| Past
Grant Winners and Proposals
2003-2004
Faculty Incentive Grant Proposals
2002-2003 Faculty Incentive Grant Proposals
2001-2002
Faculty Incentive Grant Proposals
2003-2004
Paul H. Doolen Award Proposals
2002-2003 Paul H. Doolen Award Proposals Faculty
Research Awards:
2003-2004
Initiative on Aging Incentive Grants One
goal of the Initiative on Aging is to foster an increase in extramural funding
at UIUC in the area of aging. We are especially interesting in promoting the submission
of interdisciplinary proposals that include multiple investigators across departments
and schools. To help this endeavor, the Initiative on Aging provides Incentive
Grants to faculty submitting new major grant applications to government or private
sources for the study of gerontological issues. In 2004, two incentive grants,
of $10,000 each, were awarded to faculty planning appropriate submissions.
Click on the
award winners name to see their proposals. Aging
Initiative Incentive Grant Proposals:
Dan Morrow, Ph.D., Institute of Aviation
Hong
Li, Ph.D., School of Social Work 2004
UIUC Initiative on Aging Incentive Grant Proposals
The
following is a proposal for the 2004 UIUC Initiative on Aging Incentive Grant
by Dan Morrow, Ph.D. Title:
Increasing Chronically Ill Older Adults' Medication Knowledge and Skills by Improving
Nurse/Patient Collaboration Project
Goals
Our goal is to increase medication-taking knowledge and skills among
older adults with diverse cognitive and health literacy skills. We will help nurses
to collaborate more effectively with older adults to help them develop accurate
and feasible plans for taking medication.
Background
Self-management
of chronic illnesses such as hypertension and heart failure is an important age-related
health care issue (Healthy People 2010). Self-management can be a daunting task.
For example, older adults often take 7-10 medications concurrently (Fleming, Pulliam,
Perfetto, Hanlon, & Bowling, 1993). Self-management in turn depends on effective
collaboration with health care providers.
Age-related differences in cognition
(Park et al., 1996) and health-related literacy (Baker, Gazmararian, Sudano, &
Patterson, 2000) pose challenges for older adults' ability to manage illness and
collaborate with provides to create self-care plans (Morrow, 1997). Unfortunately,
these challenges are often exacerbated by inadequate health care communication.
Providers sometimes fail to present understandable information, check patients'
comprehension of information, and explore patients' concerns (Hall, Roter, &
Katz, 1988; Stewart, 1995). These "collaborative lapses" may place older
patients at a particular disadvantage. Not surprisingly, chronically ill older
adults tend to have low levels of knowledge about their illness and treatment,
have trouble accomplishing self-care behaviors (e.g., medication nonadherence),
and experience poorer health outcomes, and this is especially the case for patients
with limited health literacy skills (Andrus & Roth, 2002). Thus, older adults
need help developing self-care plans when collaborating with providers. While
there is a growing set of recommendations for how providers should communicate
with low literacy patients (e.g., use short, simple, and action-oriented messages;
Doak, Doak, & Root, 1996), there is a need for specific communication strategies
to achieve collaborative goals.
Project
Description
We target nurses because patient education is a core nurse
responsibility and their training emphasizes patient-centered communication. However,
there is room for improvement. An earlier study found that nurses were incomplete
when teaching older adults about taking medication and rarely checked patient
comprehension, even though the frequency of checking was associated with better
patient recall (Shippee-Rice & Morrow, 2002). We hope to expand and refine
nurses' communication skills. Our earlier work suggests several "collaborative
tools", or specific strategies to help nurses work with patients to develop
plans for taking medication.
Approach.Medication schema. Older
adults share a general schema for organizing medication information (Identify
the medicationàHow to take the medicationàPossible Outcomes) and
they better remember instructions that follow this schema (Morrow, Leirer, Andrassy,
Tanke, & Stine-Morrow, 1996). Nurses will be taught to present medication
information according to this schema, which encourages patients to relate the
new information to their knowledge and provides a procedural organization that
may benefit low literacy patients (Andrus & Roth, 2002). Nurses will use the
schema interactively by checking patients' comprehension at critical schema junctures
(using "teach back" techniques that focus on the provider rather than
patient). Such techniques are associated with better patient recall (Shippee-Rice
& Morrow, 2002) and health outcomes (Schillinger et al., 2003).
Medication
timeline. An important component of developing a plan is identifying a feasible
schedule. Older adults better understand and remember medication dose and time
information that is depicted by a graphic timeline in instructions (compared to
text only, Morrow, Hier, Menard, & Leirer, 1998). Nurses will use the timeline
to support their collaboration with patients. Nurse and patient will jointly fill
out timelines indicating when patients want to take their medications (as well
as a table for multi-medication schedules). This strategy encourages them to be
more explicit about how to take the medication, uncovers barriers to adherence
(e.g., timing diuretics to fit daily activities), and provides a way to indirectly
check patient understanding. The completed timeline can be used by patients at
home to support adherence and by nurses as a more specific record of patient medications.
Pictorial tools may be especially helpful for low literacy patients (Houts et
al., 1998).
The schema and timeline tools have been incorporated into a pharmacist-based
patient education intervention to improve adherence to heart failure medications
among older adults with diverse cognitive and literacy skills (Murray et al.,
2004). We plan to expand this approach to nurse/patient communication because
nurses are critical to managing chronic illness among older adults. The approach
will be developed and evaluated in primary care settings by working with nurses
in the local community.
Planned
Studies
Focus groups. We first refine the approach by conducting focus
groups with nurses who work with older chronically ill patients (with a focus
on cardiovascular illness). The focus groups have two goals. First, because we
would modify existing practices and introduce new "cognitive artifacts"
into health care settings to support collaboration, we first want nurses to discuss
how they already teach older adults about medication as well as how information
about patients' medications are recorded in their practice. Second, the collaborative
strategies will be described and feedback from the nurses obtained in the form
of open-ended comments followed by probing specific issues (perceived benefits
for patient education and provider/patient relationship; potential drawbacks such
as limited consultation time). Sessions will be audio-taped, transcribed verbatim,
and content analyzed using standard focus group methodology (Morgan, 1988). We
anticipate the focus groups will fine-tune and tailor strategies to the realities
of clinical practice.
Simulation study. Conduct a small-scale
study in which (different) nurses are trained in the approach and then use it
to teach patients (varying in cognitive and literacy skills) about medications
prescribed for cardiovascular illness in simulated consultations. Measures include
patient medication knowledge (compared to pre-training patients' scores for the
same nurses), nurses' satisfaction with communication, and their ability to reliably
use the strategies. While this study is removed from clinical realities, it would
help establish feasibility in terms of some patient outcomes.
Clinical
practice study. Nurses are trained and use the approach in their daily
practice in primary care settings for 6-12 months. Measures would include patient
satisfaction and knowledge of medications, electronically monitored medication
adherence, nurses' ability to reliably use the techniques, and cost measures (compared
to usual care control condition).
back
to top The
following is a summary of a proposal for the 2004 UIUC Initiative on Aging Incentive
Grant by Hong Li, Ph.D. Title:
Balancing Informal and Formal Services to Improve Effectiveness of Case Management
Services for Rural, Low-Income Older Adults with Functional Disability
This
project will apply Litwak's task specific theory (1985) to the development and
testing of a case management program for rural older adults with functional disabilities
in performance of basic activities of daily living (ADLs) and instrumental activities
of daily living (IADLs). Most rural elderly who experience functional disability
rely on their family members, relatives, neighbors, or friends (Stoller, 1998).
Through case management programs, many rural older adults with limited income
are enrolled in and receive Home and Community Based Services (HCBS) including
personal care, homemaker, meals, respite, adult day care, and transportation (Krout,
1994; Coward & Krout, 1998). Although informal caregivers are the backbone
of comprehensive long-term care systems in rural communities, efforts that systematically
involve informal caregivers in the development and implementation of a HCBS plan
for older adults have been very limited.
Specific
aims of the proposed study are to:
1.
Develop a case management program that balances informal and formal services in
the development and implementation of a HCBS plan for rural older adults with
any functional disability.
2.
Examine the extent to which the case management program meets older adults' and
their caregivers' service needs at two-weeks, six-weeks, and three-months after
beginning participation.
3.
Examine the impact of the case management program on older adults' adaptation
to functional disability, quality of social relationship, and quality of life;
and informal caregivers' distress, commitment to elder care, and general well-being
at 36 weeks after participation. Study
Background and Significance
Although a majority of rural older adults
are healthy and living independently, as they age, they are likely to experience
a decline in health and functioning. Data from the National Health Interview Survey
from 1990 to 1994 showed that between approximately 40% of older adults in non-metro
communities reported functional impairments (U.S. Census, 1995). The vast majority
of these older adults need nonmedical supportive services to compensate their
functional impairments (Corburn & Bolda, 1999).
Depending on individual
states, most low-income older adults with functional disabilities are eligible
for publicly funded HCBS (Moon, 1993). With rapidly growing aging populations,
the federal and state governments annually spend approximately 66 billion on home-based
and institutional care (Feldman, 1999). However, the effectiveness of HCBS still
remains inconsistent at best (Kane, 1999). To meet older adults' service needs
and control the costs of publicly funded HCBSs, case management services have
been implemented across the country. The main goal of case management services
is to identify and determine multifaceted needs of an individual, to develop a
comprehensive care plan to address identified needs, to obtain and coordinate
appropriate services to ameliorate the needs of that individual, and to contain
service costs (Applebaum & Austin, 1990). However, the Challenging Demonstration
and Alzheimer Disease Demonstration, among largest quasi-experimental studies
on managed HCBS, have achieved only limited success in the delay of nursing home
admissions, improvement of older adults' functioning and quality of life, and
the increase of caregivers' emotional well-being (Fox et al., 1998; Kemper et
al., 1987). One of the challenges to the success of HCBS is that most of these
services are provided at a home setting and often by both informal and formal
service providers (Kane & Kane, 1987). The variations among older adults,
informal caregivers, and formal service providers in service adequacy, personal
preferences, service expectations, and caregiving skills are overwhelming. Such
variations may attenuate the true effects of HCBS (Kane, 1999)
Informal care
systems of rural older adults are the primary source of nonmedical, supportive
services. Data from the National Health Interview Survey indicate that 82% of
rural older adults received informal care, which can make up to 92% of all care
needed by older adults (Coward et al., 1990). Due to limited availability, accessibility,
affordability, and acceptability of rural formal services, approximately less
than one fifth of rural older adults used formal HCBS, and their use of formal
services is often accompanied by their use of informal care (Coward et al., 1990).
The informal care systems serving rural older adults are critical in determining
older adults' needs for formal services, so formal services may not reach older
adults if the informal care system is available (Doty, 1995).
Despite the improvement
of rural HCBS over the past twenty years, current patterns of HCBS used by rural
older adults have not adequately met their service needs. Data from the 1999 National
Long Term Care Survey reveal that more than one third of rural service users reported
they experienced barriers to needed services, and two-thirds reported that the
services received did not meet their needs (Li, under review). Leaving these service
needs unmet may exacerbate clients' health problems and result in serious consequences.
There is strong evidence suggesting that unmet service needs are associated with
increased rehospitalization and emergency room visits (Allen & Mor, 1997;
Long et al., 2002), increased incidences of undesirable outcomes such as discomfort
and injury (Desai et al., 2000), quitting services (Cox, 1997), and elevated levels
of caregiver stress (Li et al., under review).
Despite informal caregivers'
contribution to maintaining older adults in their own homes, the service needs
of informal caregivers are not recognized and the importance of informal caregivers'
involvement in the development of care plan are overlooked (Kane, 1999). This
myopia may be attributed to the case mangers' concerns about "wood effects,"
that informal caregivers will give up their caregiving responsibility and leave
older adults' service needs to formal service providers (Montgomery, 1999). Yet,
little empirical research has focused on how case managers systematically involve
informal caregivers in the development and implementation of care plan for older
adults and address informal caregivers' concerns and needs regarding the service
plan. This project has the potential to increase knowledge about how to balance
informal and formal services to optimize the effectiveness HCBS for rural adults
with functional disability.
Conceptual
Frameworks
The conceptual framework for the proposed study is informed
by task specific theory developed by Litwak (1985). In this theory, Litwak postulates
that there is a continuum of viable social structures for the delivery of care
ranging from formal service agencies, informal support networks, and the family.
Each of these is by its nature most efficient in delivery of certain kinds of
help for certain problems. Miller (1985) further argues that partnerships offer
the most promise as means for delegating role responsibilities among formal service
providers and informal caregivers and suggests that "professional caregiving
should facilitate and complement the care taking place through lay involvement
with the individual or group in need" (p. 410). Similarly, Froland (1981)
suggests that the help provided by informal support network can be "interwoven"
with the formal services to produce a partnership capable of reducing reliance
on professional care while enhancing the quality of services. Informed by task
specific theory, the proposed study will expand the case management program developed
Chen et al. (2002) to include informal caregivers to case management processes.
Study Design
Quasi-experimental
Design
O1 X1 O12
O13 O14 O15
O2 X2 O22 O23 O24 O15
Intervention:
X1(Service
as Usual): Assessment of older adults' demographic, functional and cognitive impairment,
unmet needs, assignment of services, receiving services, and follow-ups.
X2
(Improved Case Management):
1) Multi-dimensional Assessment
a. Older adults'
functional and cognitive impairments, physical and mental health, financial needs,
socialization needs, and quality of life.
b.
Informal caregivers' physical and mental health, willingness and commitment to
elder care, care provision skills, distress, and general well-being.
2)
Determination of Service Needs (Case manager-led service planning session)
a.
Presentation of multi-dimensional assessment.
b. Feedback from older adults
and Informal caregivers
3)
Development of the Service Plan (Case manager-led service planning session)
a.
Identification and agreement on goals of the HCBS plan.
b. Identification and
agreement on types and volumes of informal services.
c. Identification and
agreement on types and volumes of formal services.
d. Identification barriers
to needed services and development of strategies to overcome service barriers.
e. Identification and agreement on older adults' and informal caregivers'
service preferences and expectation.
4)
Service Plan Implementation
5)
Service Follow-ups
O1i:
Observations on Matched Comparison Group after intervention, at two-week (O12),
at three-month (O13), at 6-month (O14), and at 12-month (O15).
O2i: Observations
on Experiment Group after intervention, at two-week (O22), at three-month (O23),
at 6-month (O24), and at 12-month (O25). back
to top
Faculty
Research Awards:
2002-2003
Initiative on Aging Incentive Grants One
goal of the Initiative on Aging is to foster an increase in extramural funding
at UIUC in the area of aging. We are especially interesting in promoting the submission
of interdisciplinary proposals that include multiple investigators across departments
and schools. To help this endeavor, the Initiative on Aging provides Incentive
Grants to faculty submitting new major grant applications to government or private
sources for the study of gerontological issues. In 2003, two incentive grants,
of $10,000 each, were awarded to faculty planning appropriate submissions.
Click on the
award winners name to see their proposals. Aging
Initiative Incentive Grant Proposals:
Aaron S. Benjamin, Ph.D., Psychology
Bill Helferich, Ph.D., Food Science and Human Nutrition 2003
UIUC Initiative on Aging Incentive Grant Proposals The
following is a summary of a proposal for the 2003 UIUC Initiative on Aging Incentive
Grant by Aaron S. Benjamin, Ph.D. Title:
The locus of false remembering in the elderly Summary
Much recent evidence has shown that the elderly are particularly prone to falsely
remembering stimuli and events that did not, in fact, occur. Such "false
memory" phenomena provide a unique window into the encoding and decision
processes underlying normal memory and can serve additionally to constrain theories
of the effects of aging on mnemonic processes. The present studies evaluate two
contrasting theories on the origin of false-memory phenomena in general and the
particular susceptibility of the elderly to such effects. Generation theories
postulate that the subject mentally generates the falsely remembered item while
studying related stimuli and then, on a later test, fails to discriminate between
imagined and perceived stimuli. Response rule theories suggest that subjects employ
response criteria during the memory test that allow plausible but unstudied items
to elicit a memorial response. Critically, such theories do not require an imaginal
generation of the falsely remembered stimulus during study. With respect to the
elderly, generation theories specify impaired source memory skills as the locus
of false memory effects. Response rule theories attribute the deficit in the elderly
to the application of more liberal response criteria. Experiments are proposed
that address the viability of these theories by (1) assessing the extent of source
memory deficits in the elderly in a paradigm in which visual perceptual difficulty
is psychophysically equated between the old and the young, (2) examining the inter-individual
correlation of source memory skill and susceptibility to false memory, and (3)
implementing a version of the semantic false recognition paradigm that allows
for rigorous evaluation of decision rules via the Theory of Signal Detection (TSD). Overview
of the experimental approach
Testing the generation framework: Experiment
series 1. The first experiments address the extent of source memory deficits
in the elderly in a paradigm in which perceptual difficulty is equated for both
word identification and source discrimination. Using multiple staircases , each
subject's threshold will be estimated for (1) the necessary size to lead to 80%
correct identification of words and (2) the necessary contrast to lead to 80%
correct identification of that word's polarity: black (positive polarity) or white
(negative polarity). All words will be presented on a gray background. Given the
ubiquity of age-related perceptual deficits, higher contrasts and larger sizes
will presumably be necessary for older subjects to psychophysically equate the
perceptual difficulty across age groups.
After establishing individual subjects'
thresholds, each subject will study a long list of different words, each of which
will be presented in the center of the screen in white or black at the appropriate
size and level of contrast (again, on a gray background). On a later recognition
test, in which all words will be presented in a neutral color (e.g., green), subjects
will be asked to evaluate (1) whether they had previously studied that item and
(2) whether it had been presented in black or white. If perceptual differences
between the young and the old underlie differences in source memory, as suggested
by Ferguson et al. (1992), then source memory should be equal for the two groups
in this experiment. In addition, if memory deficits in the elderly in general
derive from differences in perceptual acuity, then recognition performance should
now also be equivalent between the groups (Murphy et al., 2000).
This psychophysical
paradigm described in Experiment 1 also allows for a novel exploration of the
finding of Ferguson et al. (1992), in which the use of more distinctive sources
improved source memory performance and reduced the age-related impairment. After
establishing individual thresholds on the polarity discrimination task, source
memory performance can be assessed using contrast levels proportionate to those
measured thresholds. Specifically, Experiment 2 will utilize contrast levels that
are 200%, 400%, and 800% of the 80% contrast discrimination threshold. Because
individual contrast functions are thought to be linear in form (cf. Burkhardt,
Gottesman, Kersten, & Legge, 1984; Cannon, 1979), and do not appear to differ
as a function of age (Dannemiller & Stephens, 2001; Muir, Barlow, & Morrison,
1996), this manipulation effects an equivalent increase in contrast discriminability
between the groups.
It is thus possible to derive the function relating source
discriminability to source memory performance, and evaluate the extent to which
memory is simply a function of source discrimination during encoding. Moreover,
if the age-related deficit in source memory performance is comprised of both perceptual
and mnemonic components, then the variance-accounted-for estimates for this function
should differ between the old and the young. A failure to find differences in
R2 would indicate no disproportionate difficulty for the elderly in the memory
portion of the source memory task.
Examining the inter-individual correlations
between source memory ability and proneness to false recognition provide a direct
means of testing the hypothesis that source confusability underlies false recognition.
Specifically, the partial correlation between source memory and false recognition
factoring out perceptual acuity will be zero if generation explanations of false
recognition are correct.
The first set of experiments utilize a psychophysical
procedure for equating perceptual source discrimination to rigorously evaluate
a perceptual explanation of apparent source memory deficits in the elderly. Because
the generation theory of false memory postulates impaired source memory as the
locus for the susceptibility of the elderly to semantic false recognition, these
experiments are critical to evaluating such a hypothesis. Signal
detection models of false memory in the elderly: Experimental series 2. The
remaining experiments in this series are aimed at testing implications of the
response rule theory on false memory. The general paradigm is taken from Roediger
and McDermott (1995), with the modifications suggested by Miller and Wolford (1999).
In that version, some of the false memory lists are studied with the critical
item, and some are presented without it. This minor change allows one to examine
the probabilities of a subject endorsing a critical item with and without a prior
study presentation. Again, the motivations for such a modification are the differences
between study-set and critical items. One additional change is proposed: Subjects
will study only one half of the normal study list of items (counterbalanced across
subjects), but will be tested on all items. In this manner, it is possible to
obtain measures of recognition bias (see, e.g., Wickens, 2001) for both critical
and noncritical items. A brief review of the relevant aspects of TSD is presented
by Green and Swets (1966) and Wickens (2001).
In the first experiment in this
series, young and old subjects will be tested in the experiment outlined above.
Measures of memory discrimination and recognition bias will be obtained for critical
and noncritical items for both groups. The response rule theory predicts an interaction
of the form that older subjects show a greater increase in bias to call stimuli
"old" from noncritical to critical items than do young subjects. Generation
theory predicts equal or no increases between the groups.
The next experiment
will explicitly address the nature of the peculiar finding of Benjamin (2001),
in which repetition increased both true and false recognition for the elderly,
but increased true and decreased false recognition in the young. The methodology
and analysis will be similar to the previous experiment, but will additionally
incorporate a study-list repetition manipulation. More liberal criteria for repeated
stimuli are predicted by response rule theory, whereas increasingly conservative
criteria are predicted by generation theory for both the young and the old.
The particular version of TSD employed here is commonly referred to as the "equal-variance"
model, in which the variances of both hypothesized distributions are constrained
to be equal to 1. However, experiments that address this issue empirically often
find the variance of the old distribution to be slightly greater than that of
the new distribution (e.g., Egan, 1958). To date, no one has evaluated the generalizability
of this finding to older adults (cf. Craik, 1971). Because such results provide
strong constraints on general models of learning and memory (cf., Ratcliff, Sheu,
& Gronlund, 1992), it is critical to theories of aging and memory to evaluate
such measures in different age groups.
In order to do so, performance must
be measured at multiple points in the bias space. One manner in which this can
be done is to elicit confidence judgments and then plot the cumulative hit rate
and false-alarm rate bidimensionally, yielding a receiver operating characteristic,
or ROC. A normal transform of the axes of the ROC (hit rate and false-alarm rate)
typically produces a linear function, the slope of which is equal to the ratio
of the variance of the noise to the variance of the signal distribution (i.e.,
sn/ss). Thus the only necessary modification to the typical recognition paradigm
described throughout is the elicitation of a confidence judgment following the
recognition judgment.
Another manner by which the ROC function can be estimated
is by explicitly manipulating bias through the use of instructions or asymmetric
payoff matrices. Because some have argued recently that the use of confidence
ratings compromises the validity of the ROC estimate (e.g., Van Zandt, 2000),
manipulating bias directly potentially provides for a more accurate evaluation.
Moreover, some authors have suggested that some of the memory deficit apparent
in amnesia owe to particularly conservative criterion-setting, and have shown
that relaxing such criteria increases performance in patients with ECT-induced
amnesia (Kihlstrom, Shames, & Dorfman, 1996), although others have failed
to replicate this finding in patients with organic amnesia (Reber & Squire,
1999). Although age-related deficits in recognition memory are not large, they
are reliable (see, e.g., Kester, Benjamin, Castel, & Craik, 2003), and it
is possible that differences in criterion-setting partly underlie such differences.
back
to top The
following is a summary of a proposal for the 2003 UIUC Initiative on Aging Incentive
Grant by Bill Helferich, Ph.D. The
proposal will be on dietary estrogenic supplements and their effect(s) on aging
with a focus on breast cancer, adipose and brain. We feel that the timing of exposure,
dosage, and target tissue will be critically important in determining whether
the biological effects are beneficial or detrimental. We will use genistein from
soy or red clover as a model dietary estrogen as this is a major component in
many of the dietary estrogenic supplements targeted to older men and postmenopausal
women. General
Information and Background: Recently, there has been a dramatic increase in
the usage of estrogenic dietary supplements in the United States. These unregulated
products are being used by both older men and women for a variety of perceived
health-related benefits. Recommended daily isoflavone consumption from these products
had a wide range, from low (less than 10 mg) to very high (800 mg). Considerable
confusion exists between what is considered a food (regulated by the FDA) and
supplement (not regulated by the FDA). For example, products made with soy germ
are not considered supplements and can be marketed as food ingredient when added
to products such as cereals. Novasoy (ADM, Decatur IL) is an extract of soy that
contains 400 mg of isoflavones per gram of extract. This extract is GRAS (generally
recognized as safe) listed by the FDA for beverages, health bars and meal replacers
and allows the content to be equivalent to what is in a serving of soy (25 mg).
This same extract can be added at much higher levels and is considered a supplement.
For example, Caltrate + soy (American Home Products, Madison, NJ ) has 25 mg of
isoflavones per tablet (from Novasoy), and two tablets are recommended per day.
Another product, Soylicious (country life.com), is a flavored soy beverage with
150 mg of isoflavones (from Novasoy) and is marked as a supplement not a food.
It is important to note that Novasoy is a very well characterized and standardized
extract from soy and is the most widely used soy isoflavone extract used in the
food and supplement industry. It is clear that Novasoy can be consumed in high
pharmacological levels and the safety of this product for breast cancer survivors
is unclear. The interaction of Novasoy with TAM therapy has not been investigated
in pre clinical laboratory tumor growth studies. This complex mixture, which is
consumed by millions of women and men, will be utilized as a dietary treatment
in each of the research projects of this PO1. Individual
Research Project Focus: Dr. Helferich has conducted a series of studies in
the past several years looking at the effects of dietary exposure to soy isoflavones
in animal models that are representative of postmenopausal women with estrogen-dependent
breast cancer. His research team has demonstrated that genistein at relevant dietary
dosages stimulate growth of estrogen-dependent tumor growth. More recently he
has shown that soy isoflavones can block the inhibitory effect of tamoxifen on
estrogen induced tumor growth. The focus of Dr. Helferich's proposal will be on
low level chronic exposure to soy isoflavones and their influence on breast cancer
progression from estrogen dependent to estrogen independent tumors. This has important
health implications for women since estrogen dependent breast tumors have a significantly
better prognosis using established endocrine therapies. Dr.
Paul Cooke would lead another of the research projects. Paul has investigated
the effects of soy isoflavones on the thymus and immune function and has shown
that genistein exposure causes thymic atrophy and immune dysfunction. More recently
he has initiated studies looking at effects of soy isoflavones on adipose tissue
and type II diabetes and this latter area would be his focus for this proposal.
His group has shown that estrogen receptor alpha has a critical role in adipose
deposition, and that estrogen receptor beta has a role in fat that is the opposite
that of estrogen receptor alpha. In addition, they have shown that the phytoestrogen
genistein has marked inhibitory effects on adipose tissue. For this project, he
would focus on adipose development, and the potential for phytoestrogens such
as genistein to alter adipose development and produce long term changes in the
amount and function of adipose tissue. Dr.
Susan Schantz will contribute a third research project. For many years her research
group has investigated the effects of hormonally active environmental contaminants
on brain function. She is now conducting studies assessing the effects of estrogen
and soy isoflavones on various aspects of cognitive functioning. It has been widely
reported that estrogen replacement improves memory function in postmenopausal
women and in ovariectomized rats. However, her research team has preliminary evidence
suggesting that estrogen replacement actually impairs other important aspects
of cognitive function including inhibitory control and time estimation in ov ex
rats. They are currently investigating whether genistein has similar negative
effects on these cognitive endpoints. This project would focus on evaluating the
effects of soy isoflavones and dietary supplements containing soy isoflavones
on various aspects of cognitive functioning including cognitive flexibility, attention,
inhibitory control, and working memory. The
focus of an additional project (a fourth project) is still under discussion. Several
faculty including Dr. Ann Nardulli, Dr. John Katzenellenbogan and Dr. Donna Korol
on this campus and Dr. Dan Doerge at NCTR have expressed an interest in participating
in the program project. Their roles as PIs or co investigators on research projects
or cores are still being worked out. One option we are considering is a project
that would evaluate a number of plant estrogens and structural modifications of
those compounds in ER-alpha and ER-beta binding assays and gene expression bioassays.
Additionally, whole cell bioassays would also be used to predict the potential
in vivo effects of these compounds. This rapid screening system would allow us
to screen numerous estrogens from a variety of supplements to identify those that
should be studied more extensively for potential beneficial and/or harmful effects
in our in vivo models.
back
to top Faculty
Research Awards:
2001-2002
Initiative on Aging Incentive Grants One
goal of the Initiative on Aging is to foster an increase in extramural funding
at UIUC in the area of aging. We are especially interesting in promoting the submission
of interdisciplinary proposals that include multiple investigators across departments
and schools. To help this endeavor, the Initiative on Aging provides Incentive
Grants to faculty submitting new major grant applications to government or private
sources for the study of gerontological issues. In 2002, four incentive grants,
of $10,000 each, were awarded to faculty planning appropriate submissions.
Click on the
award winners name to see their proposals. Aging
Initiative Incentive Grant Proposals:
Ellen M. Evans, Ph.D., Kinesiology
Donna Korol, Ph.D., Psychology
Karl
Rosengren, Ph.D., Psychology & Kinesiology
Weimo Zhu, Ph.D., Kinesiology
2002
UIUC Initiative on Aging Incentive Grant Proposals The
following is a summary of a proposal for the 2002 UIUC Initiative on Aging Incentive
Grant by Ellen M. Evans, Ph.D.
It
is estimated that the number of postmenopausal women in this country will double
by the year 2025. The risk of osteoporosis in the postmenopausal woman is well
characterized with ~50% of women over the age of 50 experiencing a fracture in
their lifetime. Recent findings in scientific literature report that the menopausal
transition produces a detrimental change in body composition both in terms of
overall body fatness and body fat distribution. Indeed, according to NHANES III,
~ 70% of peri- and postmenopausal women are overweight or obese as determined
by body mass index (BMI). Alterations in body composition in this population are
important, as it may be the link to the increased risk for diseases related to
carbohydrate metabolism seen in women after the decade of their menopause.
In the clinical setting, overweight postmenopausal women, who elect not to use
hormone replacement therapy (HRT), are typically counseled to refrain from weight
loss because adipose tissue is an important source of endogenous estrogens. Paradoxically,
when evaluating body weight status, the clinician and the postmenopausal woman
must choose between reducing the risk for a) osteoporosis OR b) glucose intolerance
or diabetes mellitus II and related cardiovascular diseases. The 1998 NIH Clinical
Guidelines on the Identification, Evaluation, and Treatment of Overweight and
Obesity in Adults Report specifically states that additional research is needed
on strategies to preserve muscle and bone in the face of weight loss. From a non-pharmacological
therapeutic perspective, exercise confers unique benefits to the postmenopausal
woman as it reduces risk for osteoporosis AND carbohydrate metabolism related
diseases.
back
to top The
following is a summary of a proposal for the 2002 UIUC Initiative on Aging Incentive
Grant by Donna Korol, Ph.D.
In all animals studied to date, aging leads to a myriad of changes in cognitive
processes and brain functions including accelerated forgetting of newly learned
material, alterations in neurotransmitter function, and modified synaptic plasticity.
Accompanying aging in females of many mammalian species is also the cessation
of the reproductive cycle. Menopause, or estropause in non-human mammals, is characterized
by a dramatic decline in estrogen, the consequences of which are poorly understood.
Many of the neurobiological effects of estrogen have been examined in young adults,
while very few studies have assessed how changes in hormones with age influence
brain functional changes resulting from age. Because of increases in health and
life expectancy, many women can now expect to spend 1/3 to 1/2 of their adult
lives post-menopause. Thus, understanding the interaction of age and hormonal
processes is important not only for understanding the neural mechanisms of aging
and menopause, but also for promoting health in our increasingly elderly population.
In working towards a model of the cognitive and neurobiological changes accompanying
menopause, my lab has obtained a series of findings in young adult females suggesting
that circulating estrogen shifts the strategy used to solve a learning task. In
particular, estrogen enhances learning of some types of tasks but impairs learning
of other types of tasks. We have also found that young rats deprived of hormone
via ovariectomy have in response to training, lowered levels of extracellular
hippocampal acetylcholine (ACh), a memory-modulating neurotransmitter, than do
rats given estrogen for 2 days prior to training. Reports from other laboratories
support the findings that estrogen interacts with the cholinergic system in young
adults, providing one mechanism for estrogen's ability to modulate learning and
memory functions. Emerging from these and other results is the idea that estrogen
may also act by shifting brain activation patterns, thereby modifying the dynamics
of information flow through the nervous system. We are currently attempting to
identify the neural site(s) of estrogen's action, the cellular locus (i.e. intra
or extracellular) and how estrogen interacts with gamma-aminobutyric acid (GABA;
which may explain ACh actions) through central injections of GABA agonists and
antagonists, and by microdialysis of GABA in intact animals engaged in learning
tasks. Whether estrogen deprivation and replacement in older animals is similarly
effective is still unknown.
Specific Aims.
This
proposal has 3 specific aims to determine whether estrogen decline in old, estropausal
female rats influences cognition in a manner that is predicted by the shifts seen
in young animals. We plan to determine whether 1) old, acyclic female rats show
shifts in learning strategy as predicted by my findings in young adult rats, 2)
estrogen treatment alters strategy selection in old, acyclic females in a dose
and duration-dependent manner, and 3) training-related changes in specific neurotransmitter
functions are sensitive to estropause and hormone treatment.
Results from
these studies will inform us about the interactions between declining gonadal
hormones and age-related changes in cognition in females. They will also point
to specific neurochemical systems known to be sensitive to estrogen that may aid
in the development of effective hormonal treatments for healthy women as well
as for victims of neurodegenerative diseases.
back
to top The
following is a summary of a proposal for the 2002 UIUC Initiative on Aging Incentive
Grant by Karl Rosengren, Ph.D.
Examining
the Effects of a 6 month Taiji and a Walking Program on the Physical and Cognitive
Function in Older Adults Specific
Aims:
1) To examine the effects of a 6 month Taiji program and a 6 month
walking program on the physical and cognitive function of older adults. Specifically,
to compare two different forms of exercise, one aerobic (walking) and one non-aerobic
(Taiji) on physical and cognitive function.
2)
To examine the relationship between activity, efficacy, perceptual function, and
cognitive function in older adults.
3)
To examine whether benefits obtained as a function of Taiji practice are related
to the level of skill acquired. Specifically, we will examine how the learning
of Taiji as a skill relates to physical and cognitive functioning in older adults.
Background:
Physical
and cognitive deficits lead to a large number of accidents, injuries, and deaths
in older adults. Improving the physical and cognitive functioning of older adults
has great benefits in terms of improving the overall health and quality of life
of older adults. Recent studies have shown that participating in a regular program
of walking can improve the cognitive functioning of older adults (Kramer et al.).
Kramer and his colleagues have hypothesized that the aerobic benefits gained from
the walking program might be the source of these cognitive benefits. Other research,
most notably that from Baltes' laboratory have suggested links between perceptual
and sensorimotor function and cognitive performance in older adults. Baltes et
al., have not, however, examined this finding longitudinally, making it difficult
to determine the underlying cause of this linkage. A number of researchers, including
McAuley, have linked a variety of health benefits associated with exercise to
an increase in efficacy. Efficacy refers to an individual's situational specific
confidence in his or her ability to perform a course of action. Other studies
have begun to explore possible benefits from participating in Taiji. Taiji is
an ancient Chinese martial art that is most strongly associated with very slow,
highly coordinated movements (this is actually only one aspect of Taiji). To date,
Taiji practice has been associated with improvements in efficacy, reduction in
fear of falling, delaying older adults first fall, and a variety of other health
benefits (reduction of stress, reduction of blood pressure). Presently, no one
has investigated whether Taiji, a non-aerobic activity involving slow controlled
movements has any impact on cognitive function. We expect that participation in
Taiji might lead to improvements in cognitive performance in older adults. In
a pilot study conducted a few years ago we found that Taiji practice significantly
improved participants' sensitivity to vestibular information relevant for balance
control. If we are able to replicate this improvement in perceptual function we
will be able to examine more closely the linkage between perceptual and cognitive
function in older adults and to examine how changes in perceptual function as
a function of Taiji practice might relate to potential changes in cognitive performance.
Taiji is a complex, three-dimensional skill, that requires a high level of concentration.
We expect that Taiji practice, due to its complexity and attentional requirements
will also lead to improvements in cognitive performance in older adults. If this
finding holds, then it would suggest a different possible connection between exercise
and cognitive function then has been previously suggested. A
secondary goal of this project is to investigate the effects of learning Taiji
on physical and cognitive function. In all of the past research examining Taiji
no measure of whether participants actually learn Taiji has been employed. This
is problematic because without some kind of measure of skill acquisition one can
not determine whether it is merely attendance in a Taiji class or actually learning
the skill that is linked to the benefits attributed to Taiji. Due to the complexity
of this form of exercise it is quite difficult to assess how individuals learn.
Rosengren has recently developed a number of methods for assessing skill acquisition
of individuals who are learning Taiji. These methods are based on recent findings
from his laboratory that suggest that individuals with Taiji training adopt a
wider base of support and different postural strategies in response to perturbations
of stance than normal adults or individuals with expertise in dance. Additional
methods of assessing Taiji skill will utilize the recently acquired Motion Analysis
System in the Beckman Institute. This research will enable us to examine whether
it is skill level, or merely participation that is linked to the health benefits
associated with Taiji. Our expectation is that the benefits attributed to Taiji
will be more strongly associated with skill level than participation. However,
it may be the case that benefits of Taiji practice will be moderated by improvements
in efficacy. These improvements in efficacy may result merely from participating
in a Taiji program. For this reason, it is important to assess the role of participation
and skill learning in any study employing Taiji. The results obtained from our
investigation are likely to have large implications for the design and implementation
of exercise interventions with older adults. back
to top The
following is a summary of a proposal for the 2002 UIUC Initiative on Aging Incentive
Grant by Weimo Zhu, Ph.D. Development
and Validation of an E-coder for Scoring
Physical Activity Diaries of Old
Adults Weimo
Zhu, University of Illinois at Urbana-Champaign Background/Needs
The past decade has seen an
increased interest in the association between physical activity and health. Considerable
evidence has accumulated to support the hypothesis that moderate levels of physical
activity (3-6 METS) are important in reducing the risks of coronary heart disease
and all-cause mortality (see, e.g., Blair et al., 1996; Manson et al., 1999).
The American Heart Association has named physical inactivity a major risk factor
for coronary heart disease, joining the more established risk factors; hypertension,
smoking and an adverse blood lipid profile (Fletcher et al., 1992). Evidence has
also accumulated linking physical inactivity to an increased risk for other chronic
conditions, such as stroke (Hu et al., 2000), cancer (Verloop et al., 2000), non-insulin
dependent diabetes (Brancati et al., 2000), and osteoporosis (Milgrom et al.,
2000). While
some electronic devices, e.g., motion sensors or pedometers, have been developed
recently to measure physical activity in a rather convenient way, they cannot
record people's physical activity patterns and only have a low correlation (r
= .3 ~ .4) with criterion measures of physical activity, such as doubly-labeled
water. This is also true for commonly used physical activity questionnaires, although
some of them can provide an estimation of people's activities in certain predetermined
activity categories. The physical activity diary is another method to record people's
physical activity participation, in which subjects are asked to recall their physical
activity participation in a predetermined interval (e.g., every 30 minutes). Physical
activity diaries could provide not only rich information of people's activity
patterns, but also have been used often in research as a criterion measure itself
in measuring physical activity (Montoye et al., 1996). The limitation of using
a physical activity diary, however, is that scoring such diaries is very labor-intensive
activity and, as a result, it becomes very expensive. In addition, raters' objectivity
is sometimes a concern when raters are not carefully trained (Montoye et al.,
1996). For these reasons, the physical activity diary is used mainly as a criterion
measure in validation studies, and its advantage of providing rich information
about physical activity patterns has never been taken in measurement practice.
Fortunately,
the above limitation can be overcome by a new technology called E-rater, which
was redeveloped in educational measurement practice to score essays. The original
idea for E-rater can be tracked back to the 1950s when the Educational Testing
Service (ETS) had pursued research in writing assessment. Using natural language
processing, an application of computational methods to analyze characteristics
of electronic files of text or speech, artificial intelligence and new computing
power, the E-rater technology has been updated recently. In February 1999, ETS
began to use the new E-rater for operational scoring of the GMAT analytical writing
Assessment (Burstein et al., 2000; Kukich, 2000). The reported discrepancy rate
between E-rater and one human reader score has been less than three percent (Burstein,
2001). That is comparable to the discrepancy rater between two human raters, but
the ability to use automatic essay scoring in operational scoring environments
reduces the time and costs associated with having multiple human readers score
essay responses. Proposal
I believe that, with some modifications, the E-rater technology can be used to
score physical activity dairies of older adults. I have contacted Dr. Richard
Swartz, president of ETS Technologies, Inc. (a subsidiary of ETS), about the possibility
and he has expressed an interest to collaborate. I have also consulted several
experts in measuring physical activity (e.g., Dr. Barbara Ainsworth at the University
of South Carolina and Dr. Richard Washburn at the University of Kansas), for the
potential of this project, and they have expressed great support. In fact, they
all believe that the development of an E-coder will significantly improve the
current capacity to score physical activity diaries and will have a great impact
on the current practice of measuring physical activity.
The E-coder will be a part of another research project I am working on in which
an E-diary system will be developed for physical activity assessment. In this
system, speech recognition technology will be employed to record physical activity
(it is currently recorded using paper-and-pencil). With a combination of both
speech recognition technology and E-coder, a new way to collect physical activity
data can be invented: Subjects can be reminded to record their physical activities
by a programmed "beep"; they then talk into a mini-tape recorder to
record their physical activities during the previous half-hour or 15 minutes,
which are then automatically transferred into electronic text; finally, the downloaded
electronic text can be analyzed automatically using E-coder so that an individualized
report of physical activity assessment and evaluation can be generated. With the
development of Web technology, the E-diary can be functional at a distance so
that large-scale exercise/physical activity intervention becomes possible.
back
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Research Awards:
2003-2004 Paul H. Doolen Awards Doolen
scholarships are awarded annually to graduate students in their second year of
study or beyond whose principal scholarly interest lies in the field of aging.
Established in 1986 by an endowment from the Retirement Research Foundation in
Oak Park, Ill., the scholarships honor the late Paul D. Doolen, a longtime member
of the foundation's board of directors and a 1927 graduate of the University of
Illinois at Urbana-Champaign. 2003-2004
Paul H. Doolen Award Proposals:
Kirk Erickson
Jason O'Connor 2003-2004
Paul H. Doolen Award Proposals The
following is the proposal for the 2003-2004 Doolen Award submitted by one of the
two Doolen Award winners, Kirk Erickson: Research
Plans: Adults
over 60 years of age often experience substantial declines in cognitive functions
such as memory and attention. With the projected explosion of persons falling
into the 60+ age category throughout the next several decades, it becomes increasingly
important to understand the functional and structural changes in the brain that
might underlie cognitive decline. Moreover, a careful examination of factors that
might reduce cognitive decline, and the functional mechanisms by which they operate
appears to be a critically important social and public health goal.
For example,
evidence from Kramer, McAuley, Colcombe, and colleagues at the University of Illinois
have shown that increasing cardiovascular fitness provides one effective way to
reduce cognitive decline in older adults [1]. Importantly, we have found that
increased levels of cardiovascular fitness reduces cortical tissue loss as measured
by structural magnetic resonance imaging [MRI] [2].
Other interventions such
as cognitive training and hormone replacement therapies have also been found to
reduce age-related deficits on many cognitive tasks, but the neural mechanisms
that underlie these changes is as of yet unknown. Additionally, the potential
benefits of combining both cognitive training and fitness training regimens are
numerous if there is an added cognitive benefit to combining training methods.
Research Methodology:
Adults of 60+ years will be recruited for this study and randomly assigned
to one of two groups (experimental and control). The experimental group will undergo
a multiphase program consisting of two MRI sessions, ten cognitive training sessions,
and one session to assess their cardiovascular fitness level. Each cognitive training
session will consist of one-hour practice sessions with feedback while performing
a task that requires them to manage two cognitive tasks simultaneously.
Additionally,
a subset of these participants will undergo structural and functional MRI assessment
before cognitive training begins, as well as after the entire cognitive training
routine is complete. These assessments will allow us to identify the way in which
the brain responds to the training (how it learns), as well as how these changes
are mediated by cardiovascular fitness.
In summary, as a Paul D. Doolen scholar,
I will investigate the neural mechanisms underlying age-related benefits of cognitive
training interventions, as well as how these changes differ as a function of cardiovascular
fitness. A deeper understanding of the older adult brain and the factors that
might help reduce or avoid senescence is essential as our modern societies become
more populated with aged individuals. The research described in this proposal
promises to make a strong contribution to that effort. I hope that you will give
my application serious consideration, and that I will have the opportunity to
pursue these issues as a Paul D. Doolen scholar.
back
to top Student
Research Awards:
2002-2003 Paul H. Doolen Awards Doolen
scholarships are awarded annually to graduate students in their second year of
study or beyond whose principal scholarly interest lies in the field of aging.
Established in 1986 by an endowment from the Retirement Research Foundation in
Oak Park, Ill., the scholarships honor the late Paul D. Doolen, a longtime member
of the foundation's board of directors and a 1927 graduate of the University of
Illinois at Urbana-Champaign. 2002-2003
Paul H. Doolen Award Proposals:
David Xavier Marquez
Eric
Deszo 2002-2003
Paul H. Doolen Award Proposals The
following is the proposal for the 2002-2003 Doolen Award submitted by one of the
two Doolen Award winners, David X. Marquez: In
the last decade, the percentage of Americans 65 and older has more than tripled
and this population will continue to grow. In addition, minority populations are
projected to represent 25% of the elderly population in 2030, up from 13% in 1990.
Specifically, between 1990 and 2030 the older Latino population will increase
by 570%. Physical activity has been shown to have numerous physical and psychological
benefits for older adults, including increasing happiness and satisfaction with
life, and decreasing loneliness. Unfortunately, Mexican Americans report less
physical activity than non-Latino Whites across education, family income, and
occupation. More dramatically, 51% of Latinos aged 65-74 report no leisure time
physical activity at all. Given these statistics, I have focused my research,
coursework, and practical experiences towards understanding the psychological
determinants and outcomes associated with physical activity in older Latino adults. During
my tenure in graduate school at UIUC I have had the opportunity to work with Dr.
Edward McAuley on several interdisciplinary randomized controlled trials that
have focused on the psychological, physical, and functional changes in older adults
as a result of physical activity interventions. As a research assistant for Dr.
McAuley, my responsibilities have included data collection, processing, and analysis,
interviewing participants, and involvement in laboratory meetings to discuss and
interpret study findings. Recently, my responsibilities have also included conducting
Senior Fitness Testing, and the training of personnel to assist with this testing.
My involvement in these trials has also led to my participation in the writing
and presentation of study findings. Results from these trials have been very promising,
as we have demonstrated increases in well-being, and cognitive functioning, and
decreases in depression and social physique anxiety as a result of physical activity
participation. Recently,
Dr. McAuley and I were awarded a National Institutes of Health (NIH) Minority
Predoctoral Fellowship through the National Institute on Aging. With Dr. McAuley's
assistance, I have analyzed data to determine the roles played by self-efficacy,
social physique anxiety, and changes in body composition and fitness in exercise
participation over the 12-month period. Outcomes such as these can help formulate
hypotheses for a randomized controlled exercise trial designed to enhance adherence
to physical activity in older Latino adults. My
practical experience with older adults has also influenced my research direction.
For two years, I was the Director of the Lifetime Fitness Program for Older Adults,
which is held three mornings per week on the University of Illinois campus and
provides a structured group or individualized fitness regimen for adults 55 and
over. My responsibilities included administrative duties, personnel training,
leading group exercise, and overall supervision and program implementation. This
program provided me with invaluable experience dealing with the everyday needs,
concerns, and experiences of older adults. My
coursework has served as a complement to my research and practical experience.
I have taken courses such as "Cognition and Aging," and "Exercise
and Health Psychology," which have focused on the interdisciplinary nature
of aging. In addition, I have taken "Posture and Gait Across the Lifespan,"
and "Physical Activity and Aging," in order to achieve a better understanding
of the physiological and functional effects of physical activity on older adults.
In addition, this semester I am enrolled in "Psychology and Aging."
This coursework has helped me learn about the psychological, physical, and cognitive
aspects of aging, and the impact of physical activity upon them. To
date, research on physical activity has clearly demonstrated that cultural factors
play a significant role in the adoption and maintenance of physical activity.
This is a noteworthy issue, given that many older Latino adults are deeply rooted
in their cultural heritage. To this end, I am currently reviewing the literature
on Latinos and exercise to develop a better awareness of these cultural factors
that may affect the physical activity patterns of Latinos. In addition, I have
hired a tutor to improve my Spanish speaking ability so that I can communicate
more effectively with older Latino adults. I am also continuing to make contacts
with the Latino community in Champaign-Urbana and am beginning to make connections
with co-investigators of my advisor, who conduct research with minority populations
in Chicago. Given
my stated research plans of bringing a stronger focus to the topic of physical
activity and health in older Latinos, my research agenda will combine two theoretical
approaches, social cognitive theory and social identity theory. I will examine
attitudes towards exercise, past exercise experience, and barriers to exercising
in Latinos, both in central Illinois and in an urban environment, Chicago. In
addition, working with professors from a variety of disciplines such as Psychology
and Kinesiology, I will study the extent to which being Latino and being involved
in the Latino culture influences exercise behavior. A cross-sectional survey study
will allow me to compare the responses of thirty individuals from each of the
following groups on these variables: Latino adults in Champaign-Urbana and Chicago,
and older Latino adults in these two areas. The results of this cross-sectional
study will help formulate my hypotheses for designing culturally tailored physical
activity interventions for older Latinos. The Paul D. Doolen Award would directly
facilitate these plans through assisting me in the cost of transportation to and
from Chicago, the cost of office resources and distribution of health materials,
translation of questionnaires, and money offered as incentive to participate in
my research.
Implementing randomized controlled trials with older Latino adults is my long-term
goal, however, addressing both the concerns of older Latinos interested in exercising
and cultural factors influencing exercise behavior are my short-term objectives.
Receiving the Paul D. Doolen Award would be an honor and would truly assist me
in fulfilling my goals.
back
to top The
following is the proposal for the 2002-2003 Doolen Award submitted by one of the
two Doolen Award winners, Eric Deszo: Respiratory
infection due to viral and bacterial pneumonia is the fifth leading cause of death
in persons 65 years of age and older. In the elderly, impaired resolution of infection
is caused by failure of the aged immune system to respond to antigen challenge.
One possible mechanism of this failure is age-related accumulation of reactive
oxygen species (ROS). We have shown that antigen presenting cell (APC) function
is tightly regulated by enzymes that are controlled by ROS. Specifically, we have
found that protein kinase C regulates APC cell development by modulating expression
of surface co-stimulatory molecules that direct T-cell development. Therefore,
our hypotheses is that age-induced accumulation of ROS activates PKC-d, suppresses
co-stimulatory molecule expression and leads to reduced adaptive immunity.
After antigen uptake and processing, macrophages differentiate into dendritic
cells, the most potent known APCs. These dendritic cells then migrate to lymph
node germinal centers where they activate T-cells. To accomplish T-cell activation,
two distinct signals must be provided: an antigen-specific signal via the T-cell
receptor and a co-stimulatory signal that is provided by the cell surface molecules
CD80 and CD86. These two signals trigger T-cell division and differentiation allowing
adaptive immunity to develop. In the absence of adequate stimulation, T-cells
fail to mature and an adaptive immune response is not generated. Therefore, it
is likely that increased ROS in aging induce a state of immune hypo-responsiveness
through the inhibition of the co-stimulatory pathway.
Research Methodology
The goal of my research is to study the impact of oxidative stress on macrophage
to dendritic cell differentiation. This goal will be explored in the following
specific aims: determine the effect oxygen free radicals have on macrophage to
dendritic cell differentiation and investigate the role PKC-d has in this process.
In previous work (J. Biol. Chem. 276:10212-10217), we have shown that increased
tyrosine phosphorylation of PKC-d enhances monocyte to macrophage differentiation
as established by the expression of macrophage markers. Subsequent preliminary
data extends this work by showing that inhibition of PKC-d significantly increases
the expression of dendritic cell markers while inhibiting macrophage markers.
Given that PKC-d is critical to macrophage differentiation and can be tyrosine
phosphorylated by oxidative stress, it is likely that ROS will inhibit macrophage
to dendritic cell differentiation.
Preliminary experiments have indicated
that it is possible to obtain human macrophage from used leukocyte reduction filters
(Sepacell R-II, Fenwall-Baxter). Therefore, I propose to study the effect that
ROS have on the expression of the dendritic cell markers CD80 and CD86. In addition,
I plan to examine the impact ROS have on the ability of dendritic cells to stimulate
the proliferation of autologous T-cells.
Among the aged, death due to unresolved
infection is a significant contributor to mortality and morbidity. Therefore,
understanding the effect aging has on dendritic cell development and function
should improve therapies for infections. I would be greatly honored to receive
the Paul D. Doolen Scholarship for the Study of Aging to call attention to this
very important area of aging research.
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