77,99 Schnieder et al141 found that tacrine in combination with estrogen was more efficacious than either agent alone in the treatment, of AD. Yet, Sano ct al142 did not find a combination of selegiline and vitamin E to be more efficacious than either agent alone. However, it must be noted that these two #selleck screening library keyword# agents may impact, similar pathophysiological mechanisms. Second, accumulating evidence suggests that individual differences in genetic and other risk factors may also affect drug response. Several studies have found a

smaller treatment response to tacrine and phosphatase inhibitor metrifonatc in AD patients positive for the ε4 Inhibitors,research,lifescience,medical allele, although some observed this effect, only in women, suggesting the existence of a gene-gender interaction.93,143,144 However, others have suggested that the impact of ε4 may vary according to therapeutic approach, with studies of other compounds (eg, Inhibitors,research,lifescience,medical the noradrenergic compound S12024) observing a better

treatment response in ε4 carriers.143,145 Many of these findings arc preliminary in nature, based on data from clinical trials of short duration, with samples sizes that are too small to yield large enough comparison groups of patients with and without the ε4 allele. Data from larger, longterm clinical trials are required to more fully elucidate Inhibitors,research,lifescience,medical the role of genetic and other risk factors in treatment response, and it is interesting to note that in a large clinical trial of galantamine, Wilcock et al146 observed no impact of the ε4 allele on drug response. Finally, variability in stage of illness, patient Inhibitors,research,lifescience,medical demographics, drug dose, duration of clinical trial, and other methodological issues also impact drug response. Many randomized clinical trials of newer pharmacological agents include

only highly selected populations, and more effectiveness studies are required, which can provide “real world” information. Typically, with respect to the AChEIs, the most efficacious effects have been observed in patients who have used higher doses for longer time periods. Indeed, with respect to agents Dacomitinib such as estrogen and anti-inflammatory drugs, where initial results have been disappointing in AD, it is important to note that the short duration of a clinical trial is in stark comparison to the lengths of use found in the epidemiological studies that, have suggested their impact, on AD. Long-term use of such therapeutic approaches may prevent or slow AD onset, but may be far less effective treatments during the acute phases of the illness.