Author Contributions: Dr Aisen had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Aisen, Schneider, Sano, Diaz-Arrastia, Thomas, Thal.
Acquisition of data: Aisen, Schneider, Sano, Diaz-Arrastia, van Dyck, Weiner, Stokes.
Analysis and interpretation of data: Aisen, Schneider, Sano, van Dyck, Bottiglieri, Jin.
Drafting of the manuscript: Aisen, Schneider, Diaz-Arrastia, Weiner, Bottiglieri, Stokes.
Critical revision of the manuscript for important intellectual content: Aisen, Schneider, Sano, Diaz-Arrastia, van Dyck, Jin, Thomas.
Statistical analysis: Aisen, Schneider, Jin, Thomas.
Obtained funding: Aisen.
Administrative, technical, or material support: Aisen, Sano, van Dyck, Weiner, Stokes.
Study supervision: Aisen, Diaz-Arrastia, van Dyck, Bottiglieri, Thomas, Thal.
Financial Disclosures: Dr Aisen reported having been a consultant to the following pharmaceutical companies involved in the development of potential treatments for Alzheimer disease: Pfizer, Novartis, Janssen, Elan, Wyeth, Roche, Merck, Lilly, Bristol-Myers Squibb, Schering Plough, Neurochem, Medivation, GlaxoSmithKline, PamLab, and Adlyfe; receiving grant support from Pfizer, Elan-Wyeth, Merck, Lilly, Neurochem, Neuro-Hitech, and Myriad; and holding stock options in Medivation. Dr Schneider reported having been a consultant to Abbott, Accera, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Forest Pharmaceuticals, Lundbeck, Merz, Novartis, Pfizer, Johnson & Johnson, Wilmar Schwabe, all manufacturers of products used in the treatment of Alzheimer disease, and Roche, who provided the vitamin preparations for this trial. He also reported having provided expert testimony in litigation involving Eli Lilly and Lundbeck, both manufacturers of products used in the treatment of Alzheimer disease. Dr Sano reported having been a consultant to the following companies involved in potential treatments for Alzheimer disease: Bristol-Meyers Squibb, Elan, Esai, Forest, GlaxoSmithKline, Janssen, Novartis, Pfizer, Medivation, and Takeda; and having received grant support from the Alzheimer Association and from the National Institutes of Health. Dr van Dyck reported having been a consultant to Bristol-Myers Squibb and Forest Laboratories, pertaining to Alzheimer disease therapeutics; and having received grant support from Elan Pharmaceuticals, Pfizer Inc, GlaxoSmithKline, Myriad Pharmaceuticals, Eli Lilly, and Wyeth Pharmaceuticals, pertaining to Alzheimer disease therapeutics. Dr Bottiglieri reports having been the Chairman of the Advisory Board for Methylation Sciences Inc; holding stock options in Methylation Sciences Inc; and having received grant/research funding from PamLab LLC, distributor of B vitamins as a medical food. None of the other authors reported any financial disclosures.
Members of the Alzheimer Disease Cooperative Study Group: Participating Investigators and Staff: Sandra Vicari, PhD, Thomas Ala, MD, Karen Luster, RN (Southern Illinois University, Springfield); Joseph Quinn, MD, Joyce Lear, RN, MN, Tera Clay (Oregon Health & Science University, Portland); Lon S. Schneider, MD, Sonia Pawluczyk, MD, Karen Dagerman, MA, Shirley Sian (University of Southern California, Los Angeles); Adam Fleisher, MD, MAS, Mary M. Pay, APRN (University of California, San Diego); Nancy Barbas, MD, MSW, Joanne Lord, LPN, BA, CCRC (University of Michigan, Ann Arbor); Elaine Peskind, MD, Murray A. Raskind, MD, Linda Mandelco (University of Washington, Seattle); Rachelle S. Doody, MD, PhD, Jamie Sims, BS, Susan Roundtree, MD (Baylor College of Medicine, Houston, Texas); Karen Bell, MD, Ruth Tejeda, MD, Evelyn Dominguez-Rivera, MD (Columbia University, New York, New York); Linda Harrell, MD, PhD, Daniel Marson, JD, PhD, Edward Zamrini, MD (University of Alabama at Birmingham); Hillel Grossman, MD, George Marzloff, BS, Sirisha Nandipait, BA (Mount Sinai School of Medicine, Bronx, New York); Neelum Aggarwal, MD, Raj Shah, MD, Julie Bach, CSW (Rush University Medical Center, Chicago, Illinois); Eric Pfeiffer, MD, Barbara Luhn, MSW, CCRC, Jennifer Hunter, MA (University of South Florida, Tampa); Steven H. Ferris, PhD, Isabel Monteiro, MD, Erica Maya, BA (New York University Medical Center, New York); Christopher Clark, MD, Monica Han, BA, Cassie Pham, BS, Marianne Watson, RN (University of Pennsylvania, Philadelphia); Steven T. DeKosky, MD, Donna Simpson, CRNP, MPH (University of Pittsburgh, Pittsburgh, Pennsylvania); Saleem M. Ismail, MD, Bonnie Goldstein, RN, Coleen McCallum, MSW (University of Rochester, Rochester, New York); Ruth A. Mulnard, RN, DNSc, Catherine McAdams-Ortiz, RN, MSN, A/GNP, Beatriz Yanez, BA (University of California, Irvine); Myron Weiner, MD, Kathleen Koch, RN, MN, CCRC, Carol Moore, MA (University of Texas, Southwestern Medical Center at Dallas); Allan Levey, MD, PhD, Janet Cellar, RN, MSN, Andrea Kippels, RN, MSN (Emory University, Atlanta, Georgia); John Ringman, MD, Jenny Bardens, RN, Alice Yau (University of California, Los Angeles); Neill R. Graff-Radford, MD, Francine Parfitt, MS (Mayo Clinic, Jacksonville, Florida); Martin R. Farlow, MD, Ann Hake, MD, Patricia Numberger, RN (Indiana University, Indianapolis); Christopher van Dyck, MD, Martha MacAvoy, PhD, Nicole Black, BA, Pamela Hoffman, BS (Yale University, New Haven, Connecticut); Charles DeCarli, MD, William Seavey, MD, Cassandra Conover, RN (University of California, Davis); Geoffrey Ahern, MD, PhD, Marjorie Baldwin, RN, BSN, Mike Malek-Ahmadi, BA (University of Arizona, Tucson); Charles Bernick, MD, Donna Munic, PhD, Gail Vranesh, RN (University of Nevada, Las Vegas); Marsel Marek-Mesulam, MD, Nancy Johnson, PhD, Stephanie Epstein-Fields, MA (Northwestern University, Chicago, Illinois); Jacobo E. Mintzer, MD, Fay Ann Davis, LPN (Medical University of South Carolina, North Charleston); Justine Kent, MD, Mark Roffman, PhD (ClinSearch Inc, Kenilworth, New Jersey); Carl Sadowdky, MD, Teresa Villena, MD, Walter C. Martinez, MD (Premiere Research Institute, West Palm Beach, Florida); Kathleen Johnson, NP, Brigid Reynolds, NP, Carolyn Ward, MSPH (Georgetown University, Washington, DC); Sibyl Salisbury, BS (Brigham and Women's Hospital, Boston, Massachusetts); Jerome A. Yesavage, MD, Wesson J. Ashford, MD, Alena Pechonkina, MD, Lisa Kinoshita, PhD (Stanford/VA Aging Clinical Research Center, Palo Alto, California); Marwan Sabbagh, MD, Donald Connor, PhD, Sanja Obradov, CCRD (Sun Health Research Institute, Sun City, Arizona); Robert C. Green, MD, MPH, Robert A. Stern, PhD, Anil Nair, MD, Margarget Brickley, MS, ACNP, GNP-BC (Boston University School of Medicine, Boston, Massachusetts); Richard Caselli, MD, Judy Lawrence, RN (Mayo Clinic, Scottsdale, Arizona); Thomas Obisesan, MD, MPH, Odunayo A. Obisesan, PharmD, Ezenwanyi Ahaghotu, MS (Howard University, Washington, DC); Paul Ogrocki, PhD, Marianne Sanders, RN, Elaine Ziol, MHS, CCRC (Case Western Reserve University, Cleveland, Ohio); Brian R. Ott, MD, Janet Grace, PhD, Teresa Erbozkurt, MA (Rhode Island Hospital, Providence).
Data and Safety Monitoring Board: Karl Kieburtz, MD (University of Rochester School of Medicine and Dentistry, Rochester, New York); Bruce Miller, MD (University of California, San Francisco); Richard Kryscio, PhD (University of Kentucky, Lexington); 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 California, San Diego); Gina Garcia-Camilo, MD, Mario Schittini, MD, MPH (Mount Sinai School of Medicine, Bronx, New York); Kris Gravanda Brugger, BA, Pamela A. Saunders, PhD (Georgetown University, Washington, DC); Janet Kastelan, MA (New York University, New York).
Funding/Support: This study was supported by grant U01-AG10483 from the National Institute on Aging (NIA), as well as grants from the General Clinical Research Center Program of the National Center for Research Resources, National Institutes of Health. Folic acid and vitamins B6 and B12 were donated by Roche Inc.
Role of the Sponsors: The study design was approved by an oversight committee of the NIA. NIA representatives participated in meetings of the Steering Committee of the Alzheimer Disease Cooperative Study during the course of the trial. The NIA was not otherwise involved in the design and conduct of the study, in the collection, management, analysis, and interpretation of the data, or in the preparation, review, or approval of the manuscript. Roche Inc did not participate in the design of the study, analysis or interpretation of the data, or in the preparation of the manuscript.