Müller et al 1993; Müller et al 2000, 2003b; van Vugt et al 2001; Ioffe 2004; Saft et al 2004). The impaired motor function found supports the concept of subclinical motor cortex disinhibition during chronic cholinergic neurodegeneration. This results in functional motor disturbances in AD and may be aggravated by the cholinergic dysfunction and the resulting frontal dysbalance of dopaminergic and cholinergic neurotransmission (Liepert et al 2001; Jefferson et al 2002; Di Lazarro et al 2004). However, further future trials with enrolment of more participants, serial evaluation, and better clinical characterization of the cognitive deﬁcit are needed to address this issue in dementia-related processes. However, no deterioration of complex motion performance was found during this transdermal rivastigmine application in AD (Muhlack et al 2006). This ﬁnding is of interest, since there is a controversial debate on onset of extrapyramidal symptoms during cholinesterase inhibition in AD patients or patients with parkinsonism in dementia with lewy bodies (Heinze et al 2002; Richard et al 2002; Hegerl et al 2003; Di Lazarro et al 2004). One may conclude that rivastigmine does not cause an impairment of complex movement performance with its demand for additional various forms of complex information processing with visual, cognitive, and sensory inputs (Pal et al 2001; Müller et al 2003a, 2003b). This may be due to the pharmacological proﬁle of rivastigmine with its selective inhibition of the G 1 cholinesterase isoform, which is predominantly located in cortical and hippocampal regions and may therefore favor the use of rivastigmine in PD patients with dementia (Weinstock 1999). Symptomatic treatment of cognitive deﬁcits in PD patients with dementia ChEI improve dementia in PD patients, which results from a distinct cholinergic deﬁcit (Tiraboschi et al 2000). The multi-center EXPRESS study compared the efﬁcacy of rivastigmine, an inhibitor of both acetylcholinesterase and butyrylcholinesterase, with placebo. In this trial, rivastigmine produced a moderate but signiﬁcant improvement in PD patients with dementia. The mean rivastigmine dosage was 8.6 mg at the end of the dose-escalation phase and remained stable throughout the maintenance phase. Predominant cho- linergic adverse effects, ie, nausea or vomiting, occurred. The rivastigmine-treated participants mostly characterized these side-effects as mild to moderate and accordingly the rate of premature withdrawal was relatively low. These trials supported the accumulating evidence that ChEI also improve symptoms of dementia in PD patients and allied conditions (Emre 2004), which remained stable in the open extension phase of this trial (Poewe et al 2006). Predominant open- label, earlier, smaller trials with donepezil and rivastigmine also demonstrated an improvement of cognitive function in various kinds of patients with impairment of motor and cognitive function (Werber and Rabey 2001; Giladi et al 2003; Leroi et al 2004). The controversial debate on onset or aggravation of extrapyramidal symptoms during cholin- esterase inhibition in PD patients is not ﬁnally answered by the EXPRESS study, since this trial allowed a modiﬁcation of the dopaminergic substitution as a minor adverse event. Symptomatic treatment of psychosis in AD, and PD, patients with dementia There is a relationship between progression of neurodegeneration, cognitive deﬁcits, and psychosis in AD, and PD, patients with dementia (Merims et al 2004). Vivid dreams, fear, predominant optic illusions, anxiety, paranoia, hallucinations, and sleep loss are initial clinical signs. Each antiparkinsonian drug may support onset of psychosis in particular in combination with dehydration. Since classical neuroleptics increase extrapyramidal symptoms, atypical neuroleptics are used for treatment of psychotic symptoms in PD. The atypical antipsychotic agent clozapine is well tested in clinical trials. It shows additional sedative and tremor-reducing components and prevents recurrence of psychosis (Parkinson Study Group 1999; Factor et al 2001). However, rare induction of leucopenia and transient low fever limit its use. The metabolism of clozapine via CYP1A2, CYP3A4, CYP2C19, and CYP2D6 may increase levels of compounds, which share these metabolic pathways. Quetiapine has structural similarities to clozapine and the same antipsychotic efﬁcacy. This drug has a distinct lower anticholinergic (muscarinergic) potency in comparison with clozapine (Matheson and Lamb 2000). Therefore open trials with quetiapine reported improved cognition in PD patients. This suggests that quetiapine is more suitable for long- term use than clozapine in neurodegenerative disorders, ie, AD or PD, or both (Juncos et al 2004; Morgante et al 2004). Conclusion Rivastigmine provides a distinct beneﬁt for AD, and PD, patients with dementia. There is some evidence that a 216 Neuropsychiatric Disease and Treatment 2007:3(2)