Authors:

PEERS, P.V., Semple, J., Lai, R.Y.K, Hopton, G.R., Altman, J.F.B, Risner, M, & Riedel, W.J.

Reference:

Year of publication:

2006

CBU number:

6314

Abstract:

There is an increasing body of evidence to suggest that PPAR? agonists such as Rosiglitazone may be beneficial for the treatment of Alzheimer’s disease (AD). Small scale trials have demonstrated beneficial effects of Rosiglitazone on tests of memory and executive function (Craft et al, 2002). Here we examine the potential use of standard clinical measures (e.g ADAS-cog) and experimental measures of simple and choice reaction time (examining attention, visuospatial abilities) to detect cognitive decline and drug effects in a subset of mild to moderate AD patients involved in a 24 week phase IIb trial of Rosiglitazone.Simple reaction time (SRT) (mean time to respond to a change in colour of a centrally presented target), and choice reaction time (CRT)(the mean time to correctly respond to a target changing colour in either the left or right visual field) data were collected at baseline and 24 weeks in addition to other standard measures in a subset of 56 patients from the main trial. The sample was divided approximately equally between 2mg, 4mg, 8mg Rosiglitazone or placebo treatments for the duration of the study.In the study sample as whole (424 patients) no differentiation was seen between placebo and treatment groups on the ADAS-cog at 24weeks. Similarly, in the subset of patients studied, SRT remained stable and did not differentiate between groups. However, placebo patients showed increased reaction times on the CRT task at 24weeks, relative to medicated patients. The change in their performance over time was significantly greater than that of the 2mg and 4mg treatment groups. Further analyses suggested that this effect was particularly marked for targets appearing in the left visual field. A growing body of evidence has shown a link between reduced alertness and bias to the right side of space. The emerging asymmetry in performance seen our placebo group may be indicative of reducing alertness with disease progression.Simple computerised tasks, such as the simple and choice reaction time tasks, may provide a more sensitive and objective measure than standard tests such as the ADAS-cog to measure placebo decline and drug effects in patient small samples.Presented at the 10th International Conference on Alzheimer's Disease and Related Disorders