R.P.M., A.E.L.), Toronto Western Hospital; and Department of Medicine, Division of Neurology, Djavad Mowafaghian Centre for Brain Health, and Pacific Parkinson's Research Centre (S.A.-C.), University of British Columbia, Vancouver, Canada.
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Douglas Hobson
From the Department of Neurology, Montreal General Hospital (R.B.P., A.P.), and Department of Epidemiology and Biostatistics (L.J.), McGill University, Montreal; Department of Neurology (J.A., A.B., D.H.), University of Manitoba, Winnipeg, Canada; Pontifical Catholic University of Parana (M.M., A.M.), Curitiba, Brazil; Department of Neurology (D.G.), Ottawa Hospital, University of Ottawa Brain and Mind Research Institute; Department of Neurology (S.F.), University of Calgary; Division of Neurology (R.P.M., A.E.L.), Toronto Western Hospital; and Department of Medicine, Division of Neurology, Djavad Mowafaghian Centre for Brain Health, and Pacific Parkinson's Research Centre (S.A.-C.), University of British Columbia, Vancouver, Canada.
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Anthony E. Lang
From the Department of Neurology, Montreal General Hospital (R.B.P., A.P.), and Department of Epidemiology and Biostatistics (L.J.), McGill University, Montreal; Department of Neurology (J.A., A.B., D.H.), University of Manitoba, Winnipeg, Canada; Pontifical Catholic University of Parana (M.M., A.M.), Curitiba, Brazil; Department of Neurology (D.G.), Ottawa Hospital, University of Ottawa Brain and Mind Research Institute; Department of Neurology (S.F.), University of Calgary; Division of Neurology (R.P.M., A.E.L.), Toronto Western Hospital; and Department of Medicine, Division of Neurology, Djavad Mowafaghian Centre for Brain Health, and Pacific Parkinson's Research Centre (S.A.-C.), University of British Columbia, Vancouver, Canada.
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Full PDF
Citation
Caffeine as symptomatic treatment for Parkinson disease (Café-PD)
A randomized trial
Ronald B. Postuma, Julius Anang, Amelie Pelletier, Lawrence Joseph, Mariana Moscovich, David Grimes, Sarah Furtado, Renato P. Munhoz, Silke Appel-Cresswell, Adriana Moro, Andrew Borys, Douglas Hobson, Anthony E. Lang
Neurology Oct 2017, 89 (17) 1795-1803; DOI: 10.1212/WNL.0000000000004568

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Abstract

Objective: To assess effects of caffeine on Parkinson disease (PD).

Methods: In this multicenter parallel-group controlled trial, patients with PD with 1–8 years disease duration, Hoehn & Yahr stages I–III, on stable symptomatic therapy were randomized to caffeine 200 mg BID vs matching placebo capsules for 6–18 months. The primary research question was whether objective motor scores would differ at 6 months (Movement Disorder Society–sponsored Unified Parkinson's Disease Rating Scale [MDS-UPDRS]–III, Class I evidence). Secondary outcomes included safety and tolerability, motor symptoms (MDS-UPDRS-II), motor fluctuations, sleep, nonmotor symptoms (MDS-UPDRS-I), cognition (Montreal Cognitive Assessment), and quality of life.

Results: Sixty patients received caffeine and 61 placebo. Caffeine was well-tolerated with similar prevalence of side effects as placebo. There was no improvement in motor parkinsonism (the primary outcome) with caffeine treatment compared to placebo (difference between groups −0.48 [95% confidence interval −3.21 to 2.25] points on MDS-UPDRS-III). Similarly, on secondary outcomes, there was no change in motor signs or motor symptoms (MDS-UPDRS-II) at any time point, and no difference on quality of life. There was a slight improvement in somnolence over the first 6 months, which attenuated over time. There was a slight increase in dyskinesia with caffeine (MDS-UPDRS-4.1+4.2 = 0.25 points higher), and caffeine was associated with worse cognitive testing scores (average Montreal Cognitive Assessment = 0.66 [0.01, 1.32] worse than placebo).

Conclusion: Caffeine did not provide clinically important improvement of motor manifestations of PD (Class I evidence). Epidemiologic links between caffeine and lower PD risk do not appear to be explained by symptomatic effects.

Clinicaltrials.gov identifier: NCT01738178.

Classification of evidence: This study provides Class I evidence that for patients with PD, caffeine does not significantly improve motor manifestations.

GLOSSARY

BDI=
Beck Depression Inventory;
CI=
confidence interval;
EQ-5D=
EuroQoL 5-dimension;
KVIQ=
Kinesthetic and Visual Imagery Questionnaire;
MDS-UPDRS=
Movement Disorder Society–sponsored Unified Parkinson's Disease Rating Scale;
MoCA=
Montreal Cognitive Assessment;
PD=
Parkinson disease;
SCOPA=
Scales for Outcomes in PD

Footnotes

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Supplemental data at Neurology.org

  • Received January 27, 2017.
  • Accepted in final form August 2, 2017.
  • © 2017 American Academy of Neurology
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