Differential activation on fMRI of monozygotic twins discordant for AD.

This is the first report of fMRI in monozygotic twins discordant for AD. FMRI brain activation patterns were examined during visuospatial and verbal working memory tasks. The affected twin had greater parietal involvement bilaterally during both working memory tasks and reduced left dorsolateral prefrontal cortex activity on the visuospatial memory task. Thus, fMRI may identify additional brain regions recruited in patients with AD to perform a given cognitive task.

Sustained-release sodium fluoride in the treatment of the elderly with established osteoporosis.

BACKGROUND: We ascertained the safety and efficacy of fluoride in augmenting spinal bone mass and reducing spinal fractures in older women with established osteoporosis. We compared a combination of sustained-release sodium fluoride, calcium citrate, and cholecalciferol (SR-NaF group) with calcium and cholecalciferol alone (control group). METHODS: Eighty-five ambulatory women aged 65 years or older with 1 or more nontraumatic vertebral compression fractures were enrolled in a 42-month randomized, double-blind, placebo-controlled trial. Primary outcome measures were vertebral fracture rate, bone mass, and safety. RESULTS: The vertebral fracture rate determined by means of computer assistance in the SR-NaF group was significantly lower than that in the control group (relative risk [RR], 0.32; 95% confidence interval [CI], 0.14-0.73; P =.007). Results of visual adjudicated inspection also confirmed a significant reduction in fracture rate (RR, 0.40; 95% CI, 0.17-0.95; P =.04). Bone mineral density in L2 through L4 increased significantly from baseline in the SR-NaF group by 5.4% (95% CI, 2.7%-8.2%; P<.001), and by 3.2% in the control group (95% CI, 0.8%-5.6%; P =.01). The between-group differences in bone mineral density were not significant. The femoral neck and total hip bone mineral density remained stable in the SR-NaF group and was not significantly different from that of the control group. There were no significant differences in adverse effects between groups. CONCLUSION: The SR-NaF group significantly decreased the risk for vertebral fractures and increased spinal bone mass without reducing bone mass at the femoral neck and total hip.

Evaluation and treatment of postmenopausal osteoporosis.

Osteoporosis is a prevalent condition among elderly women and is associated with an increased risk for fractures. With the burgeoning size of the elderly population, a practitioner is likely to face many questions regarding the evaluation and management of postmenopausal osteoporosis. This review discusses and compares available therapies. All women should have adequate calcium and vitamin D intake. Women diagnosed as having osteoporosis should be evaluated for secondary causes of osteoporosis and risk factors for falls. For women with postmenopausal osteoporosis, therapy with hormone replacement, bisphosphonates (alendronate sodium or risedronate sodium), raloxifene hydrochloride, or calcitonin should be considered. The results of ongoing studies will help refine the strategies used for management of postmenopausal osteoporosis.

Twenty-four hour growth hormone secretion in a patient with Werner's syndrome.

OBJECTIVE: To assess the 24-h endogenous secretory growth hormone (GH) profile and serum insulin-like growth factor-I (IGF-I) response to exogenous recombinant human growth hormone (rhGH) in a patient with Werner's syndrome. DESIGN: Blood sampling every 20 min for 24 h followed by three daily injections of growth hormone. SETTING: General Clinical Research Center. PATIENTS: Single patient with Werner's syndrome. MEASUREMENTS: Serum GH and IGF-I. RESULTS: Growth hormone pulses were absent during the 24-h monitoring period. Likewise, integrated GH concentrations were very low at 0.25 mu min/mL, and no peaks occurred after sleep onset. Following single daily administration of rhGH, serum GH and IGF-I rose. CONCLUSIONS: Our findings support previous but less extensive studies suggesting patients with Werner's syndrome have reduced growth hormone levels. Preliminary investigations using rhGH in patients with Werner's syndrome should be considered.

Southwestern Internal Medicine Conference: prevention of hip fractures in the elderly.

Hip fracture is a common, morbid, and costly health problem. Because our population is aging, hip fractures will remain a major health concern as we enter the next century. It has been estimated that by the year 2040, 512,000 hip fractures will occur annually in people 50 years or older. A number of factors common in the elderly increase the risk of falling. Falls and age-related changes that influence bone quality increase susceptibility to fracture. In this article, the author focuses on studies that identified risk factors and strategies to reduce falls as well as pharmacologic agents that may reduce fracture risk. Because of the multifactorial etiology of hip fractures, their prevention will ultimately require a combination of pharmacologic approaches to improve bone strength and strategies to prevent falls and limit injury.

Treating a patient with the Werner syndrome and osteoporosis using recombinant human insulin-like growth factor.

OBJECTIVE: To assess the safety and effect of recombinant human insulin-like growth factor 1 (rhlGF-1) on measures of bone metabolism in a human model of age-related osteoporosis. DESIGN: 6-month prospective case study. SETTING: General clinical research center. PATIENTS: 1 patient with the Werner syndrome, a low serum IGF-1 level, and osteoporosis. INTERVENTION: Daily subcutaneous administration of rhIGF-1 for 6 months. MEASUREMENTS: Serum alkaline phosphatase, osteocalcin, type I procollagen C-peptide and urinary hydroxyproline, calcium, and pyridinoline cross-links as measures of bone metabolism and radial shaft, femoral neck, and lumbar bone masses. RESULTS: Serum osteocalcin and type I procollagen C-peptide increased during rhIGF-1 therapy (P < 0.05). Twenty-four hour urinary calcium, hydroxyproline, and pyridinoline cross-links were also higher after treatment than they were before treatment (P < 0.05). During 6 months of treatment, the bone mineral density of the L2 to L4 vertebrae increased 3%; this value exceeded the coefficient of variation of this measurement. Bone density at the femoral neck and radial shaft changed by less than the coefficient of variation of these measurements. No significant changes in serum glucose values or other adverse effects of treatment were noted. CONCLUSIONS: Treatment with rhIGF-1 increased both bone formation and resorption in a patient with the Werner syndrome, a low baseline serum IGF-1 level, and established osteoporosis. Because lumbar bone mass increased without evidence of bone loss in the appendicular skeleton, a net increase in bone formation (formation greater than resorption) may have been responsible.

A randomized, controlled trial of outpatient geriatric evaluation and management in a large public hospital.

OBJECTIVE: To study the effect of outpatient geriatric evaluation and management on physical function, mental status, and subjective well-being. DESIGN: Prospective randomized controlled trial with a 1-year study period. SETTING: Large medical school-affiliated public hospital in an urban community. SUBJECTS: Patients at least 70 years old admitted to the medicine service were screened, randomized, and completed a 1-year follow-up interview. INTERVENTIONS: Comprehensive geriatric evaluation and an outpatient care management program. MAIN OUTCOME MEASURES: Mental status (SPMSQ), ADL (Katz Index), IADL (Five-Item OARS Scale), Life satisfaction (LSI-Z), and self-perception of health status (physical health section of OARS). RESULTS: No significant differences were found for cognitive status, ADL functioning, life satisfaction, nursing home placement, or mortality. The experimental patients reported significantly higher function in IADL and more favorable self-perception of health status compared with controls. CONCLUSION: Outpatient comprehensive geriatric evaluation and management appears to be a useful model for providing care to medically frail elderly patients.

Osteoporosis: considerations in evaluating and managing the older patient.

Osteoporosis is a common disorder that results in 1.3 million fractures each year in the United States. The resultant morbidity and mortality are substantial. While there has been considerable progress in our understanding of this disease, research studies frequently include only early postmenopausal individuals. At the same time, a number of important pathophysiologic and clinical differences exist between early postmenopausal and elderly individuals. These considerations raise the issue of the appropriateness of generalizing evaluation and treatment recommendations from younger to older patients. This review emphasizes factors important in the assessment and treatment of established osteoporosis in older patients.

Southwestern internal medicine conference: growth hormone--aging and osteoporosis.

Until recently, the use of growth hormone (GH) has been confined to the treatment of GH-deficient children. The advent of GH produced by recombinant DNA technology has increased the availability of GH. The increased availability of GH has made possible studies of the physiology and the possible therapeutic role of this hormone and its mediator insulin-like growth factor. One area where GH may play a therapeutic role is in the treatment of osteoporosis. This review will briefly summarize normal GH physiology and discuss age-related changes in GH and insulin-like growth factor 1 (IGF-1) axis and how they may relate to age-related physiologic changes. Evidence for and against a possible therapeutic role for GH/IGF-1 in the treatment of age-related (senile) osteoporosis will be discussed.

The effect of geriatric evaluation and management on Medicare reimbursement in a large public hospital: a randomized clinical trial.

OBJECTIVE: To study the effect of a geriatric evaluation and management program on health care charges and Medicare reimbursement. DESIGN: Prospective randomized controlled trial during a 1-year study period. SETTING: Large medical school-affiliated public hospital in an urban community. SUBJECTS: Patients at least 70 years old admitted to the medicine service were screened and randomized into two groups of 100 patients each. INTERVENTION: Patients randomized to the experimental group underwent initial comprehensive geriatric evaluation and once discharged from the hospital were enrolled in a geriatric care management and treatment program. The control group received usual care only. The major intervention of this study was in outpatient long-term care. MAIN OUTCOME MEASURE: Total charges for services billed to Medicare Part A and Part B and total Medicare reimbursement. The Medicare charge and reimbursement data were obtained by use of the Medicare Automated Data Retrieval System, a linked Medicare Part A and Part B utilization file. RESULTS: Total charges and reimbursement were greater for the control group but not significantly so. Subset analysis revealed significantly greater inpatient charges (P < 0.03) and Medicare reimbursement (P < 0.005) for the control patients and a greater likelihood of utilization of home health care services in the experimental group (P < 0.01). CONCLUSION: A geriatric evaluation and management program appeared to shift utilization and Medicare expenditures from inpatient services to home health care services. There was no evidence that the experimental program resulted in increased expenditures for Medicare. In selected populations, geriatric evaluation and management programs may contribute to cost containment.

Age-related osteoporosis.

Osteoporosis is a common disease that results in 1.2 million fractures each year in the United States. The morbidity and mortality as well as the financial impact from this disease is substantial. There has been considerable progress in our understanding of this disorder, but studies commonly include only early postmenopausal individuals. At the same time, it is clear that there are major epidemiologic, physiologic, and clinical differences between early postmenopausal and older individuals. These considerations raise the issue of the appropriateness of generalizing evaluation and treatment recommendations from younger to older patients. This review will focus on the age-related changes in bone physiology as it relates to osteoporosis and consider the available evidence for using commonly used (calcium) or approved (estrogen and calcitonin) agents in the elderly patient.

Urinary incontinence in the elderly.

Urinary incontinence is a prevalent problem among the elderly and has a significant clinical, social, psychological, and economical impact. In spite of these consequences, often very little is done to evaluate the problem. Furthermore, patients may be reluctant to bring their complaint to the attention of their health care provider. This broad review will discuss the anatomy, physiology, and pathophysiology of urinary incontinence. The initial evaluation and treatment options will also be outlined. As the aged population continues to grow, physicians can expect to see this problem with greater frequency. It is hoped that this discussion will facilitate the evaluation and management of this common but frequently neglected problem.