1. The New Era of Alzheimer’s
Prevention Treatment Trials
Jessica B. Langbaum, PhD
Principal Scientist, Banner Alzheimer’s Institute
Associate Director, Alzheimer’s Prevention Initiative
Phoenix, Arizona

2. Debilitating
Alzheimer’s
Not a normal part of aging

3. Alzheimer’s vs. Dementia

4. Understanding Alzheimer’s
This neurological disease causes devastating
damage, ultimately robbing an individual of mental and
physical capacity
Its cause is still unknown, but a leading scientific
hypothesis links Alzheimer’s to excessive build-up of the
protein amyloid in the brain
Some people are at higher risk of developing Alzheimer’s
because of their genetic background

5. Understanding Alzheimer’s
Subtle changes begin taking place in the brain years before
the first problems with memory or thinking appear
Advanced imaging, biomarker techniques and sophisticated
cognitive measures can detect these changes in brain
structure and function
Promising treatments may need to be started at the pre-
symptomatic stage of the disease to have their most
profound effect

6. Alzheimer’s by the Numbers
Alzheimer’s cost of care is projected to reach
$1.1 trillion by 2050
Someone is diagnosed with Alzheimer’s
every 6.9 seconds in this country
5.4 million Americans are currently affected
by Alzheimer’s
Alzheimer’s is the 6th leading cause of death
in the United States
Alzheimer’s is the only top 10 cause of death
that cannot be prevented, treated or cured

7. 77% of U.S adults
are concerned
about
personal memory loss,
while 85%
are concerned over
memory loss
in loved ones

8. Alzheimer’s Prevention Trials – why
now?
The urgent need
Suggested but unproven “healthy lifestyle” interventions
Investigational Alzheimer’s disease modifying treatments
“Too little too late”
Biomarkers & sensitive cognitive measures

9. Preclinical Alzheimer’s Disease
Treatments: a proposed definition
“interventions started before the onset of cognitive decline and
intended to postpone the onset, reduce the risk of,
or completely prevent Alzheimer’s symptoms”
Reiman et al, Biomarkers Med 2010

10. Overview of Planned Alzheimer’s
Prevention Trials Starting in 2013
Trial Participants Where? Treatment Trial Specifics
ADCS “A4” •1,000 •US TBN •3 year clinical trial
•Age 70 - 85 1000 amyloid+ randomized 1:1 •Interim analysis at
• Amyloid + treatment to placebo 18months for
•500 amyloid- in natural biomarkers
history study
API • 300 in Colombia •US crenezumab (Genentech) •5 year clinical trial
• ~ 30 in US •Colombia 200 carriers randomized 1:1 •interim analysis at
• Age 30-60 treatment to placebo; 100 year 2
• ADAD kindred noncarriers to placebo
DIAN • 240 •US • gantenerumab (Roche) •2 year biomarker trial
•Age -15 to +10 years •Europe • solanezumab (Eli Lily) •will decide which
compared to parent age •Australia Potential: treatment to continue
of onset •Others may • BACE inhibitor (Eli Lilly) for 3 year trial
• ADAD kindred be added •160 carriers randomized to 3
drug arms or placebo; ~80
noncarriers to placebo
Zinfandel / •4, 000 •US • pioglitazone (Takeda)
Takeda •Age 62-83
• TOMM40+

11. ADCS “A4” Trial of a TBN Anti-Amyloid
Treatment
Individuals age 70-85 screened with amyloid PET
Amyloid+ Amyloid+ Amyloid-
(n =500) (n =500) (n= 500)
TREATMENT PLACEBO Natural History
ARM ARM Study
RCT PORTION OF STUDY

12. DIAN Treatment Trials
ADAD Mutation Kindred Members -15 to +10 years from parent age of dementia
onset
ADAD ADAD ADAD ADAD ADAD
carrier carrier carrier carrier non-carrier
(n = 40) (n = 40) (n = 40) (n = 40) (n = 80)
gantenerumab solanezumab BACE Pooled placebo placebo
(added later)
RCT PORTION OF STUDY COHORT PORTION OF STUDY

13. Alzheimer’s Prevention Initiative / Genentech
Treatment Trial – Colombia*
• 300 participants
– 200 carriers, 100 noncarriers
– Standard of care is not to disclose genetic
status
• up to 18 months for enrollment
• 104-260 week trial in 200 carriers to study
efficacy of treatment by comparing change in
in cognition and biomarkers
• Natural history (“cohort study”) of 100
placebo-treated carrier & non-carriers
* A separate US protocol will enroll ~30 carriers and non-carriers in a similar fashion

14. 5 PS1 Mutations in Colombia

15. Gloria cares for her sister Maria, age 61, who developed AD symptoms in her 40s.
Photograph by Todd Heisler, February 2009, courtesy of the NY Times, with permission

16. Alzheimer’s Prevention Registry
Inclusive, online community of people who are
passionate about advancing research in Alzheimer’s
Designed to help generate critical public awareness
around the disease
A shared resource benefiting the general research
community and organizations nationwide
People in the Registry may have the opportunity to
participate in research studies within their community
• Participants are sent emails informing them of potential study
opportunities, but are never any obligation to join a study
• All information is kept confidential and is not shared without
your explicit permission

17. What We Hope to Accomplish
Keep enrollees informed of latest news, advocacy to
drive focus on Alzheimer’s
Provide an unprecedented resource of potential
study participants for prevention research
, decreasing enrollment time
Offer valuable resources of simple, easy to
understand news in partnership with AlzForum

18. Our important goal is to register 100,000 people
by June 30, 2013

19. Joining the Registry

20. Visit www.endalznow.org

21. Complete this page…

22. …and this page

23. And you have joined!

24. Customize your community

25. Spread the Word!

26. Acknowledgments
• Drs. Pierre Tariot, Eric Reiman, Francisco Lopera, Adam
Fleisher, Lon Schneider, Ron Thomas and many more from
the Alzheimer’s Prevention Initiative
• Drs. Reisa Sperling and Paul Aisen from ADCS “A4”
• Drs. Randy Bateman, John Morris and Anne Fagan from
DIAN
• Colleagues from the Collaboration for Alzheimer’s Prevention
• Colleagues from Genentech
• National Institute on Aging, Geoffrey Beene Gives Back
Alzheimer’s Initiative and Banner Alzheimer’s Foundation