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Abstract
Objective: This was a longitudinal single-center cohort study to comprehensively explore multimodal progression markers for Parkinson disease (PD) in patients with recently diagnosed PD (n = 123) and age-matched, neurologically healthy controls (HC; n = 106).
Methods: Thirty tests at baseline and after 24 months covered nonmotor symptoms (NMS), cognitive function, and REM sleep behavior disorder (RBD) by polysomnography (PSG), voxel-based morphometry (VBM) of the brain by MRI, and CSF markers. Linear mixed-effect models were used to estimate differences of rates of change and to provide standardized effect sizes (d) with 95% confidence intervals (CI).
Results: A composite panel of 10 informative markers was identified. Significant relative worsening (PD vs HC) was seen with the following markers: the Unified Parkinson's Disease Rating Scale I (d 0.39; CI 0.09–0.70), the Autonomic Scale for Outcomes in Parkinson's Disease (d 0.25; CI 0.06–0.46), the Epworth Sleepiness Scale (d 0.47; CI 0.24–0.71), the RBD Screening Questionnaire (d 0.44; CI 0.25–0.64), and RBD by PSG (d 0.37; CI 0.19–0.55) as well as VBM units of cortical gray matter (d −0.2; CI −0.3 to −0.09) and hippocampus (d −0.15; CI −0.27 to −0.03). Markers with a relative improvement included the Nonmotor Symptom (Severity) Scale (d −0.19; CI −0.36 to −0.02) and 2 depression scales (Beck Depression Inventory d −0.18; CI −0.36 to 0; Montgomery-Åsberg Depression Rating Scale d −0.26; CI −0.47 to −0.04). Unexpectedly, cognitive measures and select laboratory markers were not significantly changed in PD vs HC participants.
Conclusions: Current CSF biomarkers and cognitive scales do not represent useful progression markers. However, sleep and imaging measures, and to some extent NMS, assessed using adequate scales, may be more informative markers to quantify progression.
GLOSSARY
- 24FU=
- 24 months follow-up;
- α-syn=
- α-synuclein;
- AD=
- Alzheimer disease;
- BDI=
- Beck Depression Inventory;
- BL=
- baseline;
- DeNoPa=
- de novo Parkinson;
- ESS=
- Epworth Sleepiness Scale;
- HC=
- healthy control;
- LED=
- levodopa equivalent dosage;
- MADRS=
- Montgomery-Åsberg Depression Rating Scale;
- MDS=
- Movement Disorder Society;
- MMSE=
- Mini-Mental State Examination;
- MoCA=
- Montreal Cognitive Assessment Test;
- NMS=
- nonmotor signs;
- NMSS=
- Nonmotor Symptom Scale;
- p-tau=
- tau protein phosphorylated at threonine 181;
- PD=
- Parkinson disease;
- PSG=
- polysomnography;
- RBD=
- REM sleep behavior disorder;
- RBD-SQ=
- REM Sleep Behavior Disorder Screening Questionnaire;
- Scopa-AUT=
- Autonomic Scale for Outcomes in Parkinson's Disease;
- t-tau=
- total tau protein;
- UPDRS=
- Unified Parkinson's Disease Rating Scale;
- VBM=
- voxel-based morphometry
Footnotes
Coinvestigators are listed on the Neurology® Web site at Neurology.org.
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
Editorial, page 128
- Received July 8, 2015.
- Accepted in final form December 15, 2015.
- © 2016 American Academy of Neurology
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