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Fiscal Year 2003 Budget

Reducing Disease and Disability

Apart from AD, 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).7 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 offer 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 disease in older people can be complicated by the presence of other diseases and disorders and by the 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.

Comorbidity and Breast Cancer in Older Women. Most breast cancer and related deaths occur in women aged 55 years and older. Concurrent age-related health problems such as hypertension, heart disease, diabetes, chronic obstructive pulmonary disease, and cerebrovascular disease are likely to affect the course of the disease and treatment options. Researchers have found that older breast cancer patients with preexisting health conditions receive less aggressive pretreatment assessments and cancer treatment than younger, healthier women. Given the high incidence and mortality rates of breast cancer in older women, research is needed to determine how age differences and accompanying health problems should guide assessment and treatment choices.

Low-Dose Estrogen Reduces Bone Breakdown in Older Women. More than 100 women over the age of 65 participated in a study of three different doses of estrogen (17b estradiol) therapy. The highest of these doses was the amount most commonly used today in estrogen replacement therapy, and the lowest dose was one-fourth this amount. The participants were studied for 6 months: 3 months on treatment and 3 months off. The low dose markedly reduced bone breakdown as measured by several serum markers, a reduction that was similar to that produced by the highest estrogen dose. Breast tenderness, bleeding, and thickening of the lining of the uterus (an indicator of potential adverse uterine effects), were significantly less frequent with the lowest dose. In fact, low-dose therapy resulted in no more side effects than placebo. These findings suggest that a lower dose of estrogen may be just as effective as the regular dose, but have fewer side effects.

Persistence of Cognitive Decline after Coronary Artery Bypass Surgery. One of the more common types of surgeries performed in the elderly is coronary artery bypass grafting (CABG). CABG may have adverse effects on the brain including stroke, post-operative delirium, and short-term cognitive impairment. Until recently, it was believed that most cognitive decline after CABG surgery is transient. However, researchers have now found that among older individuals undergoing CABG surgery, cognitive function at discharge may predict long-term cognitive function. Following a group of 261 CABG patients, the researchers found that over half exhibited some cognitive decline at discharge. The patients, as a group, went on to show a pattern of early improvement at 6 weeks and 6 months. At the 5-year assessment, however, some 42 percent of the surgery group was performing below baseline cognitive levels. Additional predictors of later decline included older age at surgery and lower level of education. Perioperative injury, increased susceptibility to injury, or decreased ability to recover from injury, may be responsible for cognitive dysfunction after CABG surgery and will be important research issues to pursue.

Physical Exercise Prevents Disability in Older People with Arthritis. Older people with osteoarthritis of the knee often have difficulty doing basic activities of daily living (ADLs), including walking, eating, dressing, using the toilet, bathing, or even moving from bed to a chair. Although previous exercise interventions have shown positive effects, none has yet been shown to affect clinically significant outcomes such as ADLs. Researchers recently conducted a study of exercise in 250 community-dwelling people, 60 years of age or older, with knee osteoarthritis. The participants were divided into 3 groups. Two groups participated in either an aerobic exercise program to increase endurance, or a resistance training program to increase strength. The third group did not participate in structured exercise programs and served as a control group. ADL disability was measured every 3 months throughout the 18 months of the study. Participants in both exercise programs had lower incidences of ADL disability than those in the control group. Individuals who complied most diligently with the exercise program had the lowest risk for disability. These results suggest that regular exercise has great potential to prolong the independence of older people despite the presence of this common and often disabling disease.

Reducing Delirium after Hip Fracture in Older Adults. Delirium, an acute confusional state, complicates recovery from hip fracture repair in at least one-third of the 250,000 older Americans who fracture a hip each year.8 Besides being frightening to patients and their families, and difficult to manage in the hospital, delirium after hip fracture is also associated with poor recovery of function. In a recent study aimed at reducing risk factors for delirium, geriatricians provided a variety of recommendations to the orthopedic physicians caring for the hip-fracture patients. These recommendations included transfusing blood to maintain an adequate red blood cell count, limiting the use of psychoactive medications, and providing adequate pain management. This intervention led to a one-third reduction in patients who developed delirium and a one-half reduction in the proportion who developed severe delirium compared to a control group of patients. This study demonstrates that measures can be taken to prevent delirium in vulnerable older patients.

Dietary Restriction Increases Levels of Growth Factors in the Brain and Stimulates Production of New Nerve Cells. Reducing calorie intake (dietary restriction, or DR) can increase the lifespan of rodents, and can also promote resistance of rodents' brain cells to injury. The cellular and molecular mechanisms responsible for the beneficial effects of DR on the brain are unknown. In a recent study, adult rats and mice maintained on a DR feeding regimen for 3 months showed increased levels of the neuronal growth factor brain-derived neurotrophic factor (BDNF) in the hippocampus, a brain region involved in learning and memory, as well as in several other brain regions. The rats also exhibited a significant increase in the numbers of newly divided cells in a region of the hippocampus. These findings provide the first evidence that diet can affect expression of a neurotrophic factor and can also stimulate the production of new neurons in the brain; they may also help to explain the beneficial effects of DR on learning and memory in animals, and may have implications for developing new ways to combat age-related neurodegenerative disorders.

Working to Cure Prion Diseases. Prions are infectious proteins that alter the shape of a normal cellular protein, changing it into a prion. They can cause several rare but invariably fatal neurodegenerative disorders, including Creutzfeld-Jakob disease (CJD). Investigators have used a number of approaches to identify compounds that are effective in clearing prions from cells in tissue culture. Two drugs, quinacrine (an anti-malarial drug) and chlorpromazine (an anti-psychotic drug), are known to enter the brain and are among the compounds that cause the clearance of prions in tissue culture. These compounds were effective at non-toxic concentrations and have been used for many years in humans, making them likely subjects for clinical trials to test their efficacy in treating people with CJD who otherwise face certain death.

Potential New Treatment for Type 2 Diabetes Mellitus in the Elderly. Type 2 diabetes mellitus is the most common form of diabetes among the elderly. It occurs when pancreatic beta cells produce insufficient insulin or when the body cannot use its insulin efficiently. GLP-1, a gut peptide, can stimulate beta cells to produce more insulin in middle-aged people with type 2 diabetes. However, until recently it had not been tested in older adults, who make up the majority of patients with the disease. Recent studies showed that GLP-1 potently stimulated insulin release in the elderly and lowered blood glucose to normal levels. In parallel studies with elderly rodents, investigators found that when GLP-1 was given long-term, it increased the number and activity of pancreatic beta cells. Researchers are now developing longer-acting forms of GLP-1 and have begun longer-term trials of GLP-1 treatment in an elderly population.

Molecular Understanding of Disease Processes

A Large-Scale Analysis of Gene Expression in Ovarian Cancer Suggests Possible Targets for Early Detection and Treatment. Ovarian cancer is the fifth most common cause of cancer death among women in the United States, yet it is very poorly understood.9 Ovarian cancer affects older women disproportionately. Because there are few early symptoms, and no sensitive screening tests for use in the general population, it is typically diagnosed in late stages, when treatment is difficult and often unsuccessful. More detailed knowledge of gene expression in ovarian cancer is crucial to a better understanding of how ovarian tumors form and to identifying novel targets for diagnosis and therapy. Serial Analysis of Gene Expression (SAGE) is a powerful method for analyzing the genes expressed in any cell or tissue. Researchers developed SAGE libraries representing the genes active in various normal and neoplastic ovarian tissues and identified many genes that were expressed differently in normal ovary and in ovarian cancer cells. The genes identified by this method have the potential to become useful targets for early detection and therapy. In addition, this work provides a framework for a detailed understanding of how ovarian tumors form at the molecular level.

Integration of Aging and Cancer Research. Cancer is largely a disease of the elderly. However, much remains unknown about cancer diagnosis, prevention, and treatment in older people. NIA and the National Cancer Institute (NCI) have created a partnership that has resulted in support for a number of projects. Ongoing initiatives include joint program announcements and the inclusion of NIA-supported studies within the NCI Cooperative Group system (a network of consortia throughout the U. S. that collaborate frequently on clinical trials for a variety of common cancers). Recently, the NIA and NCI extended this collaboration to NCI's Cancer Centers program, which is composed of 60 major academic and research institutions that sustain broad-based, coordinated, interdisciplinary programs in cancer research. A joint workshop was held in June 2001, and an aggressive research agenda within the NCI-designated cancer centers is now developing that can reduce the burden of cancer for older persons.

  1. National Center for Health Statistics. Health, United States, 1999 With Health and Aging Chartbook. Figure 11, pg. 41. Hyattsville, MD: 1999.
  2. Marcantonio ER et al. Reducing delirium after hip fracture: a randomized trial, J. Am Geriatr Soc 49: 516-522, 2001.
  3. American Cancer Society. Cancer Facts and Figures. 2001.