entering the new era in Alzheimer s prevention research
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1 entering the new era in Alzheimer s prevention research Eric M. Reiman, M.D. Banner Alzheimer s Institute Translational Genomics Research Institute University of Arizona Arizona Alzheimer s Consortium
2 financial disclosures scientific advisor Amnestix/Sygnis, AstraZeneca, Baxter, Bayer, Chiesi, Eisai, Elan, Novartis, Eli Lilly, GlaxoSmithKline, Intellect, Novartis, Sanofi, Siemens, Takeda industry-supported research contracts Genentech, Avid/Eli Lilly, AstraZeneca NIH grants, foundation grants & philanthropy patent application biomarker strategy for the evaluation of preclinical AD treatments (pending)
3 proposition
4 why now
5 suggested but unproven risk-reducing strategies investigational disease-modifying treatments aerobic exercise mental exercise & socialization vitamins A, C, D, E, B12, B-complex supplements, folic acid anti-oxidants (but not gingko biloba) omega-3 fatty acids (in fish, nuts & leafy vegetables) curcumin (in curry) Mediterranean diet low caloric intake & weight loss copper-lowering diet, medications moderate use of wine, alcohol; resveratrol (in grapes, red wine) cholesterol-lowering agents anti-hypertensive agents insulin-sensitizing agents anti-inflammatory agents hormonal therapies (but not in older women) etcetera
6 how might you reduce your risk of AD? exercise your body & mind engage in social activity lower your cholesterol level & blood pressure lose excess weight treat your diabetes stop smoking fish, vegetables, nuts & omega-3 fatty acids help find demonstrably effective prevention therapies
7 what s been holding us back
8 APOE ε4 Copies prevalence % with AD onset age 0 73% 20% % 47% % 91% 68 adapted from Corder et al, Science 1993
9 preclinical detection and tracking of AD clinically affected at-risk Reiman et al, New Engl J Med 1996 & PNAS 2001, 2004, 2005, 2009; Chen et al, Am J Psychiatry 2007; Caselli et al, New Engl J Med 2009
10 preclinical detection and tracking of AD no APOE4 genes 1 APOE4 gene 2 APOE genes clinical AD Reiman et al, PNAS 2009
11 catch 22
12 preclinical AD treatments
13 a program to accelerate the evaluation of preclinical AD treatments
14 trial goals 1. to evaluate an anti-amyloid agent in the preclinical Rx of AD 2. to provide a better test of the amyloid hypothesis 3. to help establish reasonably likely surrogate endpoints 4. to provide a foundation for other preclinical AD trials 5. to complement, support & benefit from other initiatives 6. to provide a shared resource of data & samples 7. to help empower persons at highest imminent risk
15 Fleisher et al, Lancet Neurol 2012
16 API Composite Cognitive Test Score Rush ADC Cohorts 1. CERAD Word List Delayed Recall 2. Logical Memory Delayed Recall 3. MMSE Orientation to Place 4. MMSE Orientation to Time 5. Raven s Progressive Matrices PSEN1 E280A Antioquia Cohort 1. CERAD Word List Delayed Recall 2. Constructional Praxis 3. Boston Naming 4. MMSE Orientation to Time 5. Raven s Progressive Matrices Langbaum et al., AAIC abstr 2011, Ayutyanont et al., AAIC abstr 2011, and submitted manuscripts
17 preclinical AD trials API DIAN A4 Opal others
18 Alzheimer s Prevention Registry Executive Committee Jessica Langbaum, Marilyn Albert, Kyle Brown, Meryl Comer, Jeff Cummings, Jennifer Manly, Ron Petersen, Reisa Sperling, Gabrielle Strobel, Michael Weiner, Pierre Tariot, Eric Reiman
19 colleagues, collaborators & advisors Paul Aisen Patti Aguilar Marilyn Albert Gene Alexander Sergio Alvarez Darin Anderson Naomi Arana Jorge Arango Andrés Arbelaez Antonio Asun Napatkamon Ayutyanont Natalia Acosta-Baena Daniel Bandy Randy Bateman Laurel Beckett David Bennett Sean Bohen Donald Berry Scott Berry Regal Blanco Kaj Blennow Sarah Boggan John Breitner Helle Brand Kyle Brown Neil Buckholtz Maria Carrillo Richard Caselli Kewei Chen William Cho Meryl Comer Jeffrey Cummings Steven DeKosky Brad Dickerson Anne Fagan Tatiana Faroud Adam Fleisher Nick Fox Michel Friesenhahn Madelyn Gutierrez Gomez Margarita Giraldo Sandy Goodwin Hongbin Guo Margaret Gregorec Robert Green Gaby Hart Suzanne Hendrix Mary Lou Hernandez Nellie High Carole Ho David Holtzman Lee Honigberg Nathaniel Hudson Mathew Huentelman Debbie Intorcia Clifford Jack, Jr. Bill Jagust Laura Jakimovich Marlene Jimenez-Del-Rio Jason Karlawish Russell Katz Claudia Kawas Jennifer Keppler Louis Kirby William Klunk Robert Koeppe Kenneth Kosik Frank LaFerla Jessica Langbaum Carolyn Langlois Wendy Lee Xiaofen Liu Dona Locke Francisco Londono Francisco Lopera Liliana Lopez Facundo Manes Jennifer Manley Gary Marchant Ofelia Martinez Lazaro Martinez Chester Mathis Mark Mintun Hua Mo Candy Monarrez Tom Montine Sonia Moreno John Morris Marcelle Morrison-Bogorad Les Mullen Claudia Munoz Mark R Nishimura David Osborne Stephanie Parks Robert Paul Francisco Piedrahita Ronald Petersen Hillary Protas Anita Prouty Yakeel Quiroz Eric Reiman Rebecca Reiman Cole Reschke Hazel Richards Nicole Richter John Ringman Sarah Medina Rodriguez Auttawut Roontiva Allen Roses Adriana Ruiz Laurie Ryan Marwan Sabbagh David Salmon Christina Sampaio Jorge Santiago Karen Santoni Richard Scheller Dale Schenk Lon Schneider Aarti Shah Reisa Sperling Chantal Stern Gabrielle Strobel Joyce Suhy Shehnaaz Suliman Amy Sullivan Pierre Tariot Pradeep Thiyyagura Ronald Thomas Victoria Tirado Arthur Toga San Tran Jeff Trent John Trojanowski Carlos Velez-Pardo George Vradenburg Michael Ward Ryan Watts Michael Weiner Stacie Weninger
20 acknowledgements National Institute on Aging RF1 AG041705, R01 AG031581, P30 AG19610 Genentech Foundations Banner Alzheimer s Foundation, Anonymous Foundation, Nomis Foundation, Forget Me Not Initiative Colciencias , State of Arizona Arizona Alzheimer s Consortium Avid / Eli Lilly florbetapir PET our colleagues, collaborators, supporters & valued research participants
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