Motor and non-motor symptoms and signs in parkinsonism: clinical, morphological and molecular-genetic correlates

Even with adherence to the strict clinical criteria, the false diagnosis of Parkinson disease (PD) is established in 8-24% patients, so that this project is partially focused at improvement of differential diagnostic options and better insight into genotype-phenotype heterogeneity of PD and other forms of parkinsonism. Pathology of PD affects other regions of the brain, as well, in addition to substantia nigra (SN) and damages other transmitter systems beyond dopamine, which is the basis of motor and nonmotor symptoms not responding to conventional treatment (non-dopaminergic symptoms). Another goal of the project is to define the clinical, imaging and molecular-genetic correlates of these symptoms (e.g. identification of specific biomarkers of various entities of dementia associated with parkinsonism). Non-motor symptoms may precede the motor symptoms of PD in concert with the hypothesis presented by Braak et al. (2000) that the initial occurrence of Lewy bodies takes place in the lower parts of the brainstem, associated with symptoms such as olfactory changes, constipation, depression and REM sleep behavior disorders (pre-motor symptoms of PD), while SN is affected in only third out of 6 pathological stages of PD. This project aims at assessment of the predictive values of the described early symptoms and test results for the development of PD and recognition of its pre-motor stage.