Mental dysfunction in Parkinson's disease

The pathological hallmark of Parkinson's disease (PD) is a degeneration of the dopamine (DA) producing cells in the substantia nigra and the ventral tegmentum, resulting in a dopamine deficiency in the dopaminergic projection areas with defective functioning of specific cortico-subcortical extrapyramidal circuits. Depending on which circuits (;motor', ;association' or ;limbic') are involved, and on the extent of the accompanying noradrenergic, serotonergic and cholinergic detrition in PD, dysfunction may result in motor deficits, mood disturbances or cognitive deficits, sometimes proceeding to dementia. Drug-induced psychosis occurs in approximately 15-20% of patients treated with dopaminergic agents. In PD, mainly nigrostriatal dopamine (A9) is depleted, leading to progressive motor dysfunction with subtle cognitive disturbances. As a rule, the neuropsychological deficit in PD might be described as the inability to switch cortical behavioral programmes in situations requiring the internal regulation of behavior. In daily life, in most patients these deficits do not become manifest, due to the abundance of external information to guide behavior. When the ability to use environmental information or external cues is lost as well, significant cell loss in the ventral tegmental area, with reduced DA-innervation of the mesocorticolimbic regions and the nucleus accumbens, must be suspected. This leads to clinically overt defects not only in the ;motor' but also in the ;limbic' and ;association' circuits. In addition to more severe cognitive disturbances or even dementia, this may also lead to mood disorders and drug-induced psychosis. Depression then occurs as the cortical modulation of limbic activity has become deficient, leading to emotional reactions disproportionate to the thoughts that evoke them. The proposed mechanism of psychosis in PD is that cortical sensory input is misinterpreted, leading to misperceptions (hallucinations) or false beliefs about reality due to a reduced ;signal-to-noise' ratio by insufficient processing of relevant information.