期刊
ANNALS OF NEUROLOGY
卷 69, 期 4, 页码 655-663出版社
WILEY-BLACKWELL
DOI: 10.1002/ana.22271
关键词
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资金
- Penn-Pfizer Alliance
- National Institutes of Health [AG033101, AG10124, AG17586, AG024904, NS-053488]
- Marian S. Ware Alzheimer Program
- Burroughs Wellcome Fund Career Award for Medical Scientists
- Benaroya Fund
- American Academy of Neurology
- Avid Radiopharmaceuticals
- Teva
- Novartis
- Merck Serono
- National Institute of Mental Health Geriatrics Branch
- Allon Therapeutics
- Forest Labs
- Pfizer
- Bristol-Myers Squibb
- Elan Pharmaceuticals
- Myriad Pharmaceutical
- Ono Pharmaceuticals
- National Institutes of Health, National Institute on Aging
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 2011; 69: 655-663
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