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Principal Investigator  
Principal Investigator's Name: Andrew Reid
Institution: University of Nottingham
Department: Psychology
Proposed Analysis: The noradrenergic locus coeruleus system (NE/LC) is one of the first regions to host tau pathology early in life. This system is important for adaptive learning and is involvement in hippocampal long-term potentiation, and is a clear candidate region for the etiology and early progression of Alzheimer's disease. We have previously performed simultaneous pupillometry, EEG, and fMRI on healthy young controls, and found a robust pattern of BOLD activations which correlate with pupil dilation, an established proxy measure for NE/LC activation. Because it is infeasible to record directly from LC in humans, this proxy measure represents an important indirect measurement of LC activations. Given the hypothesis that the early AD-related pathology found in NE/LC system can lead to cognitive deficits and long-term structural changes underlying the disease, we propose to use our pupil dilation-related fMRI pattern to investigate changes in MCI and AD patients in the ADNI database, specific to the regions in this pattern. We expect reduced fMRI covariance, and reduced WM structural integrity, between the different components of this pattern, representing decreased coordination by the NE/LC system. We also expect changes to this coordination over subsequent visits to be associated with changes in cognitive performance (specifically, memory and adaptive learning) over the same interval. We are interested in investigating both ADNI and AIBL in this manner, since this allows us to evaluate how well our findings generalize across two different large cohorts.
Additional Investigators