Hip protectors: recommendations for biomechanical testing--an international consensus statement (part I).

INTRODUCTION: Hip protectors represent a promising strategy for preventing fall-related hip fractures. However, clinical trials have yielded conflicting results due, in part, to lack of agreement on techniques for measuring and optimizing the biomechanical performance of hip protectors as a prerequisite to clinical trials. METHODS: In November 2007, the International Hip Protector Research Group met in Copenhagen to address barriers to the clinical effectiveness of hip protectors. This paper represents an evidence-based consensus statement from the group on recommended methods for evaluating the biomechanical performance of hip protectors. RESULTS AND CONCLUSIONS: The primary outcome of testing should be the percent reduction (compared with the unpadded condition) in peak value of the axial compressive force applied to the femoral neck during a simulated fall on the greater trochanter. To provide reasonable results, the test system should accurately simulate the pelvic anatomy, and the impact velocity (3.4 m/s), pelvic stiffness (acceptable range: 39-55 kN/m), and effective mass of the body (acceptable range: 22-33 kg) during impact. Given the current lack of clear evidence regarding the clinical efficacy of specific hip protectors, the primary value of biomechanical testing at present is to compare the protective value of different products, as opposed to rejecting or accepting specific devices for market use.

Clock drawing: analysis in a retirement community.

OBJECTIVE: To test the hypothesis that performance on a clock-drawing test in a mailed survey to an older cohort is associated with known and potential risk and protective factors for Alzheimer's disease. DESIGN: The Leisure World Cohort Study is an ongoing study, begun in 1981, of nearly 14,000 older adults. In November 1992, the 8,406 living cohort members were mailed a follow-up questionnaire. SETTING: Leisure World Laguna Hills, a southern California retirement community. PARTICIPANTS: The study population is a predominantly white, well-educated, upper-middle-class community; approximately two-thirds are women. Data from 4,843 cohort members (mean age 80 years; range 52-101) were analyzed. MEASUREMENTS: The questionnaire included a clock-drawing task: a predrawn circle 3 1/4 inches (8.3 cm) in diameter was provided with instructions "In the circle below, draw in the numbers as on a clock face. Make no erasures." Clocks were scored on 7 items: all numbers 1-12 present without adding extra or omitting numbers, sequencing of numbers, position of numbers, orientation of numbers to circle, consistent number style (either Arabic or Roman), tilt of numbers, and superfluous marks. A total clock score was calculated by summing the number of correct individual items (0-7). We also classified individuals as cognitively impaired by a previously suggested method: individuals were affected if they did not have three numbers drawn in the upper left quadrant of the clock face. RESULTS: Ninety percent or more of the participants across all ages placed the numbers 1 to 12 on their clocks without omissions or additions; 35% completed the clock drawing without error. The mean total clock scores decreased with each successive 5-year age group in both men and women. Regression analysis indicated a significant effect for age (b = -0.15, P <.0001), education (b = 0.05, P =.0001), smoking (b = 0.13, P =.03), and female gender (b = -0.05, P =.05) and a marginally significant effect of nonrheumatoid arthritis (b = 0.05, P =.07) on total clock score. No other measured variable had a significant effect. Cognitively impaired individuals were more likely to be female and older. After adjusting for age and gender, they were also more likely to be hypertensive and to have taken blood pressure medication and less likely to be college graduates, have glaucoma or arthritis, and to have taken vitamin supplements. CONCLUSION: The clock-drawing task is an appealing measure of cognitive function for large epidemiological studies because it is a simple, self-administered test that is easily adapted to mail surveys and correlates with more-detailed and more-time-consuming cognitive screens. Although it is relatively free of influence by language, cultural, or ethnic factors, our study shows that even in a highly educated population, clock drawing is influenced by educational level and other known risk factors for Alzheimer's disease. Thus a clock-drawing task may help predict cognitive frailty and future disability in older people. Such determination can direct high-risk individuals to earlier diagnosis, potential therapies, and better management.

The validation of a mailed health survey for screening of dementia of the Alzheimer's type.

OBJECTIVE: To test the efficacy of a mailed health survey, which included the Clock Completion Test (CCT), to screen previously undiagnosed older adults for dementia of the Alzheimer's type (DAT) in a community-dwelling population, and to determine whether the addition of selected risk factors for Alzheimer's disease (AD) would enhance the screening instrument's operating characteristics. DESIGN: Comparison of the results of a self-administered screen for DAT with the diagnosis of DAT by clinician evaluation or telephone interviews. SETTING: A geriatric assessment clinic. PARTICIPANTS: Three hundred and five women age 65 and older from St. Louis, Missouri. MEASUREMENTS: The sensitivity and specificity of the CCT and the CCT plus risk factors for AD were evaluated using two standards: The Short Blessed Test (SBT) and the physician diagnosis of probable AD using National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria. RESULTS: Sensitivity and specificity for the CCT by SBT criteria were 63% and 79%, respectively. Using the physician's assessment as a criterion, the CCT had better sensitivity (67%) but poorer specificity (69%). Adding two or more risk factors for AD improved sensitivity and specificity to 71% and 89% and, in the physician assessment subgroup, to 75% and 87%, primarily by halving the false-positive rate. CONCLUSION: The combination of the simple, self-administered CCT and two or more AD risk factors is a more effective screening instrument for DAT and potentially preclinical DAT than the CCT alone. However, the instrument may be better suited for use in an office setting because of a poor response rate by subjects with dementia.

Effects of hormone replacement therapy on cognitive performance in elderly women.

OBJECTIVE: To determine the effects of 9 months of hormone replacement therapy (HRT) on cognitive performance in women aged 75 years and older. METHODS: A 9-month randomized, double-blinded, placebo-controlled parallel trial. Fifty-two elderly postmenopausal women (age range 75-91 years) without known contraindications to HRT or evidence of dementia or depression were enrolled. Participants were randomly assigned in a 1:2 ratio to placebo or conjugated estrogens at 0.625 mg/d plus trimonthly medroxyprogesterone acetate at 5 mg/d for 13 days (HRT). Main outcome measures were change from baseline and rate of change from baseline for the following psychometric tests: Verbal Fluency Test, Weschler Paired Associate Learning and 20 min Delayed Recall, Trailmaking A and B Tests, Cancellation Random Letter and Random Form Tests. RESULTS: At baseline, women in the HRT group reported a younger age of onset of menopause and a higher prevalence of hysterectomy, but otherwise did not differ from women in the placebo group. After 9 months of treatment, there were no significant group differences for any of the cognitive performance measures. The lack of an observed group-by-time difference for all cognitive tests remained after controlling for age of onset of menopause, education, and previous hysterectomy. CONCLUSIONS: Although conclusions are limited by small sample size and the relatively short duration of treatment, results suggest that 9 months of estrogen replacement in combination with trimonthly progestin does not improve cognitive performance in women over 75 years who do not have dementia or depression.

Effects of estrogen deficiency on brain function. Implications for the treatment of postmenopausal women.

A growing body of evidence suggests that postmenopausal estrogen deficiency accelerates brain aging and increases the risk of various neurodegenerative processes, including Alzheimer's disease. Recent preclinical and clinical studies have indicated that estrogen has positive effects on brain homeostasis by preserving neural plasticity and the neurotransmitter pathways involved in learning, memory, and balance. In this article, Dr Birge and his coauthors address the effects of estrogen on brain function and discuss their implications for the use of selective estrogen receptor modulators, particularly tamoxifen and raloxifene, in postmenopausal women.

A simple test of central processing speed: an extension of the Short Blessed Test.

OBJECTIVE: To evaluate the efficacy and reliability of a simple measure of central processing speed: the time to recite the months of the year in reverse order, from the Short Blessed Test of Orientation, Concentration, and Memory (SBT). DESIGN: Cross-sectional and longitudinal designs were used to establish validity and test-retest reliability. SETTING: Participants' homes and by telephone interview. PARTICIPANTS: An age-stratified sample of 120 community-dwelling women, aged 67-94, randomly selected from Medicare recipients of the St. Louis Metropolitan Statistical Area. MEASUREMENTS: Dependent variables were the SBT, the Trail Making Test, computer-generated simple and choice reaction time, and time to say the months of the year backward (TMYB). The independent variable was age. RESULTS: Significant Pearson product-moment correlations were obtained for Trail Making and TMYB with a simple and choice reaction time after controlling for age and cognitive status. An exponential relationship was observed between age and TMYB, expressed both cross-sectionally and as rate of change. Test-retest reliability for TMYB was 0.90. CONCLUSIONS: TMYB is a valid and reliable measure of central processing speed that compares favorably to the more elaborate and time-consuming Trail Making B test. Because of its simplicity and ease of administration, this test provides the clinician with a practical measure of central processing speed. TMYB extends the utility of the widely used Short Blessed Test by measuring this additional and important domain of brain function.

The relation between psychometric test performance and physical performance in older adults.

BACKGROUND: The relationship between cognitive function and physical disability in nondemented older adults is not well characterized. The purpose of this study was to determine the relationship between performance on psychometric measures and a modified Physical Performance Test (modified PPT) in older men and women. METHODS: One hundred twenty-five men and women aged 75 years and older, who were enrolled in randomized, controlled trials of exercise or hormone replacement therapy, were recruited from the community-at-large and from congregate living sites. Measures obtained included Trailmaking A and B tests, Cancellation Random Figure tests, Weschler Associate Learning and 20-minute Delayed Recall, Verbal Fluency test, a modified PPT, and self-reports about performance of activities of daily living, medication use, and hospitalization in the previous year. RESULTS: Simple regression analysis demonstrated that speed of performance on the Trailmaking B and Cancellation Random Figure tests was significantly associated with total modified PPT score (r = .29, p < .001 and r = .36,p < .001, respectively). A factor analysis of the psychometric test battery demonstrated that two factors, a cognitive speed factor and a memory factor, accounted for 55% of the variance in cognitive test performance. Hierarchical multiple regression analyses demonstrated that age, number of medications, and the cognitive speed factor were independent predictors of total modified PPT score. CONCLUSIONS: Cognitive processing speed is a significant component of physical frailty in this population, although it accounts for a small percentage of variance on a standardized physical performance test.

Peak aerobic power is an important component of physical performance in older women.

BACKGROUND: The purpose of this study was to determine the relationship between peak aerobic power (VO2peak) and performance on a modified Physical Performance Test (modified PPT) in older women. METHODS: One hundred one women aged 75 years and older seeking enrollment in randomized, controlled trials of exercise and/or hormone replacement therapy were recruited from the community-at-large and from congregate living sites. Measures obtained included VO2peak, a modified PPT, and self-reports about performance of activities of daily living. RESULTS: Simple regression analysis demonstrated that VO2peak was associated with total PPT score (r =.53, p <.001), gait speed (r =.44, p <.001), time to arise from a chair five times (r =.43, p = <.001), and time to climb one flight of stairs (r =.36, p =.007). Multiple regression analysis revealed that the relationships between VO2peak and total modified PPT score, gait speed, chair rise time, and time to climb one flight of stairs were independent of age. CONCLUSIONS: Peak aerobic power is a significant independent predictor of performance on a standardized test of physical function in older women and is an important component of physical frailty in this population.

Hormones and the aging brain.

There is a growing appreciation of the role of ovarian hormones as modulators of neuronal function within the central nervous system. Ovarian failure has long been known to result in reversible changes in mental function, affect, and behavior. Only recently have we begun to appreciate the potential role of these hormones, specifically estrogen, in the aging of the brain and in the expression of Alzheimer's disease. As a consequence of the estrogen deficiency state of the postmenopausal woman, brain aging may be accelerated, resulting in the greater incidence of injurious falls and accidental injuries in women than in men of the same age. This sex steroid deficiency in postmenopausal women may also account for the earlier expression of Alzheimer's disease in women.

HRT preserves increases in bone mineral density and reductions in body fat after a supervised exercise program.

The aims of this study were to confirm our previous finding that hormone-replacement therapy (HRT) augments exercise-induced increases in bone mineral density (BMD) in older women and to determine whether HRT preserves the adaptations when exercise is reduced or discontinued. The study included an 11-mo treatment phase and a 6-mo follow-up phase. Participants, aged 66 +/- 3 yr, were assigned to control (Con; n = 10), exercise (Ex; n = 18), HRT (n = 10), and Ex+HRT (n = 16) groups. HRT was continued during the follow-up. After the treatment phase, changes in total body BMD were -0.5 +/- 1.7, 1.5 +/- 1.4, 1.2 +/- 0.8, and 2.7 +/- 1.2% in Con, Ex, HRT, and Ex+HRT, respectively. Ex+HRT was more effective than HRT in increasing BMD of the total body and tended (P = 0.08) to be more effective at the lumbar spine. Ex+HRT was more effective than Ex in increasing BMD of the total body, lumbar spine, and trochanter. Exercise-induced gains in BMD were preserved during the follow-up only in those individuals on HRT. HRT also attenuated fat accumulation, particularly in the abdominal region, after the exercise program. These findings suggest that HRT is an important adjunct to exercise for the prevention not only of osteoporosis but also of diseases related to abdominal obesity.

Effects of exercise involving predominantly either joint-reaction or ground-reaction forces on bone mineral density in older women.

This study compared the effects of two exercise training programs, 11 months in duration, on bone mineral density (BMD) in older, sedentary women. Thirty-nine women, aged 60-74 years, were assigned to the following groups: (a) a group that performed exercises that introduced stress to the skeleton through ground-reaction forces (GRF) (i.e., walking, jogging, stairs); (b) a group that performed exercises that introduced stress to the skeleton through joint-reaction forces (JRF) (i.e., weight lifting, rowing); or (c) a no-exercise control group. BMD of the whole body, lumbar spine, proximal femur, and distal forearm was assessed five times at approximately 3-month intervals. The GRF and JRF exercise programs resulted in significant and similar increases in BMD of the whole body (2.0 +/- 0.8% and 1.6 +/- 0.4%, respectively), lumbar spine (1.8 +/- 0.7% and 1.5 +/- 0.5%, respectively), and Ward's triangle region of the proximal femur (6.1 +/- 1.5% and 5.1 +/- 2.1%, respectively). There was a significant in BMD of the femoral neck only in response to the GRF exercise program (GRF, 3.5 +/- 0.8%; JRF, -0.2 +/- 0.7%). There were no significant changes in BMD in control subjects. Among all exercisers, there was a significant inverse (r = -0.52, p < 0.01) relationship between increases in whole body BMD and reductions in fat mass, suggesting a dose response effect of exercise on bone mass. Although femoral neck BMD was responsive only to the GRF exercise program, some adaptations (i.e., increase in lean body mass and strength) that were specific to the JRF exercise program may be important in preventing osteoporotic fractures by reducing the risk for falls. It remains to be determined whether all of these benefits can be gained through a training program that combines the different types of exercises employed in this study.

Hormone replacement therapy does not augment gains in muscle strength or fat-free mass in response to weight-bearing exercise.

Lower extremity strength and fat-free mass were examined in 58 postmenopausal women aged 60-72 yr. Subjects were studied before and after an 11-mo control period (n = 16) or before and after an 11-mo weight-bearing exercise training program designed to generate relatively high ground reaction forces (n = 42). Twenty-two of the exercisers initiated hormone replacement therapy (HRT) at the outset of exercise and continued HRT for 11 mo. Hip extension and abduction strength were assessed using a hand-held dynamometer. Force production during knee extension and flexion was evaluated on an isokinetic dynamometer at 60, 90, and 180 degrees/s. Simultaneous knee and hip extension strength was also assessed on a leg press machine. Total body and lower extremity fat-free mass were determined using dual-energy x-ray absorptiometry. There were no significant changes in muscle strength or body composition in control subjects. Both exercise groups had significant increases in fat-free mass and in all strength measures. Fat-free mass increased from 38.8 +/- 4.3 to 39.7 +/- 4.3 kg in the exercise group and from 37.7 +/- 3.9 to 38.9 +/- 4.6 kg in the exercise-plus-HRT group. The average relative increase in strength was 16.2 +/- 11.0% in the exercise group and 17.0 +/- 13.0% in the exercise-plus-HRT group. Women receiving HRT did not have a gain in fat-free mass or in strength over and above that demonstrated by the women not on HRT. Our results provide evidence that HRT does not augment the increases in muscle mass or strength that occur in response to weight-bearing exercise in older women.

The role of estrogen in the treatment of Alzheimer's disease.

Multiple factors appear to contribute to the expression of Alzheimer's disease (AD). About 30 percent of cases of dementia of the Alzheimer's type can be attributed to genetic factors. These observations raise the possibility of identifying multiple interventions that may modify the disease process and, therefore, the clinical expression of the dementia. Prominent among factors that may contribute to dementia and, specifically, to dementia of the Alzheimer's type is cerebral vascular disease. Estrogen is a potent factor that not only prevents vascular disease but also improves blood flow in diseased vessels, including blood flow in regions on the brain affected by AD. Estrogen also has direct effects on neuronal function that may play an important role not only in the preservation of neurons but in repair of neurons damaged by disease process. These effects of estrogen on the CNS suggest that the hormone may be effective not only in the prevention of dementia but also in its treatment. The results of clinical trials, reviewed in this presentation, are very promising but are limited by the paucity of subjects and often the lack of adequate controls. Larger, randomized, placebo-controlled trials are needed to definitively establish the efficacy of estrogen in the treatment of dementia of the Alzheimer's type.

Serum leptin levels are reduced in response to exercise training, but not hormone replacement therapy, in older women.

The aim of this study was to evaluate the effects of exercise training and hormone replacement therapy (HRT) on serum leptin levels in older women. Previously sedentary, healthy women, aged 60-72 yr, were assigned to control (n = 16), exercise (n = 17), HRT (n = 15), or exercise + HRT (n = 13) groups. Exercise training consisted of a 2-month flexibility-exercise program followed by a 9-month exercise program that included walking, jogging, and stair climbing. HRT consisted of 11 months of continuous conjugated estrogens (0.625 mg/day) and medroxyprogesterone acetate (5 mg/day) for 13 days every third month. Body composition was assessed by dual-energy x-ray absorptiometry, and serum insulin levels were measured in the fasted state and in response to a glucose challenge. Leptin levels were reduced by 23 +/- 25% and 22 +/- 27% (both P < 0.01) in response to exercise and exercise + HRT, respectively. There was no effect of HRT on leptin. Fat mass was the strongest predictor of serum leptin concentration, both before (r = 0.81; P < 0.001) and after (r = 0.85; P < 0.001) the study period, and the change in fat mass in the exercisers was significantly correlated with the change in leptin (r = 0.55; P < 0.01). There did not seem to be an effect of exercise, independent of the reduction in fat mass, on leptin. Insulin levels were significantly correlated with leptin levels, but this was not independent of the association with adiposity. The curvilinear relationship between leptin level and fat mass and the finding that the ratio of leptin mass to fat mass decreased after weight loss suggest that fat cell size is an important determinant of circulating leptin levels.

Is there a role for estrogen replacement therapy in the prevention and treatment of dementia?

Studies in experimental animal models provide a convincing rationale for a role for ERT in the treatment and prevention of dementia. These studies establish the role of estrogen in the regeneration and preservation of neuronal elements within the CNS that are analogous to those regions of the brain most sensitive to the neurodegenerative changes associated with AD. Furthermore, behavioral studies in these animals establish a correlation between the hormone dependent changes in the neuronal architecture and learning and memory. However, extrapolation of these studies to post-menopausal women must be done with caution. Surgical and natural loss of ovarian function does not result in a clinically relevant decline in cognitive function over the short term (1 to 2 decades) or ever in some women. The modest changes that are observed may relate to the hormone's effect on neurotransmitter levels or their receptors. Although Singh et al. noted changes in neurotransmitter concentrations 5 weeks after ovariectomy, changes in cognitive performance in their rat model did not become significant until 28 weeks after ovariectomy--the equivalent of approximately 2 decades of human life. Except for the familial forms of the disease, AD is rarely seen in the first 2 decades after the menopause. However, by the third decade after the menopause, 50% of women can be expected to manifest the histopathological changes of AD. Approximately half of these women are without clinical evidence of disease. Thus, the neurodegenerative process of AD probably precedes by many years the age of onset of the disease. We do not know what factors contribute to the selective neuronal injury which, over time, eventually leads to the neuronal loss and reduced synaptic density that result in the cognitive impairment of AD. At this time we can only speculate as to estrogen's role in modifying this process. Data from experimental animal models suggest that estrogen deficiency would selectively increase the vulnerability of estrogen-responsive neural elements, for example, the cholinergic neurons of the basal forebrain and hippocampus--offulnerability mediated perhaps by the reduced expression of neurotrophic factors, decreased clearance of the amyloid protein, and/or reduced cerebral blood flow that are associated with estrogen deficiency. The brain's ability to adapt to the neuronal loss by stimulating axonal and synaptic regeneration would also be impaired by estrogen deficiency as suggested by estrogen's ability to restore the synaptic density of lesioned brains of ovariectomized animals. Thus, estrogen deficiency, like the apolipoprotein E4 allele, can be considered not a cause of AD but one of perhaps several factors modifying the neuronal injury and loss leading to AD. The limited epidemiologic data and intervention trials currently available are consistent with this interpretation. Because of the urgency and enormity of the problem of dementia in our aging society, there would now appear to be sufficient reason to allocate the resources needed to conduct the appropriate clinical trials to determine estrogen's efficacy in both the treatment and prevention of this devastating condition. These trials are needed so that women and their physicians can adequately weigh the risks and benefits of hormone replacement for the treatment and, more importantly, the prevention of dementia.

Effects of endurance exercise and hormone replacement therapy on serum lipids in older women.

OBJECTIVE: To determine the effects of 11 months of exercise training and hormone replacement therapy (HRT), alone or in combination, on serum lipids and lipoproteins, in postmenopausal women. DESIGN: Controlled, prospective, 11-month clinical trial. Healthy postmenopausal women (n = 71, age range 60-72 yrs) were assigned to four groups in a 2 X 2 design (control, exercise, HRT, exercise + HRT). SETTING: Large, midwestern urban community; subjects were recruited from the community-at-large. The exercise program was conducted at a university exercise facility. INTERVENTIONS: HRT consisted of conjugated estrogens at 0.625 mg/day and trimonthly medroxyprogesterone acetate 5 mg/day for 13 days. Exercise consisted of 2 months of low intensity exercise followed by 9 months of vigorous exercise for 45 min/day, 3 or more days/week, at 65-85% of maximal heart rate. MEASUREMENTS: Maximal aerobic power (VO2max), resting blood pressure, body composition, serum lipids and lipoproteins, and dietary intake at baseline and after 11 months. MAIN RESULTS: At the end of 11 months, subjects in the exercise group had decrease total cholesterol (TC; P < .01) and LDL-cholesterol (LDL-C; P < .05), but there was no change in HDL-cholesterol (HDL-C) or triglycerides. Women in the HRT group had decreased LDL-C (P < .001) and increased HDL-C (P < .01) and triglycerides (P < .01), but there was no change in TC. Exercise + HRT subjects had decreased TC (P < .05) and LDL-C (P < .001), and increased HDL-C (P < .001); exercise prevented the HRT-related increase in triglycerides. CONCLUSIONS: Endurance exercise training and HRT have independent and complimentary effects on serum lipids profiles in healthy postmenopausal women. Such effects are likely to reduce the risk of cardiovascular morbidity in this population.