Amyloid deposition is a characteristic feature of all patients with Alzheimer's disease. We focus in this application on the little-understood paradox revealed from autopsy data that about 20% of healthy adults have a very high level of amyloid plaques on their brain, but no behavioral evidence of Alzheimer's disease. Recent advances have, for the first time, allowed scientists to use neuroimaging techniques to measure amyloid deposition in the living human brain. We have secured funding in the past to image amyloid deposition in 300 healthy adults, aged 30 to 90, who have participated in the Dallas Lifespan Brain Study, and now request funds to complete a second wave of amyloid imaging of these participants. The DLBS provides a detailed cognitive and neural profile of each subject and includes structural and functional imaging measures of each participant. The study has two subsamples: one with high levels of education and one with lower levels. Longitudinal amyloid imaging will allow us to determine whether rate of change in amyloid has a larger effect on cognitive function for low education adults due to limited "cognitive reserve." Moreover, we will have critical data to assess whether amyloid level and education interact to affect compensatory neural activity. Finally, we will integrate the amyloid data with other measures of neural function to determine the strongest predictors of cognitive decline in a healthy aging sample over a four-year trajectory. We hypothesize that multiple markers of neural degradation will combine to predict cognitive decline, and that amyloid deposition alone will not be the most powerful marker.
Understanding the role of amyloid deposition in healthy adults is a critically-important issue, as a recent NIA working paper suggested that there appears to be a state of preclinical Alzheimer's disease -and hypothesized state when older adults have significant amyloid deposits but appear asymptomatic (Sperling et al.). This may be the most important time at which one might intervene to prevent the cascade of decline that occurs as Alzheimer's disease progresses. The only way to understand the role of amyloid deposition in healthy adults is to conduct longitudinal studies of amyloid deposition in healthy adults-this is the focus of the present request.
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