alzheimer’s research updates

Alzheimer’s Research Updates

2014 ACL/CDC/NIA Alzheimer’s Webinar SeriesSeptember 25, 2014

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DISCLOSURE STATEMENTS In compliance with continuing education requirements, all presenters must disclose any financial or other associations with the manufacturers of commercial products, suppliers of commercial services, or commercial supporters as well as any use of unlabeled product(s) or product(s) under investigational use. CDC, our planners, presenters, and their spouses/partners wish to disclose they have no financial interests or other relationships with the manufacturers of commercial products, suppliers of commercial services, or commercial supporters. Planners have reviewed content to ensure there is no bias. Please note that presentations and content will not include any discussion of the unlabeled use of a product or a product under investigational use with the exception of Dr. Craft’s discussion on intranasal insulin. She will be discussing an ongoing clinical trial of intranasal insulin for the treatment of Alzheimer’s disease. Dr. Craft’s research study receives investigational devices and drugs at no cost and with no restrictions from Kurve Technology (device) and Eli Lilly (insulin and placebo). 3

DISCLOSURE STATEMENTS (Cont.)

In addition, please note Dr. Brinton's relationship with Sage Therapeutics (biotech partnership) and her patents for PhytoSERMs and Allopregnanolone for Neurodegenerative Disease.

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mailto:[email protected]

Recruiting Older Adults into Research –ROAR (ACL-NIH-CDC)

Contact [email protected]

Materials available at: http://www.nia.nih.gov/health/publication/roar-toolkit

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mailto:[email protected]

http://www.nia.nih.gov/health/publication/roar-toolkit




ResearchMatch

Go to: https://www.ResearchMatch.org/roar You must have an email address to sign up. You can call 1-866-321-0259 if you need help with online registration.

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https://www.researchmatch.org/roar

https://www.researchmatch.org/roar

• Sources of Research Support– National Institute on Aging– Paul Slavik Trust– Norris Foundation

• Biotech Partnership– Sage Therapeutics

• Patents– PhytoSERMs– Allopregnanolone for Neurodegenerative Disease

Brinton Disclosure of Interest Statement

Alzheimer's Phenotypes of Risk: Therapeutic Opportunities

for Prevention and Treatment

Webinar on Alzheimer’s Research Updates 2014

Roberta Diaz Brinton, Ph.D.University of Southern California, Los Angeles, CASchools of Pharmacy, Engineering and Medicine

http://pharmweb.usc.edu/brinton-lab



From Discovery to Clinical Trial

Discovery Science

IND-Enabling Translational

Research

FDA Investigational

New Drug (IND) Clinical Trial

Alzheimer’s

Disease

Alzheimer’s

Multiple Phenotypes = Multiple Targets =

Multiple Therapeuticsn

n

Multiple LOAD Etiologies Multiple Prodromal PhenotypesMultiple Progression Trajectories

Roberta Diaz Brinton, Ph.D.

NIA AD Summit 2012

Pre-Cambrian AD Therapeutics

Alzheimer’s

Disease


Alzheimer’s

n

n

Lessons learned:

oTransitions of aging to AD pathology involve a set of sequential, system-level adaptions.oThe aging brain is a dynamic adapting system with survival

back-up mechanisms. oFemale and male brains bioenergetically age differentlyoPerturbing one component of the system induces

adaptations in other components- not a course correction – becomes a different functioning system. oWindows of opportunity. Therapeutics have a limited

window of opportunity. One type therapeutic will not fit all for all time.

Roberta Diaz Brinton, Ph.D., NIA AD Summit 2012

Alzheimer’s

Disease


n

n

64%36%Women Male

WHY?

Alzheimer’s Association Facts & Figures 2011

Alzheimer’s

51 75

Perimenopause

Prodromal AD

Age 45

Average Age of Menopause

Average Age of AD Diagnosis

PerimenopausalTransition

METABOLIC SHIFTRis

k of

Alz

heim

er’s

Dis

ease

Hot FlushInsomnia

Cognitive DeficitsMood Disorder

DepressionInflammation

Phenotype of Endocrine Aging of Female Brain: Time line to Alzheimer’s

Estrogen: Bioenergetic System Regulator

Estrogen

Nilsen, Irwin et al.,, J Neuroscience 2007; Brinton TINS 2008; Brinton TIPS 2008; Yao et al., Molecular Aspects of Medicine, 2011

Fatty Acid Metabolism

Beta Amyloid Processing

Mitochondrial Function

Glucose Metabolism

Reproductive Senescence is Associated with Shifts inBioenergetic and β-Amyloid Processing Gene Expression

11% of Persons are Over 65 are Projected to Develop Alzheimer’s

Rettberg, Mack, Hodis, Brinton

Cluster 1 (n = 209)Healthy Metabolic Profile• Low HOMA score• Low glucose• High HDL, low LDL• Low triglycerides• Low blood pressureCluster 2 (n = 191)High Blood Pressure • Low glucose and HOMA• Lower HDL, higher LDL• Higher triglycerides• Very high blood

pressureCluster 3 (n = 102)Poor Metabolic Profile• High HOMA score• High glucose• High triglycerides• High HbA1c

Plot of Canonical Variables Identified by Cluster

Can

on

ical

1

Canonical 2

Rettberg, Mack, Hodis, Brinton,

ELITE “Healthy Women” At RiskHodis, Mack NIA - AG0025, R01AG024154

***

*

BASELINE COGNITIVE PERFORMANCE

Adjusted for stage of menopause and randomization to treatment group

Phyto β SERMs/ Development Plan and Timeline

NIA R01 AG 033288

Team: Schneider / BrintonDevelop a standardized formulation of ER-β selective phytoSERMs for vasomotor symptoms and to prevent for

age-related cognitive decline and dementia.http://clinicaltrials.gov/ct2/show/NCT01723917?term=phytoserms&rank=1

AIMS

1. Develop the formulation of ERβ-selective PhytoSERMs.

2. Perform first-to-human, dose-ranging, placebo-controlled, bridging studies (phase 1b) in postmenopausal women with vasomotor and memory complaints to assess tolerability, feasibility, PK, potential outcomes, and potential peripheral biomarkers (peripheral lipid peroxidation and mitochondrial function) to support a subsequent proof of concept trial.

3. Conduct a proof of concept (Phase 2a), double-blind treatment with placebo or 1 of 2 doses of PhytoSERMs for 12 weeks. 72 participants. Dose-ranging trial using doses obtained to assess tolerability, safety, potential efficacy, and biomarkers.

Estrogen Receptor-β PhytoSERMs for Management of Menopause and Age-Associated Memory Decline

http://clinicaltrials.gov/ct2/show/NCT01723917?term=phytoserms&rank=1

http://clinicaltrials.gov/ct2/show/NCT01723917?term=phytoserms&rank=1

White Matter Degeneration

Decline in Regenerative Capacity

Hypometabolism / Mitochondrial Dysfunction

Inflammation

Neurofibrillary Tangles

Severe Brain Atrophy

Beta Amyloid Plaque

Sta

ges

of P

atho

logy

Dev

elo

pme

nt in

Alz

heim

er’s

Dis

ease

Prodromal Diagnosis Death

Usual Therapeutic Intervention

Allo Therapeutic Intervention

Allopregnanolone as a Regenerative Therapeutic

Brinton, Nature Reviews Endocrinology, 9:241-250, 2013

Wang, et al.,J Neurosci. 11; 25(19): 4706-18, 2005

Allopregnanolone as a Regenerative and Disease Modifying Therapeutic


Allopregnanolone Restores Learning and Memory in Transgenic Mouse Model of Alzheimer’s

Allopregnanolone Development Plan and Timeline

Allopregnanolone Preclinical and Clinical Safety Profile

Allopregnanolone as a Regenerative TherapeuticStage of Development

Discovery & Mechanism of Allo Action- Achieved

Translational Feasibility / Formulation Development

Achieved

IND-Enabling /

FDA Approved

IND Achieved

Phase 1 Multiple

Ascending Dose /

3 month Allo treatment


Predicted Therapeutic Window forAllopregnanolone as Regenerative Therapeutic

Allopregnanolone as a Regenerative TherapeuticPhase 1 Multiple Ascending Dose and Safety Trial

Phase 1:

Determine Maximally Tolerated (Sedative) Dose

4 Ascending Doses /

Once week/ for 3 months

USC ADRC

Participants:

16 post-menopausal women

16 men

MCI due to AD or early AD

55-80 yrs of age

Primary Outcomes: Maximally Tolerated Dose

MRI for ARIASecondary Outcomes:

Exploratory Chronic Safety and Feasibility at 4-Doses

MRI Based BiomarkersCognition

NIA UF1-AG046148

http://clinicaltrials.gov/ct2/show/NCT02221622?term=Allopregnanolone&rank=2



Exploratory Outcomes of Allopregnanolone Clinical Trial

Alzheimer’s

Disease


Alzheimer’s

Multiple Phenotypes = Multiple Targets = Multiple

Therapeuticsn

n

Roberta Diaz Brinton, Ph.D.NIA Webinar 2014

Lessons learned (recap):oTransitions of aging to AD bioenergetic phenotype

involve a set of sequential, system-level adaptions.oThe aging brain is a dynamic adapting system with

survival back-up mechanisms. oFemale and male brains bioenergetically age

differentlyoPerturbing one component of the system induces

adaptations in other components- not a course correction – becomes a different functioning system. Systems biology therapeutics.oWindows of opportunity. Therapeutics have a

limited window of opportunity. One type therapeutic will not fit all for all time.

Discovery ,Translation and Clinical Trial Teams and Supporters

Discovery to Clinical Trial

Roberta Diaz Brinton, Ph.D.

Junming Wang, Ph.D.

Ronald Irwin, Ph.D.

Shuhua Chen, Ph.D.

Jia Yao, Ph.D.

Christine Solinsky

Karren Wong

Claudia Lopez

Regulatory

Ronald Irwin, Ph.D.

Frances Richmond, Ph.D.

Benson Kuo, Ph.D.

Toxicology

Kathleen Rodgers, Ph.D.

Ronald Irwin, Ph.D.

Clinical

Lon S. Schneider, M.D.

Wendy Mack, Ph.D.

Helena Chui, M.D.

Karen Dagerman

Steve Paul, M.D.

William Potter, M.D.

Allo cGMP & PK UC Davis

Michael Rogawski, M.D.

Gerhard Bauer, Ph.D.

Brain Imaging

Meng Law, M.D.

Michael Weiner, M.D.

Synarc

Arthur Toga, Ph.D.

DSMB

Claudia Kawas, M.D.

David Elashoff, Ph.D.

Charles DiCarli, M.D.

iPS Cells

Justin Ichida, Ph.D.

Christine Solinsky

CROs

SRI

WIL Research

Supporters

National Institute on Aging

Norris Foundation

Whittier Foundation

ADDF

New Advances in Prevention and

Treatment of Alzheimer’s DiseaseSuzanne Craft, PhDProfessor of Internal MedicineResearch Director, Sticht Center on Aging

Wake Forest Baptist Medical Center

Disclosures

• Suzanne Craft’s research study receives investigational device and drug at no cost and with no restrictions from Kurve Technology (device) and Eli Lilly (insulin and placebo)


Overview A new view of a major path to Alzheimer’s

disease: The epidemic of insulin resistance

How does insulin resistance and related conditions such as diabetes and hypertension increase the risk of Alzheimer’s disease?

Can treating insulin resistance optimize healthy brain aging, prevent or treat Alzheimer’s disease and other types of dementia?


Insulin Resistance:A Major Pathway in Alzheimer’s disease

Role of insulin in a healthy brain: Increases energy and blood flow in

specific brain regions Increases levels of chemicals and

connections used by brain cells to communicate

Increases brain activity Protects against toxic proteins

(amyloid) Enhances memory at optimal levels


Insulin Resistance:What happens when insulin can not function?Insulin resistance: Cells in body and brain no longer respond to normal amounts of insulinCommon causes: Poor diet, physical inactivity, obesity, chronic stress or sleep disruption, genetic vulnerability

Conditions associated with insulin resistance are increasing dramatically

Type 2 diabetes, pre-diabetes, obesity• 65% of adults in U.S. > 60 years have one or more of these

conditions Alzheimer’s Disease

• Insulin resistance, diabetes, prediabetes and obesity increase risk of Alzheimer’s disease


Novel Approaches to Boost Brain Insulin Function: Intranasal Insulin

Insulin administered through the nose reaches the brain in 15 minutes without changing blood sugar or insulin

Insulin flows along channels following nerves adjacent to upper nasal cavity [Thorne et al. 01]

Can providing insulin directly to the brain via intranasaladministration “normalize” brain insulin and improve memory in adults with AD?

Promising Early Results: Study of Nasal Insulin to Fight Forgetfulness (SNIFF)

Baseline Month 4

Cognition (ADAS-Cog) Functional Status (ADCS-ADL)

Brain Energy Metabolism (PET scan)

104 AdultsWith Early AD

IntranasalInsulin (20 or 40 IU) for 4 months

Placebo


Dec

line

in C

ogni

tion

Series10

0.02

0.04

0.06

0.08

0.1

0.12

0.14

0.16

0.18

0.2 Placebo

20 IU

40 IU

Series1-0.1

-0.08

-0.06

-0.04

-0.02

0

Placebo

20 IU

40 IU

Dec

line

in F

uncti

on

Results: Cognitive and Functional Change over 4 Months


Intranasal Insulin Prevents Decline in Brain Energy Metabolism

20 IU 40 IU

Slowing Down Disease Progression?


Next Steps for Intranasal Insulin as a Therapy for AD Large trial of intranasal insulin has begun at

30 sites across the country this fall led by Wake Forest School of Medicine and the AD Cooperative Study Group in San Diego

One of 3 projects funded by the new National Alzheimer Project

If successful, seek FDA approval for intranasal insulin as a treatment for AD

To find out more about the insulin trial call Erin Caulder at 336-713-8847

Next Step for Insulin Resistance and AD Prevention is to Address Most Common

Causes of Insulin Resistance: Poor Diet and Inactivity

Prevalence of insulin resistance-related conditions dramatically increased, likely due to:

Reduced physical activity

Increased intake of saturated fat and sugar: “Western Diet” vs. “Mediterranean Diet”

Mid-life inactivity and poor diet increase risk of Alzheimer’s disease



Evolution of the Western Diet

Pounds of sugar consumed per person per year

Average number of calories consumed per day

Diet and Risk of AD Bayer-Carter et al. JAMA Neurology, 2011

Compared effects of one month of “bad” diet (high saturated fat and sugar) with same calorie “good” diet (low sat fat and sugar) on AD brain markers (amyloid and inflammation) in spinal fluid of healthy adults

* Changes reversed after resuming normal diet

Good Bad

Change in Amyloid

Good Bad

Change in Inflammation



New Physical Activity Patterns in Western Society


Preventing Insulin Resistance: EXERCISE Most potent insulin sensitizing

intervention Effects of exercise on the brain

include:

Increased brain energy metabolism

Increased brain volume

Protection against memory impairment in older adults

6-month trial of aerobic exercise improved brain volume in older adults [Colcombe et al 2006] and cognition in early AD [Baker et al 2010]


NIA-Supported ADCS Multi-Site Exercise Trial Enrollment Spring 2015

Enroll 300 adults with mild cognitive impairment

Conducted at 15 sites across the US

Assessments: cognition, brain imaging, chemicals in cerebrospinal fluid and blood


Summary Insulin resistance and associated conditions increase

risk of:

Age-related cognitive decline Alzheimer’s disease and other forms of dementia

Increasing prevalence of insulin-resistance in an aging population foreshadows impending dementia epidemic?

Normalizing insulin function may offer a powerful approach to optimal brain and cognitive health, and to preventing or treating Alzheimer’s disease


Thank you!

Recruiting Minority Participants in the NIA ASPREE

Study: ASPirin in Reducing Events in

the Elderly

Anne Murray, MD, MS

Professor of Medicine and Geriatrics

US ASPREE Geriatric PI

Berman Center for Outcomes and Clinical Research

Hennepin County Medical Center

Minneapolis, MN

ASPREE: Study Design, Primary Aim

• Double-blind, randomized, placebo-controlled primary prevention trial of 100 mg enteric-coated aspirin in 19,000 healthy participants aged ≥ 70 years (Caucasian) or ≥ 65 years (minorities: AA and Hispanics)

• Primary aim: does daily 100 mg enteric-coated aspirin extend the duration of dementia and disability-free life (healthy independent life), and whether the potential benefits outweigh the risks (particularly severe gastrointestinal bleeding and hemorrhagic stroke)

ASPREE Primary Endpoint: Prolong

Independence Primary endpoint – prolongation of dementia- free and disability-free life (not CV events)

Secondary endpoints: Fatal and non-fatal CV events ion-fatal cancer, cognitive decline - 10 point decline on 3MS, disability on grip strength, ADL, major hemorrhagic events

ASPREE: ASPirin in Reducing Events in the Elderly

• Largest international trial ever funded by NIA• 19,000 participants (Australia & US)- 16500 AUS,

2500 US• Healthy participants age 65+ (no ADL disability,

dementia, CVD or stroke; life expectancy ≥ 5 years)• Randomized to either daily aspirin or placebo for

about 5 years • Must be willing to cease current ASA use• US mandate to recruit minorities

Why Minority Recruitment Focus in US?

• Very few Minorities in AUS– More cost-effective recruitment of Caucasians there

than US• To maintain diversity, US to recruit large % of Minority

participants– Aug 2011- began exclusively recruiting Minority

participants.• Significant challenges, steep learning curve• For over 2 years, US ASPREE exclusively recruited

minorities. Sought advice from consultants, government agencies, successful sites, successful studies, community leaders, etc.

• June 2013 Limited US Caucasian

recruitment

US ASPREE Recruitment

June 2010

14 Original

Sites

Oct. 2011

14 Additional

Sites

Dec. 2012

12 Additional

Sites

June 2013

Limited Caucasian recruitment

Aug. 2011

Stopped Caucasian recruitment

Finding Participants in AUS…• AUS = Practice-based recruitment

– Benefit of unified health care/ medical recordsAUS ASPREE Staff

GP

Participant

Participant

GP

Participant

Finding ASPREE Participants in the US…

• Community-based recruitment– Mailings- they really work for some sites!– Media– Community presentations (senior living,

churches, etc.)– Clinic referrals– Flyers, posters, etc.– Health fairs– All must be culturally- specific

40 US ASPREE sites- 4 Hubs: Berman, HPartners, UT, Wake)

Texas, Detroit/Ann Arbor, Chicago(Rush) highest minorities

US ASPREE Randomizations

US Recruitment Update: 51% Minority Participants! Total Recruitment: 18,200: US 2,300 & AUS 15,900

49%

33%

16%

1% 0% 1% US ASPREE Randomizations

CaucasianAfrican AmericanHispanicAsianAmerican IndianMore than 1 race/ other

What we’ve learned…• While advocated, there is still little support, either financially or

within the health care system for minority participation. • Establish partnerships and long- term relationships with key

community resource people - View these as investments Learn how people access & use health care (health literacy)• You have to BUILD TRUST• Learn why people are mistrusting:

– African Americans had 5 times the odds of having highest distrust scores compared to Caucasians (Arch Int Med 2002)

– Hispanic adult children & grandchildren provide healthcare knowledge: Desire a personal relationship with Doctor

Share Study Results at community functions

The BRINK - BRain IN Kidney disease- Memory Study

A. Murray, PI• Longitudinal epi study of cog impairment and stroke in

Chronic Kidney Disease (CKD) at 4 sites in Twin Cities, MN

• Recruiting 400 CKD (GFR < 60), 130 controls (eGFR 60+)

• Primary goal: pursue why CKD patients have 2-3x higher rates of Cog Imp: inflammation+ microvascular disease + AD?

• Measuring cog fn, stroke, serum/urine biomarkers: brain MRI

• Initial analyses indicate higher risk of CI in AA’s with CKD:

• Thus new NIMH/NIA Supplement to pursue causes of higher CI rates by adding 30 AA’s w brain MRI, new biomarkers and literacy test

• NIA R01 AG-037751

Thank You to:ASPREE TEAM at BERMAN CENTER and Australia

Richard Grimm, MD, PhD, US PI, Julie Levin, Director, Berman Center, Brenda Kirpach, Project Director, Ramona Robinson-O’Brien, PhD, ACES Project Manager, Nate Tessum, Recruitment & Communications Director, Katelyn Hanneman, Research Assistant

Australian PI: John McNeil, MD, PhD, Executive Director: Robyn Woods, PhD

__________________________________________________Some people with more minority recruitment experience…

Neelum Aggarwal, MD, Rush University Medical Center Karen Graham & Raj Shah, MD ,Rush Alzheimer’s Disease

Center Darrick Lam, M.S.W. US Administration on Aging Mildred Hunter, Office of Minority Health

Non-pharmacologic Approaches to Improve Quality of Life of Persons with Dementia and their Caregivers

Key Outcomes and Challenges

Laura N. Gitlin, Ph.D.Professor, Schools of Nursing and MedicineDirector, Center for Innovative Care in Aging

Johns Hopkins [email protected]

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Funding Sources – Thank You

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• National Institute on Aging• National Institute on Nursing Research• National Institute of Mental Health• Alzheimer’s Association• PA Department of Health – Tobacco Funds

Role of Nonpharmacologic Approaches in Dementia Care

• Dementia - a worldwide epidemic• No cure in sight, pharmacologic agents do not

address most distressful aspects of disease:– Functional dependence– Behavioral symptoms– Caregiver burden, need for education and skills

• Need for new (nonpharmacologic) interventions, clinical management tools and systems of care

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NIA – Reducing Behavioral Symptoms N=272

70

Project ACT• 11 sessions (9 by occupational

therapists; 2 by nurses)• Rule out underlying medical

factors contributing to behaviors

• Problem solve to identify modifiable social and physical factors

• Train caregivers in modifying social and physical environment

Project ACT (N=272)Effect on Families at 4 Months

Caregiver Emotional Well-being:• Improved Mood (p = .001)• Decreased depressive symptoms (p= .045)• Decreased upset with behaviors (p = .001)• Decreased subjective burden (p = .044)Caregiver Skills:• Confidence managing behaviors (p = .007)• Decline in negative communications (p = .009)• Improved management skills (p = .001)Undetected Medical Issues• 35% untreated infection or blood disorderGitlin, et al., (2010). Journal of the American Geriatrics Society.

58 (6) 1465-1474. 71

Tailored Activity Program (N=60)% Reporting Patient Agitation at 4-months

72

-8 home sessionsby occupational

therapists-Match capabilities

and interests, train families in using

Activities Base-line

4 months

0

10

20

30

40

50

TAP Control Grp

P=.014; Cohen’s d=.75

TAP - % Reporting Improvement and Worsening of Behavioral Symptoms (4 months-baseline)

Im-prove-ment

Worsening0%

10%

20%

30%

40%

50%

60%

70%

80%

TAP

Control

P=.004

73

P=.004

74

Hours on Duty

10

11

12

13

14

15

16

17

18

19

Baseline Four Months

Assessment Timepoint

Mean

Numb

er of H

ours

Control

Experimentalp = .001

Hours Caregiver Doing Things for Dementia Patient

4

5

6

7

8

9

Baseline Four Months

Assessment Timepoint

Mean

Numb

er of H

ours

Control

Experimental

p = .001

Caregiver Hours on Duty vs. Hours Caregiver Doing Things for Dementia Patient

Discovery – Phase I Phase III Translation

TAP –HOSPITAL

(Alzheimer’s grant)

VA-TAP Australia TAP

Baltimore TAP

(NIA RCT)

Kentucky TAP (AOA)

Home

Scotland, Brazil, England, States in USA

Adult Day

Tailored Activity Programs

COPE Trial (n=207) at 4-months (Gitlin et al., JAMA, 2010)

Baseline4-Month Follow-

up

Control COPE Control COPE

Patient Outcomes

M (SD) M (SD) M (SD) M (SD)

Difference of

Adjusted Means

95% CI p d

Overall functional dependence

2.8 (1.3)

3.0 (1.2) 3.3 (1.3)

3.7 (1.3) .24 .03, .44 .02 .21

IADL dependence

1.8 (1.0)

1.8 (1.0) 2.5 (1.1)

2.8 (1.2) .32 .09, .55 .01 .43

Activity engagement

2.0 (0.4)

1.9 (0.4) 1.9 (0.5)

2.0 (0.4) .12 .07, .22 .03 .26

Quality of life

2.1 (0.5)

2.1 (0.4) 2.1 (0.5)

2.2 (0.5) .10 -.00, .20

.06 .14

Project COPETargeted Problem Areas

77

0.00%

10.00%

20.00%

30.00%

40.00%

50.00%

60.00%

70.00%

Percent Eliminating Care Challenges

COPEControl

62.7%

44.9%

p=.010

0

10

20

30

40

50

60

70

80

Improved patient's life Helped you keep patient at home

Per

cen

t

Response = "A great deal"

COPE

Control

p < .0001

p = .023

Perceived Patient Benefits at 9 Months

78

MIND Pilot Trial at 18 Months (N=303)Samus et al., AJGP, 2014

MIND Pilot Trial 19-41 Months(N=303)Samus et al., AJGP, 2014

Web-based Behavioral Management ToolKales and Gitlin Co-PIs (R01NR014200)

81

WeCare Advisor Example

82

Recruitment and Retention Challenges

Participant Yield and Cost per Recruitment Source for COPERecruitment

SourceInquiries Enrolled

DyadsTotal Yield(%)

Yield Non-White

(%)

Total Cost

Cost per Dyad

Mailings total 158 135 .85 .27 $8,541 $63

ADS 62 57 .92 .30 - -

Study Registry 34 31 .91 .16 - -

FCSPs 19 15 .79 .33 - -

Other mailings 43 32 .74 .31 - -

Newspaper Advertisements

73 62 .85 .30 $13,899 $224

Community Outreach

53 40 .75 .30 $14,000 $350

Total 284 237 .84 .29 $36,440 $154

Morrison, K., Winter, L., & Gitlin, L. N. (2014). Recruiting community-based dementia patients and caregivers in a nonpharmacologic randomized trial: What works and how much does it cost? Journal of Applied Gerontology. 84

InquiriesN=210

Telephone screenN=168 (80%)

Completed baseline and randomizedN=48 (57%)

Screened eligible and willing for baseline interview

N= 84 (50%)

23%

NIA – Reducing Agitation in

Persons with Dementia

Tailored Activity Program

Recruitment Flow

85

Summary• Nonpharmacologic interventions are

promising. Evidence for improvements in:– Daily physical function– Behavioral symptoms– Caregiver quality of life, skills, affect and well-being– Time spent providing care

• Trials are dependent upon recruitment– Volume “business” requiring resources and extensive

outreach– Attrition high due to death, hospitalization, relocation,

stress, lack of time

86

Materials, including slides, audio and transcript will be posted on-line, generally within 2 weeks after the live

webinar. Free CE for Webinars 1, 2 & 3 will be available for up to 2 years after each live webinar.

All materials for 2012, 2013 & 2014 webinar series available under Resources and Useful Links at:

http://www.aoa.gov/AoARoot/AoA_Programs/HPW/Alz_Grants/index.aspx#resources

87

Questions?

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alzheimer’s research updates

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