Monitoring of 30 marker candidates in early Parkinson disease as progression markers.

Here we have important results from a longitudinal study aiming to define progression markers in early PD. The results are not surprising in many ways (at least to me). As expected there is progression in non-motor symptoms in the patients with early PD, but most of these (except for RBD) are not objectively measured. Previous studies have warned of the wide heterogeneity and variability of CSF markers, but I was surprised that there was no significant change on cognitive measures. As time passes I suspect detailed structural and functional MRI will give the best read outs of progression...

Neurology. 2016 May 6. pii: 10.1212/WNL.0000000000002651. [Epub ahead of print]

Mollenhauer B, Zimmermann J, Sixel-Döring F, Focke NK, Wicke T, Ebentheuer J, Schaumburg M, Lang E, Trautmann E, Zetterberg H, Taylor P, Friede T, Trenkwalder; DeNoPa Study Group.

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.

© 2016 American Academy of Neurology.