Alzheimer's disease (AD) is characterized by a progressive loss of cognitive functions. Studies of apolipoprotein E (APOE) genotype have suggested that the presence of the c4 allele substantially increases the risk for developing AD and is associated with reductions in cerebral metabolism even prior to the onset of clinical symptoms. We propose a new approach for detecting the very early effects of AD in individuals with increased genetic risk with the e4 allele, but without clinical symptoms using computerized tasks as cognitive """"""""stress tests"""""""" that systematically vary attentional load and perceptual difficulty. By increasing the attentional or perceptual demands of a task in an experimentally controlled manner, we hypothesize that cohort differences in genetic risk for AD may be detected through alterations in speed of information processing and that differences in task performance may be related to brain changes that have been previously observed with neuroimaging techniques in these non-demented, healthy subjects. In this study, 25 e4 homozygotes, 25 c4 heterozygotes, and 25 s4 non-carriers who are matched in age, gender, and educational level will be included. These subjects will be healthy volunteers, ages 50 - 65, who report a family history of Alzheimer's dementia and are participants in a separate longitudinal study of the neuroimaging effects of increased risk for AD with the E4 allele. An information-processing approach will be used to test their cognitive function in two experiments: 1) with visual attention tasks that experimentally vary the number of target-relevant distractors and 2) using a face-matching task in which perceptual difficulty is incrementally increased. Analyses will test group differences in performing the tasks and will relate subject differences in task performance to patterns of brain metabolism and atrophy using neuroimaging results obtained for these subjects from the separate longitudinal study. Determining under what conditions differences in such cognitive tasks occur in persons at risk for AD may aid efforts for early detection, for understanding the mechanism of cognitive dysfunction, and for evaluating prevention therapies in AD.
