Plasma epidermal growth factor levels predict cognitive decline in Parkinson disease

Alice S. Chen-Plotkin, William T. Hu, Andrew Siderowf, Daniel Weintraub, Rachel Goldmann Gross, Howard I. Hurtig, Sharon X. Xie, Steven E. Arnold, Murray Grossman, Christopher M. Clark, Leslie M. Shaw, Leo McCluskey, Lauren Elman, Vivianna M. Van Deerlin, Virginia M.Y. Lee, Holly Soares, John Q. Trojanowski

Research output: Contribution to journalArticlepeer-review

99 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)655-663
Number of pages9
JournalAnnals of Neurology
Volume69
Issue number4
DOIs
StatePublished - Mar 2011
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology

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