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Abstract:
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Cognitive decline is common in aging, with Alzheimer's (AD) the most common and one of the most feared diseases. AD brain damage begins long before clinical symptoms. Neuroimaging allows us to visualize such features of brain damage as amyloid or tau protein accumulation, decreased metabolism, and cortical atrophy. Longitudinal measurement can help to characterize the earliest signs and their timing relative to each other and to cognitive impairment. The classic hypothesis for AD has been that the first stage is amyloid plaques, followed by cell death and atrophy. Post-mortem data and neuroimaging increasingly suggest, however, that amyloid is not the whole story. I will present statistical methods for analyzing longitudinal data from multiple neuroimaging modalities that address three questions: 1. What are the earliest features of brain damage? 2. What is the timing of onset relative to each other and to cognitive impairment? 3. Are there distinct subgroups that suggest different underlying syndromes? The answers will help us to determine the timing and targets for interventions to prevent or delay the onset of cognitive impairment or dementia. We illustrate with data from ADNI.
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