Due to the increasing life span of the average US citizen, cognitive dysfunction in the elderly has become a major health care problem. The increasing incidence of disorders such as senile dementia of the Alzheimer type (SDAT) has prompted intensive research activity, at both the basic and clinical level, directed toward the development of an effective pharmacological treatment for this ultimately lethal disease. A serious obstacle to the establishment of effective pharmacological treatments for age-related cognitive disorders is the lack of adequate assessment instruments with which to evaluate the clinical therapeutic potential of new drug candidates. We propose to develop a new set of psychometric tests for the assessment of drug-effects upon the cognitive impairment associated with SDAT and other cognitive dysfunctions of the elderly. The battery will differ from currently available tests for the cognitive abilities of the aged and demented in at least two important respects. A key feature will be face validity, relevance to the cognitive demands, situational variables, and environmental stimuli encountered by the subjects in everyday life. This feature enhances a test's meaningfulness as a pragmatic measure of the subject's ability to function from day-to-day. A second test criterion, even more rarely satisfied, is comparability to the behavioral tests used to evaluate cognition-enhancing drugs in animals. Comparability to animal memory tests will facilitate the transition from pre-clinical to clinical assessment of potential pharmacological treatments. The new test battery will also be fully automated, by means of a high-speed, high-resolution computer graphics system which is already operational. The new test battery will include measures of language function, concept formation, spatial memory, psychomotor coordination, and distractability. We propose to evaluate the battery's discriminant validity based upon data collected from young normal, elderly normal, and elderly demented subjects. The assessment battery will be compared to currently available psychological, clinical, and neurophysiological measures, and will be evaluated for its repeatability, difficulty range, sensitivity to severity of dementia, longitudinal sensitivity, and pharmacological sensitivity. The cognitive battery derived from these studies will provide measures with improved validity and utility for the assessment of the efficacy of pharmacological treatments for SDAT and other age-related cognitive dysfunctions.
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