Rebecca Edelmayer, Ph.D.Director, Scientific EngagementMedical & Scientific Relations

Advancing the Science: The Latest in Alzheimer’s and Dementia Research

• I have no disclosures.• I am a full time employee of the Alzheimer’s

Association.

DISCLOSURES

Our mission is to lead the way to end Alzheimer's and all other dementia —by accelerating global research, driving risk reduction and early detection, and maximizing quality care and support.

• Landscape of Alzheimer’s and Dementia Science• Highlights in Early Detection and Diagnosis• Latest Advances in Clinical Trials, Treatments and

Lifestyle Interventions

OUR TIME TODAY

• Almost two-thirds of Americans with Alzheimer’s are women.

• Older African Americans and Hispanics are more likely, on per-capita basis, than older whites to have Alzheimer’s.

• Mostly due to health, lifestyle and socioeconomic risk factors

*2019 Alzheimer’s Disease Facts and Figures

GENDER, RACIAL AND ETHNIC DIFFERENCES IN ALZHEIMER’S PREVALENCE

• Allows the results to be a representation of the general public

• To investigate potential biological differences across diverse groups and their effects on drug efficacy and adverse events

• To identify socio-economic, behavioral and cultural risk factors

DIVERSITY IN CLINICAL TRIALS AND DEMENTIA RESEARCH

• Dementia is a collection of symptoms related to cognitive decline

• Can include cognitive, behavioral and psychological symptoms

• Due to biological changes in the brain• Alzheimer’s is most common cause• Mixed dementia is very prevalent• Some causes of cognitive decline are

reversible and not truly dementia

60%-80%

10%-40%~ 10%

10%-25%

~ 50%

DEMENTIA IS A SYNDROME

Cognitively Unimpaired

Mild Cognitive

ImpairmentMild

DementiaModerate Dementia

Severe Dementia

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

Impairment does not interfere with activities of daily living

Impairment in two or more cognitive functions that interfere with activities of daily living

CONTINUUM OF COGNITIVE IMPAIRMENT

Primary care providers may be especially well-positioned to perform this evaluation, ensure timely follow-up.

Early detection has medical, social, emotional, planning and financial benefits.

A cornerstone of early detection is assessment of cognitive impairment.

Resources from ALZ

https://www.alz.org/professionals/health-systems-clinicians/clinical-resources/cognitive-assessment-tools

https://www.alz.org/professionals/health-systems-clinicians/clinical-resources/cognitive-assessment-tools

Resources from ALZ

By working with the Alzheimer’s Association, your network will gain the knowledge and tools needed to:

assess cognition,

provide a timely diagnosis of Alzheimer’s or other dementias,

and receive the support required to direct patient management, including quality care.

HIGHLIGHTS IN BIOMARKERS

Cognitively Unimpaired Alzheimer’s Dementia

Biomarkers History & Cognition

MODERNIZING THE DIAGNOSIS

20years or more before symptoms appear,

the brain changes of Alzheimer’s may begin.

BIOMARKERS ARE CHANGING THE GAME

Biofluid Analysis Emerging MarkersBrain Imaging

National study on utility of amyloid PET scans~18,500 Medicare beneficiariesWith mild cognitive impairment (MCI) or dementia of uncertain cause

Aim 1: Impact of scan on care management planAim 2: Impact of scan on major medical outcomes

Two-thirds of participants had a change in their diagnosis and/or care management as a result of their PET scan results

THE IDEAS STUDY

• Recruit diverse cohort of 7,000 Medicare beneficiaries– At least 2,000 Black/African-American and 2,000

Hispanic/Latino– Early-onset and late-onset dementia– Typical and atypical clinical presentations of AD– Biorepository (DNA and plasma) and image archive

• Study approved by CMS 4/23/2020– Starting Fall 2020 enrollment, COVID-19 permitting– Approximately 350 sites, 3 years enrollment– Website: IDEAS-Study.org

NEW IDEAS: A STUDY TO IMPROVE PRECISION IN AMYLOID PET COVERAGE AND PATIENT CARE

FDA REGULATORY REVIEW NEWS

Flortaucipir / Tauvid

FDA REGULATORY REVIEW NEWS

CSF DiagnosticsLumipulse®G

β-Amyloid Ratio (1-42/1-40)

• 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

IN THE NEWS

PROGRESS TOWARDS A BLOOD TEST

TAU: ANOTHER BLOOD BIOMARKER EMERGES

While still in research stages, blood tests are easier to administer and more accessible than current methods of evaluating Alzheimer’s

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.

https://alz.org/aaic/pressroom.aspBarthelemy et al 2020 JEMHaanson et al 2020 JAMA

ADVANCES IN DRUG TREATMENTS

Adapted from PhRMA 2018

3 - 6 years 6 - 7 years 0.5 - 2 years

COMPLEXITY OF THERAPEUTIC DISCOVERY PIPELINE

FDA Approved Therapies for Alzheimer’s

AVAILABLE THERAPIES

Cholinesterase Inhibitorsdonepezil (Aricept) All Stagesrivastigmine (Exelon) Mild – Moderate Stagegalantamine (Razadyne) Mild – Moderate Stage

Glutamate Moderatorsmemantine (Namenda) Moderate – Severe Stage

Combinationdonepezil + memantine Moderate – Severe Stage(Namzaric)

• Currently, there are no therapies that can cure Alzheimer’s

• Some drugs are available to temporarily improve symptoms

• The field is making great progress in developing new and better therapies

Adapted from Cummings J., et al., 2020

ALZHEIMER’S DRUG DISCOVERY PIPELINE

The total number of participants required for

currently recruiting trials is 31,314

Over 350,000 Users

alz.org/trialmatch

300+ Clinical Studies at 500+ Locations

TrialMatch is a free clinical studies matching service designed to provide a customized list of potential study matches to each user.

HOW TO GET INVOLVED IN RESEARCH

BIOGEN SEEKS FDA APPROVAL FOR ADUCANUMAB

• Aducanumab (Anti-amyloid therapy)– Trial Population: MCI due to Alzheimer’s &

mild Alzheimer’s dementia• Futility Analysis Halted Trial: Mar 2019• Expanded Data Analysis Reported: Dec 2019

– Reduction in clinical decline– Effects on cognition and function– Reduction in amyloid/tau biomarkers

• FDA grants ‘Priority Review’: August 2020• FDA Advisory Board November 6, 2020• FDA decision anticipated: March 2021

MEDICINES FOCUSED ON BEHAVIORAL AND PSYCHOLOGICAL SYMPTOMS OF DEMENTIA

Pimavanserin (Nuplazid)• Dementia-Related Psychosis• Includes dementia related to Alzheimer’s,

Parkinson’s, Lewy Body, Vascular, Fronto-temporal

• Potential to be 1st FDA-approved psychosis drug in dementia population

• FDA grants ‘Standard Review’: Jul 2020• FDA decision anticipated: Apr 2021

Suvorexant (Belsomra)• Insomnia• Mild-to-Moderate Alzheimer’s• 1st FDA-approved insomnia

drug in dementia population

MEDICINES FOCUSED ON BEHAVIORAL AND PSYCHOLOGICAL SYMPTOMS OF DEMENTIA

• Environmental Mediated Factors• Sleep & Circadian Rhythms• Cell Death• Presenilin Biology• Proteostasis/Proteinopathies• Growth Factors and Hormones• Synaptic Plasticity/Neuroprotection• Neurogenesis• Multi-target• Others

• Amyloid Beta• Tau• Vascular• Genetics• APOE & Lipid Neurobiology• Immunity and Inflammation• Metabolism and Bioenergetics• Epigenetic Regulators• Oxidative Stress• Neurotransmitter Receptors

DIVERSE THERAPEUTIC MECHANISMS UNDER INVESTIGATION

UNDERSTANDING RISK & INTERVENTIONS TO REDUCE RISK

WHAT MAY IMPACT RISK:

• Age• Genetics• Race / Ethnicity• Environmental and Lifestyle Factors• Cardiovascular Health• Physical Activity• Diet• Sleep• Social / Cognitive Engagement• Education• Traumatic Brain Injury

Need to Study

Dementia Risk from

ALL Angles

40%Global Dementia May be

Preventable

FOCUS ON RISK REDUCTION 2020*

*Air PollutionTraumatic Brain InjuryExcessive Alcohol Use

The Lancet 2020 Commission on Dementia Report

Late-lifeMid-lifeAdult-life

Obesity

Hypertension

Dyslipidemia

Neuronal damage

Vascular insultsFirst Degree Family History

Dementia

APOE,other genes

DiabetesUnhealthy diet

Alcohol misuseSmoking Depression

Across the Lifespan

0 20 60 75

Education

Physical Activity Cognitive & Social ActivityAcross the Lifespan

Brain Reserve

Cognitive ReserveProtectiveFactors

Risk Factors

AD Riskimpact on neuron viability, inflammation, oxidative stress, glucose metabolism, endothelial cell damage, clearance of tau and b-amyloid from brain

Importance of Chronic Exposure to Multiple FactorsHEALTHY AND PATHOLOGICAL AGING?

• Combining 4 or 5 factors 59% lower risk• Combining 2 or 3 factors 39% lower risk• May even offset risk associated with genetics

COMBINING MULTIPLE HEALTHY LIFESTYLE FACTORS

HEALTHY DIET MODERATE TO VIGOROUS PHYSICAL ACTIVITY

LIGHT TO MODERATE ALCOHOL INTAKE

LITTLE TO NO SMOKING COGNITIVE STIMULATION

Investigating the long-term impact of

exposure to the novel coronavirus (SARS-CoV-2) on the brain, including cognition, behavior

and function.

ALZHEIMER’S ASSOCIATION SARS-CoV-2 INTERNATIONAL RESEARCH STUDY TO UNDERSTAND IMPACT ON THE BRAIN

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

ALZHEIMER’S ASSOCIATION SARS-CoV-2 INTERNATIONAL RESEARCH STUDY TO UNDERSTAND IMPACT ON THE BRAIN

de Erausquin GA et al., A&D 2021: https://alz-journals.onlinelibrary.wiley.com/doi/full/10.1002/alz.12255

Both observational and interventional studies are needed to translate research findings into community-based programs

Observational StudiesWhat factors increase or decrease our risk for dementia?

Interventional Studies What is the impact of reversing those risk factors?

• 9,000+ people, Over age 50, All-cause dementia risk

• Standard vs. Intensive Blood Pressure Intervention

• Intensive treatment 120 systolic vs. 140 systolic

• Dramatic reduction of small vessel disease on MRI

First Study to Demonstrate Reduction of New Cases of Cognitive Impairment

THE SPRINT-MIND STUDY 19% REDUCEDrisk for MCI

17% REDUCEDrisk for Dementia

15% REDUCED combined risk for MCI and Dementia

There are things you can do to reduce your risk of MCI and dementia –especially regarding cardiovascular disease risk factors.

WHY IS THIS IMPORTANT?

Immediate opportunity with life changing impact potential

• 1260 cognitively healthy60-77 year old adults, at increased risk for cognitive decline due to medical conditions

• 2-year study of Lifestyle Intervention vs. Usual Care

FINGER TRIAL

Cog

nitio

n

A 2 year study of Lifestyle intervention vs.Usual Care

Interpretation Findings from this large, long-term, randomized controlled trial suggest that a multidomain intervention could improve or maintain cognitive functioning in at-risk elderly people from the general population.Tiia Ngandu, Jenni Lehtisalo, Alina Solomon, Esko Lefälahti, Satu Ahtiluoto, Riita Antikainen, Lars Bäckman, Tuomo Hänninen, Anti Jula, Tiina Laatikainen, Jaana Lindström, Francesca Mangialasche, Teemu Paajanen, Satu Pajala, Markku Peltonen, Rainer Rauramaa, Anna Stigsdotter-Neely, Timo Strandberg, Jaako Tuomilehto, Hilkka Soininen, Miia Kivipelto

“A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial.” The Lancet. 2015 June 6

Number of subjects: 1260

Cognitively Healthy Adults: with increased risk for cognitive decline due to medical conditions

Age range: 60-77 years

Time: 2 years

MULTIDOMAIN INTERVENTION• Nutrition• Exercise • Cognitive training • Vascular risk monitoring

REGULAR HEALTH ADVICE

North Carolina Chicagoland

Northern CaliforniaHouston

Rhode Island/New England

Recruiting400 participants

per site

Participants will be randomized into either

Structured or Self-Guided lifestyle groups

Length of study

2000participants

5sites

2interventions

2years

500Randomized

If the interventions prove effective, this study will lead the way in the development of an accessible and sustainable community-based program for prevention

Physical Activity | Nutrition | Intellectual Engagement | Health Coaching

StructuredLifestyle

Intervention

Differ in format, expectations, and

accountability

A LANDMARK STUDY: TWO LIFESTYLE INTERVENTIONS

Self-GuidedLifestyle

Intervention

POINTER-Neuroimaging

NIA SUPPORTED ANCILLARY STUDIES |

POINTER-zzz

POINTER-Neurovascular POINTER-Microbiome

Countries in the planning phase for FINGER-like studies

Currently planning or implementing a FINGER-like study

U.S. POINTER

U.K.FINGER

FINGER

MIND-CHINA

MAINTAIN YOUR BRAIN

AU-ARROW

MIND-AD

GOIDZ-ZAINDUPENSA

LATAM-FINGER

CAN-THUMBS-UP

INDIA-FINGER

J-MINTSUPERBRAIN

SINGER

U.S. POINTER ISN'T ALONE

World-Wide FINGERS is a large,

international network sharing experiences and

data, and is collaborating to

prevent cognitive impairment &

dementia worldwide.

GLOBAL

2015

20252050

5.7million people

expected to develop Alzheimer’s in 2050 would not.

If we develop a treatment by 2025 that delays the onset of Alzheimer’s by just 5 years…

CHANGING THE TRAJECTORY OF ALZHEIMER’S DISEASE:

Delayed Onset

• 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– New resources and strategies to promote diverse

participation

• New research leading to future of therapy that combines drugs and modifiable risk factor interventions

• There is HOPE in research

IN SUMMARY…

ALZ.ORG

1-800-272-3900