Marker for a preclinical diagnosis of Parkinson's disease as a basis for neuroprotection.

Abstract

Neuroprotective therapy is a pivotal aim in the treatment of the relentlessly progressive disorder Parkinson's disease. However, more than 60% of the dopaminergic neurons of the substantia nigra have already degenerated, when the diagnosis may be established. At this "advanced stage" neuroprotective strategies will - if at all - only have limited effect. It is, therefore, essential to establish markers to identify subjects at risk before motor manifestation. A number of such "premotor" signs have been discovered and investigated lately. Such signs include a genetic vulnerability and hyperechogenicity of the substantia nigra as well as premotor symptoms like olfactory and autonomic dysfunction, depression, REM sleep behaviour disorder, visual and neuropsychological impairment. Moreover, first signs of affection of the substantia nigra like PET and SPECT abnormalities and slight motor signs can be included, as they may be detected before a definite diagnosis can be made. Although most of these signs and symptoms are unspecific if singularly evaluated a combination of these features may indeed be valuable to detect a subgroup of the population at risk for PD. However, future studies are necessary to establish the predictive value of these "markers" singularly and in combination.