Alzheimers Disease:

Impact, Policy and Science

10

State Policy: Examples of Topics

Early Detection and Diagnosis

Care and Case Management
Quality of Care
Workforce Development and Training
Caregiver Support
Home- and Community-Based Services
Long-Term Care
Safety
Legal Issues

11

12

How Much Federal Funding is

Required for Adequate Progress?
Alzheimers Association
Workgroups
Conclusion:
At least $2 billion per
year
Reaffirmed additional
groups over past
several years

13

$2B
4x

$450M

14

15

Alzheimers funding on cruise

control

16

What has happened to Alzheimers

funding instead

17

The Senates Recent Action

on Alzheimers Funding

18

The Senates Recent Action

on Alzheimers Funding

19

Advances in Alzheimers
Research

Maria Carrillo, PhD

Chief Science Officer
Alzheimers Association

Outline
Alzheimers Association & our leadership in
science
Dementia vs. Alzheimers disease
Risk factors associated with Alzheimers
Modernizing guidelines for Alzheimers and
advances in early detection / biomarkers
Possible prevention next generation of clinical
trials
Future of research

21

Alzheimers Association:
Who We Are

22
2 2

Nationwide Network of Support

Information and referral

Support groups
Care consultation
Safety services
Education, local conferences

24/7 Nationwide Helpline

800-272-3900
Information and referral
Over 140 languages
2 3

Resources to help YOU

By phone
800.272.3900

In person
alz.org/findus

Online
alz.org/care

2 4

Largest Non-Profit Funder of Alzheimers &

Related Dementia Research In World

Currently funding $80+

million to ~300 active
projects in 20 countries
Most Impactful Non-Profit
Funder of Alzheimers &
Dementia Thompson Reuters Web of
Science, 2015
2 5

Goal: Accelerate and fund what others

wont or cant to advance Alzheimers &
related dementia research:
Early Career Investigators
Innovative Ideas
Accelerate High Risk Trials
2 6

What is Cognitive Aging

Blazer et al. JAMA. 2015;313(21):2121-2122

2 7

Cognitive Function, By Age

Institute of Medicine, 2015

2 8

Developing Brain Gives Clues to

Brain Change with Age

Corel JL. Harvard

University Press, 1975

2 9

Age Related Changes

Many changes of our bodies as we age, including
our brains
Examples of changes in brain with age:
Shrinkage of specific parts of brain, especially prefrontal
cortex, hippocampus.
Changes in how brain cells communicate.
Changes in the brains blood vessels/ blood flow.
Damage by free radicals increases.
Increase in inflammation.

Adapted from NIA/NIHs Alzheimers

Disease: Unravelling the Mysteries

3 0

Alzheimers Disease & Related

Dementia

3 1

The Alzheimers Epidemic

Continues to Grow

5.4

$1.1
TRILLION IN 2050

$236

BILLION
BILLION IN
IN 2016
2016

million Americans of ALL ages

will have Alzheimers in 2016

Total cost of care for those with Alzheimers,
with more than two-thirds paid by Medicare and Medicaid

Alzheimers
Association Facts &
Figures 2016

3 2

Alzheimers Plaques & Tangles

tangles

plaques

3 3

TAU

TDP-43
Clinical
Spectrum
CN MCI Dementia

Other (i.e.
Oxidation,
Inflammation,
Insulin)

Alpha
Synuclein

Clinical
Brain Changes

Vascular
Disease

Adapted from Dr. Ronald Petersen, Mayo Clinic

Risk Related to Cognitive Decline &

Alzheimers Disease
Age
Heart-head connection
Increased risk suspected if
high blood pressure, heart
disease, stroke, diabetes and
high cholesterol

Head injury
Our Genes: Family History
and Sex (XX or XY)
35

Understanding Genetics &

Alzheimers
Deterministic

Risk
APOE

Relatively rare: 1-3% of all

cases of Alzheimers
36

In the News: Validation of Ethnicity

Specific Genetic Risk Factor
In 2013, ABCA7 shown to increase
risk in African Americans
specifically
Unable to validate due to lack of
African American participants in
clinical studies
Alzheimers Association provided
funding to support validation
studies
First confirmation of this linkage
validated in independent
population
et al. 2016
Nature Genetics
Cukier

3 7

Lifetime Risk for Alzheimers is

Greater for Women

AD Risk

Yang and Levey, Womens

Health Issues 2015

AD Caregiver

AD Risk + Caregiver

3 9

Duration & Course of Illness:

Different for Men and Women

Duration of AD
Yang and Levey, Womens
Health Issues 2015

Nursing Home Stay

Community

4 0

Womens Alzheimers
Research Initiative
Convened think tank on
Gender Vulnerabilities for
Alzheimers in May 2015
Focus on biological
mechanisms, lifestyle factors
Launched Sex & Gender in
Alzheimers (SAGA)
Received over 150+ applications
Expect have $$$ for ~8 awards
Estimate 24 meritorious projects

41

Baumgart et al. 2016

Alzheimers &

4 2

Factors that Increase/ Decrease

Risk of Cognitive Decline

Baumgart et al. 2016

Alzheimers &

4 3

Factors that Increase/ Decrease

Risk of Dementia

Baumgart et al. 2016

Alzheimers &

4 4

Statement of Evidence: Modifiable Risk

Factors for Cognitive Decline & Dementia
(1) Regular physical activity and management of
cardiovascular risk factors (diabetes, obesity,
smoking, and hypertension) have been
shown to reduce the risk of cognitive decline
and may reduce the risk of dementia;
(2) Healthy diet and lifelong learning/cognitive
training may also reduce the risk of cognitive
decline;
(3) There are still many unanswered questions
and significant uncertainty with respect to the
relationship between individual risk factors
and dementia.
Baumgart et al. 2016
Alzheimers &

4 5

10
Ways
to
LOVE
Your
Brain
4 6

Modernizing the Diagnosis of

Alzheimers Based on a Continuum
2011

4 7

Continuum of Alzheimers Disease

Normal

Alzheimers disease

Adapted from Sperling et al. 2011

4 8

Modernizing the Diagnosis of

Alzheimers Based on a Continuum
Normal

Pre-clinical

Biological changes,
Cognitively normal

MCI

Subjective problem
in memory or another
domain, informant
corroborated and
measurable on tests;
normal overall
cognition and ADLs

Alz dementia

Clear deficits in 2 or
more core cognitive
domains;
ADLs affected

4 9

PET/CSF

?CSF

Clinical
Brain Changes
Biomarker

TDP-43

TAU
Clinical
Spectrum
CN MCI
Dementia

Alpha
Synuclein
?CSF

PET/CSF

Other
Vascular
Disease

MRI

Adapted from Dr. Ronald Petersen, Mayo Clinic

Alzheimers
Disease

DVR = 1.0

2.0

Normal
Aging

PET Amyloid Imaging

Figures courtesy of
Drs Keith Johnson/
Reisa Sperling

5 1

100 minutes

80 minutes

Alzheimers disease: Tau Imaging

Healthy
Individual

Mild Cognitive
Impairment

Mild
Alzheimers

Severe
Alzheimers

JT Chien et al. Journal of Alzheimers Disease 2013

5 2

Accelerating Progress: Bench to Bedside

PET Amyloid Imaging
2001: First Alzheimers Association grant to Dr.
William Klunk, PiB
2006: Alzheimers Association funding of PiB Add
On in ADNI ($2.1M)
2010: FDA Testimony on standard for approval of
Amyloid Imaging
2012: FDA approval of first amyloid imaging
agent
2013: Testimony to CMS on Appropriate Use of
Amyloid Imaging
2013: FDA approval two additional amyloid
imaging agents
2015: CMS Approval of the IDEAS Study
5 3

IDEAS (Imaging Dementia Evidence

for Amyloid Scanning) STUDY
2013 CMS denied coverage except
Coverage with Evidence Development
(CED) Demonstrate that technology
improves health outcomes for people with
Alzheimers
IDEAS Study Protocol:
4-year, $100 million new dollars, 2016
Announced on April 16 by the Alzheimers
Association and the American College of
Radiology (ACR).
$80M CMS, $19M Manufacturers,
$1M Alzheimers Association
Image adapted from
Clark et al. (2011) JAMA
305(1).

5 4

IDEAS (Imaging Dementia Evidence

for Amyloid Scanning) STUDY
Goal: To determine clinical usefulness, value in
diagnosing Alzheimers (and other dementias) of a
brain PET scan that detects amyloid plaques a
core feature of AD.
18,488 Medicare beneficiaries, 65 or older, w/
uncertain diagnosis will be enrolled at approximately
300 sites throughout the United States.
Data from this study will help determine if Medicare
will reimburse the cost of amyloid PET scans for
diagnostically uncertain cases. Medicare does not
currently cover amyloid PET scans.
5 5

Where are amyloid agents

available in USA?

IDEAS-Study.org

How Do People Enroll in the

IDEAS Study?
Enrollment through a Dementia
Specialist who is participating in the
study.
Once enrollment begins (expected Jan
2016), a list of Dementia Specialists
and Imaging Sites will be available.

IDEAS-Study.org

For Information and Registration

Go to:
ideas-study.org

IDEAS-Study.org

Prevention of Alzheimers?

59

Collaboration for Alzheimers

Prevention (CAP)

60

DIAN-TU: DIAD Trial

Dominant Inherited Alzheimers
Disease (DIAD) Network Trials Unit
2 prevention trial & biomarker
validation
Two drugs being tested:
Solanezumab & Gantenerumab
$4.2 million invested by the
Association to launch the trial
Additional $500,000 to initiate tau
imaging in DIAN-TU trial

First report out anticipated late 2016

(Biomarkers) and late 2017
(Cognition)
6 1

Accelerates DIAN NexGen Trial with

$4.3 Million Award
Award supports foundation for
next generation of clinical trials,
includes: tau PET imaging and
home based cognitive
assessments
Accelerates testing of potential
therapies in DIAN NexGen
launch by at least 1 year
Sets foundation to consider &
execute combination therapy
62

Alzheimers Prevention Initiative:

APOE4 Study
Two Copies of Risk Gene
1,300 adults, age 60-75
Partnering with Novartis two
drugs:
CAD106: active immunotherapy
Beta secretase inhibitor

Received NIH $33.2 million

Alzheimers Association lead
funder in partnership for a $10
million commitment
63

Rx?

PET/CSF

Rx?

Rx?
?CSF

Clinical
Brain Changes
Biomarker
Therapy
?CSF

TDP-43

PET/CSF

TAU
Clinical
Spectrum
CN MCI
Dementia

Alpha
Synuclein

Other
Vascular
Disease

Rx?

?
Rx?

MRI

Rx?

Adapted from Dr. Ronald Petersen, Mayo Clinic

Alzheimers Combination Therapies

Opportunity (ACTO)
Combination therapies treat
complex diseases (cancer,
HIV/AIDS, TB & heart diseases)
Launched ACTO in partnership
with ADDF and Alzheimers
Society in the UK
Goal: To facilitate & launch
clinical trials with new
investigational drugs in combo
in late 2016/early 2017
6 5

If Alzheimers onset is delayed

by 5 years

6 6

In Summary
Alzheimers Association is the global leader in
research, providing care and support to all of
those affected, and leading the public policy
efforts
Significant increases in research funding are
moving in right direction
Alzheimers disease is a continuum; need to
identify earliest biological change and intervene
at that time point
There is hope in research!
6 7

alz.org

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