Advancing the Science: The Latest in

Alzheimer’s and Dementia Research

Rebecca Edelmayer, Ph.D.
Sr. Director, Scientific Engagement
Medical & Scientific Relations
DEMENTIA IS A SYNDROME
Dementia
An ‘umbrella’ term used to describe a
range of symptoms associated with
• Dementia is a collection of symptoms cognitive impairment
related to cognitive decline
• Can include cognitive, behavioral and Alzheimer’s
psychological symptoms 60%-80%

• Due to biological changes in the brain

Vascular Lewy
• Alzheimer’s is most common cause
10%-40% Bodies
• Mixed dementia is very prevalent 10%-25% Frontotemporal
~10%
• Some causes of cognitive decline are
reversible and not truly dementia Mixed Dementia = > 1 Neuropathology Prevalence ~50%
 CONTINUUM OF COGNITIVE IMPAIRMENT

Impairment does not interfere Impairment in two or more cognitive functions

with activities of daily living that interfere with activities of daily living

Mild
Cognitively Mild Moderate Severe
Cognitive
Unimpaired Dementia Dementia Dementia
Impairment

MCI is a known risk factor for dementia

Everyone who experiences dementia passes through MCI
When you prevent new cases of MCI, you are preventing new cases of dementia
GENDER, RACIAL & ETHNIC DISPARITIES IN ALZHEIMER’S
PREVALENCE & CLINICAL TRIALS

Ethnoracial groups have

Older Black and Hispanic
been historically
Americans are
underrepresented in
disproportionately more
clinical studies,
Almost two-thirds of likely than older Whites to
underscoring the need for
Americans with have Alzheimer’s or other
more diversity in
Alzheimer’s are women. dementias.
dementia research.

Facts and Figures 2021

 Importance of Chronic
HEALTHY AND PATHOLOGICAL AGING? Exposure to Multiple Factors

Across the Unhealthy Alcohol

Risk Smoking Depression Diabetes
Lifespan diet misuse
Factors

APOE, Obesity Neuronal

other genes damage
Hypertension
First Degree
Vascular insults
Family History Dyslipidemia

0 20 Adult-life 60 Mid-life 75 Late-life Dementia

Brain Reserve
Education
Protective AD Risk Cognitive Reserve
Factors impact on neuron viability, inflammation, oxidative stress, glucose metabolism,
endothelial
Across cell damage, clearance
the Lifespan of tau and b-amyloid
Physical Activity from brain
Cognitive & Social Activity
GENETICS AND ALZHEIMER’S
GENETICS AND ALZHEIMER’S
Effect sizes of disease-associated gene
variants can differ between populations
APOE
-AA: 1.93 (1.72-2.17)
-EUR: 3.32 (3.20-3.45)
-JAP: 5.5 (4.4-6.9)*

ABCA7
-AA: 1.41 (1.21-1.65)
-EUR: 1.13 (1.09-1.18)
-JAP: NS

SORL1
-AA: NS
-EUR: 0.81 (0.76–0.88)
-JAP: 0.75 (0.66–0.85)*

*Miyashita et al. 2013. PLoS One; Beloy et Adapted from Shea Andrews and Alison Goate,
Ichan School of Medicine, Mt Sinai
al. 2019. Neuron
TIME FOR A PARADIGM SHIFT

While traditional risk factors studied in

predominantly White samples provide
useful information for understanding
disparities, we must incorporate “lived
experiences” of diverse participants
Hill, Perez-Stable, Anderson, Bernard, Ethn Dis 2015

Adapted from Barnes, L., AAIC 2020

 IMPACT OF COVID-19
IN PEOPLE LIVING WITH DEMENTIA

Most people with

dementia are 65 or 42,000 more deaths Many people with
older, which puts attributed to dementia are likely to
them at increased Alzheimer’s and have underlying health
risk of COVID-19. dementia during problems. This can
Many also may be COVID-19 in 2020 increase their risk for
living in —– 16% increase. COVID-19
congregate complications
settings.
IMPACT OF DEMENTIA ON COVID-19 INFECTION RISK

Dementia
African-
Americans COVID-19
Healthcare
close to 3x Disparities Racial
risk of COVID- disparities
Researchers analyzed health record 19 infection as
data from almost 62 million American Whites
adults

Potential Factors contributing to increased

vulnerability include comorbidities such as
Risk of contracting COVID-19 was 2x hypertension and diabetes, forgetting to
as high for people in the study with wash hands/social distance & living in
dementia than for those without it long-term care facilities.

Wang et al., Alzheimer’s & Dementia, 2021

COVID-19 AND THE BRAIN

• Studies have suggested COVID-

19 is able to get into the brain

• Impact may be direct or indirect

– Blood brain barrier
– Inflammation/ Immune response
– Vascular connections
– Other mechanisms?

de Erausquin GA et al., A&D 2021: https://alz-

journals.onlinelibrary.wiley.com/doi/full/10.1002/alz.12255
 ALZHEIMER’S ASSOCIATION SARS-CoV-2 INTERNATIONAL
RESEARCH STUDY TO UNDERSTAND IMPACT ON THE BRAIN

Investigating the
long-term impact of
exposure to the
novel coronavirus
(SARS-CoV-2) on
the brain, including
cognition, behavior
and function.

More Information: http://alz.org/SARS-CoV2-study

Photo courtesy Alissa Eckert, Dan Higgins, CDC
EARLY DETECTION AND DIAGNOSIS
BIOMARKERS ARE CHANGING THE GAME

Brain Imaging Biofluid Analysis Emerging Markers

PROGRESS TOWARDS A BLOOD TEST

• Global race to uncover and develop blood

based biomarkers for Alzheimer’s and other
dementia
• More research validating amyloid beta and
tau in blood by comparing to imaging and
cognitive testing
• New research on blood tests for alpha
synuclein and neurofilament light and other
markers
 TAU: ANOTHER BLOOD BIOMARKER EMERGES

Research suggests that a form of tau

called p-Tau217 is very specific to
Alzheimer’s and, when measured in
the blood, is highly accurate in
distinguishing Alzheimer’s from other
neurodegenerative disorders.

While still in research stages, blood tests are easier to administer

and more accessible than current methods of evaluating Alzheimer’s
https://alz.org/aaic/pressroom.asp
Barthelemy et al 2020 JEM
Haanson et al 2020 JAMA
 PROGRESS TOWARD
MORE EFFECTIVE DRUG TREATMENTS
 LANDSCAPE OF CLINICAL TRIALS FOR
ALZHEIMER’S & DEMENTIA: DRUGS AND DEVICES *

Phase I Phase II Phase III

129 191 62
Always a Need for Diverse Participants
* As of Apr. 2021
TREATMENTS BEING TESTED MAY BENEFIT…

Clinical Symptoms of Dementia or Change Disease Progression

Cognitive Behavioral & Psychological

• Memory • Depression
• Learning • Anxiety
• Thinking • Delusions
• Planning • Hallucinations
• Apathy
• Agitation
• Sleep disturbances
 Medicines Focused on Cognitive &
Functional Symptoms of Dementia
Lilly's Donanemab Slows
Clinical Decline of Donanemab (anti-amyloid therapy)
Alzheimer's Disease in
Positive Phase 2 Trial
INDIANAPOLIS, Jan. 11, 2021 /PRNewswire/ -- Donanemab,
• Cognition
an investigational antibody that targets a modified form of beta
amyloid called N3pG, showed significant slowing of decline in a • Early symptomatic Alzheimer’s
composite measure of cognition and daily function in patients
with early symptomatic Alzheimer's disease compared to
placebo in results from Eli Lilly and Company's (NYSE: LLY) • Phase 2 trial show significant slowing of cognitive decline &
Phase 2 TRAILBLAZER-ALZ study. Donanemab met the
primary endpoint of change from baseline to 76 weeks in the
Integrated Alzheimer's Disease Rating Scale (iADRS), slowing
daily function
decline by 32 percent relative to placebo, which was statistically
significant. The iADRS is a clinical composite tool combining • Novel aspects of trial design
the cognitive measure ADAS-Cog13 and functional measure
ADCS-iADL, two commonly used measures in Alzheimer's
disease. Donanemab also showed consistent improvements in • Must test positive on amyloid and tau PET
all prespecified secondary endpoints measuring cognition and
function compared to placebo but did not reach nominal
statistical significance on every secondary endpoint.
• Volunteers switched to placebo once amyloid plaque level
was lowered to normal levels
• A second, larger Phase 2 trial is still ongoing
 BIOGEN SEEKS APPROVAL FOR ADUCANUMAB

• Aducanumab (Anti-amyloid therapy)

– Ph 3 Trial Population: MCI due to Alzheimer’s &
mild Alzheimer’s dementia
• Futility Analysis Halted Trial: Mar 2019
• Expanded Data Analysis Reported CTAD: Dec 2019
– Reduction in clinical decline
– Effects on cognition and function
– Reduction in amyloid/tau biomarkers
• Open Label Extension Studies Launced: Mar 2020
• FDA grants ‘Priority Review’: Aug 2020
• FDA decision anticipated: June 7, 2021
CHANGING THE TRAJECTORY OF ALZHEIMER’S DISEASE:
Delayed Onset
If we develop a treatment by
2025 that delays the onset of
Alzheimer’s by just 5 years… 2050
2025

5.7
expected to
develop
2015 Alzheimer’s in
million people 2050 would not.
 IN SUMMARY…

• Alzheimer’s Association is the global leader for

Alzheimer’s and dementia science
• Exciting time in research
– New tools for detection and diagnosis
– Growing diversity of therapies under
investigation
• There is HOPE in research
1-800-272-3900

ALZ.ORG