Full Text PA-97-050
 
MANAGING THE SYMPTOMS OF COGNITIVE IMPAIRMENT
 
NIH GUIDE, Volume 26, Number 10, March 28, 1997
 
PA NUMBER:  PA-97-050
 
P.T. 34

Keywords: 
  Cognitive Development/Process 
  Disease Prevention+ 

 
National Institute of Nursing Research
National Institute on Aging
National Institute of Mental Health
National Institute of Neurological Disorders and Stroke
National Institute of Child Health and Human Development
 
PURPOSE
 
The National Institute of Nursing Research (NINR), National Institute
on Aging (NIA),
National Institute of Mental Health (NIMH), National Institute of
Neurological Disorders and Stroke (NINDS), and the National Center
for Medical Rehabilitation Research of the National Institute of
Child Health and Human Development (NICHD) are interested in
facilitating investigator-initiated research into nonpharmacological
intervention strategies designed to deal with symptoms associated
with cognitive impairment in adults.  Several conditions can result
in cognitive impairment, including Alzheimer's disease, multi-infarct
dementia, AIDS-related cognitive dysfunction, traumatic brain injury,
stroke, and other neurological conditions such as Parkinson's
disease.  The overall goals are to deter or delay symptoms requiring
costly services or institutionalization and improve health-related
quality of life for patients, caregivers, and families.
 
HEALTHY PEOPLE 2000
 
The Public Health Service (PHS) is committed to achieving the health
promotion and disease prevention objectives of "Healthy People 2000,"
a PHS-led national activity for setting priority areas.  This Program
Announcement (PA), Managing the Symptoms of Cognitive Impairment, is
related to the priority area of chronic disabling conditions.
Potential applicants may obtain a copy of "Healthy People 2000" (Full
Report:  Stock No. 017-001-00474-0 or Summary Report:  Stock No.
017-001-00473-1) through the Superintendent of Documents, Government
Printing Office, Washington, DC 20402-9325 (telephone 202-512-1800).
 
ELIGIBILITY REQUIREMENTS
 
Applications may be submitted by domestic and foreign, for- profit
and non-profit organizations, public and private, such as
universities, colleges, hospitals, laboratories, units of State and
local governments, and eligible agencies of the Federal government.
Foreign institutions are not eligible for First Independent Research
Support and Transition (FIRST) (R29) awards.  Racial/ethnic minority
individuals, women, and persons with disabilities are encouraged to
apply as Principal Investigators.
 
MECHANISM OF SUPPORT
 
The mechanisms of support will be the National Institutes of Health
(NIH) research project grant (R01) and FIRST (R29) award.
Responsibility for the planning, direction, and execution of the
proposed project will be solely that of the applicant.  Individuals
applying for the FIRST award must comply with the 1994 NIH Guidelines
for FIRST awards and the Just-in-Time procedures announced in the NIH
Guide, Vol. 25, No. 10, March 29, 1996.
 
RESEARCH OBJECTIVES
 
Cognitive impairment associated with dementia or other brain
disorders is a significant public health problem, with major
implications for morbidity and mortality, quality of life, and
health-care costs. The financial burden of dementia, including direct
care costs and lost productivity, is estimated at 100 billion dollars
annually.  This estimate does not include the costs of care provided
by family caregivers.  This program announcement encompasses
conditions which might cause cognitive impairment, such as
Alzheimer's disease and related disorders (ADRD), multi-infarct
dementia, AIDS-related cognitive dysfunction, traumatic brain injury,
stroke, and other neurological conditions such as Parkinson's
disease.
 
Until more is known about the neurobiological mechanisms underlying
these conditions and until treatments are developed to target those
processes, research is needed to deal with the symptoms of cognitive
impairment.  Five symptoms -- wandering, aggression, agitation,
incontinence, and sleep disruption -- have been proposed as the most
frequent reasons for institutionalization among ADRD patients.  Thus,
if methods were found to deal effectively with these problems, costly
and disruptive change in living situations might be delayed or
prevented.
 
Symptoms
 
Although the pathology underlying cognitive impairment cannot be
altered at the present time, interventions are showing that some
behaviors can be changed, functional ability improved, quality of
life increased, and institutionalization delayed.  If improvements
are not always possible, maintaining function or delaying a decline
for a period of time may provide a valuable contribution.  Symptoms
that may occur during the course of the targeted conditions include:
 
o  cognitive changes: memory deficits, language impairment,
visuospatial changes, decreased executive function
 
o  affective changes: irritability, lability, disinhibition, anxiety,
dysphoria, delusions, hallucinations, apathy, withdrawal
 
o  dementia-related behaviors: wandering, pacing, agitation,
disruptive vocalizations, repetitive behaviors
 
o  functional changes: loss of instrumental activities of daily
living (telephone, financial activities); loss of activities of daily
living (dressing, feeding); incontinence; immobility
 
o  other changes: sleep and circadian rhythm disturbances, sexual
alterations, appetite disturbances.
 
The physical status of persons with cognitive impairment also needs
careful research attention.  Factors such as the correction of
hearing and vision impairment might improve physical status, and may
also positively influence cognition and behavioral symptoms,
functioning, and quality of life.  Persons with cognitive impairment
are at risk for infections, falls and injury, poor nutrition, and
delirium.  Delirium can be a complication or a presenting symptom of
a coexisting condition and needs careful research attention.
Dementia is a significant risk factor for the development of delirium
during hospitalization or surgery and is associated with increased
mortality  in the hospitalized elderly.  Research instruments exist
to diagnose delirium and to distinguish the confusion from the
dementia, but new strategies to decrease delirium need to be
developed and tested.  Additionally, drug interactions cause by the
simultaneous use of multiple drugs is a common cause of cognitive
decline.
Thus, the effect of polypharmacy in these individuals may also be
considered.
 
Interventions
 
Promising interventions to treat the symptoms of cognitive impairment
may take one or more of several approaches, including behavioral,
cognitive, psychosocial, or environmental.  The goals of the
interventions may vary with the specific underlying condition and
stage of the disease, but can generally be classified as maximizing
potential, preventing undesirable consequences, delaying the onset of
symptoms, or providing palliative measures.  The types of
interventions proposed for testing may include, but are not limited
to the following examples.
 
o  Interventions directed at cognitive function are difficult given
the progressive decline in several of the types of dementia.  But
despite being perhaps less amenable to change, even achieving small
improvements or maintaining function for a time can be perceived by
patients and caregivers as worthwhile.
 
o  Interventions directed at activities of daily living are showing
some promise, but need further attention.  Highly targeted training
in continence, dressing, and other functions have been shown to have
favorable outcomes in some settings.
 
o  Behavioral interventions to deal with agitated and disturbed
behaviors are showing some promise.  Research is underway in both
homes and long-term care facilities to determine effective
techniques.  Additional research is needed including methods to train
staff and family in administering these treatments and strategies to
sustain the treatment and outcomes over time.
 
o  Targeted interventions to influence social participation and to
determine the effects of increased social involvement are needed.
Particular attention should be given to individual patient
preferences.
 
o  Interventions related to the patients' affective states are
needed.  Some research has shown that both positive and negative
patient states can be measured based on nonverbal and sometimes
verbal behavior.  However, additional study is needed to determine
how it can be assessed more accurately and how it can be used in
family and formal treatment programs.
 
o  Environmental interventions dealing with the context of care are
based on the assumption that the environment has an important effect
on behavior.  Studies, such as reducing distraction or controlling
excessive stimulation in long-term care facilities, need testing in a
variety of settings for their effect on the symptoms of cognitive
impairment.
 
o  A variety of interventions are being tested with family
caregivers, notably in the NIA/NINR cooperative agreement, Resources
for Enhancing Alzheimer's Caregiver Health (REACH).  Six sites across
the country are testing promising home and community based
interventions for enhancing family caregiving, particularly with
minority families.  In addition to a common core database managed by
a coordinating center, data are being collected on interventions
including an in-home skills training program, a telephone linked
computer program, a primary care based intervention in the context of
office visits, a family counseling program with a computer-phone
component, a psychoeducational program with a support group
component, and a home environmental skill building program.  Minority
groups receiving special attention include Hispanic, Cuban-Hispanic,
and Black family caregivers.  Additional research needs to be done
with careful attention to placing the proposed studies in the context
of what
 is already known.
 
Consideration may be given to several variables that could influence
the effectiveness of various nonpharmacologic approaches, including
type and severity of cognitive impairment; noncognitive impairments
such as neurological deficits; psychiatric problems, such as
depression; other physical health problems and sensory impairments;
as well as differences due to personality characteristics; age;
gender; ethnicity and culture; and previous life experiences and
lifestyle factors.  There is a need for careful identification in the
research literature of which particular approaches are effective
given different patient factors.
 
Both community and institutional settings and various services are
appropriate for research related to symptom management. These might
include long-term care facilities, homes, adult day care, hospitals,
assisted living sites, home health care, special care units, respite
care, and rural versus urban settings.  Research on testing specific
services needs to address the issue of dose-response, including clear
quantification of both the treatment and the response patterns, as
well as the general services provided and the outcomes to be
achieved.
 
Some studies are finding that the symptoms and effective treatment
strategies may vary based on gender and ethnic issues.  Continued
research on these factors is encouraged.
 
Careful attention to methodological issues is critical, including
treatment integrity, masked assessment or control of rater bias,
randomization, and appropriate control group(s). The theoretical
basis for the planned study must be clearly explicated and linked to
the intervention to be tested.  In addition to ensuring that measures
have adequate psychometric properties, the instruments should be
carefully linked to the outcomes and should be sensitive to change.
 
Some symptoms associated with cognitive impairment have had more
research than others, therefore applicants are encouraged to ensure
that the proposed studies are well-grounded in the research
literature.  Likewise, some interventions are ready for larger scale,
multi-site studies of efficacy while other interventions need smaller
scale studies to determine feasibility and effectiveness.
 
Applications in response to this program announcement may also
include animal and other basic science studies of the mechanisms
underlying behavioral symptoms of dementia, and of potential clinical
interventions directed at these symptoms.  These might include, for
example, studies of learning and memory impairment, aggression, or
circadian disturbances in transgenic animal models of AD, animal
models of traumatic brain injury, or models of cerebral
hypoxia/ischemia.  The therapeutic strategies to be tested may
encompass non-behavioral, as well as behavioral, components.
 
Outcomes
 
Health outcomes, defined as changes in health status that can be
attributed to care, are critical components of this research
endeavor.  Several of the following possible variables have been used
successfully in prior research while others have not received
adequate conceptual and psychometric attention. Investigators are
cautioned to select measures that are specific to the targeted
outcomes and that are sensitive to change.  Multiple outcomes are
generally indicated in clinical intervention research.  Consideration
should be given to incorporating measures such as cognitive function,
specific functional status, neurological performance, and other
health status indicators.
 
The following list provides some possible outcomes for consideration:
 
o  physical status: health goals may include avoidance of
complications and/or coexisting conditions of dementia, e.g.,
infections, malnutrition, incontinence, delirium, or in later stages,
seizures or pressure ulcers.
 
o  cognitive abilities: memory, language, visuospatial skills,
executive function
 
o  affect and neuropsychiatric disorders: depression, pleasure, mood,
hallucinations, delusions
 
o  functional performance: such as mobility, activities of daily
living including feeding, toileting, bathing, dressing and
instrumental activities of daily living such as household tasks,
shopping, managing money, using the telephone.
 
o  behavioral symptoms: wandering, pacing, agitation, disruptive
behaviors, aggression, hostility, repetitive behaviors, sleep
disruption,
 
o  psychosocial variables: communication, intimacy, sexuality,
satisfaction, independent living status, vocational skills
 
o  decision making: food preferences, end of life decisions
 
o  quality of life: well-being, competence, environmental quality,
meaningful time use
 
o  caregiver outcomes: stress, burden, physical and psychosocial
status, productivity, commitment, satisfaction, resource use,
decision making, social well-being, bereavement
 
o  costs of care, service use, institutionalization
 
Applications from institutions that have a General Clinical Research
Center (GCRC) may wish to identify these programs as a resource for
conducting the proposed research.  If so, a letter of agreement from
the program director or Principal Investigator should be included
with the application.
 
Summary
 
Research applications may address the issues noted in the narrative
above as well as research objectives such as:
 
o  test nonpharmacological interventions to manage the behavioral,
physical, and functional problems associated with cognitive
impairment, such as wandering, falls, sleep disturbances, and
inadequate nutrition.
 
o  evaluate interventions for the cognitive rehabilitation of people
with conditions such as traumatic brain injury or stroke that are
aimed at either remediating  cognitive impairments or encouraging
compensatory strategies for them.
 
o  investigate cognitive, behavioral, attitudinal, and physiological
interventions to prevent or delay the onset of cognitive impairment.
 
o  support basic and clinical studies of neurobehavioral and
cognitive effects of dementia and delirium to determine similarities
and differences in these conditions and ways to assess and treat
them.
 
o  test interventions for family caregivers that mitigate the
deleterious effects of the caregiving role on mood, immune function,
and productivity.
 
o  investigate interventions targeted to differences in patient
management and family caregiving due to gender, ethnic, cultural, and
socioeconomic factors.
 
Primary Sources:
 
1.  Conference: "Defining and Measuring Outcomes in Alzheimer's
Research: Do We Agree?"  Sponsored by Alzheimer's Association,
Advisory Panel on Alzheimer's Disease, Agency for Health Care Policy
and Research, Department of Veterans Affairs, National Institute on
Aging, National Institute of Mental Health, National Institute of
Nursing Research, University Hospitals of Cleveland.  September
11-12, 1996, Washington, DC.  To be published in a special issue in
Alzheimer's Disease and Associated Disorders: An International
Journal.  A summary of conference discussions and findings may be
obtained from The Alzheimer's Association, Washington office, phone
202-393-7737.
 
2.  Conference: "Alzheimer's Disease Research Plan II," sponsored by
National Institute on Aging and Fisher Medical Foundation, August
9-11, 1994, Washington, DC.  Published in International
Psychogeriatrics, Volume 8, Supplement 1, 1996.
 
3.  NIA/NINR Cooperative Agreement, Research to Enhance Alzheimer's
Caregiver Health (REACH); including investigators: L. Burgio at
University of Alabama, Birmingham; R. Burns at VA, Memphis; C.
Eisdorfer at University of Miami; D. Gallagher-Thompson at VA, Palo
Alto; D. Mahoney at Boston Medical Center; R. Schulz at University of
Pittsburgh; L. Gitlin at Thomas Jefferson University, and NIH staff:
M. Ory at NIA; and M. Leveck at NINR.
 
4.  Conference:  "Outcomes Research in Medical Rehabilitation"
sponsored by NCMRR on August 29-31, 1994.  Fuhrer, J.J., & Richards,
J.S. (1996).  Medical Rehabilitation Outcomes for Persons with
Traumatic Brain Injury:  Some Recommended Directions for Research in
B.P. Uzzell & H.H. Stonnington (Eds.), Recovery After Traumatic Brain
Injury (pp. 247-255). Mahwah, NJ: Lawrence Erlbaum Associates.
 
INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN
SUBJECTS
 
It is the policy of the NIH that women and members of minority groups
and their subpopulations must be included in all NIH supported
biomedical and behavioral research projects involving human subjects,
unless a clear and compelling rationale and justification is provided
that inclusion is inappropriate with respect to the health of the
subjects or the purpose of the research.
 
All investigators proposing research involving human subjects should
read the "NIH Guidelines For Inclusion of Women and Minorities as
Subjects in Clinical Research," which have been published in the
Federal Register of March 28, 1994 (FR 59 14508-14513) and reprinted
in the NIH Guide for Grants and Contracts, Volume 23, Number 11,
March 18, 1994.
 
Investigators may access the policy via Internet on the NIH Website
(http://www.nih/gov) or may obtain copies of the policy from the
program staff listed under INQUIRIES.  Program staff may also provide
additional relevant information concerning the policy.
 
APPLICATION PROCEDURES
 
Applications are to be submitted on grant application form PHS 398
(rev. 5/95) and will be accepted at the standard application
deadlines as indicated in the application kit.  Applications kits are
available at most institutional offices of sponsored research and may
be obtained from the Grants Information Office, Office of Extramural
Outreach and Information Resources, National Institutes of Health,
6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910, telephone
301/435-0714, email:  ASKNIH@odrockm1.od.nih.gov.
 
Receipt dates for new research grant applications are February 1,
June 1, and October 1.
 
On page 1 of form PHS 398, check "Yes" in Item 2 and enter the number
and title of this program announcement in the space provided.
 
Applications for the FIRST Award (R29) must include at least three
sealed letters of reference attached to the face page of the original
application.  FIRST Award (R29) applications submitted without the
required number of reference letters will be considered incomplete
and will be returned without review.
 
The complete original application and five legible copies must be
sent or delivered to:
 
DIVISION OF RESEARCH GRANTS
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710
BETHESDA, MD  20892-7710
BETHESDA, MD  20817 (for express/courier service)
 
A number of other Institutes, Centers, and Divisions (ICDs) at the
NIH may be interested in the general subject of this program
announcement.  Applications submitted in response to this PA that
propose research in scientific areas that overlap ICD interests will
receive a funding component assignment in accord with existing
referral guidelines and procedures established by the Division of
Research Grants, NIH.
 
REVIEW CONSIDERATIONS
 
Applications will be assigned on the basis of established PHS
referral guidelines.  Applications will be reviewed for scientific
and technical merit by  study sections of the Division of Research
Grants, NIH in accordance with the standard NIH review procedures.
Following scientific and technical review, the applications will
receive second-level review by the appropriate national advisory
council.
 
Review Criteria
 
o  Scientific, technical, and clinical significance and originality
of proposed research;
 
o  Appropriateness and adequacy of the experimental
approach and methodology proposed to carry out the research;
 
o  Qualifications and research experience of the Principal
Investigator and staff;
 
o  Availability of the resources necessary to perform the research;
 
o  Appropriateness of the proposed budget and duration in relation to
the proposed research;
 
o Adequacy of plans to include both genders and minorities and their
subgroups as appropriate for the scientific goals of the research.
Plans for the recruitment and retention of subjects will also be
evaluated.
 
The initial review group will also examine the provisions for the
protection of human and animal subjects and the safety of the
research environment.
 
AWARD CRITERIA
 
Applications will compete for available funds with all other approved
applications assigned to that institute or center.  The following
will be considered in making funding decisions: quality of the
proposed project as determined by peer review, availability of funds,
and program priority.
 
INQUIRIES
 
Inquiries are encouraged.  The opportunity to clarify any issues or
questions from potential applicants is welcome.
 
For general scientific and program questions, contact
 
Mary D. Leveck, PhD, RN
Scientific Program Administrator
National Institute of Nursing Research
Building 45, Room 3AN12, MSC 6300
Bethesda, MD 20892-6300
Telephone: (301) 594-5963
Fax: (301) 480-8260
Email: mleveck@ep.ninr.nih.gov
 
Neil Buckholtz, PhD
Neuroscience and Neuropsychology of Aging Program
National Institute on Aging
Gateway Building, Suite 3C307
7201 Wisconsin Avenue MSC 9205
Bethesda, MD 20892-9205
Telephone: (301) 496-9350
Fax: (301) 496-1494
Email: BuckholN@GW.NIA.NIH.GOV
 
Jane L. Pearson, PhD
Mental Disorders of the Aging Research Branch
National Institute of Mental Health
Parklawn Building, Room 18-101
5600 Fishers Lane
Rockville, MD 20957
Telephone: (301) 443-1185
Fax: (301) 594-6784
Email: jp36u@nih.gov
 
Eugene J. Oliver, PhD
Division of Stroke, Trauma, and Neurodegenerative Disorders
National Institute of Neurological Disorders and Stroke
Federal Building, Room 806
7550 Wisconsin Avenue
Bethesda, MD 20892-9150
Telephone: (301) 496-5680
Fax: (301) 480-1080
Email: EO11C@NIH.GOV
 
Louis A. Quatrano, PhD
National Center for Medical Rehabilitation Research
National Institute of Child Health and Human Development
6100 Executive Building 2A03
Bethesda, MD 20892-7510
Telephone: (301) 402-2242
Fax:  (301) 402-0832
Email: Quatranl@hd01.nichd.nih.gov
 
Direct inquiries regarding fiscal matters to:
 
Jeff Carow
Grants Management Officer
National Institute of Nursing Research
Building 45, Room 3AN-12 MSC 6301
Bethesda, MD  20892-6301
Telephone:  (301) 594-6869
Fax:  (301) 480-8260
Email:  jcarow@ep.ninr.nih.gov
 
Joseph Ellis
Grants Management Officer
National Institute on Aging
Gateway Building, Suite 2N212
7201 Wisconsin Avenue MSC 9205
Bethesda, MD 20892-9205
Telephone: (301) 496-1472
Fax: (301) 402-3672
Email: ellisj@GW.NIA.NIH.GOV
 
Diana S. Trunnell
Assistant Chief, Grants Management Branch
National Institute of Mental Health
Parklawn Building, Room 7C-08
Rockville, MD 20857
Telephone: (301) 443-2805
Fax: (301) 443-6885
Email: Diana_Trunnell@nih.gov
 
Ms. Pat Driscoll
Grants Management Branch
National Institute of Neurological Disorders and Stroke
Federal Building, Room 1004
7550 Wisconsin Avenue
Bethesda, MD 20892-9190
Telephone: (301) 496-9231
Fax:  (301) 402-0219
Email: PD23N@NIH.GOV
 
Mary Ellen Colvin
Grants Management Branch
National Institute of Child Health and Human Development
Building 6100, 8A17 MSC 7510
Bethesda, MD 20892-7510
Telephone: (301) 496-1303
Fax: (301) 402-0915
Email: ColvinM@hd01.nichd.nih.gov
 
An additional contact for support of research in this area is the
Alzheimer's Association, Inc.  This association is a private,
national voluntary agency dedicated to research, service, and policy
development related to ADRD.  Research grant opportunities are
described at www.alz.org.
 
AUTHORITY AND REGULATIONS
 
This program is described in the Catalog of Federal Domestic
Assistance No. 93.361, Nursing Research and No 93.866 Aging Research.
Awards are made under authorization of the Public Health Service Act,
Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158,
42 USC 241 and 285) and administered under PHS grants policies and
Federal Regulations 42 CFR 52 and 45 CFR Part 74 and 92.  This
program is not subject to the intergovernmental review requirements
of Executive Order 12372 or Health Systems Agency review.  Awards by
PHS agencies will be administered under PHS grants policy as stated
in the Public Health Service Grants Policy Statement (April 1, 1994).
 
The PHS strongly encourages all grant and contract recipients to
provide a smoke-free workplace and promote the non-use of all tobacco
products.  In addition, Public Law 103-227, the Pro-Children Act of
1994, prohibits smoking in certain facilities (or in some cases, any
portion of a facility) in which regular or routine education,
library, day care, health care or early childhood development
services are provided to children.  This is consistent with the PHS
mission to protect and advance the physical and mental health of the
American people.
 
.

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