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Current
Research
 -Alzheimer's
Disease and Related Dementia's
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ALZHEIMER'S DISEASE AND RELATED
DEMENTIAS
ALZHEIMER'S
DISEASE AND RELATED DEMENTIAS
The portion of the U.S. population age 85 years or older
will double during the next decade, and researchers in the
IOA are studying a wide range of issues concerning persons
with age-associated cognitive impairment. Almost 40% of these
"old-old" Americans will experience severe cognitive
loss characteristic of dementia. Many other older adults will
experience milder degrees of cognitive impairment, especially
forgetfulness, which is often the first symptom of intellectual
decline. Eventually, this decline can disturb individuals'
abilities to care for themselves and control their behaviors.
At this point, families often cannot handle these problems
and must place their loved ones in a nursing home. The high
concentration of persons at risk for displaying disruptive
behaviors in nursing homes presents significant challenges
to the nursing staff.
While researchers have suggested many interventions to quell
behaviors such as disruptive vocalization, they often apply
them with inadequate consideration of the factors precipitating
the behavior. Thus, a better understanding of the background
variables (e.g., health state, demographic factors, and psychosocial
factors) and proximal variables (e.g., physiologic and psychosocial
need states and physical and social environments) will permit
the targeting of multiple interventions reported in the literature.
In a related matter, program planners, policy makers, and
health care providers have little to guide their decisions
on both the outcome and the cost-effectiveness of the many,
diverse services available to persons of various cultural
backgrounds who are cognitively impaired. Early, accurate
diagnosis may prevent the use of costly medical resources,
take advantage of treatments and pharmacologic agents that
are available, and allow patients and family members to prepare
for future medical, financial, and legal challenges.
The research program on cognitive impairment focuses on the
following:
- Improving the quality of care in nursing homes
- Dealing with problem behaviors
- Promoting sleep
- Increasing the use of community-based services
- Improving recruitment of African Americans into studies
on aging and dementia
- Examining the interaction between diet, genetic factors,
and cognitive decline
- Improving the early diagnosis of dementia
Other research on cognitive impairment focuses on a better
understanding of brain-behavior relationships that underlie
particular patterns of cognitive loss, better means of diagnosing
and treating AD and related forms of dementia, and genetic
and environmental factors that might predispose to memory
loss or dementia. IOA researchers have presented papers locally,
nationally, and internationally and have published on each
of these topics.
Table of Contents
Improving the Quality of Care
in Nursing Homes
Dr. Cornelia Beck and colleagues have completed the fourth
year of an NIH-funded project, "A Partnership Approach
to Sustaining Best Practices" (funded at $2,690,059).
The aim of this partnership grant, a nursing home project,
is to demonstrate organizational change in an experimental
nursing home through development of sustained partnership
behaviors. These behaviors capitalize on the unique perspectives
of residents, families, staff, and management, all of whom
serve as partners. Since the project started, the following
changes have occurred in the nursing home: regular weekly
management meetings, written resident progress reports given
to families, and development of a certified nursing assistant
(CNA) orientation program and training programs for continuing
education of managers, licensed practical nurse supervisors,
and CNAs. In addition, several groups have formed. These include
the CNA Council, Family Education Group, Alzheimer's Disease
and Related Dementias Support Group, and a Family Council.
Partnership Approach Teams, with representatives from all
partner groups, have addressed facility issues such as restraint
reduction, a hydration program, CNA orientation, staff incentives,
and the management of linens. Software called Stream Analysis
has helped in the problem-solving process.
In spring 2001, researchers introduced the use of prompted
voiding as a best-practice protocol for reducing urinary incontinence.
Front-line caregivers (CNAs and nurses) in the experimental
home and a control home received training in the use of the
urinary incontinence assessment/protocol software. Once this
best practice is implemented at an 80% level of adherence,
the researchers will stop their involvement in the activities
of the experimental nursing home and only collect data to
determine whether the caregivers sustain prompted voiding
in the experimental home longer than in the control home.
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Dealing with Problem Behaviors
The NIH-funded study "Problematic Vocalizations: Background
and Proximal Factors" ($412,337), with Dr. Beck as
principal investigator, is in year 2. This study is one in
a trio of interactive projects designed to develop a preliminary
explanatory model of problem behaviors. This model will serve
as a basis for empiric testing of targeted interventions that
ultimately will improve the quality of life of persons with
dementia and their caregivers. Data collection began in June
2000. As of May 31, 2001, data have been collected on 53 nursing
home residents with dementia in six community nursing homes.
Instruments and protocols for data collection have been modified
on the basis of problems noted during data collection and
reliability studies. Additional sites for data collection
have been secured. Instruments are being scanned by the Teleform
system and entered into Statistical Package for the Social
Sciences software. Audiotapes are being analyzed, but
there is no data analysis at this time.
Data collection on eight patient-family-staff triads has
concluded for an investigation into the feasibility of individualized
music, implemented by nursing staff and family members of
residents, for persons with dementia in three long-term care
facilities in central Arkansas, including one all-African-American
facility. Taped interviews are being transcribed and quantitative
data analyzed. The study, under the leadership of postdoctoral
fellow Linda A. Gerdner, PhD, RN, was funded ($6,000) by the
University of Iowa Gerontological Nursing Intervention Research
Center. Outcome measures expand on Dr. Gerdner's previous
work by encompassing variables that serve as quality indicators
for the care of persons with dementia. These include not only
the frequency of agitation but also the frequency of falls,
use of restraints and psychotropic medications, and cost-benefit
issues.
Behavioral problems are also the focus of research by postdoctoral
fellow Carla Gene Rapp, PhD. Such problems occur frequently
in long-term care facilities for older adults, where many
health care providers have noted that agitation or aggressive
behaviors can, and often do, escalate to violence. The results
of preliminary testing supported Dr. Rapp's proposed conceptual
model consisting of a continuum of behaviors ranging from
agitation to aggression and finally to violence: 63% of episodes
began with agitation, and violence occurred at least once
in 79% of episodes. The most common pattern was agitation
before and/or after aggression.
During the past year, Dr. Rapp began developing a proposal
for Career Development Award funding that she will submit
to NIH and the Department of Veterans Affairs. The research
will seek to (1) understand which behaviors displayed by cognitively
impaired nursing home residents are identified by CNAs as
problematic enough to nursing staff to require an intervention;
(2) describe the decision-making process used by CNAs to determine
whether a behavior requires an intervention, and then to specify
which intervention(s) will be used; and (3) propose an alternative
to the current training of CNAs related to managing problem
behaviors that would provide CNAs with knowledge and skills
that are congruent with their interpretations of problem behaviors.
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Promoting Sleep
Dr. Kathy Richards and her colleagues are continuing in their
efforts to gauge the effect of an individualized activity
program on daytime sleep, psychological well-being, and disruptive
behaviors in separate studies funded by the NIH (3 years)
and the Department of Veterans Affairs (4 years). Underlying
this research is the recognition that persons with cognitive
impairment often experience sleep-activity rhythm disturbance:
Their nighttime sleep is light and ineffectual, accompanied
by frequent arousals or awakenings, and during the day, they
often take several naps, which interfere with their activities
and functioning. The research team has collected data on 85
subjects in the NIH study and 70 subjects in the VA study.
In addition, Dr. Richards received a minority supplement to
the NIH grant to mentor Michelle Seigers, a nursing student.
Ms. Seigers is studying the effect of individualized activities
on cognitive status to determine the most effective activities
for persons with dementia. Findings indicate that elders involved
in an individualized activity program had significantly improved
nighttime sleep and daytime alertness.
Data collection is in progress for the pilot study "Effect
of Social Activity and Exercise on Sleep in Cognitively Impaired
Elders," also under the direction of Dr. Richards
as principal investigator. This study aims to evaluate the
effects of individualized social activities, high-intensity
exercise, a combination of social activities and exercise,
and a control condition on the percentage of non-rapid eye
movement sleep, rapid eye movement sleep, and wakefulness
in nursing home residents.
Dr. Richards is also in the second year of a Career Development
Award from the Department of Veterans Affairs Health Services
Research and Development Service to pursue training in the
area of sleep disorders. Dr. Dennis H. Sullivan serves as
her primary mentor, committing approximately 5% of his time
to the effort. He will ensure that she has access to adequate
resources to conduct her research, advise her on observational
research methods and VA organizational issues, facilitate
collaboration with other VA investigators, and direct her
readings on health services research. This award provides
Dr. Richards with full salary support and operating expenses
for up to 6 years. A renewal application is due within 3 years.
In her Career Development Award, Dr. Richards is investigating
the causes and consequences of sleep disturbance, as well
as the best practice for sleep promotion, in cognitively impaired
elderly veterans. She and her research team have collected
data on 150 subjects, and data analysis is in progress. Underlying
her research is the view that certain provider practice patterns
(medical diagnostic and treatment patterns), nursing home
patterns (nursing practice and environmental patterns), and
individual factors (biologic and psychological factors) place
elders with cognitive impairment at risk for sleep disturbance.
This work will enable her to develop research skills to identify
correlates of sleep disturbance that will lead to more informed,
effective interventions for cognitively impaired older persons.
Finally, Dr. Richards is pursuing a feasibility study, funded
by the RDG's Pilot Grant Program, to determine the need for
adult night care services in Arkansas and the characteristics
of the services desired by potential consumers. She has conducted
two focus groups with potential consumers and developed a
questionnaire based on the results of the focus groups. The
questionnaire will be mailed to caregivers throughout the
state of Arkansas via the Alzheimer's Association newsletter.
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Use of Community-based
Services by Caregivers and Persons with Dementia
Marisue Cody, PhD, RN, is principal investigator for the study
"Outcomes Assessment for Dementia Care,"
funded by the Department of Veterans Affairs Health Services
Research and Development Service ($626,681). The long-term
goal of this project is to improve the treatment of persons
with dementia by providing reliable, valid information about
the outcomes of services provided to persons with dementia
and their caregivers. Dr. Cody and her colleagues developed,
pilot-tested, and revised, and are in the process of validating,
an outcomes-assessment module for persons with dementia who
receive care in an outpatient setting. The prototype module
is being tested in a university-based geriatrics clinic, a
Veterans Healthcare System geriatrics clinic, and an office-based
clinic that conducts AD clinical trials. The module consists
of a patient interview and self-administered surveys for caregivers
about the patient and themselves. A medical review form was
either completed for all subjects at baseline (for the test-retest
group) or will be completed after 6-month follow-up (for the
longitudinal sample). Sixty dyads were recruited for test-retest
reliability. These data have been entered and data analysis
was completed this summer. Two hundred and ten dyads were
recruited for validity testing, and 150 are in the process
of longitudinal follow-up 6 months postbaseline. The follow-up
interviews will be completed in October 2001. The attrition
rate is close to 20%, with about one-third of the follow-ups
completed. Anecdotal reports indicate that caregivers are
in need of continued information and support regarding the
management of difficult behaviors. Investigators are preparing
an application to translate existing educational materials
into a variety of formats that caregivers can easily understand
and use as problems occur.
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Improving the Recruitment of
African-Americans
To effectively interact with ethnic-minority patients, health
care providers must understand how patients and their families
view the origin, significance, and treatment of an illness.
The medical model has traditionally focused solely on the
physiologic aspects of an illness. This perspective may conflict
with an individual's cultural beliefs or lack the major dimensions
for a complete understanding of how a specific culture perceives
an illness. Culture has a strong influence on health-seeking
behaviors, and geographic location in the U.S. and residence
(rural versus urban) are important factors interacting with
ethnicity to establish health behaviors.
In a pilot ethnographic study funded by the Dementia Center
of Arkansas to investigate these issues, Dr. Linda Gerdner
conducted interviews with persons of African and of European
descent in the Arkansas Delta region who provide in-home care
to a family member with dementia. The goal was to construct
and compare explanatory models of dementia. Explanatory models
are constructed from five major clinical topics: etiology,
time and mode of symptom onset, pathophysiology, course of
illness, and treatment. These five topics serve as the basis
for constructing open-ended questions for the interviews.
This study also aims to explore and compare the perceived
roles of caregiving and social support between these groups,
as well as providing a description of caregiver needs, social
support, and care needs of persons with dementia. Approximately
19 subjects have been interviewed. The last batch of audiotapes
is being sent to Dr. Gerdner for transcription. Enough data
have been collected to conduct data analysis, which will get
under way shortly.
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Dietary and Genetic
Risk Factors for Cognitive Decline
In the fourth year of a 5-year Mentored Research Career Development
Award from the NIA, Sandra K. Pope, PhD, MPH, continues her
study of the influence of dietary and genetic risk factors
on cognitive decline over time. This research examines the
relationship of antioxidant intake and genetic polymorphisms
with cognitive change over time, using data collected from
3,075 adults (41.7% African American and 58.3% white; ages
70-79 years) in the 7-year, multi-site Healthy Aging and Body
Composition (HEALTH ABC) program. Preliminary analyses examining
antioxidant supplement use and cognitive function data at
baseline found no association between antioxidant supplement
intake and better cognitive function in white men or women
and no association in African American men. The data, however,
showed a strong association between supplement intake and
cognitive function in African American women (odds ratio,
2.03; confidence interval, 1.36-3.02) that was independent
of site, age, education, or income. These results suggest
that dietary supplements may reduce the effects of genetic,
environmental, or hormonal factors on cognitive impairment
in African American women.
A mentoring program is also part of Dr. Pope's Career Development
Award. Her mentoring committee includes Dr. Beck, a geriatrics
researcher with expertise in AD; Stephen Kritchevsky, PhD,
a nutritional epidemiologist at the University of Tennessee
in Memphis; and Christine Ambrosone, PhD, a molecular epidemiologist
at Mt. Sinai School of Medicine in New York. Drs. Sue Griffin
and Victor Henderson are consultants for this award.
Dr. Pope has also submitted a pilot study proposal to the
VISN 16 (South Central VA Health Care Network) Mental Illness
Research, Education and Clinical Center (MIRECC) program of
the Department of Veterans Affairs' Veterans Health Administration
to study two additional genetic polymorphisms thought to be
associated with cognitive decline (but not included in the
NIA award discussed above) in the HEALTH ABC cohort. In particular,
this study will examine the interaction of genetic polymorphisms
with dietary and supplemental intake of antioxidants and the
relationship of these factors to cognitive decline over time
in this cohort of well functioning adults.
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Improving the Early Diagnosis
of Dementia
"Physicians Survey on Persons with Dementia and Their
Families," a project funded by Novartis Pharmaceuticals
($16,705) and led by Dr. Beck, examined the self-reported
practices of physicians in disclosing the diagnosis of AD.
Dr. Beck and her colleagues conducted a survey of primary
care physicians (PCPs) and geriatric specialists to determine
their diagnostic and referral practices and use of community
services by administering a brief, anonymous questionnaire
to convenience samples of both groups. The sample consisted
of 154 U.S. geriatricians and 145 Arkansas PCPs. The researchers
modified the Scottish General Practitioner Survey to make
the terminology more consistent with U.S. medical practice
and added items on referral practices. Researchers found that
physicians who had fewer patients with dementia reported more
difficulty establishing a diagnosis (P<0.05). Compared
with geriatric specialists, PCPs reported more difficulty
in establishing the diagnosis (P<0.001), and fewer
PCPs would assess depression (P<0.010) or functioning
(P<0.010), make a referral to a social worker (P<0.001),
or discuss issues such as reminder aids (P<0.050).
Findings support the importance of training PCPs in geriatrics
and providing tools to improve the care of persons with dementia
in both groups.
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UAMS Alzheimer's Disease Center
The UAMS Alzheimer's Disease Center, established by a major
grant from the National Institutes of Health in 2001 (P30
AG19606), is directed by Cornelia Beck, PhD, RN and co-directed
by Sue Griffin, PhD and Victor Henderson, MD. Drs. Hart, Hogervorst,
and Pippenger are key participants. Like other Alzheimer's
Disease Centers nationwide, the UAMS center brings together
scientists, physicians, and other health care professionals
dedicated to finding causes and effective treatments for Alzheimer's
disease and related disorders. Further information on the
UAMS Alzheimer's Disease
Center or the Clinical
Core is available online or from Kathy Tyler-King, MNSc,
RN, Clinical Coordinator (tel. 501-526-6500). Further information
on Alzheimer's disease research by faculty in the Division
of Cognitive Disorders and Neurogerontology is also available
(Faculty involvement in Alzheimer's disease research).
Reynolds Institute on Aging:
Programs for Rural Arkansas
Rural Aging & Memory Study (RAMS)
Programs for Rural Arkansas, funded by a grant from the federal
Administration on Aging (90AM2518), is directed by Dr. Henderson
and includes five separate projects that focus on rural health.
Project 1, the Rural Aging & Memory Study (RAMS), is also
directed by Dr. Henderson. This study, which takes place entirely
within Bradley County, AR, seeks to expand knowledge about
memory loss that occurs in middle-age and old-age and to help
find ways to preserve memory as people grow older. Dr. Hogervorst
is a key collaborator on the RAMS project. Further information
is available from Kristin Ward, MS, RAMS Project Coordinator
(tel. 501-526-5741). Other UAMS project leaders are Drs. Beck,
Beverly, Chernoff, Evans, and Sullivan.
Electroencephalographic
studies of aging and dementia
This new grant from GlaxoSmithKline to Dr. Hart establishes
an electrophysiology laboratory for the study of memory and
"binding." Dr. Hart's work has shown that semantic
memory may be mediated by the thalamus, which modulates synchronization
of neural activity in different cortical regions (binding)
that encode this form of memory. The collaboration with GlaxoSmithKline
will focus on measuring how binding is disrupted and developing
therapeutic interventions.
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Herpes
Simplex Encephalitis Neuropsychological Sub-study
Dr. Hart serves as the sub-study co-P.I. for a multicenter,
international treatment trial (Acyclovir and Valcyclovir)
of a common form of encephalitis. Research is designed to
evaluate cognition, viral load, and MRI brain scan findings.
Association between Sex Hormones, Cognitive Function and
Confirmed Alzheimer's Disease
The Alzheimer's Association has funded Dr. Hogervorst (NIRG
00-2258) to undertake a longitudinal study of sex hormone
levels in Alzheimer's disease and persons without dementia
and to determine whether the association between hormone levels
and dementia status is influenced by apolipoprotein E genetic
variations.
Genetic Polymorphisms
and Memory Decline
Funding from the national Alzheimer's Association (IIRG-01-2684)
to Dr. Henderson is designed to evaluate age-associated memory
decline in a well-defined population of middle-age women in
Melbourne, Australia. One important goal is to determine whether
common genetic variations, including variations related to
hormones like estrogen, might play a role in memory loss that
affects nearly everyone during "normal" aging. This
project is co-directed by Professor Lorraine Dennerstein at
the University of Melbourne.
Table of Contents
Gonadal Hormone Levels
in Alzheimer's Disease and Age-Related Cognitive Decline
This grant to Dr. Hogervorst from the Brain Institute of The
Netherlands (Hersenstichting Nederland) supports a collaborative
project between the University of Maastricht and the University
of Oxford on the relation between serum concentrations of
gonadal hormones and cognitive function.
B-Vitamin Atherosclerosis Intervention
Trial
This NIH-funded randomized, controlled trial seeks to examine
the effect of B vitamins on the progression of atherosclerosis
in 450 healthy at-risk men and women residing in California.
Dr. Henderson's role as coinvestigator is to assess whether
B vitamins will improve cognitive function in these older
adults.
Detection of Cognitive
Impairment in Aging and Dementia
When AD or another dementing disorder develops, the tragic
results are eventually all too apparent. As newer forms of
specific dementia therapy become available, however, it becomes
more important to be able to detect milder degrees of cognitive
impairment at a time when preventive interventions might be
most effective. To study large groups of people at risk of
early dementia, new, more efficient, and less expensive screening
instruments are needed. The development of such tools is the
goal of a grant to Dr. Henderson funded through the John Douglas
French Alzheimer's Foundation and involving collaborators
in the School of Engineering at the University of Southern
California.
Table of Contents
Correlations of Herpes Simplex Virus
(HSV) Viral Load with Neuropsychological Outcomes
In his role as co-principal investigator for the herpes simplex
encephalitis sub-study, Dr. Hart is examining long-term effects
of this form of viral encephalitis on memory and other cognitive
functions.
Estrogen
Effects on Associative Learning
Animal and human studies have yielded strong evidence that
steroid hormones such as estrogen exert important effects
on brain functions relevant to memory and dementia. Under
recent funding from the Alzheimer's Association, Dr. Henderson
and his colleagues investigated the effects of estrogen on
a particular type of learning that is modulated by the hippocampal
region of the brain and is known to be affected in Alzheimer's
disease. Analyses of their findings are underway.
Verb-
and Sentence-Processing Impairments in Alzheimer's Disease
How do different aspects of language influence the way in
which the brain processes information contained within sentences?
How does information processing differ in healthy older adults
and persons with AD? These two topics are the focus of NIH-funded
research by A. Almor, PhD, at the University of Southern California.
Dr. Henderson is involved in this project as a coinvestigator.
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