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Fiscal Year 2004 Budget

Reducing Disease and Disability

Chronic disease and disability can compromise the quality of life for older people. Some 79 percent of people age 70 and older have at least one of seven potentially disabling chronic conditions (arthritis, hypertension, heart disease, diabetes, respiratory diseases, stroke, and cancer).4 The burden of such chronic conditions poses a challenge to individuals as well as families, employers, and the health care system. Research to improve understanding of the risk and protective factors for chronic disease and disability can lead to the development of effective prevention strategies. This section describes some of the latest findings on the treatment and prevention of various age-related diseases, as well as the molecular underpinnings of disease.

Treatment and Prevention of Disease

Treatment of any specific disease in older people can be complicated by the presence of other diseases and disorders and by the concomitant use of multiple medications to treat various conditions. Potential interactions of medications, including those of prescribed drugs with over-the-counter drugs and dietary supplements, represent additional concerns. Moreover, adherence to treatment regimens can be difficult, as older patients often must maintain a complex schedule for taking several different medications. Research is ongoing to determine the best treatment approaches for older patients, particularly those with concurrent medical conditions, and to identify strategies for improving adherence and minimizing potentially adverse effects of medications.

Beneficial Effects of an Anti-diabetes Hormone on Metabolism. New studies show that GLP-1, a gut peptide hormone that is present in the blood and that induces secretion of insulin from the pancreas, has beneficial effects on cellular absorption of glucose among people with insulin resistance, a prediabetic condition. In one study, GLP-1 increased glucose uptake among insulin-resistant people over age 70 in whom insulin secretion had been artificially suppressed. The investigators also found that, in young people who were severely insulin resistant due to obesity, administration of GLP-1 brought their glucose uptake capability into line with that of their lean counterparts.

Bisphosphonates May Combat Glucocorticoid-Induced Bone Loss. Glucocorticoids, often used to treat a variety of conditions that arise in the elderly, also cause a rapid and marked decrease in bone mineral density, making a population that is already susceptible to osteoporosis even more subject to bone loss. Common treatments for osteoporosis, such as calcium, vitamin D, or fluoride, are not very effective against glucocorticoid-induced bone loss. However, a class of drugs known as bisphosphonates shows promise. Now, NIH-supported researchers have dissected the individual actions and the interactions of glucocorticoids and bisphosphonates on bone. This work demonstrates that each of these drugs tips the balance between bone formation and bone resorption in mice in both an early and later phase. The early phase of bone resorption caused by glucocorticoids cannot be counteracted by bisphosphonates, but in the longer term this balance shifts as bone-resorbing cells die and the lifespan of bone-building cells is extended due to bisphosphonate treatment. Understanding how bisphosphonates work has direct implications on the treatment of osteoporosis, a common condition among older Americans, and other diseases and conditions involving bone loss.

Structured Restorative Home Care Produces Better Health and Function After Acute Illness and/or Hospitalization in Older Persons. Illness and hospitalization often initiate functional decline in older persons, and this decline can often persist long after the acute episode is over. An increasing number of older persons receive home care services after such episodes. In a recent NIA-supported study, patients on a "restorative care program" were significantly less likely to need rehospitalization, nursing home placement, or emergency room care after hospitalization as compared to people receiving "usual" home care. The restorative home care program consisted of the establishment of integrated teams of nurses and other health professionals and the application of structured interventions for disabilities, including exercises, behavioral changes, environmental adjustments and adaptive equipment, medication adjustments, and patient and family education. Functional abilities for living at home such as preparing meals, using transportation, shopping, doing laundry, and taking medicines appropriately were also significantly better in the restorative care group, as was mobility.

Benefits and Costs of Cervical Cancer Screening Into Old Age. Although mortality rates for cervical cancer have declined substantially because of widespread use of Papanicolaou (Pap) screening, the test may fail to detect cancer. An increased understanding of the role of human papillomavirus (HPV) infection in the development of cervical cancer and advances in technologies for HPV detection have prompted exploration of HPV testing as an adjunct or primary screening tool. As with many common conditions, a critical public health issue regarding HPV screening is the cost-effectiveness of screening persons of all ages versus setting an upper age limit for screening.

Researchers constructed a model based on U.S. cervical cancer incidence, current screening rates, accuracy of diagnostic tests, and effectiveness of treatment, to examine the cost-benefit ratios of different population screening strategies every two years or every three years -- joint Pap and HPV testing, Pap testing alone, and HPV testing alone. The benefits of screening were measured by the gains in years of survival adjusted for the absence or presence, and severity, of cervical cancer. This model was used to estimate cost-benefits of the different strategies for women beginning at age 20 and continuing to either age 65, to age 75 years, or death. They found that the greatest benefits of screening came from combined Pap and HPV testing every two years through death, with only a modest increase in cost above Pap screening alone. 98 percent of the benefits were retained if an upper age limit of 75 was set for screening. However, the proportion of the benefits retained was substantially lower (87 percent) if the upper age limit was set at 65.

Age Does Not Influence the Response to Resistive Strength Training. Loss of muscular strength and muscle mass with age (termed sarcopenia) is associated with the development of disability and frailty in the elderly. Men and women in two age groups - 20-30 and 65-75 - participated in a resistive strength training program. Both age groups increased strength, and showed similar increases in muscle mass. In addition, both age groups showed similar increases in resting metabolic rates, which generally decrease with age.

A Drug To Improve Bone Marrow Transplant Success. In an allogeneic bone marrow transplant (BMT), in which the recipient receives bone marrow from a donor, the recipient must be given drugs that suppress the immune system in order to prevent the body from rejecting the transplant. Immunosuppressive drugs commonly used with BMT patients include Cyclosporin A (CsA) and FK506, which are also used to treat a number of autoimmune diseases. However, these drugs have a limited success rate; the body resists their activity through a specific molecular pathway. NIH researchers have demonstrated recently that the immunosuppressive drug rapamycin, an antibiotic, blocks this pathway, suggesting that the success of immunosuppressive therapy in allogeneic bone marrow transplantation and autoimmune disorders could be improved by combination treatment with CsA/FK506 and rapamycin.

Lifestyle Change and Medication Can Prevent Type 2 Diabetes, but Efficacy of These Interventions May Vary by Age. NIA-supported researchers participated in the Diabetes Prevention Program, a major, multi-institutional study that was initiated by the National Institute on Diabetes and Digestive and Kidney Diseases and was designed to identify interventions that could prevent or delay the development of type 2 diabetes. The researchers found that people who are at high risk for diabetes can sharply reduce their risk by adopting a low-fat diet and moderate exercise regimen. This effect was most pronounced among study participants age 60 and over. Treatment with the drug metformin (Glucophage®) also reduced diabetes risk among study participants, but for unknown reasons was less effective among older participants. Nearly half of the study participants were members of racial and ethnic groups that suffer disproportionately from type 2 diabetes, including African Americans, Hispanic Americans, Asian Americans and Pacific Islanders, and American Indians.

Molecular Understanding of Disease Processes

Old Immune Systems Are Less Responsive to New Infections. The immune system becomes less effective as we age, and this loss of function contributes to illness and death in the elderly. B cells, or specialized white blood cells that produce antibodies against invading pathogens, are critical to the immune response, but their role in the aging immune system is not yet well understood. Researchers have observed that subsets of B cells respond to each new infection by producing antibodies that react specifically to the infectious agent. These "experienced" B cells are then highly effective at responding to re-encounter with the original infectious agent, but are less able to respond to new infections. The body also produces "naïve" B cells that are capable of tailoring their response to new infections, but as people age, fewer new B cells are produced. In a recent study, NIH-supported investigators closely examined B cells in young and elderly mice and found that the aged mice have much higher levels of experienced, as opposed to naïve, B cells when compared to younger mice. They suggest that the experienced B cells are retained in the body as a result of chronic stimulation from the environment. This is correlated with a decline in generation of new B cells in the bone marrow, with the consequence that the overall immune response is less effective for new infections.

Lipid Abnormalities Linked to Lou Gehrig's Disease. NIH investigators have identified severe abnormalities in the metabolism of cholesterol and of sphingolipids, a type of fat, in the spinal cords of amyotrophic lateral sclerosis (ALS, or Lou Gehrig's disease) patients and in mice that have been genetically engineered to manifest symptoms of ALS. These abnormalities result in the production of increased levels of sphingolipid byproducts and accumulation of cholesterol which prove toxic to motor neurons at high levels. In mice, the appearance of metabolic abnormalities precedes the development of symptoms, suggesting that the abnormalities have a role in killing the neurons. The researchers also found that drugs that rein in sphingolipid synthesis can prevent the accumulation of toxic byproducts and thereby protect motor neurons from damage. The ability of a drug that prevents accumulation of sphingolipids and their byproducts to protect motor neurons suggests that this and related drugs, as well as modifications of dietary intake of fats, may reduce the risk of ALS.

  1. National Center for Health Statistics. Health, United States, 1999 With Health and Aging Chartbook. Figure 11, pg. 41. Hyattsville, MD: 1999.