The prevalence of memory disorders increases with advancing age, presenting a challenge for clinicians who must differentiate a benign condition from a serious and progressive disorder. The early diagnosis of degenerative conditions such as Alzheimer's Disease (AD) is particularly important given the continuing development of novel pharmacological agents that show promise in decreasing the rate of progression of memory impairment. Future agents will likely be most effective by limiting the extent of brain impairment when administered early in the development of the disease, making early diagnosis critical. ? ? The purpose of the proposed investigation is to assess the utility, among Hispanic and non-Hispanic elderly who are at risk for cognitive decline, of two newly developed neuropsychological tests: the Semantic Interference Test (SIT) and the Prospective Memory Test (PMT). The SIT assesses proactive and retroactive semantic interference, whereas the PMT assesses event- and time-based prospective memory. Pilot work in our laboratories using English- and Spanish-speaking elderly indicates that vulnerability to semantic interference as measured by the SIT is a more sensitive indicator of cognitive impairment in the early stages of AD than traditional neuropsychological tests that assess delayed memory or rate of forgetting. Our data also indicate that the PMT has good sensitivity and specificity in differentiating mildly impaired AD patients from normal elderly controls. ? ? A unique aspect of this study is that the predictive utility of semantic interference and prospective memory measures will be compared to traditional neuropsychological tests in predicting cognitive decline and progression to dementia among elderly Hispanic and non-Hispanic patients who are normal or who have mild cognitive impairment (MCI). Genetic risk factors such as apolipoprotein E (ApoE) status will also be assessed with regards to its ability to predict, alone and in combination with SIT and PMT measures, which individuals will develop cognitive decline and progression to dementia. The study of increased vulnerability to semantic interference and decline in prospective memory may enhance the detection of MCI and the prediction of progression to dementia in at risk populations, thus having important clinical, heuristic, and treatment implications.
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