Diagnostic aspects of early Parkinson's disease

Insidious onset of mild, unspecific, sensitive, vegetative, psychopathological, cognitive and perceptive disturbances, i.e., visual and olfactory dysfunction, with a resulting change of personal behavior, i.e., reduced stress tolerance, precede the initially intermittently occurring motor symptoms in patients with Parkinson's disease (PD). Novel neuropathological findings suggest an expansion pattern of the neuro-degenerative process beyond the nigral dopaminergic neurons with the initial event located outside the brain. This underlines the clinical concept of an initial premotor phase, which starts in non-dopaminergic areas in PD. Moreover a more global general understanding of chronic neuro-degeneration enables the performance of clinical trials on neuro-protection, since there is increasing evidence that diagnosis of PD at the threshold of onset of motor symptoms or cognitive symptoms in Alzheimer's disease is too late. Such an earlier diagnosis of chronic neuro degeneration will allow a more convincing demonstration of the efficacy of a neuroprotective or disease modifying compound. It will also support the concept of a clinically effective pharmacological intervention on a disease process, which is also more and more demanded by the health authorities for drug approval.