K. R. Chaudhuri, L. Yates, and P. Martinez-martin, The non-motor symptom complex of Parkinson's disease: A comprehensive assessment is essential, Curr Neurol Neurosci, vol.5, pp.275-283, 2005.

J. W. Langston, The Parkinson's complex: Parkinsonism is just the tip of the iceberg, Ann Neurol, vol.59, pp.591-596, 2006.

S. Jain, Multi-organ autonomic dysfunction in Parkinson disease, Parkinsonism Relat Disord, vol.17, pp.77-83, 2011.

W. Dauer and S. Przedborski, Parkinson's disease: Mechanisms and models, Neuron, vol.39, pp.889-909, 2003.

W. Dauer and S. Przedborski, Parkinson's disease: mechanisms and models, Neuron, vol.39, pp.889-909, 2003.

S. Fahn, Parkinson disease, the effect of levodopa, and the ELLDOPA trial, Arch Neurol, vol.56, pp.529-564, 1999.

C. W. Olanow, K. Kieburtz, and A. H. Schapira, Why have we failed to achieve neuroprotection in Parkinson's disease?, Ann Neurol, vol.64, issue.2, pp.101-110, 2008.

A. E. Lang, E. Melamed, W. Poewe, and O. Rascol, Trial designs used to study neuroprotective therapy in Parkinson's disease, Mov Disord, vol.28, pp.86-95, 2013.

J. H. Ko, A. Feigin, P. J. Mattis, C. C. Tang, Y. Ma et al., Network modulation following sham surgery in Parkinson's disease, J Clin Invest, vol.124, pp.3656-66, 2014.

S. Fahn, D. Oakes, and I. Shoulson, Levodopa and the progression of Parkinson's disease, N Engl J Med, vol.351, pp.2498-2508, 2004.

C. W. Olanow, O. Rascol, and R. Hauser, A double-blind, delayed start trial of rasagiline in Parkinson's disease, N Engl J Med, vol.361, pp.1268-78, 2009.

P. Michael, W. J. Mcdermott, D. Hall, S. Oakes, and . Eberly, Design and analysis of two-period studies of potentially disease-modifying treatments, Control Clin Trials, vol.23, pp.635-649, 2002.

F. R. Biaggioni, J. Mathias, C. Low, P. , H. L. Kaufmann et al., Randomized Withdrawal Study of Patients With Symptomatic Neurogenic Orthostatic Hypotension Responsive to Droxidopa, on behalf of Droxidopa 302 Investigators, vol.65, pp.101-107, 2015.

. Tandon, J. Cucchiaro, D. Phillips, D. Hernandez, Y. Mao et al., A doubleblind, placebo-controlled, randomized withdrawal study of lurasidone for the maintenance of efficacy in patients with schizophrenia, J Psychopharmacol, vol.30, issue.1, pp.69-77, 2016.

R. L. Findling, K. Chang, A. Robb, V. J. Foster, J. Horrigan et al., Adjunctive Maintenance Lamotrigine for Pediatric Bipolar I Disorder: A Placebo-Controlled, Randomized Withdrawal Study, J Am Acad Child Adolesc Psychiatry, vol.54, pp.1020-1031, 2015.

. Parkinson-study-group, Effects of tocopherol and deprenyl on the progression of disability in early Parkinson's disease, The New England Journal of Medicine, vol.32, pp.176-183, 1993.

, Mixed lineage kinase inhibitor CEP-1347 fails to delay disability in early Parkinson disease, Parkinson Study Group PRECEPT Investigators, vol.69, pp.1480-1490, 2007.

C. D. Marsden, Parkinson's disease, Lancet, vol.335, pp.948-952, 1990.

G. W. Ross, H. Petrovitch, and R. D. Abbott, Parkinsonian signs and substantia nigra neuron density in decendents elders without PD, Ann Neurol, vol.56, pp.532-539, 2004.

O. , Disease-modification" trials in Parkinson disease: target populations, endpoints and study design, Neurology, 2009.

C. J. Van-der-schyf, Rational drug discovery design approaches for treating Parkinson's disease, Expert Opin. Drug Discov, vol.713, issue.741, 2015.