Our results suggest that treatment with donepezil improves cognition and hallucinations without increasing parkinsonian symptoms, and its sudden withdrawal is usually detrimental, producing acute cognitive and behavioural decline. Although recommencement on donepezil appears to reverse this deterioration we do not advise its abrupt discontinuation in this population.

Risk factors predicting an increased risk of dementia in Parkinson's disease (PD) are not fully established. The dementia associated with PD (PDD) closely resembles dementia with Lewy bodies (DLB). Based upon a high frequency of non-dopaminergic mediated clinical features in DLB, we predicted that a motor subtype comprising postural instability and balance problems would be more common in PDD. We examined extrapyramidal, cognitive, and affective features in 38 PD, 43 PDD, and 26 DLB patients in a cross-sectional study design. Motor subtype was subdivided into postural-instability gait difficulty (PIGD) or tremor (TD) dominant. The PIGD-subtype was more common in PDD (88% of cases) and DLB (69% of cases) groups compared with the PD group (38% of cases), in which TD and PIGD sub-types were more equally represented (P < 0.001). Although the mean depression scores overall were modest, PDD patients scored significantly higher than PD, but not DLB patients (Cornell; P = 0.006, and Geriatric Depression scale, GDS-15; P = 0.001), while within the PD group, those patients with a PIGD subtype had greater depression scores than the TD subtype (GDS-15; P < 0.05). We conclude that non-dopaminergic motor features are frequent in PDD. Neurodegeneration within the cholinergic system is likely to mediate many of these motor problems, as well as playing a significant role in determining the neuropsychiatric symptomatology of both PDD and DLB.

Donepezil produced similar improvements in cognition and behaviour in DLB and PDD. This supports the hypothesis that the two disorders are closely related clinically and neurobiologically. Larger scale, placebo controlled clinical trials are needed to provide an evidence base to guide the clinical use of cholinesterase inhibitors in Lewy body disease.

Background: We examined attention-enhancing effects of the cholinesterase inhibitor donepezil in Dementia with Lewy bodies (DLB) and Parkinson’s disease with dementia (PDD) by means of open label study. Methods: 22 DLBs and 23 PDDs were assessed over 20 weeks using the Cognitive Drug Research Computerized Attentional Tasks. We examined how much closer our patients moved towards being normal for their age by comparing them to a non-demented elderly control sample (n = 183, aged 71–75 years). Results: Donepezil treatment improved power of attention, continuity of attention and reaction time variability. The deficit in responses was moved towards normal by 38 and 56% for power of attention and 22 and 10% for continuity of attention in PDD and DLB, respectively. Conclusions: Improvements in attention were found with donepezil in PDD and DLB.