MacArthur Foundation 100Change Competition Citations

  1. The 2016 report of Alzheimer’s Disease International, the global federation of 85 Alzheimer’s Associations, projects 135 million dementia cases by 2050; global cost is projected to rise from $818 billion in 2016 to $1 trillion by 2018. 
    Global aging demographics outweigh a recent dip in incidence in developed countries (Apr 2016 Alzforum news), hence case numbers continue to grow. 
    Weuve J, Hebert LE, Scherr PA, Evans DA. Prevalence of Alzheimer disease in US states. Epidemiology. 2015 Jan;26(1):e4-6. PubMed.
    Hurd MD, Martorell P, Delavande A, Mullen KJ, Langa KM. Monetary costs of dementia in the United States. N Engl J Med. 2013 Apr 4;368(14):1326-34Hurd et al. 2013. PubMed
  2. Alzforum Therapeutics Database.
    UsAgainstAlzheimer’s Phase 2 Pipeline Report.
  3. Arizona Alzheimer’s Consortium, statewide collaboration on Alzheimer’s research.
    The Alzheimer’s Prevention Initiative persuaded industry to test their top potential therapies in two presymptomatic populations in Colombia and internationally who are at highest genetic risk of Alzheimer’s.
    The Dominantly Inherited Alzheimer’s Network and DIAN Trials Unit built global platforms to unite mutation carriers, track preclinical disease, and conduct prevention trials, and convened a broad industry consortium to support financially and with expertise (Dec 211 Alzforum news).
    The NIH launched AMP, a public-private partnership to find new targets for therapy.
    Collaboration for Alzheimer's Prevention (CAP), a leadership group to promote method harmonization and data sharing to spread the impact of prevention trials research (Weninger S, Carrillo MC, Dunn B, Aisen PS, Bateman RJ, Kotz JD, Langbaum JB, Mills SL, Reiman EM, Sperling R, Santacruz AM, Tariot PN, Welsh-Bohmer KA. Collaboration for Alzheimer's Prevention: Principles to guide data and sample sharing in preclinical Alzheimer's disease trials. Alzheimers Dement. 2016 May;12(5):631-2. PubMed; Aug 2012 Alzforum News).
  4. Perry D, Sperling R, Katz R, Berry D, Dilts D, Hanna D, Salloway S, Trojanowski JQ, Bountra C, Krams M, Luthman J, Potkin S, Gribkoff V, Temple R, Wang Y, Carrillo MC, Stephenson D, Snyder H, Liu E, Ware T, McKew J, Fields FO, Bain LJ, Bens C. Building a roadmap for developing combination therapies for Alzheimer's disease. Expert Rev Neurother. 2015 Mar;15(3):327-33. PubMed.
    Team leaders on this proposal publicly made a case for combination trials of two or more investigational therapies, before each has moved through the entire development process individually (Feb 2013 Alzforum news series, Jun 2013 Alzforum conference news).
  5. Reiman EM, Langbaum JB, Fleisher AS, Caselli RJ, Chen K, Ayutyanont N, Quiroz YT, Kosik KS, Lopera F, Tariot PN. Alzheimer's Prevention Initiative: a plan to accelerate the evaluation of presymptomatic treatments. J Alzheimers Dis. 2011;26 Suppl 3:321-9. PubMed.
    Langbaum JB, Fleisher AS, Chen K, Ayutyanont N, Lopera F, Quiroz YT, Caselli RJ, Tariot PN, Reiman EM. Ushering in the study and treatment of preclinical Alzheimer disease. Nat Rev Neurol. 2013 Jul;9(7):371-81. PubMed.
    Kozauer N, Katz R. Regulatory innovation and drug development for early-stage Alzheimer's disease. N Engl J Med. 2013 Mar 28;368(13):1169-71. PubMed.
    Expert commentary on FDA guidance on biomarker use in drug approval (Mar 2013 Alzforum news).
  6. The Lancet Neurology. Alzheimer's disease: a time for cautious optimism. Lancet Neurol. 2015 Aug;14(8):779. PubMed.
    Alzheimer’s Association Research Roundtable; Carrillo MC, Brashear HR, Logovinsky V, Ryan JM, Feldman HH, Siemers ER, Abushakra S, Hartley DM, Petersen RC, Khachaturian AS, Sperling RA. Can we prevent Alzheimer's disease? Secondary "prevention" trials in Alzheimer's disease. Alzheimers Dement. 2013 Mar;9(2):123-131.e1. PubMed.
    Nature article.
    Geriatric Medicine article about the Alzheimer’s Prevention Registry.
    TIME magazine article.
    Washington Post story about prevention research.
    Wall Street Journal story about Colombia trial.
    NPR segment on A4 trial.
    New Yorker article on A4, Alzheimer's prevention research.
  7. Boston Globe story on $8 million grant for A4 trial. 
    New York Times story on $33 million grant for Colombia trial.
    Of the 81 team members, nine (Eric Reiman, Reisa Sperling, Michael Weiner, William Jagust, Takeshi Iwatsubo, Clifford Jack, Ronald Petersen, John Morris, and Chet Mathis) have won the Potamkin Prize of the American Academy of Neurology, widely seen as the Nobel Prize of the Alzheimer's field.
    Miia Kivipelto, Randall Bateman, Chet Mathis, Ron Petersen, and John Morris won the MetLife Foundation Awards for Medical Research in Alzheimer's Disease; Keith Johnson and Randall Bateman won the Alzheimer’s Association Zenith Fellows award; numerous other awards among team.
  8. The paradigm shift and potential of prevention trials in populations at high genetic or biomarker risk of Alzheimer's has been widely recognized in media coverage around the world. "NOVA" documentary by Sarah Holt. Selected examples:
    New York Times story/video  by Pam Belluck
    CNN documentary by Felipe Barral.
    BBC Radio 4 story by Bill Law.
    "Today" show segment with Reisa Sperling.
    "CBS Evening News" segment on A4 prevention study, Reisa Sperling.  
    "CBS News" segment on DIAN network.
    2015 CBS segment on Alzheimer's prevention via DIAN.
    Article in Germany's Der Spiegel about DIAN as path to Alzheimer prevention therapies.
    Segment on CBS' "60 Minutes," scheduled to air in October/November 2016.
    Arizona Republic article on Banner’s AD prevention research.
    Scientific American article about prevention trial in Colombia.
    Fivethirtyeight article about DIAN.
    NPR story about DIAN.
    BBC story on DIAN.
    Huffington Post story on DIAN.
    CNN story on DIAN.
    New York Times story on DIAN.
    The Times Herald story on Generation study;
    Toronto Star story on API Colombia trial.
  9. NIH director Francis Collins announces API prevention trial in Colombia of Genentech antibody (May 2012 Alzforum news).
    NIH director’s blog about API Colombia research.
    New York Times editorial about this pioneering trial.
  10. No. 4, Scientific American World-Changing Ideas 2012 
  11. Alzheimer’s Prevention Initiative (Reiman EM, Langbaum JB, Fleisher AS, Caselli RJ, Chen K, Ayutyanont N, Quiroz YT, Kosik KS, Lopera F, Tariot PN. Alzheimer's Prevention Initiative: a plan to accelerate the evaluation of presymptomatic treatments. J Alzheimers Dis. 2011;26 Suppl 3:321-9. PubMed).
    Dominantly Inherited Alzheimer’s Network (Morris JC, Aisen PS, Bateman RJ, Benzinger TL, Cairns NJ, Fagan AM, Ghetti B, Goate AM, Holtzman DM, Klunk WE, McDade E, Marcus DS, Martins RN, Masters CL, Mayeux R, Oliver A, Quaid K, Ringman JM, Rossor MN, Salloway S, Schofield PR, Selsor NJ, Sperling RA, Weiner MW, Xiong C, Moulder KL,Buckles VD. Developing an international network for Alzheimer research: The Dominantly Inherited Alzheimer Network. Clin Investig (Lond). 2012 Oct 1;2(10):975-984. PubMed; Mills SM, Mallmann J, Santacruz AM, Fuqua A, Carril M, Aisen PS, Althage MC, Belyew S, Benzinger TL, Brooks WS, Buckles VD, Cairns NJ, Clifford D, Danek A, Fagan AM, Farlow M, Fox N, Ghetti B, Goate AM, Heinrichs D, Hornbeck R, Jack C, Jucker M, Klunk WE, Marcus DS, Martins RN, Masters CM, Mayeux R, McDade E, Morris JC, Oliver A, Ringman JM, Rossor MN, Salloway S, Schofield PR, Snider J, Snyder P, Sperling RA, Stewart C, Thomas RG, Xiong C, Bateman RJ. Preclinical trials in autosomal dominant AD: Implementation of the DIAN-TU trial. Rev Neurol (Paris). 2013 Oct;169(10):737-43. PubMed.).
    Anti-Amyloid Treatment in Asymptomatic Alzheimer’s Disease (A4) (Sperling RA, Rentz DM, Johnson KA, Karlawish J, Donohue M, Salmon DP, Aisen P. The A4 study: stopping AD before symptoms begin?. Sci Transl Med. 2014 Mar 19;6(228):228fs13. PubMedA4 Study).
    EARLY Trial  in cognitively healthy people at high risk of late-onset Alzheimer’s due to the presence of abnormal biomarkers in their central nervous system, 
    Accelerating Medicines Partnership.
    Alzheimer’s Disease Neuroimaging Initiative (ADNI): 10-year update in July 2015 Special issue of Alzheimer’s & Dementia journal.
    Alzheimer’s Disease Genome Consortium ADGC.
    European prevention of Alzheimer’s dementia consortium, EPAD website.
    Global Alzheimer’s Platform FoundationAug 2016 Alzforum news series on GAP/EPAD.
    Generation study—pioneering trial of two different investigational therapies in healthy people who carry ApoE4 risk gene. NIA calls Generation study "groundbreaking."
    Arizona Alzheimer’s Association. 
  12. The team united in this proposal has started registries to accelerate engagement and enrollment into prevention trials. e.g., Alzheimer’s Prevention Registry,
    Brain Health RegistryAug 2016 Alzforum conference news on EPAD registry, DIAN Expanded Registry.
    Dec 2015 Alzforum news on GeneMatch, a program to enable recruitment of ApoE4 risk gene carriers into the Generation trial and future prevention therapy trials.
    Ongoing research on safe and ethical disclosure of genetic and biomarker risk status to individuals (Sept 2016 Alzforum news).
  13. Eric Reiman leads six NIH grants for more than $100 million in NIH, more than $500 million in total funding. If this grant is funded, he will reduce other responsibilities to achieve the proposed goals. Reiman and team member Pierre Tariot led the formation of the Arizona Alzheimer's Consortium, the nation's leading statewide collaboration in Alzheimer's research. Since 1998, it leveraged state and in-kind funds to generate more than $1 billion in new contracts, grants, and organizational commitments, produced several thousand research publications, and launched leading research programs. Reiman proposed the NIH-funded AD Genetics Consortium to provide a large resource of DNA from well-characterized Alzheimer’s cases and controls. This collaborative paradigm has led to the discovery of about 20 new genetic risk factors. Reiman, Tariot, and colleagues established API, including the first prevention trials of persons at highest risk and exceptionally large registries to promote enrollment in prevention studies. They manage high-profile international collaborative projects. Reiman was asked by the Nobel Committee to share lessons learned from API's pioneering public private partnership. He has been asked by leaders from NIH, leading research consortiums, and other state legislators to offer lessons learned from the Arizona Alzheimer's Consortium's Collaborative model.
    Randall Bateman, with team member John Morris, has pioneered the DIAN network and prevention trials platform, widely viewed along with API to have inspired similar global efforts such as EPAD and A4. Bateman also developed research breakthroughs required for therapy development, such as techniques to quantify the production and breakdown to pathogenic proteins in the cerebrospinal fluid of people in real time.
    The Alzheimer's Association is positioned to support the work proposed here through its convening, fundraising, and advocacy platforms. As its CSO, Maria Carrillo serves as liaison to the scientific community and has catalyzed past and present initiatives to bring scientific advances into the practice of treatment and care, including Research Roundtable consensus meetings, development of new diagnostic guidelines, and evidence-gathering of new diagnostic procedures to obtain insurance reimbursement.
    In his role overseeing therapy development for Alzheimer's disease at the U.S. Food and Drug Administration, Billy Dunn has declared secondary prevention research a top priority. Dunn confers closely with his regulatory counterparts in Europe and Japan to ensure a harmonized regulatory approach to advising and guiding academic and industry scientists developing prevention trials.
    Laurie Ryan is chief of the Dementias of Aging Branch in the Division of Neuroscience at the National Institute on Aging and in this role oversees grant-making for clinical trials, including API, DIAN, A4 and others. 
    Reisa Sperling leads the A4 and well as the EARLY trials. They expand the pioneering prevention work the DIAN and API Colombian trials conduct in rare populations of people at highest genetic risk to the much larger general population. Sperling is a leader in developing brain imaging as a biomarker of presymptomatic Alzheimer's.
    Stacie Weninger oversees a private funding program that has supported DIAN, API, and many other innovative research projects from their earliest days. She leads and advises data and sample sharing initiatives such as CAP, see ref 3.