Metal protein attenuating compounds for the treatment of Alzheimer's disease

Background

Alzheimer's disease (AD) may be caused by the formation of extracellular senile plaques comprised of beta-amyloid (Aß). In vitro and mouse model studies have demonstrated that metal protein attenuating compounds (MPACs) promote the solubilisation and clearance of Aß.

Objectives

To evaluate the efficacy of metal protein attenuating compounds (MPACs) for the treatment of cognitive impairment due to Alzheimer's disease.

Search strategy

The Cochrane Dementia and Cognitive Improvement Group's Specialized Register was searched on 15 February 2007 using the terms clioquinol, PBT*, MPAC*. The Register contains records from major health care databases, many ongoing trial databases and grey literature and is updated regularly. The Internet was searched using the term: clioquinol, PBT*, MPAC*

Selection criteria

Randomised double-blind trials in which treatment with clioquinol was administered to participants with Alzheimer's disease in parallel group comparison with placebo are included.

Data collection and analysis

Three reviewers (RM, LJ, ELS) independently assessed the quality of trials according to the Cochrane Collaboration Handbook.

The primary outcome measures of interest were cognitive function (as measured by psychometric tests). The secondary outcome measures of interest were in the following areas: quality of life, functional performance, effect on carer, safety and adverse effects, and death.

Main results

There was one included trial of clioquinol (PBT1) compared with placebo in 36 patients. There was no statistically significant difference in cognition (as measured on the ADAS-Cog scale) between active treatment and placebo groups at 36 weeks. One subject in the active treatment group developed neurological symptoms (impaired visual acuity and colour vision) which resolved on cessation of treatment and was thought to be possibly attributable to the drug.

Authors' conclusions

There is an absence of evidence as to whether clioquinol (PBT1) has any positive clinical benefit for patients with AD, or whether the drug is safe. We have some concerns about the quality of the study methodology, particularly the randomisation (subjects in the active treatment group had higher mean pre-morbid IQ as measured by the NART and this may have biased the results), the secondary analyses of results stratified by baseline disease severity and whether the study was adequately powered for the analysis of the other data collected on Aß, zinc and copper levels.