Journal article

Determining clinically meaningful decline in preclinical Alzheimer disease

Philip S Insel, Michael Weiner, R Scott Mackin, Elizabeth Mormino, Yen Ying Lim, Erik Stomrud, Sebastian Palmqvist, Colin L Masters, Paul T Maruff, Oskar Hansson, Niklas Mattsson



OBJECTIVE: To determine the time required for a preclinical Alzheimer disease population to decline in a meaningful way, use estimates of decline to update previous clinical trial design assumptions, and identify factors that modify β-amyloid (Aβ)-related decline. METHODS: In 1,120 cognitively unimpaired individuals from 3 international cohorts, we estimated the relationship between Aβ status and longitudinal changes across multiple cognitive domains and assessed interactions between Aβ and baseline factors. Power analyses were performed to explore sample size as a function of treatment effect. RESULTS: Cognitively unimpaired Aβ+ participants approach mild cognitive impairment (MCI) levels o..

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Awarded by National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering


Funding Acknowledgements

Different funding agencies supported work at Lund University (for overall study coordination, and for the BioFINDER study) and the ADNI and AIBL studies. Work at Lund University in the authors' laboratory is generously supported by The Knut and Alice Wallenberg foundation, the Medical Faculty at Lund University, Region Skane, the European Research Council, the Swedish Research Council, the Marianne and Marcus Wallenberg foundation, the Strategic Research Area MultiPark (Multidisciplinary Research in Parkinson's disease) at Lund University, the Swedish Alzheimer Association, the Swedish Brain Foundation, the Skane University Hospital Foundation, the Bundy Academy, and the Swedish federal government under the ALF agreement. Data collection and sharing for the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Alzheimer's Association; Alzheimer's Drug Discovery Foundation; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; GE Healthcare; Innogenetics, N. V.; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Medpace, Inc.; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Synarc Inc.; and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research provided funds to support ADNI clinical sites in Canada. Private sector contributions were facilitated by the Foundation for the National Institutes of Health ( The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. A complete listing of ADNI investigators can be found at: List. pdf. Partial financial support of AIBL was provided by the Alzheimer's Association (US), the Alzheimer's Drug Discovery Foundation, an Anonymous foundation, the Science and Industry Endowment Fund, the Dementia Collaborative Research Centres, the McCusker Alzheimer's Research Foundation, the National Health and Medical Research Council (AUS), and the Yulgilbar Foundation, plus numerous commercial interactions supporting data collection. Details of the AIBL consortium can be found at and a list of the researchers of AIBL is provided at