Translating Observational and Lab-based Trials to Community-based

Interventions: Why and How Michelle C. Carlson, PhD

Johns Hopkins Bloomberg School of Public Health Department of Mental Health, Center on Aging and Health

Workshop on Understanding Pathways to Successful Aging:

Behavioral and Social Factors Related to Alzheimer’s Disease National Academy of Sciences, Engineering and Medicine

June 12-13, 2017

1

Overview • Why do community interventions? • Any movement is good (Revenge of the Sit I & II)

• Building Metrics Around Movement- incorporating wearable devices to develop indices that inform evaluation, mechanism and intervention design

• Why do people move? Social, purposeful and other motivations to tap into

• Why don’t people move? Barriers related to the individual’s health and to the environment

• Environment as key intervention design factor- includes safety, available infrastructure, community partners

• Challenges & Opportunities- engaging & building trust with stake holders, sustaining & growing a community-based intervention post study

Why Do Interventions in the Community?

• Translating Beneficial Behaviors into Everyday Life styles=> Behavior change – Physical activity/exercise – Cognitive activity – Retain/regain social purpose

• Reaching at risk populations in their communities

• Scaling up from clinic/lab to generalize to real-world environments

2.5

33.

54

4.5

0 5000 10000 15000 20000 25000avg_steps

Fitted values Lhippocampus

1000 more steps/ day is associated with a larger hippocampus, a brain region important to memory and dementia risk

Varma, Chuang, Harris, Tan, & Carlson, 2014, Hippocampus

Even small increases in daily walking activity may matter

Lifestyle Physical Activity and Brain Health

PA associated with subiculum in women Varma, Tang, & Carlson, 2015 Hippocampus

Physical Activity (PA) Guidelines for Older Adults: Determined by Environment

• Current Guidelines: 30 minutes/day of moderate-intensity PA ; 20 minutes/day of vigorous-intensity PA three days/week

• Difficulties in reaching PA targets for older adults; particularly those of low socioeconomic status (SES)

• Benefits of low-intensity physical activity in enriched, daily environments?

Sources: HHS: Health People 2020; Tudor-Locke & Basset, 2004; PAG Report, 2008; Marshall, et al. 2007; Parra-Medina, 2010

Linking Physical Activity to Social Engagement with a Purpose: Volunteering -Desire to remain generative & productive -Harnessing one’s lifetime of accumulated wisdom • Volunteers 60 and older

• Serve in public elementary schools: K-3 • Multiple roles to exercise executive function,

memory – Reading literacy – Library support – Math support – Behavioral support

• >15 hours per wk • Travel to & from schools; walking within schools • Sustained dose: full school year

Freedman & Fried, 1997; Fried et al., 2004; Fried et al., 2013; Glass et al., 2004

Baltimore Experience Corps Trial • Evaluation funded by NIA BSR: 2006-

2013 • Randomized:

– 702 60 yrs. and older to EC or low-activity control

– Matched 25 public elementary schools with EC to control

• Exposure: 2 years of high-intensity service

• Outcomes: – Physical: Disability, mobility, walking

speed – Cognitive: Memory, executive function – Psychosocial well-being

• Nested Brain Health Substudy(N=120)

Brain plasticity; Executive function

MESSAGE:

Generative Service

Intervention Primary Pathways Mechanisms Performance-based outcomes

Strength, balance

Social Integration & Support

Generativity

Physical Activity

Cognitive Activity

Social Activity, Engmnt. Psycho-Social

Well-being

Memory

Walking Speed

Frailty

Recruitment Message & Mechanisms: Causal Pathway

IADLs

Falls

Women in Experience Corps maintained average steps/day over 24 months post-Intervention while Controls declined.

5000

6000

7000

8000

9000

Ave

rage

ste

ps/d

ay

Baseline 12-months 24-months

Control

Intervention

Varma, Tan, Gross, Harris, Romani, Fried, Rebok, Carlson, 2015 AJPM

Men had significantly higher baseline levels of daily physical activity than women and maintained these levels.

Did We Increase Daily Physical Activity Following Program Participation? Step Activity (N=115):

Women EC= red; Control= blue

Does Experience Corps Lead to Changes in Brain Health?

• 2-year improvement in memory related to 2-year increase in whole brain volume in EC (blue.

5000

5500

6000

6500

7000

7500

Baseline 12 month 24 month

Volu

me

(mm

3 )

Men: Hippocampal Volume (mm3)

Intervention

Control

Carlson, Kuo, Chuang, Varma, et al., 2015 Alz & Dementia

• Men in the Experience Corps arm showed a 0.8-1.6% increase in total cortical and hippocampal brain volumes v. declines in controls.

• Women in Experience Corps also tended to exhibited modest gains of 0.3-0.54% by 24 months of exposure.

-4 -2 0 2 42-year change in Whole-Brain volume

InC

11

Experience Corps also impacts the amygdala, a region important to socially salient information and a biomarker for AD risk (Miller et al., 2013) (see nice meta-review by Bruhl et al., 2014)

• Using shape diffeomorphometry, we see specific patterns of change

Only the left amygdala shows significant group differences post-intervention, after correction for multiple-comparisons (p=0.0052)

Con

trol

Inte

rven

tion

Gro

up D

iff

Carlson, Varma, Miller, & Tang, under review

From School to Community: Building Metrics to Identify Opportunities for Purposeful Activity in Daily Life

• Measure real-time contexts in daily life when it occurs by expanding use of real-time mobile assessment in the community – Are there “hot spots”? – Are there diurnal patterns when individuals are most

able to exercise? – Is meaningful vs. any social engagement a magic

ingredient? • Create opportunities, particularly in low-

resourced neighborhoods

Using GPS+ accelerometers to determine where the greatest amounts of outdoor activity occur in daily life

Carlson, Varma, Adam, Crainiceanu, & Zipunnikov, under review

Environmental Barriers to Physical and Social Activity Distribution of BECT participants across Baltimore City (n=535)

HotSpot analysis of participants with poor global cognition (MMSE scores <26) (left panel) and with poor memory (right panel)

Adam, Varma, Harris, & Carlson, under review

Double Jeopardy- At risk individual in at-risk environment Community interventions can target both

Place Matters • Location where intervention takes place

– Is accessible, in members’ neighborhoods – capitalizes on existing school & other community

infrastructures – Schools & senior centers offer safe access in & around

(e.g., side walks) (Tan et al., 2010 Am J. Public Health)

• Examples of Community-based Interventions:

– Community Choirs (Johnson, UCSF; NIA 2012-17) conducted in partnership with San Francisco Community Music Center & SF Dept. of Aging & Adult Services

– SYNAPSE Project (Park et al., 2014) – Senior Odyssey of the Mind (Stine-Morrow et al., 2008) – Theatre acting (Noice & Noice, 2004, 2014)

Identifying & Engaging Stake Holders in Research-Community Partnerships

• Identify all stake holders’ needs: – Older adults: cognition, physical function, disease

management – Children & young adults: literacy, obesity, bullying,

substance abuse • Identify community partners

– local gov’t & non-profit agencies, senior centers, etc. • Listen & share in intervention design =

collaboration…Build trust! • Challenges & opportunities

– Sustainability beyond research enterprise – Cost effectiveness

It Takes a Village: Research Team and Collaborators

• Jeremy Barron - JHU • Michelle Carlson - JHU • Yi-Fang Chuang - Natl Yang Ming U • Kay Dickersin - JHU • Kirk Erickson - U Pittsburgh • Constantine Frangakis - JHU • Linda Fried - Columbia U • Kevin Frick – JHU • Alden Gross - JHU • Tara Gruenewald – USC • Jin Huang - JHU • Arthur Kramer - Northeastern U • Sylvia McGill - EC Baltimore • Jeanine Parisi - JHU

• Christine Ramsey – VA CT • George Rebok - JHU • William Romani – AARP • David Roth - JHU • Roberta Scherer - JHU • Teresa Seeman - UCLA • Erwin Tan – AARP • Elizabeth Tanner – JHU • Vijay Varma – NIA, LBN • Keith Whitfield – Wayne State U • Paul Willging - JHU • Qian-Li Xue - JHU

Funding Acknowledgments Experience Corps Trial • Alzheimer’s Drug Discovery

Foundation • NIA BSR Grant #

P01AG027735-03 supplement • Greater Homewood

Community Corporation • Johns Hopkins OAIC Pepper

Center Grant #P30AG021334 • Johns Hopkins

Neurobehavioral Research Unit

• S.D. Bechtel Award

Geo-Coded Activity • Johns Hopkins ADRC Pilot

Grant • Johns Hopkins OAIC

Pepper Center Grant #P30AG021334

Trial Methods: Analysis of Older Adults

• Intention-to-treat (ITT): Intervention vs. Control ignoring compliance (i.e., N1+N2 vs.

N3+N4) • Complier average causal effect (CACE): Intervention vs. Control among compliers (i.e., N1 vs. N3)

CACE

Complier Non-Complier

ITT Intervention N1 N2

Control N3 N4

Some Terms • Active Control: Control condition is the principal method of removing the

influence of unwanted variables to determine the effectiveness of the Intervention condition in a randomized, controlled trial (RCT)

• Community-based Intervention: interventions embedded within community settings and infrastructures

• Equipoise: Ethical considerations, including assurances of receiving the best available standard therapy (clinical) and non-maleficence

• Generalizability: as applied to outcomes, the impact of an intervention on outcomes beyond those abilities and systems trained or exercised. May also be described as near and far transfer.

• Prevention: interventions designed to delay and reduce the risk of onset of clinical disease(s)

• Randomized Controlled Trial: provides critical evidence for the efficacy or effectiveness of behavioral interventions

• Risk/Protection Factor: behavioral, health, demographic, and/or environmental factors that may increase/reduce one’s risk for an adverse health outcome

• Sustainability: program maintenance independent of research funding, often done in collaboration with community stakeholders