Download - Alzheimer’s Research Updates
Alzheimer’s Research Updates
2014 ACL/CDC/NIA Alzheimer’s Webinar SeriesSeptember 25, 2014
ACCREDITATION STATEMENTSCNE: The Centers for Disease Control and Prevention is accredited as a provider of Continuing Nursing Education by the American Nurses Credentialing Center's Commission on Accreditation. This activity provides 1.5 contact hours. CEU: The Centers for Disease Control and Prevention is authorized by IACET to offer 0.2 CEU's for this program.
CECH: Sponsored by the Centers for Disease Control and Prevention, a designated provider of continuing education contact hours (CECH) in health education by the National Commission for Health Education Credentialing, Inc. This program is designated for Certified Health Education Specialists (CHES) and/or Master Certified Health Education Specialists (MCHES) to receive up to 1.5 total Category I continuing education contact hours. Maximum advanced level continuing education contact hours available are 0 CDC provider number GA0082.
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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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• For best functioning, please use a browser other than Internet Explorer (e.g., Firefox, Chrome)
• Go to http://www.cdc.gov/TCEOnline, and log in (you may need to register as a new participant).
• After successful log in, the “Participant Services” menu displays. Select “Search and Register”. Select option 2, “Keyword Search”, and enter the course WD2463 and select “View”.
• Select the course “092514”to open the Course Description page. Scroll down to the box labeled “Register Here”, choose the appropriate credit type, and select “Submit”.
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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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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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• 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
Multiple LOAD Etiologies Multiple Prodromal PhenotypesMultiple Progression Trajectories
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
Multiple LOAD Etiologies Multiple Prodromal PhenotypesMultiple Progression Trajectories
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
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
Brinton, Nature Reviews Endocrinology, 9:241-250, 2013
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
Brinton, Nature Reviews Endocrinology, 9:241-250, 2013
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
Multiple LOAD Etiologies Multiple Prodromal PhenotypesMultiple Progression Trajectories
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)
Wake Forest Baptist Medical Center
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?
Wake Forest Baptist Medical Center
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
Wake Forest Baptist Medical Center
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
Wake Forest Baptist Medical Center
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
Wake Forest Baptist Medical Center
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
Wake Forest Baptist Medical Center
Intranasal Insulin Prevents Decline in Brain Energy Metabolism
20 IU 40 IU
Slowing Down Disease Progression?
Wake Forest Baptist Medical Center
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
Wake Forest Baptist Medical Center
Wake Forest Baptist Medical Center
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
Wake Forest Baptist Medical Center
Wake Forest Baptist Medical Center
New Physical Activity Patterns in Western Society
Wake Forest Baptist Medical Center
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]
Wake Forest Baptist Medical Center
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
Wake Forest Baptist Medical Center
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
Wake Forest Baptist Medical Center
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
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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
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Questions?