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• W2912109148 abstract "Event Abstract Back to Event PET staging of amyloidosis using striatum helps predicting cognitive decline in non-demented elderly Bernard J. Hanseeuw1, 2* 1 Cliniques Universitaires Saint-Luc, Neurology, Belgium 2 Massachusetts General Hospital, Radiology, United States Background: Brain amyloid-β (Aβ) deposition, one of the defining pathologies of Alzheimer’s disease is now detectable in-vivo with high specificity using positron emission tomography (PET). It is well established that elevated PET measures of brain Aβ increase risk for subsequent cognitive decline in both cognitively impaired and normal populations, and Aβ measures have been widely adopted as part of eligibility criteria for anti-Aβ therapeutic trials. However, the subsequent decline of clinically normal individuals with elevated Aβ occurs slowly over several years, and alternative Aβ PET measures that could predict decline over a shorter interval could potentially improve the efficiency of prevention trials. We explored an alternative PET measure seeking to stage Aβ pathology in-vivo, based on striatum, a subcortical structure in which Aβ is typically detected at autopsy only after cortical deposition. We reasoned that since striatal involvement reflects a more progressive amyloidosis at postmortem, an in-vivo striatum PET measure may provide predictive information that differs from the typical neocortical PET measure, and have a stronger relation to cognitive decline. Objective: To evaluate striatal amyloidosis as a predictive marker of cognitive decline among individuals either clinically normal (CN) or with mild cognitive impairment (MCI) from two longitudinal studies of aging: the Harvard Aging Brain Study and the Alzheimer’s Disease Neuroimaging Initiative. Methods: We included 643CN and 573MCI with baseline Aβ-PET and longitudinal MMSE over an average 3.3-year follow-up. We classified subjects in three Aβ-stages. Stage0: Low-Aβ; Stage1: High-neocortical, low-striatal Aβ; and Stage2: High-neocortical, high-striatal Aβ. We used mixed-models to assess the association between Aβ-stages and subsequent MMSE decline, adjusting for demographics and cohort. Results: Decline rate (MMSE-points/year) in Stage2-CN (0.28) was faster than in Stage1-CN (0.16;p=0.026) and decline in Stage1-CN was faster than in Stage0-CN (0.04;p=0.002). Decline rate in Stage2-MCI (1.2) was faster than in Stage1-MCI (0.25;p<0.00001) and decline in Stage1-MCI was faster than in Stage0-MCI (0.07;p=0.003). To compare striatal and neocortical Aβ contributions within the high-Aβ group, we used a 2-by-2 design based on striatum (Stage1/2) and neocortex (high/very high: +/++). Decline rates (MMSE-points/year) were 0.17(Stage1+), 0.43(Stage1++), 0.65(Stage2+), and 0.95(Stage2++). All pairwise comparisons were significant (p<0.05), indicating faster progression associated with striatal than neocortical Aβ. Lastly, we calculated the minimal slowdown in cognitive decline a hypothetical clinical trial could detect with 300 subjects (2 arms over 3-year duration; 80% power; α=0·05) if the trial would selectively enroll Stage2 instead of unselected high-Aβ individuals. In MCI, we found that a trial would detect an effect on MMSE of 24·7% or greater in Stage2-MCI compared to 51·3% in unselected high-Aβ. We found that a trial in CN would detect a drug effect on MMSE of 52·8% or greater in Stage2-CN compared to 93·8% in unselected high Aβ. Conclusions: Striatal Aβ-PET signal indicates increased risk of subsequent decline amongst high-Aβ non-demented individuals. PET staging including both striatal and neocortical Aβ measures may be useful in the context of anti-Aβ therapeutic trials as an inclusion criteria to select individuals most at risk of progression in the years following PET imaging. Further work will evaluate striatum as a potential endpoint in anti-Aβ trials. Figure 1 Acknowledgements This research is supported by an FNRS grant (SPD28094292), Stichting Alzheimer Onderzoek/Fondation Recherche Alzheimer, the NIH/NIA: P01AG036694/R01AG046396/P50AG00513421, the Alzheimer’s Association and the Harvard Neuro-Discovery Center Keywords: Aging, Cognition Disorders, Alzheimer Disease, PET imaging, Striatum, Amyloid, MMSE Conference: 12th National Congress of the Belgian Society for Neuroscience, Gent, Belgium, 22 May - 22 May, 2017. Presentation Type: Oral Presentation Topic: Disorders of the Nervous System Citation: Hanseeuw BJ (2019). PET staging of amyloidosis using striatum helps predicting cognitive decline in non-demented elderly. Front. Neurosci. Conference Abstract: 12th National Congress of the Belgian Society for Neuroscience. doi: 10.3389/conf.fnins.2017.94.00112 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 13 Apr 2017; Published Online: 25 Jan 2019. * Correspondence: Dr. Bernard J Hanseeuw, Cliniques Universitaires Saint-Luc, Neurology, Brussels, 1200, Belgium, bernard.hanseeuw@uclouvain.be Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Bernard J Hanseeuw Google Bernard J Hanseeuw Google Scholar Bernard J Hanseeuw PubMed Bernard J Hanseeuw Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page." @default.
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• W2912109148 title "PET staging of amyloidosis using striatum helps predicting cognitive decline in non-demented elderly" @default.
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