Müller double-blind phase responded more robustly to subsequent rivastigmine treatment (according to the ADAS-Cog and Progressive Deterioration Scale [PDS] scores). Other studies have found that factors besides drug safety and efﬁcacy inﬂuence patterns of ChEI use. Gill et al, in comparing 6400 new users of donepezil versus 3400 subjects enrolled in 10 randomized, controlled trials, found that 51%–78% would not have been eligible to participate in randomized trials because of advanced age, medical additional morbidities, or residence in long-term care. In addition, 28% of new users had stopped taking donepezil by 8 months of treatment, with discontinuation more likely in patients with greater additional morbidities (Gill et al 2004). This suggests that physicians may not be conﬁdent in prescribing ChEI for patients who differ from typical participants of randomized, controlled trials, and that more data are needed on clinical outcomes in these “real world” patient populations. With rivastigmine it is obvious that in comparison with the ﬁxed-dose regimen with donepezil, a more ﬂexible-dose rivastigmine titration regime enables improved drug tolerability through slower escalation of dosing with individualized titration. Caregivers and social demographic factors also play an important role in decisions about ChEI use. Belle and colleagues examined predictors of use by patients with dementia whose caregivers were enrolled in the multi-site caregiver intervention Resources for Enhancing Alzheimer’s Caregiver Health (REACH) trial (Belle et al 2004). Only 31% of care recipients used a cognitive enhancer at baseline; use was predicted by race (white), higher levels of education, less severe dementia, care giving time, and being a spouse rather than a parent of the caregiver. Over the course of the study, a higher proportion of patients stopped taking ChEI than started the treatment. This study suggests that educating caregivers about the benefits of long-term treatment could improve rates of sustained use required for optimal outcomes. The long-term effects of rivastigmine have been examined in an open-label extension of the placebo-controlled trials. Regardless of the treatment arm to which patients had been allocated until week 26, they were restarted on rivastigmine and titrated upward to the maximum tolerated dose, but not exceeding 12 mg/day. Patients already on a high dose in the double- blind study phase remained above their cognitive baseline level until week 40 and slowly declined thereafter. Patients who had received a low dose of rivastigmine or placebo in the double-blind study phase showed a rapid improvement when restarted on rivastigmine but did not catch up with the high-dose group. This implies that for maximum beneﬁt, treatment should be started as early as possible. After week 40 cognitive ability slowly declined also in the two latter groups. Importantly, all three groups performed better on the ADAS-cog at 1 year than the placebo group had performed at 6 months. Apparently patients beneﬁt from treatment even after the 40-week period of cognitive stabilization (Farlow et al 2000; Darreh-Shori et al 2002; Erkinjuntti et al 2002; Farlow 2002; Farlow et al 2003; Darreh-Shori et al 2004; Farlow and Lilly 2005). To date, there is only one relevant head-to-head trial on the efﬁcacy of ChEI, rivastigmine, and donepezil. This study describes similar efﬁcacy of rivastigmine and donepezil on cognition and behaviour, and greater beneﬁt in activities of daily living and global functioning in the rivastigmine arm is concluded (Bullock et al 2005; Winblad et al 2006). Essentials points to sustained ChEI treatment Sustained treatment requires consideration of individual differences between patients, the magnitude of therapeutic response, the likelihood of response to a speciﬁc drug, and tolerance for dose escalation. Active anticipation, management, and monitoring are required for additional morbidities such as heart or lung disease, urinary incontinence, and complications of dementia (eg, dehydration, hypotension, obstipation, undernutrition, falls). In addition, an attitude of realistic optimism about management and a perspective rooted in principles of chronic disease management are key attributes of physicians and families caring for patients with dementia. A comprehensive, long-range, collaborative dementia care partnership, with a focus on the goals of slowing decline and prolonging quality of life, is the means by which overall outcomes can be optimized (Giacobini 2000; Frankfort et al 2005, 2006). Novel delivery approaches of rivastigmine – the IDEAL study Transdermal drug delivery systems (usually by drug “patches”) are designed to provide controlled, continuous delivery of drugs through the skin, thereby maintaining more consistent blood levels of the drug. Patches also minimize processing of the drug in the liver, stomach, and intestines. These advantages may make it easier to achieve therapeutic levels of the drug in the bloodstream with lower dosages than pills, thereby possibly reducing side-effects. Since AD initially affects memory, reasoning, and decision-making abilities, it can be a problem for people with the disease to 214 Neuropsychiatric Disease and Treatment 2007:3(2)