Effects of cholinesterase inhibitors in Parkinson's disease dementia: a review of clinical data

Abstract

Aims: Cognitive impairment and dementia are common features of Parkinson's disease (PD). Patients with Parkinson's disease dementia (PDD) often have significant cholinergic defects, which may be treated with cholinesterase inhibitors (ChEIs). The objective of this review was to consider available efficacy, tolerability, and safety data from studies of ChEIs in PDD.

Discussions: A literature search resulted in the identification of 20 relevant publications. Of these, the treatment of PD patients with rivastigmine, donepezil, or galantamine was the focus of six, eleven, and two studies respectively, while one study reported use of both tacrine and donepezil. The majority of studies were small (<40 patients), with the exception of two large randomized controlled trials (RCTs) that are the main focus of this review. In the smaller studies, treatment benefits were reported on a range of outcome measures, though results were extremely variable. While the full results of a large RCT of donepezil in patients with PDD are not yet available, significant treatment differences were reported on the CIBIC-plus at the highest treatment dose. A trend toward improvement was also observed in treated patients on the ADAS-cog. The second large RCT found significant improvements in rivastigmine-treated patients compared with placebo on both the ADAS-cog (P < 0.001) and the ADCS-CGIC (P < 0.007), as well as on all secondary efficacy outcomes. Consequently, rivastigmine is now widely approved for the symptomatic treatment of mild to moderate PDD.

Conclusions: Taken together, these studies suggest that ChEIs are efficacious in the treatment of PDD.

Figure 1

Flow diagram of publication selection for review of ChEIs in PDD.

Figure 2

Changes from baseline in mean MMSE score* in studies of galantamine [51, 52], donepezil [34, 35, 39, 40, 46, 48, 49, 50], donepezil or tacrine (with pooled results) [65], and rivastigmine [30, 38, 41, 53]. *Positive changes from baseline on the MMSE indicate improvement; negative values indicate deterioration.

Figure 3

Changes from baseline in ADAS‐cog scores at 24 weeks in patients with PDD in an RCT of rivastigmine (efficacy population*) [30]. *All randomized patients receiving at least one dose of study medication who were assessed at baseline and at least once after baseline.

Figure 4

Changes at Week 24 in ADCS‐CGIC scores in patients with PDD in an RCT of rivastigmine (efficacy population*) [30]. *All randomized patients receiving at least one dose of study medication assessed at baseline and at least once after baseline.

Figure 5

Changes from baseline in ADAS‐cog scores at 24 weeks in patients with PDD in an RCT of donepezil (ITT‐LOCF population) [31].