The mid-1980s saw the development of flic first CDR prototypes,4 and the CDR system currently used for demented patients

has now been widely validated.3,124 The methodology has now been disseminated,125 and the system has been used to identify the full impairments in attention which accompany the widely recognized memory deficits in AD.105-107,126 Inhibitors,research,lifescience,medical These attentional impairments have been shown to be a result of cholinergic dysfunction104,106,107 and thus to be legitimate targets for anti-Alzheimer drugs.104,127 The system has been shown to be particularly sensitive for differentiating different types of dementia from AD, for example, Huntington’s disease.128 It has been contrasted favorably Inhibitors,research,lifescience,medical with a wide range of traditional measures in dementia including

the Mini-Mental State Examination,3,128 the Alzheimer’s Disease Assessment Scale (ADAS), 128 the Mattis Dementia Rating Scale, 128 the Wechsler Memory Scale, 128 the Cambridge Cognitive Examination (CAMCOG), 129 the Kendrick Battery,3 the Kew Test of memory, aphasia, Inhibitors,research,lifescience,medical and parietal function, 3 and the Stockton Rating Scale.3 In trials where the sensitivity and discriminality of the CDR system in AD and other types of dementia have been directly compared with various traditional assessments and the ADAS, the CDR system has been found to show higher discriminability than the other techniques, and also to be more sensitive Inhibitors,research,lifescience,medical in identifying AD patients than traditional measures as well as the ADAS.128 Such work has

led the International Working Group on Dementia Drug Guidelines to recommend that check details future AD trials incorporate assessments of attention (currently not assessed by the cognitive subscale of the ADAS), and that computerized systems should be used alongside Inhibitors,research,lifescience,medical traditional techniques wherever possible.130. The CDR system has been used in various therapeutic trials. The CDR system was the primary outcome variable in a large Food and Drug Administration (FDA)-approved multicenter trial of D-cycloserine in AD.131,132 Sadly, the compound showed why no signs of efficacy, despite showing promise in single doses in animal work and the scopolamine model.120,121 However, in subsequent publications, the beneficial effects seen in single doses in animal work disappeared with repeated testing, suggesting that this tachyphylaxis might, have also occurred in the AD study.131 S-12024 was tested in a 4-week acceptability and clinical activity trial of S12024 in 53 inpatients with moderate-to-severe AD, but no clear signs of positive effects were identified.133 Various anticholinesterases have been shown to be effective in improving both attentional and memory function, including tacrine,134 velnacrine,115,135 and galanthamine.