When most people think about Alzheimer disease (AD), they think about what researchers call sporadic AD – it has a number of risk factors, but there is much to its onset that is random. While we have examined preclinical AD (the time before symptoms occur), we needed longer periods of time to examine how biomarker changes (seen in cerebrospinal fluid [CSF] and brain imaging) occur in those years before Alzheimer symptoms occur. In this paper, we looked at various biomarkers including CSF, brain imaging, structural brain changes, and cognition to see how they each change before and after the start of symptoms. We analyzed data from 664 individuals aged 42 to 90 years, who were followed up to nearly 17 years. Of those, 145 (21.8%) people developed symptoms of AD. Our findings suggest that the change from being cognitively normal (no memory problems) to having some dementia is characterized by not only the amount of molecular biomarkers in the brain, but also the rate of change of the amount of those biomarkers.

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