Abstract Details

Title Lack of Substantial Progression of Cognitive Deficits in Patients with Negative Amyloid Imaging: Implications for Clinical Trials

Topic Aging and Dementia

Presentation(s) IN3 - (-)

Poster/Presentation
Number 006

Objective

Background Patients without amyloid pathology may be enrolled in clinical trials for AD and may make these trials less efficient. Positron Emission Tomography (PET) imaging with the amyloid imaging tracer, florbetapir F18, could be used to improve patient selection for therapy trials, but data on how this could alter the power of a trial is limited.

Design/Methods Data from three trials with baseline florbetapir PET scans and 18 months of clinical follow up (one observational study of subjects with MCI or dementia, and the placebo arms of two randomized trials for AD) were combined for this analysis. We calculated progression on the ADAS-cog in subjects with a negative scan (SUVr?1.10), and compared it to progression subjects with a positive scan.

Results 73 out of 264 subjects had negative florbetapir scans (25/46 (54%) with MCI and 48/218 (22%) with dementia). In subjects with a negative scan, ADAS-cog scores increased by 1.19 points (SE = 0.85, p=0.16 compared to no change). The degree of cognitive decline after a negative scan did not differ between subjects with MCI or dementia (p=0.47 for the between-group difference). Subjects with positive imaging worsened significantly from baseline to 18 months (4.8 points, SE=0.54, p<0.001 compared to no change and compared to amyloid negative subjects). Depending on trial design and treatment assumptions, it can be calculated that trials could be up to 35% smaller if subjects with negative scans were excluded.

Conclusions Both MCI and dementia subjects with negative amyloid imaging demonstrate significantly less cognitive decline over 18 months of follow up than those with positive scans. These findings may have important implications for design of trials of disease-modifying treatments for AD.

Authors/Disclosures
Andrew D. Siderowf, MD PRESENTER	Dr. Siderowf has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Siderowf has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mitsubishi. Dr. Siderowf has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Boehringer-Ingelheim. Dr. Siderowf has received personal compensation in the range of $500-$4,999 for serving as a Consultant for askbio. Dr. Siderowf has received personal compensation in the range of $500-$4,999 for serving as a Consultant for capsida. Dr. Siderowf has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Parkinson Study Group. Dr. Siderowf has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Theravance. Dr. Siderowf has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurocrine. Dr. Siderowf has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Prilenia. Dr. Siderowf has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Wave. Dr. Siderowf has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Neurogastrix. Dr. Siderowf has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Prevail. Dr. Siderowf has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alerity. Dr. Siderowf has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Clintrex. Dr. Siderowf has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Inhibikase. Dr. Siderowf has a non-compensated relationship as a Scientific Advisory Board with NeuroPacs that is relevant to AAN interests or activities.
	No disclosure on file
Mark S. Freedman, MD, FAAN (University of Ottawa)	Dr. Freedman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Actelion(Janssen/J&J). Dr. Freedman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alexion. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BiogenIdec. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS/Celgene. Dr. Freedman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for EMD Inc. Dr. Freedman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi-Genzyme. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Freedman has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Actelion (Janssen/J&J). Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Atara Biotherapeutics. Dr. Freedman has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Bayer Healthcare. Dr. Freedman has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for BiogenIdec. Dr. Freedman has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Clene Nanomedicine. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for GRI Bio. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Magenta Therapeutics. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck Serono. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Freedman has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi Genzyme. Dr. Freedman has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Sanofi Genzyme. Dr. Freedman has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for EMD Serono. The institution of Dr. Freedman has received research support from Sanofi Genzyme.
Ming Lu	Ming Lu has received personal compensation for serving as an employee of Eli Lilly and Company. Ming Lu has stock in Eli Lilly and Company.
Mark A. Mintun, MD	Dr. Mintun has received personal compensation for serving as an employee of Eli Lilly & Co.
Michael J. Pontecorvo, PhD (Avid Radiopharmaceuticals)	Dr. Pontecorvo has received personal compensation for serving as an employee of Eli Lilly. Dr. Pontecorvo has stock in Eli Lilly.

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