unique feature of this trial, developed in consultation with AIDS advocacy groups, these patients are offered the option of immediate treatment, deferral of treatment until their retinitis becomes sight threatening, or participation in a randomized comparison of immediate versus deferred treatment. All treated patients are randomly assigned to ganciclovir or foscarnet therapy. The major outcome measures for this trial are survival, retinitis progression, and drug toxicity.

Question. Do you have enough funds in this budget to continue these trials?

Answer. Because of the escalating cost of patient care and increased cost of doing research having out paced funding realities, the funding requirements of this trial continue to increase. However, we will continue to support the AIDS trial within the amount of funds provided in the budget.

NATIONAL PLAN FOR VISION RESEARCH

Question. When does the National Advisory Eye Council expect to complete its next five year plan?

Answer. The National Advisory Eye Council is expected to complete its work on the 1992-1996 national plan for vision research by summer 1991.

Question. Please send a copy of this plan to the Subcommittee when it is completed.

Answer. We look forward to providing the Subcommittee a copy of this plan.

OPPORTUNITIES IN GLAUCOMA

Question. According to the congressional justification, two million Americans are known to have glaucoma, a leading cause of blindness, and an additional million people may have the disease and not know it. Are there significant applied research opportunities in glaucoma that require additional funding?

Answer. In the past, advances in glaucoma have been seriously limited, but now opportunities abound for scientists to make a concentrated attack against the disease. There are a number of significant applied research opportunities and approaches that have been developed to manage this disease that are ready to be exploited that require additional funding:

Studies that focus on preventing blindness from glaucoma and

on maximizing gains in the quality of life;

Determining why the rate of open-angle glaucoma is higher and possibly a more severe disease in blacks and development of effective modalities for early detection and improved diagnosis, treatment and control of glaucoma;

Exploiting advances in molecular biology, cell biology, and immunology;

Comparing the effectiveness of immediate surgery to medical treatment in reducing visual loss in black patients with newly diagnosed open-angle glaucoma;

Evaluating the functional status and patient quality of life in a clinical trial that compares medical (drug) treatment with surgery for glaucoma; and

Determining whether treatment to lower elevated intraocular pressure prevents or delays damage to the eye in people who are at increased risk for developing open-angle glaucoma.

Capitalizing on these opportunities should offer rapid progress in determining the causes of the various forms of glaucoma and ultimately their cure.

NATIONAL INSTITUTE ON AGING

STATEMENT OF DR. T. FRANKLIN WILLIAMS, DIRECTOR

BUDGET REQUEST

Senator HARKIN. Dr. Williams, back to you now.

Your funding request of $348.5 million is 7.7 percent more than 1991. The Aging Institute enjoyed the largest percentage increase in 1991 compared to 1990 of any institute, due largely to the increases for Alzheimer's research initiated by this committee.

So, Dr. Williams, we are delighted to have you with us again today and look forward to hearing your statement. Please proceed. Dr. WILLIAMS. Thank you very much, Senator Harkin. It is really a pleasure to present some of our recent accomplishments and outline our future directions and plans, including our use of the funds that Congress has given us.

The research funded by the National Institute on Aging is crucial for keeping suffering, disability, and medical expenditures for older Americans from increasing in magnitude with the graying of America. Older people can age and remain healthy. This gives us the challenge to identify and reduce risks leading to disease and cost of long-term care. Our ultimate goal is to assure independence and a high quality of life throughout the lifespan.

ALZHEIMER'S DISEASE

Alzheimer's disease is certainly our highest priority, and we coordinate research efforts with other institutes, including the National Institute of Neurological Disorders and Stroke, and several others. This disease, as you well know, is currently responsible for disability and misery in up to 4 million older Americans and their families costing them and society an estimated $80 billion annually. A high percentage of those of us alive today will be at risk for this disease in the next century unless we can stop this terrible condition.

We are making rapid and significant progress in understanding the disease, particularly its biochemical defects and possibilities for treatment. In terms of understanding the basic biochemical defects, we learn more all the time about genetic roles. For example, a recent publication identified a specific mutation in the amyloid protein gene which is associated with the damage in Alzheimer's disease. In terms of the makeup of both the amyloid protein that causes the damage at the cellular level and the neurofibrillary tangles, which are the other major pathological finding, we are learning more almost every week about the nature of these proteins. This gives us insights into understanding how we might intervene in the production of these proteins and prevent their progress.

In terms of treatment, we have just concluded a very thorough clinical trial of the drug tetrahydroaminoacridine, or THA, and the results will be published very shortly and available to the scientific medical community. I, myself, do not have the results yet, but will have them very shortly.

We are moving ahead to encourage and develop clinical trials on other potential intervention agents for Alzheimer's disease. Work with nerve growth factors has now progressed from animal research to clinical trials, and we are working with other metabolic intervening agents and agents that affect brain vascular function. We have a real prospect of identifying medications that will delay the progress of this disease, if not halt it entirely. I agree with Dr. Goldstein's comments earlier when he was speaking of Parkinson's disease and Alzheimer's disease, that our first major goal is really to delay the progress of this disease. For example, if we could simply delay the progress of Alzheimer's disease by 5 or 6 years, we could cut in one-half the numbers and costs of this dis

ease.

BURDEN OF PHYSICAL FRAILTY

Another area that is equally important is that of the burden of physical frailty in older people where the costs are estimated to be between $50 and $80 billion a year. These disabilities include hip fractures, the problems of osteoporosis, and other causes of disabil ity causing loss of independence, including visual and hearing impairments.

It is increasingly evident that one is never too old for prevention or reduction of frailty. In one study supported by our Institute, which received wide notice this past year, 90-year-old nursing home residents showed a remarkable improvement in muscular function and ability to walk through muscle-strengthening exercises, including a documented marked increase in muscle mass. One of our emphases in physical frailty is to intervene to strengthen muscles, improve balance, and modify use of medications. In this area among others, we are giving particular attention to research related to women because of their longer lifespan and because they suffer disproportionately from disorders such as osteoporosis and incontinence.

We are also expanding our attention to changes in the vascular system associated with aging which may underlie changes found in other organ systems including the brain. There is, in addition, very promising basic research showing that there are nonproliferative genes which act in a balanced way with genes which promote proliferation in cells. These nonproliferative genes, at least some of them, can counteract the effects of oncogenes, or in other words, cancer promoting genes, under certain circumstances. What we are seeing at the cellular level is a balance of proliferative and nonproliferating influences which may allow us to intervene with cancer. This is a very exciting finding at the cellular and molecular biological level relating to aging.

Just a couple of other brief comments. With the participation of other Federal agencies, we are providing funds for the new health and retirement survey, which was approved by the last Congress.