UCLA Older Americans
Independence Center
David B. Reuben, MD
Center Director
UCLA OAIC Theme
“Preventing Disease and Disability in
Vulnerable Populations:
A Translational Approach”
“Vulnerable”
1) underserved (i.e., low income, uninsured,
and minorities)
2) at increased risk of losing independence
because of chronic diseases or conditions,
advanced age, or functional impairment
UCLA OAIC
Addresses health disparities that
vulnerable older persons face because of:

–Inadequate understanding of contributors
(e.g., socioeconomic status, inflammation) to
health and specific illnesses (e.g., HIV, sleep
disorders, depression)
–Lack of effective preventive or therapeutic
approaches (biomedical and behavioral), or
–Inadequate ability to get needed treatment
to vulnerable older populations (e.g., cultural
barriers, ineffective health systems).
UCLA OAIC
RCDC Activities

CDAs
– Co-funding with CTSI and Departments
– Didactic components
– Individualized training programs
– Mentorship Committee (primary and 2-4
secondary mentors); meets quarterly

Academic Advancement
Current RCDC CDAs

Jordan Lake, MD, MSCR (3rd year CDA)
Assistant Professor-Infectious Disease
– Mechanisms by which chronic inflammation
accelerates aging processes in HIV patients

Lee Jennings, MD, MSPH (1st year CDA)
Assistant Professor-Geriatric Medicine
– Improving the quality and delivery of care for older
adults with advanced illness
Incidence Rate Ratios for fall-related injury (FRI) by screening
response and prior claim for FRI, N=1776
Predictor
N (%)
IRR for 24
months
Response to Individual Screening Question (McFadden’s Adj R2=0.035)
Fallen twice in past 12 months
659 (37%)
1.57 *
Fallen and hurt self since last doctor’s visit 420 (24%)
1.20
Afraid may fall because of balance or
1495 (84%)
1.09
walking problems
Number of Positive Screening Responses (McFadden’s Adj R2=0.034)
One
1166 (65%)
REF
Two
422 (24%)
1.33*
Three
188 (11%)
1.84 *
Prior FRI
Prior claim for FRI only (McFadden’s Adj R2=0.029)
198 (11%)
1.58 *
Predicted FRI
per person over
24 months
0.31
0.28
0.25
0.21
0.28
0.38
0.36
*p<0.05 //Additional significant positive predictors in all models: age, comorbidity count, site
Current and Future CDAs

Joseph Dzierzewski, PhD (1st year CDA)
Assistant Researcher GRECC
- Cognitive and inflammatory responses of
co-morbid sleep disordered breathing and
insomnia in late life

Hyong Jin Cho, MD, PhD (start CDA 7/14)
Assistant Professor Psychiatry
- Risks for inflammation-related depression and
prevention of late-life depression
PESC Activities
2 Classes of Pilots


Standard [Discontinued]
Rapid Grant Awards
– Co-Funded by UCLA CTSI
– Maximum 10K
– PI: Jr. faculty or advanced trainee, with
identified faculty mentor
– Review by Core director and content
experts with 4-week turn-around
High Throughput Screening to
Identify Hepcidin Antagonists
Elizabeta Nemeth, Pilot Awardee
Background



Excess hepcidin may contribute to anemia of
inflammation by inhibiting iron delivery to plasma
by degrading iron’s receptor, ferroportin (Fpn)
Pilot funding: conduct high throughput small
molecule screen for hepcidin antagonists
Collaboration with Molecular Shared Screening
Resource Core (UCLA)
High Throughput Screening to
Identify Hepcidin Antagonists
Elizabeta Nemeth, Pilot Awardee

~70,000 compounds screened; 2642
preliminary hits based on GFP

2 chemically distinct groups of compounds
– Cardiac glycosides (at nanomolar levels)
– 3 compounds with a sulfur moiety that could
interact with hepcidin’s thiol group;
– fursultiamine most promising, tight binding, potent
hepcidin inhibitor, specific to Fpn

Tested fursultiamine in mouse model
– Not a robust antagonist in vivo
– Metabolized to thiamine
Research Cores Activities

Consultation (e.g., providing up to
several hours of advice, reading a
paper/proposal)

Short-term (e.g., up to 2-3 days of
consultation, performing assays

Ongoing or long-term support (e.g.,
ongoing, part of the project team

Partnership on new proposals
RRC Activities

Identify potential recruitment sites

Introductions to specific community organizations

Review plans for minority recruitment

Assistance with enrollment and retention

Teach effective strategies for recruitment and
retention of minority elders
Joint CTSI-RCMAR-OAIC Project



Goal: identify best practices for recruiting Latino
and African American seniors
Methods: Qualitative study with 6 focus groups
(n=72) and 15 stakeholder interviews
Results: major negative experiences included
– poor communication by research team
– perceived lack of transparency in the recruitment
process
– lack of notification of study findings
– failure to use appropriate language and cultural
references
ROC Activities


Provide support for data collection, data
management, & proposal preparation
Enhance interoperability between Pepper
Informatics and REDCap

Provide periodic workshops on research
methods and operations
ROC-supported findings
Randomized trial of ER observational protocol
for syncope vs usual care




PI: Benjamin Sun, MD (OAIC trainee), RC1-NIA
15% of patients in observational protocol arm
versus 90% in usual care admitted to hospital
No difference between arms for adverse events and
6-month re-admissions
Published in 2013 in Annals of Emergency
Medicine; Basis for larger R01 proposal submitted
through OHSU
ROC-supported findings


Assessment of sub-epidermal moisture to detect
early skin damage in multi-ethnic sample of nursing
home residents
PI: Barbara Bates-Jensen, PhD, RN, R01-NINR
Difference in incidence of Stage 1 pressure sores
(erythema) explained by skin tone, not ethnicity
Skin tone of AfricanAmerican NH residents
Light
Medium
9%
Dark
54%
37%
Early skin damage by ethnicity and skin tone
100
Early stage PU/erythema
incidence (%)

80
60
40
20
0
African American
Asian
Light
Medium
Hispanic
Dark
White
ACEC Activities



Support junior researchers’ study design,
statistical data analysis, and interpretation of
findings
Assess the cost-effectiveness of successful
clinical interventions
Provide training workshops on statistical,
comparative effectiveness, and cost
effectiveness analysis methods
ACEC-Supported Findings
Junior Researcher: Albert Shieh, MD
Research Question: Can markers of bone resorption and
formation be combined to assess bone metabolic balance?
Findings (Abstract, ASBMR, Oct 2013):
• A bone balance index can be created by combining
formation markers (BSAP, P1NP) with resorption marker (NTx)
BBI = 7.0 + 0.178*BSAP + 0.070*P1NP – 0.022*weight – NTx
• The index is higher in post-menopausal women on
hormone therapy than in those not on hormone therapy
(+1.06 vs. -0.46, p<0.05)
• A larger index predicts greater bone density in the lumbar
spine (0.07 SD increment in BMD per SD of BBI)
IBC Activities

Support the analysis of inflammatory biology
 Study design, proposal preparation
 immunologic and genetic data generation
and interpretation

Facilitate/expedite development of innovative
technical approaches for inflammatory biology

Provide training in immunologic and molecular
aspects of inflammatory biology
IBC-Supported Findings
Elderly depressed patients have diminished varicella zoster
virus (VZV) specific immune responses to zoster vaccine,
and treatment with antidepressant medication is associated
with normalization of these responses
VZV–specific Responder Cell Frequency
(per 100,000 PBMC)

Clin Infect Dis 2013, 56:1085-1093
IBC-supported Findings

Among stressed family dementia caregivers (mean age=
60.5 y), brief daily yogic meditation intervention reverses
the pattern of decreased IRF1-related transcription of
innate antiviral response gene and increased NF-kBrelated transcription of pro-inflammatory cytokines
Log2-transformed mean fold-difference ( SE)
Meditation / Control
in prevalence of transcription factor-binding motifs
Psychoneuroendocrinology 2013, 38:348-55
The Data Access Pilot Project
Collaboration of PESC, ROC, and ACEC
Rationale:
 Senior faculty have access to and indepth familiarity with several rich but
under-utilized data sets
 Trainees and junior faculty need for
access data & need guidance to utilize it
optimally
 Generic web sites that describe some
data sets are available, but are often
difficult for the naïve user to understand
DAPP: Methods
Research faculty interact with potential users to…
 Clarify research questions

Discern whether a data set is a good match

Mentor application to access data, if needed

Guide application for funding, if required

Mentor data analysis or conduct the data analysis
as appropriate (requires payment for DAPP staff)
DAPP: Initial Data Sets

Study of Women's Health Across the Nation
(SWAN)

Postmenopausal Estrogen/Progestin
Interventions (PEPI) Study

Osteoporotic Fractures in Men (MrOS) Study


Study of Osteoporotic Fractures (SOF)
Rancho Bernardo Study

Health and Retirement Study (HRS)

Cardiovascular Health Study (CHS)
DAPP: Initial Data Sets

National Health and Nutrition Examination
Survey (NHANES)

Multiethnic Study of Atherosclerosis
(MESA)

Midlife in the United States (MIDUS)

Atherosclerosis Risk in Communities
(ARIC) Study
Yoga for Kyphosis Trial
Yoga Empowers Seniors Study (YESS)


UCLA OAIC Conclusions




1 OAIC > 0.5 OAIC > 0.0 OAIC
Limitations in funding new pilots,
providing, short-term support and
building new relationships
Must rely on established relationships
and partnering on new proposals
Can still do excellent work both as an
independent OAIC and collaboratively
with other OAICs