136 The work with velnacrine indicates that improvements can occur rapidly with anticholinesterases,115,135 and early phase 2 trials would benefit greatly if a range of doses could be rapidly evaluated. In fact, it is quite feasible that many compounds could produce acute improvements, as have been seen with volunteers in the previous section. To evaluate such effects, short repeatable tests would be necessary, and one recent study suggests this is feasible in AD patients using the CDR system.33 Here, the acute cognitive effects of

intravenous flumazenil were identified Inhibitors,research,lifescience,medical in AD patients by assessing them prior to infusion and again at 15, 40, and 240 minutes later. Three tests from the CDR system were employed, two to measure attention (simple and choice reaction time), and a test of episodic secondary memory (picture recognition). This enabled a double-blind, placebo-controlled, single-dose, 2-way crossover trial to be conducted in AD patients, Inhibitors,research,lifescience,medical the first time to the knowledge of these authors that multiple repeated testing over so short a period has been possible in AD. The sensitivity of the system was demonstrated by identifying short-term Inhibitors,research,lifescience,medical impairments with the compound in two of the tasks, despite the trial only having 11 patients. Dementia with Lewy bodies An important newly identified dementia

is dementia with Lewy bodies (DLB), believed to account for up to 20 % of all dementias, and previously Inhibitors,research,lifescience,medical largely mistaken for AD.137-141 The condition is known to be more cholinergically specific than AD, and thus more likely to respond to cholinergic treatment. There is also a larger nicotinic component to the cholinergic damage. Here, unlike other dementias, attentional deficits are recognized as a core symptom of the disease, and recent, work with the CDR system has shown greater attentional impairments in DLB patients than in Inhibitors,research,lifescience,medical AD patients, while showing a double dissociation with DLB patients having smaller verbal memory deficits than

AD patients.137-141 The condition can also be differentiated from vascular dementia.142 In comparative work using the CDR system with four types of dementia, AD, DLB, vascular dementia, and Huntington’s disease, it, is clear that, each has its unique profile of cognitive impairment, over the various tasks and measures. Any ABT-263 mw scales therefore that, yield single scores for cognitive impairment, will not properly reflect the diversity of the cognitive impairment seen nor see more the implications of this diversity for the true behavioral profile of the different diseases. The cholinergic nature of the attentional deficits has been further confirmed by comparing nonhallucinators with patients who do hallucinate.143 It has been shown that hallucinators have greater cholinergic deficits than nonhallucinators, and comparing the two groups on CDR tests of attention showed greater attentional deficits in the hallucinators.