take drugs on a regular schedule. As the disease advances, people may not know what drugs are for or even what they are. With further advance of the disease, sometimes the ability to swallow is affected. Transdermal drug delivery has the potential to eliminate issues such as forgetting to take the drug or to take it at the right time, and also ease challenges associated with getting the person with Alzheimer’s to take or swallow a pill. It also provides visual reassurance for the caregiver that the medication has been taken. At the same time, possible skin irritation and the presence of a new or unknown object on their body may be confusing or annoying to the person with Alzheimer’s, so a skin patch may not work for everyone (Muhlack et al 2006; Priano et al 2006). The IDEAL (Investigation of TransDermal Exelon in ALzheimer’s disease) was a 24-week, multi- center, randomized, double-blind, placebo- and active- controlled evaluation of once-daily rivastigmine patches versus twice-daily capsules in 1195 patients with moderate stage Alzheimer’s. Patients were 50–85 years of age. Tested patch sizes were 10 cm2 (9.5 mg/24 hours) or 20 cm2 (17.4 mg/24 hours), and capsules were 6 mg twice-daily. Primary outcome measures were the ADAS-cog and Alzheimer’s Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC). The rivastigmine patch showed statistically signiﬁcant beneﬁts versus placebo on both of these measures and the ability to perform activities of daily living. The recommended target dose 10 cm2 patch showed similar efﬁcacy to the highest doses of rivastigmine capsules with three times fewer reports of nausea (7.2% vs 23.1%) and vomiting (6.2% vs 17.0%), which are well-known side-effects of ChEI. The 20 cm2 patch showed improved cognitive scores versus capsules and similar tolerability to capsules. Local skin tolerability was good. Abnormal redness of the skin was present at moderate or severe levels in only 7.6% and 6.2% of patients receiving 10 and 20 cm2 patches, respectively. A questionnaire was given to more than 1000 caregivers whose loved ones were AD patients. The caregivers signiﬁcantly preferred the patch to capsules for ease of following the treatment schedule, overall ease of use, and less interference with daily life (Winblad et al 2006). Rivastigmine and its impact on motor behavior in AD, and PD, patients There are reports on deterioration of ﬁne motor behavior during treatment with ChEI, but concomitant application of typical and atypical neuroleptics confounded study outcomes Rivastigmine in AD or case reports in AD, or PD, patients with dementia (Heinze et al 2002; Richard et al 2002; Werber and Rabey 2001; Bohnen et al 2004). A further drawback of these reports was a missing compliance control of AD individuals due to oral ChEI administration with their sometimes nausea-inducing effects. One placebo-controlled trial showed a discrete, non- signiﬁcant improvement of smoothness of hand movements following oral intake of donepezil during a 12-week interval with the use of a standardized handwriting paradigm (Hegerl et al 2003). This positive effect was independent of changes in cognitive function, and conﬁrmed outcomes of a study suggesting normalization of disturbances in the motor cortex of patients with AD treated with donepezil (Liepert et al 2001). However, writing with the non-dominant hand in particular is rather complex and demands a certain cognitive load, and moreover hand dominance may inﬂuence outcomes of assessment of motor activity (Van Hilten et al 1993). Therefore more simple instrumental motor tests are also suitable, to address this issue on impact of cholinesterase inhibition on motion. A standardized peg insertion procedure is such a tool. It requires conduction of a complex motion series. This instrumental tool did not show a signiﬁcant change of outcomes during an open label treatment with donepezil during an interval of 12 weeks, whereas there was a non- signiﬁcant trend for improvement of simple motions apparent within a ﬁnger tapping paradigm (Bohnen et al 2004). A further trial that investigated the impact of transdermal rivastigmine administration on motor performance with an altered standardized peg insertion paradigm showed that patients with predominant cholinergic neurodegeneration need longer for performance of the peg insertion paradigm in comparison with controls. Thus this study conﬁrms a deterioration in carrying out of complex motion series in neurodegenerative processes, because this was also shown in disorders with preponderant functional basal ganglia disturbances, ie, Huntington’s disease or PD (Müller et al 2000; Saft et al 2003, 2004). This trial also conﬁrmed that assessment of co-ordinated movements with the non- dominant hand better reﬂects disturbances of ﬁne motor behavior during neurodegeneration probably due to regular training and use (Müller et al 2000, 2003b; Pal et al 2001; van Vugt et al 2001; Saft et al 2003, 2004). An improved brain plasticity of the dominant brain hemisphere with secondary better compensation of motor deﬁcits may additionally be responsible for the inferior sensitivity of the applied instrumental paradigm to reﬂect motor disturbances of the upper limb during a neurodegenerative process (Van Hilten Neuropsychiatric Disease and Treatment 2007:3(2) 215