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Statement of the Director, National Institute regarding Aging on NIA's FY 1998 Budget
National Institutes of Health
U.S. Department of Health and Human Services

Before the House Appropriations Committee, Subcommittee on Labor, Health and Human Services, Education and Related Agencies
March 4, 1997

Mr. Chairman, age-associated dementia, disease, and frailty have long been considered by many to be the inevitable, unalterable effects of living to an old age. This simply is not true. During the past twenty years, research on the aging process has contributed to the realization that aging need not be equated with inevitable decline and disease. Instead, the later years of life can be healthy, fulfilling, and productive.

The National Institute on Aging (NIA) promotes research to understand the mechanisms of aging and seeks approaches to extend the healthy, active years of life for all Americans. Some of the diseases and issues that NIA-supported researchers are investigating include Alzheimer's disease, the biological processes that control aging, cardiovascular aging, menopause, osteoporosis and musculoskeletal aging, long-term care and caregiving, and interventions to improve the quality of life of older people.

The NIA leads national efforts to gain greater understanding of the biological mechanisms underlying Alzheimer's disease and to develop preventive measures and treatments based on research findings. Alzheimer's disease (AD) is a progressive brain disorder marked by changes in behavior and personality and by an irreversible decline in intellectual abilities. It is the most common cause of decreased mental function among people over age 65 and currently affects an estimated four million Americans. The devastating effects on patients and the long clinical course of AD impose a heavy personal and economic burden on families, caregivers, and society in general. The cost is estimated to be as much as $100 billion per year.

Since 1990 we have greatly increased our understanding of AD's genetic risk factors. Genetic mutations linked to AD have been found on four separate chromosomes. At least three of the genetic loci identified, those on chromosomes 1, 14, and 21, are associated with early-onset, familial AD - - an aggressive form of the disease that affects approximately 10 percent of AD cases and causes symptoms in people as young as 30 years of age. The remaining gene, on chromosome 19, codes for a variant of Apolipoprotein E (ApoE4), a protein now recognized as the first genetic risk factor identified for the more common, late onset form of AD. Scientists are trying to understand the complex mechanisms that cause the nerve cell damage seen in AD and the key steps that, together with environmental factors, play a role in the disease process. A diagnostic test for AD that combines brain imaging and ApoE4 screening has been developed based on this genetic research. Using this test, it may be possible to identify brain function abnormalities in individuals who are at a high risk for Alzheimer's disease but are clinically asymptomatic, as much as 20 years before they would be expected to develop symptoms. This opens opportunities for the development of early interventions that would delay or prevent the brain damage seen in fully developed AD.

Based on evidence from basic and epidemiologic research, NIA's Alzheimer's Disease Cooperative Study is pursuing several promising therapies that may prevent or treat AD. Clinical trials investigating the effects of combination treatment with the Parkinson's disease drug, selegiline (Deprenyl), and the antioxidant vitamin E; the effect of the anti-inflammatory agent, prednisone; and the impact of psychoactive drugs and behavior management techniques on reducing disruptive, agitated behavior in AD patients are underway. In addition, a recent epidemiologic study provides the strongest evidence to date that taking estrogen after menopause may delay the onset and reduce the risk of AD in postmenopausal women. This finding has prompted the planned initiation of a clinical study on the efficacy of estrogen replacement therapy. NIA researchers have also genetically engineered the first animal model (a transgenic mouse), that exhibits both the behavioral and neuropathological symptoms of AD. This mouse model provides an important research tool for understanding AD and for expediting the testing of potential AD drug therapies.

Investigators are also conducting basic neurologic research to understand the complex mechanisms that cause nerve cells to die or gradually lose their ability to communicate with each other, as they do in AD. These studies are expected to make important contributions to understanding and treating AD, as well as a wide range of other neurologic diseases, including Parkinson's disease, stroke, Huntington's disease, and amyotrophic lateral sclerosis (ALS).

NIA's basic science research program forms the foundation for the Institute's applied clinical, social, and behavioral studies. Investigations on the biology of aging explore the gradual or programmed alterations of structure and function that characterize normal aging as well as the abnormal changes that accompany or serve as risk factors for disease states. The ultimate goal is to develop interventions that reduce or delay age-related degenerative processes in humans.

NIA-supported researchers use multiple approaches in their quest to improve understanding of the aging process. Immunologists are investigating the age-related loss of immune function and the mechanisms underlying this decline while molecular biologists seek to understand the molecular mechanisms that regulate cell replication. If these basic science initiatives are successful, they may lead to new approaches to cancer treatment and vaccine development.

In other basic science laboratories, NIA-supported genetic researchers have identified several "longevity genes" in mammals and lower organisms. These genes have provided insight into biologic control of life span and in some cases appear to act by making the animals less susceptible to environmental stresses. An understanding of life span regulation in simple animals will provide a basis for effective studies of life span control in more complex animals and humans. Continued research on longevity assurance genes is viewed as a critical first step in the design of biologically based interventions to promote human longevity, extend health span, and improve the quality of life in older individuals.

Another genetic research initiative supported by NIA is the study of Werner's syndrome - - a rare inherited disease with clinical symptoms that resemble premature aging. Werner's syndrome results in shortened life span and early susceptibility to a number of age-related diseases, including atherosclerosis, cancer, diabetes, and osteoporosis. As a result, this syndrome is considered a partial model of human aging. Researchers have identified the genetic defect that causes Werner's syndrome in a gene on chromosome 8. Follow-up research is expected to yield important insights into the biological processes of aging, into cancers (because of the rare tumors associated with Werner's syndrome), and into other age-related diseases.

Another example of the importance of basic aging research is the investigation of the effects of life-long caloric restriction. Rodents fed a nutritionally balanced but 30 percent calorie reduced diet maintained vitality, had delayed or reduced incidence of neoplasms and other age-associated diseases, and increased their lifespan by as much as 35 percent. Continuing research, now being conducted in monkeys, seeks to understand the mechanisms involved and their relationship to increased longevity and other anti-aging effects, and to suggest interventions appropriate for humans.

In addition to basic aging research, NIA supports applied research initiatives. One such initiative addresses the effects of physical frailty and the loss of independent function in older people. Physical disability, often the result of multiple, complex, interacting factors, is a major concern to older persons and contributes significantly to annual long-term care costs. Change in body composition in old age, particularly an increase in body fat and decline in lean mass and bone mineral, appears to represent a common pathway by which multiple diseases contribute to disability. NIA's Health, Aging, and Body Composition (ABC) study which began in 1996 will characterize the extent of these changes in body composition, identify clinical conditions that accelerate them and examine their health impact on strength, endurance, disability, and diseases of the elderly. The study will provide valuable information for interventions to prevent or reverse these changes in high-risk groups.

Previous research has demonstrated that a healthy lifestyle and modest amounts of regular exercise can significantly improve the health and functioning of older people. Studies have shown that deficits in muscular strength and response time (frequent contributors to falls and injury) can be ameliorated with exercise. Similarly, an NIA clinical study reports that elderly people with osteoarthritis of the knee who participated in either aerobic exercise or weight training experienced a significant improvement in physical functioning and a reduction in knee pain, compared to a control group that received health education only.

Another area that is of great interest to NIA researchers is cardiovascular disease (CVD). CVD is the leading cause of death of older Americans, responsible for almost 50 percent of deaths among persons age 65 and older. A recent study identified stiffening of large and medium-sized elastic arteries, such as the aorta, as a potential risk factor for cardiovascular morbidity in the elderly. This arterial stiffening occurs in healthy older people, but for approximately half of Americans age 65 and older, the degree of vascular stiffening becomes great enough to lead to isolated systolic hypertension, a major risk factor for stroke and other cardiovascular disorders. Researchers are studying interventions that would reduce vascular stiffening and other cardiovascular risk factors associated with age-related CVD. One recent investigation concluded that after five years of treatment of isolated systolic hypertension with low doses of diuretic-based anti-hypertensive medication, men and women aged 60 and older had fewer strokes, heart attacks, and other coronary heart disease, as well as lower overall mortality, than those given a placebo. The reduction in the rate of major cardiovascular disease with treatment was 34%, and the absolute risk reduction was twice as great for diabetic as compared with nondiabetic patients. Another treatment study is using non-invasive arterial imaging to determine the efficacy of vitamin E supplementation in reducing progression of early atherosclerosis. The potential benefit of preventing or reducing age-associated cardiovascular disease is enormous, both in terms of cost savings and quality of life of older Americans.

Other NIA researchers are focusing their investigative efforts on two areas that have particular significance to women -- osteoporosis and menopause. Osteoporosis afflicts 25 million Americans, most of them older women. The loss of bone mass due to osteoporosis contributes to 1.5 million fractures annually. NIA intramural scientists have shown that minocycline, a tetracycline-like antibiotic, improves bone strength and formation and slows bone resorption in aged laboratory animals with surgically induced menopause. Researchers are now launching a one-year clinical trial to study the effects of minocycline in postmenopausal women with osteoporosis.

The biological and psychosocial significance of menopause in the lives of women is an understudied area. After menopause, women lose bone density and strength, and become more prone to developing diseases and disorders, such as osteoporosis, osteoarthritis, cardiovascular disease, urinary incontinence, and Alzheimer's disease. There is also evidence that women of various ethnic and racial groups experience and respond to menopause differently. The recently initiated Study of Women's Health Across the Nation (SWAN), co-funded with NIA by the National Institute of Nursing Research and the Office for Research on Women's Health, NIH, will gather valuable new information on the biological and psychosocial aspects of menopause from women of various ethnic and racial groups. This information is crucial in designing future clinical interventions for health conditions associated with menopausal changes.

Demographic trends pointing to a "graying of America" have stimulated interest in the factors that contribute to the quality of life of older Americans. The number of Americans aged 65 and over, now approximately 34 million, is expected to more than double by 2030. Within this group, the over 85 population is the fastest growing segment of the U.S. population, and tends to be most vulnerable to disease and disability. As Americans live longer, it becomes increasingly important to seek ways of improving the quality of life for elderly persons.

NIA supports several behavioral and social research efforts on such quality of life topics as: improving the long-term care of older people in institutional and residential settings, analyzing the efficacy of special care units (i.e. dementia, rehabilitation and AIDS) in institutional settings, identifying factors that influence the understanding and compliance of elderly persons with medical regimens, developing strategies to help older people improve their lives in such areas as computer skills, driving, exercise, etc., and developing and testing cognitive interventions that would postpone age-associated declines in cognitive functioning.

Unfortunately, for too many elderly Americans, the "golden years" are none too golden. Their later years are burdened with disease, disability, and costly care options. However, we can report that there are hopeful trends in disability rates. In absolute terms, the differences in disability prevalence suggest that there are approximately 1.2 million fewer disabled older persons in 1994 than would have been predicted if the 1982 disability rates had remained the same. These lower than predicted rates of disability among the elderly coincide with recent data from the 1995 National Nursing Home Survey indicating that since 1985, the number of nursing home residents increased by only 4 percent despite an 18 percent increase in the population 65 and over during that period. Reductions in disability, among other factors contributing to nursing home use, could result in substantial cost savings. Through NIA support, researchers will strive to understand the dynamics underlying this apparent decline and work to ensure a future where age is associated more with experience and independence than it is with decline and deterioration.

Mr. Chairman, the FY 1998 budget request for the National Institute on Aging is $495,202,000. We will continue to identify initiatives that maximize scientific and management efficiency. I would be happy to answer any questions.

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