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Abstract

Objective

Most people with Parkinson disease (PD) eventually develop cognitive impairment (CI). However, neither the timing of onset nor the severity of cognitive symptoms can be accurately predicted. We sought plasma-based biomarkers for CI in PD.

Methods

A discovery cohort of 70 PD patients was recruited. Cognitive status was evaluated with the Mattis Dementia Rating Scale-2 (DRS) at baseline and on annual follow-up visits, and baseline plasma levels of 102 proteins were determined with a bead-based immunoassay. Using linear regression, we identified biomarkers of CI in PD, that is, proteins whose levels correlated with cognitive performance at baseline and/or cognitive decline at follow-up. We then replicated the association between cognitive performance and levels of the top biomarker, using a different technical platform, with a separate cohort of 113 PD patients.

Results

Eleven proteins exhibited plasma levels correlating with baseline cognitive performance in the discovery cohort. The best candidate was epidermal growth factor (EGF, p < 0.001); many of the other 10 analytes covaried with EGF across samples. Low levels of EGF not only correlated with poor cognitive test scores at baseline, but also predicted an 8-fold greater risk of cognitive decline to dementia-range DRS scores at follow-up for those with intact baseline cognition. A weaker, but still significant, relationship between plasma EGF levels and cognitive performance was found in an independent replication cohort of 113 PD patients.

Interpretation

Our data suggest that plasma EGF may be a biomarker for progression to CI in PD. Ann Neurol 2010