THE AGING SENSES:  RELATIONSHIPS AMONG MULTIPLE SENSORY SYSTEMS

Release Date:  June 30, 1999

PA NUMBER: PA-99-123

National Institute on Aging
National Institute of Child Health and Human Development
National Institute on Deafness and Other Communication Disorders
National Institute of Dental and Craniofacial Research
National Institute of Diabetes and Digestive and Kidney Diseases
National Eye Institute
National Institute of Neurological Disorders and Stroke

THIS PA USES THE "MODULAR GRANT" AND "JUST-IN-TIME" CONCEPTS.  IT INCLUDES
DETAILED MODIFICATIONS TO THE STANDARD APPLICATION INSTRUCTIONS THAT MUST BE
USED WHEN PREPARING APPLICATIONS IN RESPONSE TO THIS PA.

PURPOSE

The National Institute on Aging (NIA), in collaboration with the National
Institute of Child Health and Human Development (NICHD), the National
Institute on Deafness and Other Communication Disorders (NIDCD), the National
Institute of Dental and Craniofacial Research (NIDCR), the National Institute
of Diabetes and Digestive and Kidney Diseases (NIDDK), the National Eye
Institute (NEI), and the National Institute of Neurological Disorders and
Stroke (NINDS), invites grant applications in the area of age-related changes
in multiple sensory systems.  A major goal of aging research is directed
toward the public health issue of maintaining functional independence of the
elderly individual.  Aside from specific diseases, sensory declines represent
a broad category of normal age-related changes that can lead to diminished
quality of life for the elderly individual, loss of independence, and
increased costs for society as a whole.  Although declines in single sensory
systems have been studied, there is less information about the effects of
concurrent changes in multiple systems, at either the population or basic
science level.  The purpose of this program announcement is to stimulate
research investigating:  (1) the prevalence and extent of concurrent declines
in multiple sensory systems in the elderly,  (2) the effects such declines
might have on the functional capacities of the individual, and (3) the
underlying mechanisms responsible for commonalities in age-related sensory
changes at central nervous system, cellular, molecular or genetic levels.

HEALTHY PEOPLE 2000

Each NIH PA addresses one or more of 22 Health Promotion and Disease
Prevention priority areas identified. These areas can be found via the WWW at
http://odphp.osophs.dhhs.gov/pubs/hp2000/hppub97.htm.

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. Racial/ethnic minority individuals, women,
and persons with disabilities are encouraged to apply as principal
investigators.

MECHANISM OF SUPPORT

Support for this program will be through the National Institutes of Health
(NIH) research project grant (R01) mechanism.  Responsibility for the
planning, direction, and execution of the proposed project will be solely that
of the applicant. All applicants are strongly encouraged to talk with a
program official prior to submitting an application.

An applicant planning to submit a grant application requesting $500,000 or
more in direct costs for any year is required to contact, in writing or by
telephone, Institute or Center program staff when the application development
process begins.  Furthermore, the applicant must obtain agreement from
Institute/Center staff that the Institute or Center will accept the
application for consideration for award.  The applicant Principal Investigator
must identify, in a cover letter sent with the application, the program staff
member and Institute or Center that has agreed to accept assignment of the
application.  An application received without indication of prior staff
concurrence and identification of that contact will be returned to the
applicant without review.

Beginning with the June 1, 1999 receipt date, "MODULAR GRANT APPLICATION AND
AWARD" procedures will apply to all competing individual research project
grant (R01) applications requesting up to $250,000 direct costs per year. 
Complete and detailed instructions and information on Modular Grant
applications can be found at
http://www.nih.gov/grants/funding/modular/modular.htm

Applications that request more than $250,000 in any year must use the standard
PHS 398 application instructions.

RESEARCH OBJECTIVES

Age-related changes have been reported in all sensory systems studied to date.
Epidemiological studies on single senses independently have shown that among
Americans 75 years and older, 11% have non-correctable visual impairment (1)
and 36% have hearing impairment (1). Age-related declines are known to exist
in the other sensory modalities, such as taste, smell, vestibular function and
somatosensation, but population data are not available in those modalities.
While many elderly individuals may experience declines in more than one
sensory system, most previous research studies have dealt with individual
senses.  Quality of life is likely to be more adversely affected by multiple
sensory deficits than by change in a single sense.  Epidemiological studies
have investigated the effects of sensory deficits on morbidity and mortality,
as well as the impact of sensory deficits on the functional status of the
individual as determined by measures such as the Activities of Daily Living
scale.  One recent study suggested that individuals with deficits of both
visual and auditory functions have increased mortality in comparison to those
with a single deficit (2).  Other work on functional status in the elderly
showed that increasing dependence was associated with an increase in the
number of domains in which a decline was present (3).  One possible
explanation for the greater deleterious effects of multiple deficits over a
single deficit could be the loss of the ability of one relatively intact
modality to compensate for a declining one.

Although age-related changes in single sensory systems have been investigated
in human and animal studies using both epidemiological and psychophysical
approaches, only a few studies have addressed interactions or commonalities
among sensory systems.  At the population level, a recent epidemiological
study has found that individuals with late age-related macular degeneration
(AMD) were more likely to have a hearing loss than individuals without AMD;
the physiological basis of this association remains to be determined (4).  In
a recent laboratory study, utilizing the same subjects to investigate age-
related changes in multiple sensory modalities, correlations were found among
changed threshold levels for tactile, gustatory, olfactory and high frequency
auditory stimuli (but not low frequency auditory stimuli) (5).  Some
characteristics of stimuli show similarities among the various senses.  For
example, the elevated auditory threshold, which is characteristic of aging
humans and animals, affects the reception of high frequency signals earlier
and to a greater extent than that of lower frequency signals (6).  Similarly,
the detection threshold for vibrotactile stimulation shows an age-related
increase, which is greater at higher frequencies than lower ones (7).  The
underlying mechanisms of such correlated changes remain to be elucidated.
These changes could take place at the receptor level, where transduction of
the sensory stimulus to a neural signal occurs, or at a more central level,
which could involve decreased effectiveness of a given neurotransmitter,
imbalance between excitatory and inhibitory transmission or loss of synapses,
neurons, etc. At the receptor level, a similarity exists between the gustatory
and visual systems since two closely related G proteins, gustducin and
transducin, were found to be involved in signal transduction in taste receptor
cells and photoreceptors, respectively (8). Whether or not parallel changes
with age might be observed in these systems remains to be determined.

Specific diseases may also accelerate normal aging processes and contribute to
sensory neuropathies. For example, neuronal damage by advanced glycation end
products has been implicated in both aging and diabetes. Such common
pathogenic mechanisms may be of significance in an elderly population where
approximately 15% of individuals may not know they have diabetes.

One sensory-motor function which is by nature "multimodal" (i.e., dependent
upon contributions from more than one sensory system) is that of balance,
which is dependent upon the integration of inputs from the visual, vestibular
and somatosensory systems (9). Age-related declines in postural stability may
lead to falls. Approximately one third of Americans 65 years and older
experience at least one fall each year (10). Falls in the elderly can have
devastating effects resulting in increased morbidity and mortality, costly
hospitalizations and rehabilitative regimens, as well as declines in quality
of life and activity level. Under optimal environments for balance control and
spatial orientation, the central nervous system integrates an array of sensory
inputs in order to maintain static and dynamic posture. Under conditions of
degraded sensory cues and intersensory conflict, however, the likelihood of
falling greatly increases with age; elderly subjects show greater dependence
upon visual (11) or somatosensory (12) cues for balance than upon vestibular
cues. The possibility exists that one relatively intact sensory system among
these three may compensate for declining function in another. Understanding
the intersensory compensatory strategies of the central nervous system will
help avoid injuries due to falls and improve the lives of the elderly.

Since sensory responses require a complex series of events, where relevant,
studies should take into consideration the cognitive and motoric capabilities
of the subjects being studied. Specific examples of research topics
appropriate for inclusion in applications responsive to this announcement
include, but are not limited to, the following:

o  Development of screening tests that can be used in population studies to
assess sensory function, especially in modalities in which current information
is limited, e.g., olfaction, taste, vestibular function, proprioception,
chronic pain, and somatosensation

o  Epidemiological studies in which more than one sensory modality is studied
in a given population in order to measure the prevalence and extent of decline
as well as to elucidate interactions among modalities

o  Laboratory-based studies in which more than one sensory modality is studied
in a given group of subjects

o  Animal models of age-related multiple sensory loss

o  Studies of commonalities in basic mechanisms underlying physiological,
biochemical, cellular or molecular age-related changes in multiple sensory
systems

o  Investigations of mechanisms whereby age-related changes in one sensory
system can be compensated by functional or structural changes in a different
sensory system

o  Studies of the effects of multiple sensory deficits on functional status
and quality of life in elderly humans

o  Human and animal age-related studies using electrophysiological or
neuroimaging techniques in multiple sensory regions of the brain or in brain
areas that are responsive to multiple sensory inputs

o  Psychophysical studies to determine the underlying mechanisms whereby given
stimulus parameters, e.g., temporal and spatial characteristics, show age-
related similarities in multiple systems

o  Investigations of age-related changes in signal transduction, which could
underlie common functions in multiple sensory systems

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 sub-populations 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.  This policy results from the NIH Revitalization Act of 1993
(Section 492B of Public Law 103-43).

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 in the NIH Guide for Grants and Contracts, Volume 23,
Number 11, March 18, 1994,
https://grants.nih.gov/grants/guide/notice-files/not94-100.html.

APPLICATION PROCEDURES

Applications are to be submitted on the grant application form PHS 398 (rev.
4/98).  Application kits are available at most institutional offices of
sponsored research and may be obtained from the Division of Extramural
Outreach and Information Resources, National Institutes of Health, 6701
Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910, telephone 301-710-0267,
email: GRANTSINFO@NIH.GOV. Applications are also available on the World Wide
Web at: http://www.nih.gov/grants/funding/phs398/phs398.html.

The program announcement title and number must be typed on line 2 of the face
page of the application form and the YES box must be marked.

Submit the signed, original, single-sided application, along with five exact,
single-sided copies and five collated sets of appendix materials to:

CENTER FOR SCIENTIFIC REVIEW
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, ROOM 1040-MSC 7710
BETHESDA, MD  20892-7710
BETHESDA, MD  20817 (for express/courier service)

SPECIFIC APPLICATION INSTRUCTIONS FOR MODULAR GRANTS

These instructions apply to applications requesting up to $250,000 direct cost
per year.

The modular grant concept establishes specific modules in which direct costs
may be requested as well as a maximum level for requested budgets. Only
limited budgetary information is required under this approach.  The just-in-
time concept allows applicants to submit certain information only when there
is a possibility for an award. It is anticipated that these changes will
reduce the administrative burden for the applicants, reviewers and Institute
staff.  The research grant application form PHS 398 (rev. 4/98) is to be used
in applying for these grants, with the modifications noted below.

BUDGET INSTRUCTIONS

Modular Grant applications will request direct costs in $25,000 modules, up to
a total direct cost request of $250,000 per year. (Applications that request
more than $250,000 direct costs in any year must follow the traditional PHS
398 application instructions.)  The total direct costs must be requested in
accordance with the program guidelines and the modifications made to the
standard PHS 398 application instructions described below:

PHS 398

o  FACE PAGE:  Items 7a and 7b should be completed, indicating Direct Costs
(in $25,000 increments up to a maximum of $250,000) and Total Costs [Modular
Total Direct plus Facilities and Administrative (F&A) costs] for the initial
budget period.  Items 8a and 8b should be completed indicating the Direct and
Total Costs for the entire proposed period of support.

o  DETAILED BUDGET FOR THE INITIAL BUDGET PERIOD - Do not complete Form Page 4
of the PHS 398.  It is not required and will not be accepted with the
application.

o  BUDGET FOR THE ENTIRE PROPOSED PERIOD OF SUPPORT - Do not complete the
categorical budget table on Form Page 5 of the PHS 398.  It is not required
and will not be accepted with the application.

o  NARRATIVE BUDGET JUSTIFICATION - Use a Modular Grant Budget Narrative page.
(See http://www.nih.gov/grants/funding/modular/modular.htm for sample pages.) 
At the top of the page, enter the total direct costs requested for each year.

o  Under Personnel, list key project personnel, including their names, percent
of effort, and roles on the project. No individual salary information should
be provided.  However, the applicant should use the NIH appropriation language 
salary cap and the NIH policy for graduate student compensation in developing
the budget request.

For Consortium/Contractual costs, provide an estimate of total costs (direct
plus facilities and administrative) for each year, each rounded to the nearest
$1,000.  List the individuals/organizations with whom consortium or
contractual arrangements have been made, the percent effort of key personnel,
and the role on the project.  The total cost for a consortium/contractual
arrangement is included in the overall requested modular direct cost amount.

Provide an additional narrative budget justification for any variation in the
number of modules requested.

o  BIOGRAPHICAL SKETCH - The Biographical Sketch provides information used by
reviewers in the assessment of each individual's qualifications for a specific
role in the proposed project, as well as to evaluate the overall
qualifications of the research team.  A biographical sketch is required for
all key personnel, following the instructions below.  No more than three pages
may be used for each person.  A sample biographical sketch may be viewed at:
http://www.nih.gov/grants/funding/modular/modular.htm.

- Complete the educational block at the top of the form page
- List position(s) and any honors
- Provide information, including overall goals and responsibilities, on
research projects ongoing or completed during the last three years
- List selected peer-reviewed publications, with full citations

o  CHECKLIST - This page should be completed and submitted with the
application.  If the F&A rate agreement has been established, indicate the
type of agreement and the date. It is important to identify all exclusions
that were used in the calculation of the F&A costs for the initial budget
period and all future budget years.

o  The applicant should provide the name and phone number of the individual to
contact concerning fiscal and administrative issues if additional information
is necessary following the initial review.

Applications requesting up to $250,000 direct cost per year and not conforming
to these guidelines will be considered unresponsive to this PA and will be
returned without further review.

REVIEW CONSIDERATIONS

Applications will be assigned on the basis of established PHS referral
guidelines.  Applications that are complete will be evaluated for scientific
and technical merit by an appropriate peer review group convened in accordance
with NIH peer review procedures.  As part of the initial merit review, all
applications will receive a written critique and undergo a process in which
only those applications deemed to have the highest scientific merit, generally
the top half of applications under review, will be discussed, assigned a
priority score, and receive a second level review by the appropriate national
advisory council or board.

Review Criteria

The goals of NIH-supported research are to advance our understanding of
biological systems, improve the control of disease, and enhance health.  In
the written comments, reviewers will be asked to discuss the following aspects
of the application in order to judge the likelihood that the proposed research
will have a substantial impact on the pursuit of these goals.  Each of these
criteria will be addressed and considered in assigning the overall score,
weighting them as appropriate for each application.  Note that the application
does not need to be strong in all categories to be judged likely to have major
scientific impact and thus deserve a high priority score.  For example, an
investigator may propose to carry out important work that by its nature is not
innovative but is essential to move a field forward.

o  Significance:  Does this study address an important problem?  If the aims
of the application are achieved, how will scientific knowledge be advanced? 
What will be the effect of these studies on the concepts or methods that drive
this field?

o  Approach:  Are the conceptual framework, design, methods, and analyses
adequately developed, well-integrated, and appropriate to the aims of the
project?  Does the applicant acknowledge potential problem areas and consider
alternative tactics?

o  Innovation:  Does the project employ novel concepts, approaches or method?
Are the aims original and innovative?  Does the project challenge existing
paradigms or develop new methodologies or technologies?

o  Investigator:  Is the investigator appropriately trained and well suited to
carry out this work?  Is the work proposed appropriate to the experience level
of the principal investigator and other researchers (if any)?

o  Environment:  Does the scientific environment in which the work will be
done contribute to the probability of success?  Do the proposed experiments
take advantage of unique features of the scientific environment or employ
useful collaborative arrangements? Is there evidence of institutional support?

o  The adequacy of plans to include both genders, 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.

o  The reasonableness of the proposed budget and duration in relation to the
proposed research

The adequacy of the proposed protection for humans, animals or the
environment, to the extent they may be adversely affected by the project
proposed in the application.

AWARD CRITERIA

Applications will compete for available funds with all other recommended
applications.  The following will be considered in making funding decisions:

o  Quality of the proposed project as determined by peer review
o  Availability of funds
o  Program priority

INQUIRIES

Inquiries are encouraged. The opportunity to clarify any issues or questions
from potential applicants is welcome.

Direct inquiries regarding programmatic issues to:

Judith A. Finkelstein, Ph.D.
Neuroscience and Neuropsychology of Aging
National Institute on Aging
7201 Wisconsin Avenue, Suite 3C307, MSC 9205
Bethesda, MD  20892-9205
Telephone:  (301) 496-9350
FAX:  (301) 496-1494
Email:  jf119k@nih.gov

Lisa Freund, Ph.D.
Center for Research for Mothers and Children
National Institute of Child Health and Human Development
Building 6100, Room 4B05D, MSC 7510
Bethesda, MD  20892-7510
Telephone:  (301) 435-6875
Email: lf88X@nih.gov

Daniel A. Sklare, Ph.D.
Division of Human Communication
National Institute on Deafness and Other Communication Disorders
6120 Executive Boulevard, Room 400-C - MSC 7180
Bethesda, MD  20892-7180
Rockville, MD 20852 (for express/courier service)
Telephone:  (301) 496-1804
FAX:  (301) 402-6251
Email:  daniel_sklare@nih.gov

Kenneth A. Gruber, Ph.D.
Chief, Chronic and Disabling Diseases Branch
National Institute of Dental and Craniofacial Research
45 Center Drive, Room 4AN-18C, MSC 6401
Bethesda MD  20892-6401
Telephone: (301) 594-4836
FAX: (301) 480-8318
Email: kenneth_gruber@nih.gov

Barbara Linder, M.D., Ph.D.
Division of Diabetes, Endocrinology and Metabolic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases
45 Center Drive, MSC 660
Bethesda, MD 20892-660
Telephone: (301) 594-0021
FAX: (301) 480-3503
Email: Linderb@extra.niddk.nih.gov

Michael D. Oberdorfer, Ph.D.
Strabismus, Amblyopia, and Visual Processing Program, and Visual Impairment
and Its Rehabilitation Program
National Eye Institute
6120 Executive Boulevard, Suite 350, MSC 7164
Bethesda, MD 20892-7164
Telephone: (301) 496-5301
Email:  oberdorfer@nei.nih.gov

William Heetderks, M.D.
Division of Stroke, Trauma, and Neurodegenerative Disorders
National Institute of Neurological Disorders and Stroke
Federal Building, Room 8A13
Bethesda, MD 20892-9155
Telephone: (301) 496-1447
FAX: (301) 402-1501
Email: Heet@NIH.GOV

Direct inquiries regarding fiscal matters to:

Joe Ellis
Grants and Contracts Management Office
National Institute on Aging
7201 Wisconsin Avenue, Suite 2N212
Bethesda, MD  20892-9205
Telephone:  (301) 496-1472
FAX:  (301) 402-3672
Email:  je14j@nih.gov

Mary Ellen Colvin
Grants Management Branch
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 8A17G
Rockville, MD  20852
Telephone:  301-496-1304
Email:  mc113b@nih.gov

Sharon Hunt
Division of Extramural Activities
National Institute on Deafness and Other Communication Disorders
6120 Executive Boulevard, Room 400-B - MSC 7180
Bethesda, MD  20892-7180
Rockville, MD 20852 (for express/courier service)
Telephone:  (301) 402-0909
FAX:  (301) 402-1758
Email:  sh79f@nih.gov

Bonnie Smith
Division of Extramural Research
National Institute of Dental and Craniofacial Research
45 Center Drive, Room 4AN-44 MSC 6402
Bethesda, MD ,20892-6402
Telephone: (301) 594-4800
Email:  Bonnie.Smith@nih.gov

Denise Payne
National Institute of Diabetes and Digestive and Kidney Diseases
45 Center Drive, MSC 6600
Bethesda, MD 20892-660
Telephone: (301) 594-8845
FAX: (301) 480-3505

Carolyn E. Grimes
Division of Extramural Research
National Eye Institute
Telephone: (301) 496-5884
Fax: (301) 402-0528
Email: cg23w@nih.gov

Brenda Kibler
Grants Management Specialist
National Institute of Neurological Disorders and Stroke
Federal Building, Room 1004
Bethesda, MD  20892
Telephone: (301) 496-9231
Email: bk29j@nih.gov

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance Nos.
93.866, 93.173, 93.929, 93.867, 93.853, 93.121, and 93.847.  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 NIH grants policies and Federal Regulations 42 CFR 52 and
45 CFR Part 74.  This program is not subject to the intergovernmental review
requirements of Executive Order 12372 or Health Systems Agency review.

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.

REFERENCES

Vital and Health Statistics, National Center for Health Statistics, Series 10,
No. 193, CDC, PHS, December 1995.

Appollonio, I., Carabellese,C., Magni,E., Frattola,L., Trabucchi,M. Sensory
impairments and mortality in an elderly community population: A six-year
follow-up study. Age and Ageing, 1995, 42:30-36.

Tinetti,M.E., Inouye,S.K., Gill,T.M., Doucette,J.T. Shared risk factors for
falls incontinence, and functional dependence. JAMA, 1995, 273:1348-1353.

Is age-related maculopathy related to hearing loss? Arch. Ophthalmol., 1998,
116:360-365.Klein,R., Cruickshanks,K.J., Klein,B.E., Nondahl,D.M., Wiley,T.

Stevens,J.C., Cruz,L.A., Marks,L.E., Lakatos,S. A multimodal assessment of
sensory thresholds in aging. J. Gerontol., 1998, 53B:1-10.

Brant,L.J., Fozard,J.L. Age changes in pure-tone hearing thresholds in a
longitudinal study of normal human aging. J. Acoust. Soc. Amer., 1990, 88:
813-820.

Van Doren,C.L., Gescheider,G.A., Verrillo,R.T. Vibrotactile temporal gap
detection as a function of age. J. Acoust. Soc. Amer., 1990, 87:2201-2206.

McLaughlin,S.K., McKinnon,P.J., Margolskee,R.F. Gustducin is a taste-cell-
specific G protein closely related to the transducins. Nature, 1992, 357:563-
569.

Horak,F.B., Shupert,C.L., Mirka,A. Components of postural dyscontrol in the
elderly: A review. Neurobiol. Aging, 1989, 10:727-738.

Tinetti,M.E., Speechley,M., Ginter,S.F. Risk factors for falls among elderly
persons living in the community. N. Engl. J. Med., 1988, 319:1701-1707.

Peterka,R.J., Black,F.O. Age-related changes in human posture control: sensory
organization tests. J. Vestib. Res., 1990, 1:73-85.

Woollacott,M., Shumway-Cook,A., Nashner,L. Aging and posture control: Changes
on sensory organization and muscular coordination. J. Aging Hum. Dev., 23:97-
114..

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