Subproject 3 will be a direct extension of our ongoing work, and will develop objective and quantitative criteria for classifying dementia in Down syndrome (DS) based upon the assessment methods we have been employing in our current studies. With few exceptions, adults with DS have substantial cognitive limitations of long-standing duration, and the impact of Alzheimer's disease (AD), as well as any other old-age associated pathology, has to be assessed against a background of pre-existing impairment. The degree of impairment due to MR will vary substantially among individuals, and therefore any criteria for defining dementia must take this variation in "baseline" levels of performance into consideration. Current recommendations in the literature address this issue by emphasizing the importance of documenting declines in capabilities over time in domains of function and cognition that parallel the diagnostic profile typically seen in the general population. However, while some instruments have been suggested, no standards are available that define degrees of decline that have diagnostic significance. Further, with few exceptions, these declines can really be measured objectively only from the time of initial concern, delaying possible treatment, given that baseline results for the specific procedures included in dementia assessment batteries are rarely available in clinical practice. This planned effort addresses these issues. Based upon a substantial body of data collected during our current funding period, we have generated sets of criteria referenced to baseline IQ that seem to differentiate demented from nondemented individuals with high sensitivity and specificity. However, because these criteria have been generated from our obtained data, the frequency ofmisclassifications due to measurement imprecision is minimized. Therefore, it is necessary to validate these criteria on a set of new cases, and this is what we are now proposing. Should this validation prove successful, we will have in hand a cognitive and functional assessment battery with standardized procedures and objective classification criteria that can be broadly disseminated for making dementia diagnoses in clinical settings. In addition, we will evaluate our objective measures of change over time to determine the types and magnitudes of decline that have clinical significance.