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January 21, 2014; 82 (3) Article

Predicting dementia in Parkinson disease by combining neurophysiologic and cognitive markers

Kim T.E. Olde Dubbelink, Arjan Hillebrand, Jos W.R. Twisk, Jan Berend Deijen, Diederick Stoffers, Ben A. Schmand, Cornelis J. Stam, Henk W. Berendse
First published December 18, 2013, DOI: https://doi.org/10.1212/WNL.0000000000000034
Kim T.E. Olde Dubbelink
From the Department of Neurology, Neuroscience Campus Amsterdam (K.T.E.O.D., D.S., H.W.B.), Department of Clinical Neurophysiology and Magnetoencephalography Center (A.H., C.J.S.), and Department of Clinical Epidemiology and Biostatistics (J.W.R.T.). VU University Medical Center, Amsterdam; Department of Clinical Neuropsychology (J.B.D.), VU University, Amsterdam; and Department of Psychology (B.A.S.), University of Amsterdam, the Netherlands.
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Arjan Hillebrand
From the Department of Neurology, Neuroscience Campus Amsterdam (K.T.E.O.D., D.S., H.W.B.), Department of Clinical Neurophysiology and Magnetoencephalography Center (A.H., C.J.S.), and Department of Clinical Epidemiology and Biostatistics (J.W.R.T.). VU University Medical Center, Amsterdam; Department of Clinical Neuropsychology (J.B.D.), VU University, Amsterdam; and Department of Psychology (B.A.S.), University of Amsterdam, the Netherlands.
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Jos W.R. Twisk
From the Department of Neurology, Neuroscience Campus Amsterdam (K.T.E.O.D., D.S., H.W.B.), Department of Clinical Neurophysiology and Magnetoencephalography Center (A.H., C.J.S.), and Department of Clinical Epidemiology and Biostatistics (J.W.R.T.). VU University Medical Center, Amsterdam; Department of Clinical Neuropsychology (J.B.D.), VU University, Amsterdam; and Department of Psychology (B.A.S.), University of Amsterdam, the Netherlands.
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Jan Berend Deijen
From the Department of Neurology, Neuroscience Campus Amsterdam (K.T.E.O.D., D.S., H.W.B.), Department of Clinical Neurophysiology and Magnetoencephalography Center (A.H., C.J.S.), and Department of Clinical Epidemiology and Biostatistics (J.W.R.T.). VU University Medical Center, Amsterdam; Department of Clinical Neuropsychology (J.B.D.), VU University, Amsterdam; and Department of Psychology (B.A.S.), University of Amsterdam, the Netherlands.
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Diederick Stoffers
From the Department of Neurology, Neuroscience Campus Amsterdam (K.T.E.O.D., D.S., H.W.B.), Department of Clinical Neurophysiology and Magnetoencephalography Center (A.H., C.J.S.), and Department of Clinical Epidemiology and Biostatistics (J.W.R.T.). VU University Medical Center, Amsterdam; Department of Clinical Neuropsychology (J.B.D.), VU University, Amsterdam; and Department of Psychology (B.A.S.), University of Amsterdam, the Netherlands.
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Ben A. Schmand
From the Department of Neurology, Neuroscience Campus Amsterdam (K.T.E.O.D., D.S., H.W.B.), Department of Clinical Neurophysiology and Magnetoencephalography Center (A.H., C.J.S.), and Department of Clinical Epidemiology and Biostatistics (J.W.R.T.). VU University Medical Center, Amsterdam; Department of Clinical Neuropsychology (J.B.D.), VU University, Amsterdam; and Department of Psychology (B.A.S.), University of Amsterdam, the Netherlands.
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Cornelis J. Stam
From the Department of Neurology, Neuroscience Campus Amsterdam (K.T.E.O.D., D.S., H.W.B.), Department of Clinical Neurophysiology and Magnetoencephalography Center (A.H., C.J.S.), and Department of Clinical Epidemiology and Biostatistics (J.W.R.T.). VU University Medical Center, Amsterdam; Department of Clinical Neuropsychology (J.B.D.), VU University, Amsterdam; and Department of Psychology (B.A.S.), University of Amsterdam, the Netherlands.
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Henk W. Berendse
From the Department of Neurology, Neuroscience Campus Amsterdam (K.T.E.O.D., D.S., H.W.B.), Department of Clinical Neurophysiology and Magnetoencephalography Center (A.H., C.J.S.), and Department of Clinical Epidemiology and Biostatistics (J.W.R.T.). VU University Medical Center, Amsterdam; Department of Clinical Neuropsychology (J.B.D.), VU University, Amsterdam; and Department of Psychology (B.A.S.), University of Amsterdam, the Netherlands.
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Citation
Predicting dementia in Parkinson disease by combining neurophysiologic and cognitive markers
Kim T.E. Olde Dubbelink, Arjan Hillebrand, Jos W.R. Twisk, Jan Berend Deijen, Diederick Stoffers, Ben A. Schmand, Cornelis J. Stam, Henk W. Berendse
Neurology Jan 2014, 82 (3) 263-270; DOI: 10.1212/WNL.0000000000000034

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Abstract

Objective: To assess the ability of neurophysiologic markers in conjunction with cognitive assessment to improve prediction of progression to dementia in Parkinson disease (PD).

Methods: Baseline cognitive assessments and magnetoencephalographic recordings from 63 prospectively included PD patients without dementia were analyzed in relation to PD-related dementia (PDD) conversion over a 7-year period. We computed Cox proportional hazard models to assess the risk of converting to dementia conveyed by cognitive and neurophysiologic markers in individual as well as combined risk factor analyses.

Results: Nineteen patients (30.2%) developed dementia. Baseline cognitive performance and neurophysiologic markers each individually predicted conversion to PDD. Of the cognitive test battery, performance on a posterior (pattern recognition memory score < median; hazard ratio (HR) 6.80; p = 0.001) and a fronto-executive (spatial span score < median; HR 4.41; p = 0.006) task most strongly predicted dementia conversion. Of the neurophysiologic markers, beta power < median was the strongest PDD predictor (HR 5.21; p = 0.004), followed by peak frequency < median (HR 3.97; p = 0.016) and theta power > median (HR 2.82; p = 0.037). In combination, baseline cognitive performance and neurophysiologic measures had even stronger predictive value, with the combination of impaired fronto-executive task performance and low beta power being associated with the highest dementia risk (both risk factors vs none: HR 27.3; p < 0.001).

Conclusions: Combining neurophysiologic markers with cognitive assessment can substantially improve dementia risk profiling in PD, providing potential benefits for clinical care as well as for the future development of therapeutic strategies.

GLOSSARY

AAL=
automated anatomical labeling;
AD=
Alzheimer disease;
CAMCOG=
Cambridge cognitive examination;
HR=
hazard ratio;
IED=
intra-extra dimensional set shifting;
MCI=
mild cognitive impairment;
MEG=
magnetoencephalography;
PD=
Parkinson disease;
PDD=
Parkinson disease–related dementia;
PRM=
pattern recognition memory;
RCI=
reliable change index;
SOC=
stockings of Cambridge;
SSP=
spatial span;
SWM=
spatial working memory

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 www.neurology.org

  • Received May 14, 2013.
  • Accepted in final form September 24, 2013.
  • © 2014 American Academy of Neurology
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