Key words: Parkinson's disease; clinical trial; rivastigmine; executive function; cholinesterase inhibitor; dementia.

Introduction and Overview

Dementia is common in Parkinson's disease (PD), with an average prevalence of 40% (Cummings, 1988). The clinical phenotype of dementia associated with PD (PDD) is characterized by cognitive slowing, attentional, executive, and visuospatial dysfunction and memory impairment (Emre, 2003). PDD, also shares many clinical and pathological similarities with dementia with Lewy bodies (DLB) (McKeith et al., 2004b).

Extensive Lewy body pathology is seen in the brainstem and neocortex in both DLB and PDD, in some cases with mild degrees of Alzheimer's disease (AD)-type pathology, and there is a pronounced loss of dopaminergic neurons in the substantia nigra (Esri & McShane, 1997). Recent studies using immunohisto-chemical staining techniques for identification of Lewy bodies show that in patients with PD, dementia correlates mostly with the presence of cortical and subcortical Lewy bodies – more so than with AD-like pathological changes (Braak et al., 2005; Apaydin et al., 2002). Lewy bodies are now known to be concomitant in a substantial proportion of AD patients and their presence is associated with faster cognitive and functional decline (Kraybill et al., 2005; Jellinger, 2004). PDD and DLB are associated with marked cholinergic as well as dopaminergic deficits. Cholinergic deficits, which are generally more severe and more widespread than those seen in AD, are the most consistent neurochemical finding associated with cognitive and neuropsychiatric symptoms of both PDD and DLB (Bohen et al., 2003; Tiraboschi et al., 2000; Perry et al., 1985).