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information indicates that many of these disturbances may be related to pathological processes that are associated with aging.

Basic research, especially using the powerful new techniques of modern biology, is critical to the understanding of the brain mechanisms of sleep and sleep disorders associated with aging. Sleep research supported by the NIA is addressing questions of:

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the diagnosis, management, and treatment of these

Some recent findings are summarized below:

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A large NIA-supported, community-based epidemiologic
study has indicated that over half of the persons over 65
years of age report some form of regular disruption of

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While increased nighttime wakefulness and decreased time in deeper stages of sleep are associated with age, relatively few healthy older persons who have these changes complain about poor quality and disrupted sleep. In healthy older people sleep complaints are infrequent although the markers of impaired sleep quality, increased nighttime wakefulness and decreased time in deeper stages of sleep were present. Thus, the age-related changes in sleep are independent of medical disorders.

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Sleep problems are not only distressful but can have
serious consequences. A sample of 1,855 older community-
dwelling residents were followed for over three years
following initial interview. For males, insomnia was the
strongest predictor of both mortality and nursing home
placement. For females, insomnia was a borderline
predictor of mortality and did not predict nursing home
placement at all. In a separate study, 70 percent of
caregivers indicated that "sleep disturbance" was the
most important factor in their decision to

The body's internal clock gradually speeds up as a person
ages. This appears to be associated with an age-related
loss of neurons in this area. This may be one reason
many older people report early awakenings and other sleep
complaints. Light is a powerful synchronizer of the
circadian clock; carefully timed exposures to bright
lights can "reset" the circadian pacemaker and correct
the age-related changes in circadian timing found in
older people.

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Spontaneous exercise, in addition to improving the consolidation of sleep and wakefulness periods, provides

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physiological feedback to the biological clock.
Therefore, exercise and activity play important roles in
the normal processes of the timing of physiological and
behavioral circadian rhythms, and the absence or non-
optimal timing of exercise and activity may exacerbate
the age-related alterations in circadian timing.

Mr. Stokes: What are some of the treatment strategies?

Dr. Williams: Therapy for sleep disorders and disturbances is aimed at reducing morbidity, reducing excess mortality, and improving quality of life. The principal sleep complaints in the aging population are hypersomnia, primarily obstructive sleep apnea; and insomnia, which is a complaint reflecting underlying psychosocial, psychiatric, and medical disorders. Research needs to be directed at the development of new and more effective therapeutic modalities which are targeted at correcting the underlying pathological mechanisms rather than treating the disorders symptomatically.

Therapy for insomnia should be driven by the cause and severity of the symptoms. Since a large proportion of chronic insomniacs may have psychiatric complaints, treatment should be directed towards the underlying disorder; hypnotics should not be the mainstay of treatment of insomnia. Although short-term intermittent use of hypnotics and sedative tricyclics may be useful for temporary problems, such as bereavement, social disruptions, or situational anxiety, no studies attest to their long-term effectiveness. All medication, especially those with long half-lives, should be used with caution given the changes in drug metabolism seen in later life and the risk for adverse drug reactions, Potential new drug approaches using a natural hormone, melatonin, involved in the control of the sleep/wake cycle are ready to proceed to initial small clinical trials.

Non-pharmacological therapeutic alternatives need to be developed, such as the establishment of good sleep hygiene practices which include getting regular exercise, setting regular bedtimes, and avoiding alcohol, caffeine, and fluid intake before bedtime. The role of phototherapeutic management of disorders of circadian rhythm is currently under study and needs further investigation.


Mr. Stokes: Last year, the Senate report noted that "as evidenced by a growing body of medical research, the nation's ability to control health care costs will be directly related to the ability to prevent and/or cure age-dependent disease and conditions which produce the greatest need for long-term care. a result of this finding, the committee deemed achieving independence for older Americans, through research which reduce dependent care, needs to become a major health priority. Do you concur with the Senate's findings?


Dr. Williams : Evidence is accumulating that the conditions which cause dependence in old age are not inevitable, but potentially preventable and treatable. Because of the massive

costs imposed by these conditions, even modest progress in preventing or delaying their onset could produce impressive savings in health costs. For example, we have already begun to see promising treatments for osteoporosis which could lessen the rapid rise in hip fracture rates with advancing age. Merely reducing an older person's fracture risk to that of a person five years younger could lower the number of hip fractures per year by over 130,000, and save approximately $6 billion per year. This is just one example of how interventions that reduce physical frailty could yield major savings in health costs. Even modest reductions, sufficient to reduce nursing home and home care needs by 25 percent, could spare as many as 350,000 persons from needing nursing home care, and could save approximately $14 billion per year.

What action has NIA taken to address this

Mr. Stokes: concern?

Dr. Williams : A major step NIA has taken this year is initiation of the Claude D. Pepper Older Americans Independence Centers. Establishment of these Centers was authorized by Congress last year. Testing the efficacy of interventions in preventing and reducing dependence is a required component of these Centers. Other key aspects of the Centers include career development of new investigators to test further interventions to increase independence, studies of factors affecting older persons' willingness and ability to participate in new interventions, studies of cost effectiveness of new treatments, and information dissemination to translate research results of the Centers into health care practice.

There is intense research interest in these Centers. NIA has received 41 letters of intent to submit proposals. Potential interventions for testing include techniques to increase muscle strength, mobility, balance and/or endurance in frail older persons; prevention of disabling falls; prevention of institutionalization by improved identification and treatment of health problems in frail older persons; reducing disability from cardiovascular disease through better drug treatment; preventing dehydration, malnutrition, and their debilitating consequences common problems among frail older persons; and better treatments for urinary incontinence.

In addition to the Pepper Centers, NIA's research programs on physical frailty and other sources of dependence which I described earlier support clinical studies and basic research aimed at developing and testing better interventions against the causes of dependence.


Mr. Early: What is the average increase in the size of noncompeting research project grants under the budget proposal? What about new and competing research grants? Why are you proposing an increase which is less than the BRDPI?

Dr. Williams : The average increase for a noncompeting research grant is 4.8% and 5.1% for a competing grant. This increase is less than the BRDPI because of the need to balance research requirements against available resources.

Mr. Early: What was the downward negotiation rate for competing grants in FY 89 and FY 90?

Dr. Williams : In FY 1989, the downward negotiation rate for competing grants was 10.0% and 15.7% in FY 1990.

Mr. Early: What are you projecting for FY 91?

Dr. Williams : Beginning in FY 1991, the NIA instituted cost containment policies that eliminate the arbitrary downward reductions used in past years. Each potential competing grant will be carefully examined to determine what level of budgetary adjustments can be effected without damaging the science of the proposed project. While one of the long term goals of the NIH Financial Management Plan is to heighten the sensitivity of Initial Review Group members to cost issues, it is likely that change in study section behavior will not occur immediately. NIA has instructed its study sections to pay special attention to proposed budgets in light of the cost containment issue. It must be emphasized that each grant proposal is considered individually by NIA staff, and that budgetary adjustments are made on a caseby-case basis.

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Dr. Williams: The downward negotiation rate for noncompeting grants was 12.5% in FY 1989 and 13.2% in FY 1990. In FY 1991, NIA staff will ensure that future year costs budgeted for each award reflect an approximate four percent increase from the first year adjusted cost, taking into consideration any recommendations concerning scientific needs for the future years of the project.

Mr. Early: What is the BRDPI for these years?

Dr. Williams : The BRDPI for FY 1989 was 5.20%; for FY 1990, 5.80% and for FY 1991, 5.998.

Mr. Early: Doctor, doesn't this institutionalize the lar downward negotiations the institute has had to make in competing grants these past few years?

Dr. Williams: While we have eliminated the practice of arbitrary downward negotiations from recommended levels by NIA staff, we do examine each grant individually, and budgetary adjustments are made on a case-by-case basis to ensure the most effective use of our resources.

Mr. Early: Will the NIA be able to fund noncompeting grants at the commitment level under the FY 92 request? New and competing grants at the peer reviewed levels?

Dr. Williams: Under the FY 1992 request, the NIA will be able to fund noncompeting grants slightly below the commitment level. We project we will be able to fund new and competing grants on the average of 15.6% below the peer reviewed level.


Mr. Early: What percentage of new and competing grants will the institute fund under the FY 92 budget request, and how does this compare to FY 91 and FY 90?

Dr. Williams: Our estimated award rate for FY 1992 is 22.8% and 39.4% for FY 1991. The award rate for the NIA in FY 1990 was 24.0%.

Mr. Early: How does this compare to the award rate of five years ago? Ten years ago?

Dr. Williams: Our award rate for 1986 (five years ago) was 31.1% and 23.6% in 1981 (ten years ago).

Mr. Early: What is the projected "success rate" and how does this compare to FY 91 and FY 90?

Dr. Williams : Our projected success rate for FY 1992 is 22.1$; for FY 1991, our estimated success rate is 37.0%. In FY 1990, the success rate for the NIA was 21.6%.

Mr. Early: Five years ago? Ten years ago?

Dr. Williams: Our success rate five years ago was 25.0% and ten years ago it was 15.4%.

Mr. Early: How would you characterize the quality of research applications the institute is receiving today? What kinds of comparisons would you make to prior years?

Dr. Williams: With the continually growing interest in and resources available for aging-related research, and our encouragement of many of the best scientists in relevant fields, we see steadily increasing numbers of applications of very high quality.

Mr. Early: To what payline percentile will the institute be able to fund under the budget request and how does this compare to FY 91 and FY 90?

Dr. Williams : The budget request would permit funding to the 22nd percentile. The estimated payline for FY 1991 is 34; in FY 1990 the payline was 24.2.

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