Serum Epidermal Growth Factor Predicts Cognitive Functions In Early, Drug-Naive Parkinson’s Disease Patients

Dr. Maria Teresa Pellecchia

Center for Neurodegenerative Diseases, Department of Medicine, University of Salerno, Salerno, Italy.

Victoria Murphy:

My guest today is Dr. Maria Teresa Pellecchia from the department of medicine, university of selerno, centre for neurodegenerative diseases. Dr. Pellecchia, a very warm welcome to you, thank you for joining us

Dr. Pellecchia:

Thank you and good morning to everyone

Victoria Murphy:

Today we are here to discuss an article you authored in the Journal of Neurology in August 2012. The title of your article was ‘Serum epidermal growth factor predicts cognitive functions in early, drug-naive Parkinson’s Disease patients.

Dr. Pellecchia,

What were the objectives of your study?

Dr. Pellecchia:

We know that twenty-five percent of patients who have been newly diagnosed with PD may present some cognitive dysfunction. Cognitive function may decline over time, with many patients eventually developing dementia.We also know that epidermal growth factor (EGF) acts as a neurotrophic factor on dopaminergic nigrostriatal neurons. Expression of EGF is widespread in the neocortex and limbic cortex, cerebellum, hippocampus and the midbrain, and one of the best known role of EGFR in the brain is the maintenance of memory pattern formation in the hippocampus. In the present study, we aimed to assess the relationships between serum EGF levels and cognitive functions in a cohort of drug-naïve PD patients and to evaluate the predictive value of EGF levels on neuropsychological functions after a 2-year follow-up.

Victoria Murphy:

How was it designed?

Dr. Pellecchia:

The study was designed as a prospective one evaluating patients at baseline and after two years of follow-up by means of clinical and neuropsychological evaluations.

Victoria Murphy:

What types of patients were included?

Dr. Pellecchia:

We enrolled de-novo, drug-naïve patients with parkinsonism. Inclusion criteria were the presence of parkinsonian syndrome defined as the presence of bradykinesia associated to tremor or rigidity or postural instability, disease duration less than two years. Exclusion criteria were the presence of clinical signs satisfying the criteria of possible atypical parkinsonisms, secondary or iatrogenic parkinsonisms, familial parkinsonism and dementia.

Victoria Murphy:

What were the study endpoints?

Dr. Pellecchia:

We measured EGF levels in serum samples at baseline. Motor symptoms were assessed by means of the UPDRS part III. A complete neuropsychological battery including executive function, memory and visuospatial tasks, was performed at baseline and follow-up to evaluate cognitive functions and their relationships with EGF levels.

Victoria Murphy:

What were the results?

Dr. Pellecchia:

At baseline, we found an association between EGF levels and cognitive tasks evaluating verbal memory, visuospatial abilities, and attention/executive functions, indicating that higher EGF levelsmay predict a better performance on these tasks. Moreover, low EGF levels were found associatedwith poor performance on semantic fluency task by means of linear regression analysis.At 2-year follow up, we found that EGF levels were positively related to different cognitive tasks evaluating both attention/executive functions and colour naming. After regression analysis, we found that EGF levels predict performance on semantic fluency task and colour naming of Stroop test independently from other variables potentially affecting cognitive functions. Repeated-measures ANOVA showed that performance on both semantic fluency and colour naming of Stroop test were found to be significantly worse in patients with lower EGF values than in patients with higher EGF values at baseline and this significant difference persisted at 2-year follow-up.

Victoria Murphy:

Are there any limitations to the study?

Dr. Pellecchia:

Unfortunately, 25 patients didn’t undergo neuropsychological follow-up after 2 years due to refusing to repeat the test. However, their clinical features were not different from those of the patients completing follow-up, so we think that our results can de considered valid for the entire cohort.

Victoria Murphy:

What conclusions can be drawn from these results?

Dr. Pellecchia:

Our results suggest that low EGF levels are associated with altered cognitive functions mediated by frontal and posterior cerebral areas. We think that EGF is a potential serum biomarker for early cognitive impairment in Parkinson’s disease. If our results will be confirmed by other studies, the measurement of EGF might be useful both as a clinical diagnostic tool and in the design of trials aimed at preserving cognitive functions in Parkinson’s disease.

Victoria Murphy:

Can these results be considered conclusive?

Dr. Pellecchia:

Our study was designed to explore relationship between EGF and cognition in the early disease stage, however further follow-up of our cohort of de novo patients is ongoing to assess the predictive value of EGF levels on the development of dementia.

Victoria Murphy:

Thank you so much for joining us today, it has been a pleasure.

Dr. Pellecchia:

Thank you, it was a pleasure for me.

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