Submitted for Publication: August 23, 2010; final revision received January 11, 2011; accepted February 22, 2011.
Author Contributions: Dr Tariot had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Alzheimer's Disease Cooperative Study Group Members: Participating investigators and staff are Sandra Vicari, PhD (Southern Illinois University, Springfield); Lon Schneider, MD (University of Southern California, Los Angeles); Jody Corey-Bloom, MD, PhD (University of California, La Jolla); Nancy Barbas, MD, MSW (University of Michigan, Ann Arbor); Karen Bell, MD (Columbia University, New York, New York); Ranjan Duara, MD (Wien Center for Clinical Research, Miami Beach, Florida); Paul Rosenberg, MD (Johns Hopkins University, Baltimore, Maryland); M. Saleem Ismail, MD (University of Rochester Medical Center, Rochester, New York); Ruth Mulnard, RN, DNSc (University of California, Irvine); Myron Weiner, MD (University of Texas Southwestern Medical Center, Dallas); Larry Tune, MD (Emory University, Atlanta, Georgia); Jeffrey Burns, MD (University of Kansas, Kansas City); John Ringman, MD (UCLA [University of California, Los Angeles]); Martin Farlow, MD (Indiana University, Indianapolis); Geoffrey Ahern, MD, PhD (Arizona Health Sciences Center, Tucson); Paul Solomon, PhD (The Memory Clinic, Bennington, Vermont); John (Chuang-Kuo) Wu, MD, PhD (Northwestern University, Chicago, Illinois); Jacobo Mintzer, MD (Medical University of South Carolina, North Charleston); Walter Martinez, MD (Premiere Research Institute, West Palm Beach, Florida); David Geldmacher, MD (University of Virginia, Charlottesville); George Grossberg, MD (Saint Louis University, St Louis, Missouri); Zinaida Lebedeva, MD (North East Ohio Health Services, Beachwood); Marwan Sabbagh, MD (Banner Sun Health Research Institute, Sun City, Arizona); Thomas Obisesan, MD, MPH (Howard University, Washington, DC); Stephen Thein, PhD (Pacific Research Network, San Diego, California); Andrius Baskys, MD, PhD (Veterans Administration Healthcare System, Long Beach, California); Alan Lerner, MD (Case Western Reserve University, Beachwood, Ohio); William Petrie, MD (Psychiatric Consultants, Franklin, Tennessee); Smita Kittur, MD (Neurological Care of Central New York, Syracuse); Sanjay Gupta, MD (Global Research and Consulting, Olean, New York); Vernice Bates, MD (Dent Neurologic Institute, Amherst, New York); Yuval Zabar, MD (Lahey Clinic, Inc, Burlington, Massachusetts); Earl Zimmerman, MD (Albany Medical College, Albany, New York); Kevin Foley, MD (Saint Mary's Health Care, Grand Rapids, Michigan); Susan Schultz, MD (University of Iowa, Iowa City); Brian Ott, MD (Rhode Island Hospital, Providence); Jerome Yesavage, MD (Stanford/Palo Alto Institute for Research and Education, Palo Alto, California); Charles Bernick, MD (Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, Nevada); and Jason Karlawish, MD (University of Pennsylvania, Philadelphia).
Members of the Data and Safety Monitoring Board: Karl Kieburtz, MD (Chair, University of Rochester Medical Center, Rochester, New York), Bruce Miller, MD (University of California, San Francisco), Richard Kryscio, PhD (University of Kentucky, Lexington), and George Alexopoulos, MD (Weill Cornell Medical College, New York, New York).
Clinical Monitors: Karen Croot, BA, Viviana Messick, BS, Alan Pamoleras, BA, Rebecca Ryan-Jones, PhD (University of California, San Diego); Gina Garcia-Camilo, MD, Mario Schittini, MD, MPH, Amer Malik, MD (Mount Sinai School of Medicine, Bronx, New York; Kris Gravanda Brugger, BA, Pamela A. Saunders, PhD (Georgetown University, Washington, DC); and Janet Kastelan, MA (New York University, New York).
Financial Disclosure: During the trial, Dr Tariot served as a consultant to Abbott Laboratories, and the Banner Alzheimer's Institute received support as an investigative site in a multicenter Abbott-sponsored trial of a different antidementia agent. Dr Tariot also received grant or research support from AstraZeneca, Avid, Baxter, Elan Pharmaceuticals, GlaxoSmithKline, Johnson& Johnson, Eli Lilly, Medivation, Merck, Myriad, Pfizer, Takeda, and Wyeth; served as a consultant for or received consulting fees from AC Immune, Acadia, Adamas, Allergan, AstraZeneca, Avid, Baxter, Bristol-Myers Squibb, Eisai, Elan, Eli Lilly, Epix, Forest, GlaxoSmithKline, Medavante, Medivation, Merck, Myriad, Pfizer, Roche, sanofi-aventis, Schering-Plough, Toyama, Transition Therapeutics, Worldwide Clinical Trials, and Wyeth; and received stock options from Adamas and Medavante. Dr Schneider served as an editor on the Cochrane Collaborations Dementia and Cognitive Improvement Group, which oversees systematic reviews of drugs for cognitive impairment and dementia; received a grant from the Alzheimer's Association for a registry for dementia and cognitive impairment trials; received grant or research support from AstraZeneca, Baxter, Elan Pharmaceuticals, Forest Laboratories, Johnson& Johnson, Eli Lilly, Myriad, Novartis, Pfizer, Takeda, and Wyeth; and served as a consultant for or received consulting fees from Abbott Laboratories, AC Immune, Accera, Allergan, Allon, Alzheimer Drug Discovery Foundation, AstraZeneca, Bristol-Myers Squibb, Elan, Eli Lilly, Exonhit, Forest, GlaxoSmithKline, Institute IPSEN, Johnson& Johnson, Lundbeck, Myriad, Medavante, Medivation, Merck, Novartis, Pfizer, Roche, sanofi-aventis, Servier, Schering-Plough, Schwabe, Teva, Toyama, Transition Therapeutics, Voyager, and Wyeth. Dr Cummings served as a consultant to Abbott Laboratories, Acadia, Accera, ADAMAS, Astellas, Avanir, Bristol-Myers Squibb, CoMentis, Eisai, Elan, EnVivo, Forest, GlaxoSmithKline, Janssen, Lilly, Lundbeck, Medivation, Merck, Merz, Myriad, Neuren, Neurokos, Novartis, Noven, Orion Pharmaceuticals, Pfizer, Prana, reMYND, Schering-Plough, Signum Bioscience, Sonexa, Takeda, Toyama, and Wyeth; owns stock in ADAMAS, Prana, Sonexa, and Neurokos; owns the copyright of the NPI; and has served as an expert consultant on risperidone and ropinerol. Dr Loy received an investigator-initiated grant from Abbott Laboratories during the trial. Dr Ismail served on speakers' bureaus for Novartis, Pfizer, Merck, and Forest Pharmaceuticals, and received research support from the National Institute on Aging (NIA), National Institute of Mental Health, Bristol-Myers Squibb, Pfizer, and Merck. Dr Porsteinsson served on speakers' bureaus for Abbott, AstraZeneca, Eisai, Forest, Janssen, Ortho-McNeil, and Pfizer; consulted to Abbott, Eisai, Elan, Janssen, Medivation, Pfizer, Takeda, Transition Therapeutics, and Toyama; and received research support from Abbott, AstraZeneca, Baxter, BMS, Eisai, Elan, Eli Lilly, Forest, Janssen, Medivation, Merck, Mitsubishi, Myriad Neurosciences, Neurochem, Ono Pharma, Pfizer, Sanofi, Takeda, Toyama, and Wyeth. Dr Weiner served as an editor for Alzheimer's& Dementia: The Journal of the Alzheimer's Association; received research support from Merck and Avid; served as a consultant to Bayer Schering Pharma, Lilly, CoMentis, Neurochem, Sam and Rose Stein Institute for Research on Aging–University of California, San Diego, Eisai, Avid, Aegis, Genentech, Allergan, Bristol-Myers Squibb, Forest, Pfizer, McKinsey, Mitsubishi, Novartis, the National Institutes of Health (NIH), Department of Defense, and the Veterans Administration; received travel support from several nonprofit organizations; and received stock options from Synarc and Elan. Dr Jack received research support from the NIH, Pfizer, and Baxter; and consulted to GE, Lean, and Lilly. Dr Aisen served on a scientific advisory board for NeuroPhage; served as a consultant to Elan Corporation, Wyeth, Eisai Inc., Schering-Plough, Bristol-Myers Squibb, Eli Lilly, NeuroPhage, Merck, Roche, Amgen, Genentech, Abbott, Pfizer, Novartis, Bayer, Astellas, Dainippon, Biomarin, Solvay, Otsuka, Daiichi, and Medivation; received research support from Pfizer, Baxter, and the NIH (grants NIA U01-AG10483 [principal investigator], NIA U01-AG024904 [coordinating center director], NIA R01-AG030048 [principal investigator], and R01-AG16381 [Co-investigator]); and received stock options from Medivation and NeuroPhage.
Funding/Support: The NIA supported this trial (U01 AG 10483). Additional support was provided by a research grant and material support from Abbott Laboratories.
Role of the Sponsors: The study design was approved by an oversight committee of the NIA. Representatives of the NIA participated in steering committee meetings of the ADCS during the trial. The NIA was not otherwise involved in the design and conduct of the trial; in the collection, management, analysis, or interpretation of the data; or in the preparation, review, or approval of the manuscript. Abbott Laboratories did not participate in the design of the study, analysis or interpretation of the data, or preparation of the manuscript.
Additional Contributions: We acknowledge the valuable contribution of Husseini Manji, MD.