Comparisons of patient characteristics in subpopulations of the optimising transdermal exelon in mild-tomoderate Alzheimer's disease (optima) study

Background: The OPTIMA study design provides the unique opportunity to compare patients with Alzheimer's disease (AD) with different rates of decline. Methods: Patients with AD were assessed at Weeks 24 36 and 48 of initial open-label (IOL) treatment with 9.5 mg/24 h rivastigmine patch for functional (investigators' judgement) and cognitive decline (i.e.- 2-point decrease on the Mini-Mental State Examination [MMSE] scale from previous visit, and/or 3-point decrease on the MMSE from baseline). Decliners were randomised to a 48-week double-blind phase (9.5 or 13.3 mg/24 h rivastigmine patch); non-decliners entered a 48-week extended OL (EOL) phase (9.5 mg/24 h rivastigmine patch). Reported baseline patient demographics, characteristics and medical histories; incidence of adverse events and use of prior medications were used to compare subpopulations. Results: Of the 1584 patients enrolled, 68.5% completed the IOL phase; 567 were randomised in the double-blind phase (decliners) and 459 entered the EOL phase (non-decliners).Baseline demographics and the safety profilewere similar between decliners and non-decliners. Decliners had a lower MMSE score at baseline than non-decliners (mean 6 SD; 16.9 6 3.60 vs 18.8 6 3.25) Compared with non-decliners, a slightly higher proportion of decliners had a history of psychiatric disorders (44.7% vs 48.0%, for non-decliners vs decliners, respectively); whereas the opposite was observed for the frequency of metabolic and nutritional disorders (51.4% vs 48.9%; for non-decliners vs decliners, respectively). Prior use of cholinesterase inhibitors (ChEI) was more frequent in decliners than in non-decliners (62.1% vs 45.3%, respectively) as was the use of other anti-dementia drugs (e.g. memantine; 36.5% vs 20.9%). Fewer decliners, compared with non-decliners, had received platelet aggregation inhibitors (33.7% vs 37.5%) and salicylic acid derivatives (30.5%vs 35.1%). Conclusions: Compared with non-decliners, decliners exhibited a lowerMMSE score, a more frequent history of psychiatric disorders, and a higher proportional consumption of ChEI and other anti-dementia drugs (e.g., memantine).We conclude that decliners were in a more advanced stage of AD which, compared with non-decliners, led to the disadvantage of functional and cognitive decline. However, the concept of non-linear decline in AD is an important consideration, and may impact on the interpretation of these data.