Predictors of maintaining cognitive function in older adults: the Health ABC study.

BACKGROUND: Although several risk factors for cognitive decline have been identified, much less is known about factors that predict maintenance of cognitive function in advanced age. METHODS: We studied 2,509 well-functioning black and white elders enrolled in a prospective study. Cognitive function was measured using the Modified Mini-Mental State Examination at baseline and years 3, 5, and 8. Random effects models were used to classify participants as cognitive maintainers (cognitive change slope > or = 0), minor decliners (slope < 0 and > 1 SD below mean), or major decliners (slope < or = 1 SD below mean). Logistic regression was used to identify domain-specific factors associated with being a maintainer vs a minor decliner. RESULTS: Over 8 years, 30% of the participants maintained cognitive function, 53% showed minor decline, and 16% had major cognitive decline. In the multivariate model, baseline variables significantly associated with being a maintainer vs a minor decliner were age (odds ratio [OR] = 0.65, 95% confidence interval [CI] 0.55-0.77 per 5 years), white race (OR = 1.72, 95% CI 1.30-2.28), high school education level or greater (OR = 2.75, 95% CI 1.78-4.26), ninth grade literacy level or greater (OR = 4.85, 95% CI 3.00-7.87), weekly moderate/vigorous exercise (OR = 1.31, 95% CI 1.06-1.62), and not smoking (OR = 1.84, 95% CI 1.14-2.97). Variables associated with major cognitive decline compared to minor cognitive decline are reported. CONCLUSION: Elders who maintain cognitive function have a unique profile that differentiates them from those with minor decline. Importantly, some of these factors are modifiable and thus may be implemented in prevention programs to promote successful cognitive aging. Further, factors associated with maintenance may differ from factors associated with major cognitive decline, which may impact prevention vs treatment strategies.

Dietary factors in relation to daily activity energy expenditure and mortality among older adults.

OBJECTIVES: To examine the association between dietary factors to daily activity energy expenditure (DAEE) and mortality among older adults. DESIGN AND SETTING: A sub-study of Health, Aging, and Body Composition study. PARTICIPANTS: 298 older participants (aged 70-82 years) in the Health, Aging, and Body Composition Energy Expenditure sub-study. MEASUREMENTS: Dietary factors, DAEE, and all-cause mortality were measured in 298 older participants. Dietary factors include dietary intake assessed by the Block Food Frequency Questionnaire (FFQ), Healthy Eating Index (HEI), and self-reported appetite and enjoyment of eating. DAEE was assessed using doubly labeled water. All-cause mortality was evaluated over a 9 year period. RESULTS: Participants in the highest tertile of DAEE were more likely to be men and to report having a 'good' appetite; BMI among men, proportion married, IL-6 and CRP levels and energy intake were also higher. Fewer black participants were in the 'good' HEI category. Participants in the 'good' HEI category had higher cognitive scores and a higher education level. Participants who reported improvement in their appetite as well as participants who reported a 'good' appetite were at lower risk for mortality (HR (95% CI): 0.42 (0.24-0.74) and 0.50 (0.26-0.88), respectively) even after adjusting for DAEE, demographic, nutritional and health indices. CONCLUSIONS: We showed an association between DAEE and appetite and mortality among well-functioning, community-dwelling older adults. These findings may have some practical use for the health providers. Inclusion of a question regarding appetite of an elderly patient may provide important information regarding risk for health deterioration and mortality.

The association between weight history and physical performance in the Health, Aging and Body Composition study.

OBJECTIVE: Although the association between current obesity and physical disability is well known, the cumulative effect of obesity is unknown. Using data from the Health, Aging and Body Composition study, we examined the association between weight history in young and middle adulthood and weight status in late adulthood with physical performance in late adulthood. DESIGN: Longitudinal cohort study. SUBJECTS: White and black men and women aged 70-79 years at study baseline (n=2803). MEASURES: Body mass index (BMI; kg/m(2)) was calculated using recalled height at age 25 and weight at age 25 and 50 and measured height and weight at ages 70-79. Physical performance at ages 70-79 was assessed using a short physical performance battery (SPPB) and a 400-m walk test. RESULTS: In this well-functioning cohort, approximately 24% of men and 8% of women reported being overweight or obese (BMI > or =25 kg/m(2)) at age 25, 51% of men and 37% of women reported being overweight or obese at age 50, and 69% of men and 66% of women were overweight or obese at ages 70-79. Men and women who were obese (BMI > or =30 kg/m(2)) at ages 25, 50 and 70-79 had significantly worse SPPB scores and 400-m walk times than those who were normal weight. Women who were overweight (BMI 25-29.9 kg/m(2)) at ages 25, 50 and 70-79 also had significantly worse physical performance. Furthermore, men and women who had a history of being overweight or obese at ages 25 or 50 had worse physical performance compared to those who were normal weight throughout or who were overweight or obese at ages 70-79 but not in midlife or earlier. CONCLUSIONS: Maintaining a healthy body weight throughout adulthood may play a role in preventing or delaying the onset of physical disability.

Cognitive ability is associated with suspected reporting errors on food frequency questionnaires.

OBJECTIVE: To examine potential for bias in reported total energy intake on a Food Frequency Questionnaire (FFQ) among older adults. DESIGN: Longitudinal cohort study. SUBJECTS/SETTING: 2,706 Community-dwelling Black and White older adults, aged 70-79 years, enrolled in the Health, Aging, and Body Composition study. Multivariate logistic regression analyses were conducted with potential errors on reported total energy intake on the Food Frequency Questionnaire (FFQ) as the outcome variable and with cognitive ability, measured by the Modified Mini Mental State Exam (3MS) as the primary independent variable. The regression model controlled for site, race, gender, age, body size, and physical activity. Separate models were fit using 3MS as a continuous variable and for multiple 3MS cutpoints. All models revealed similar findings. RESULTS: Cognitive ability was inversely associated with potential errors in reporting total energy intake, whereby a five-point increase in 3MS scores was associated with a 14% decreased likelihood of reporting errors (Odds Ratio=0.86, 95% Confidence Interval: 0.77, 0.95). Additionally, compared to White women, White men were 2 times more likely, and Black women and Black men were 3 times more likely, to have errors in reporting total energy intake. CONCLUSION: This study provides evidence that for older adults, lower cognition scores are associated with increased potential errors in reporting total energy intake. APPLICATIONS: Dietary reporting from older adults may be inaccurate due to cognitive deficits. A brief assessment of cognitive function may assist clinicians in dietary evaluations and recommendation and may benefit studies using FFQ data where the measure of cognitive function could be utilized to stratify data analyses and conduct sensitivity analyses.

Characterization of the effects of nonspecific xenon-protein interactions on (129)Xe chemical shifts in aqueous solution: further development of xenon as a biomolecular probe.

The sensitivity of (129)Xe chemical shifts to weak nonspecific xenon-protein interactions has suggested the use of xenon to probe biomolecular structure and interactions. The realization of this potential necessitates a further understanding of how different macromolecular properties influence the (129)Xe chemical shift in aqueous solution. Toward this goal, we have acquired (129)Xe NMR spectra of xenon dissolved in amino acid, peptide, and protein solutions under both native and denaturing conditions. In general, these cosolutes induce (129)Xe chemical shifts that are downfield relative to the shift in water, as they deshield the xenon nucleus through weak, diffusion-mediated interactions. Correlations between the extent of deshielding and molecular properties including chemical identity, structure, and charge are reported. Xenon deshielding was found to depend linearly on protein size under denaturing solution conditions; the denaturant itself has a characteristic effect on the (129)Xe chemical shift that likely results from a change in the xenon solvation shell structure. In native protein solutions, contributions to the overall (129)Xe chemical shift arise from the presence of weak xenon binding either in cavities or at the protein surface. Potential applications of xenon as a probe of biological systems including the detection of conformational changes and the possible quantification of buried surface area at protein-protein interfaces are discussed.

Functionalized xenon as a biosensor.

The detection of biological molecules and their interactions is a significant component of modern biomedical research. In current biosensor technologies, simultaneous detection is limited to a small number of analytes by the spectral overlap of their signals. We have developed an NMR-based xenon biosensor that capitalizes on the enhanced signal-to-noise, spectral simplicity, and chemical-shift sensitivity of laser-polarized xenon to detect specific biomolecules at the level of tens of nanomoles. We present results using xenon "functionalized" by a biotin-modified supramolecular cage to detect biotin-avidin binding. This biosensor methodology can be extended to a multiplexing assay for multiple analytes.

Evidence of nonspecific surface interactions between laser-polarized xenon and myoglobin in solution.

The high sensitivity of the magnetic resonance properties of xenon to its local chemical environment and the large (129)Xe NMR signals attainable through optical pumping have motivated the use of xenon as a probe of macromolecular structure and dynamics. In the present work, we report evidence for nonspecific interactions between xenon and the exterior of myoglobin in aqueous solution, in addition to a previously reported internal binding interaction. (129)Xe chemical shift measurements in denatured myoglobin solutions and under native conditions with varying xenon concentrations confirm the presence of nonspecific interactions. Titration data are modeled quantitatively with treatment of the nonspecific interactions as weak binding sites. Using laser-polarized xenon to measure (129)Xe spin-lattice relaxation times (T(1)), we observed a shorter T(1) in the presence of 1 mM denatured apomyoglobin in 6 M deuterated urea (T(1) = 59 +/- 1 s) compared with that in 6 M deuterated urea alone (T(1) = 291 +/- 2 s), suggesting that nonspecific xenon-protein interactions can enhance (129)Xe relaxation. An even shorter T(1) was measured in 1 mM apomyoglobin in D(2)O (T(1) = 15 +/- 0.3 s), compared with that in D(2)O alone (T(1) = 506 +/- 5 s). This difference in relaxation efficiency likely results from couplings between laser-polarized xenon and protons in the binding cavity of apomyoglobin that may permit the transfer of polarization between these nuclei via the nuclear Overhauser effect.

Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial.

CONTEXT: Alendronate sodium reduces fracture risk in postmenopausal women who have vertebral fractures, but its effects on fracture risk have not been studied for women without vertebral fractures. OBJECTIVE: To test the hypothesis that 4 years of alendronate would decrease the risk of clinical and vertebral fractures in women who have low bone mineral density (BMD) but no vertebral fractures. DESIGN: Randomized, blinded, placebo-controlled trial. SETTING: Eleven community-based clinical research centers. SUBJECTS: Women aged 54 to 81 years with a femoral neck BMD of 0.68 g/cm2 or less (Hologic Inc, Waltham, Mass) but no vertebral fracture; 4432 were randomized to alendronate or placebo and 4272 (96%) completed outcome measurements at the final visit (an average of 4.2 years later). INTERVENTION: All participants reporting calcium intakes of 1000 mg/d or less received a supplement containing 500 mg of calcium and 250 IU of cholecalciferol. Subjects were randomly assigned to either placebo or 5 mg/d of alendronate sodium for 2 years followed by 10 mg/d for the remainder of the trial. MAIN OUTCOME MEASURES: Clinical fractures confirmed by x-ray reports, new vertebral deformities detected by morphometric measurements on radiographs, and BMD measured by dual x-ray absorptiometry. RESULTS: Alendronate increased BMD at all sites studied (P<.001) and reduced clinical fractures from 312 in the placebo group to 272 in the intervention group, but not significantly so (14% reduction; relative hazard [RH], 0.86; 95% confidence interval [CI], 0.73-1.01). Alendronate reduced clinical fractures by 36% in women with baseline osteoporosis at the femoral neck (>2.5 SDs below the normal young adult mean; RH, 0.64; 95% CI, 0.50-0.82; treatment-control difference, 6.5%; number needed to treat [NNT], 15), but there was no significant reduction among those with higher BMD (RH, 1.08; 95% CI, 0.87-1.35). Alendronate decreased the risk of radiographic vertebral fractures by 44% overall (relative risk, 0.56; 95% CI, 0.39-0.80; treatment-control difference, 1.7%; NNT, 60). Alendronate did not increase the risk of gastrointestinal or other adverse effects. CONCLUSIONS: In women with low BMD but without vertebral fractures, 4 years of alendronate safely increased BMD and decreased the risk of first vertebral deformity. Alendronate significantly reduced the risk of clinical fractures among women with osteoporosis but not among women with higher BMD.

Efficacy of screening mammography. A meta-analysis.

OBJECTIVE: To determine the efficacy of screening mammography by age, number of mammographic views per screen, screening interval, and duration of follow-up. DESIGN: Literature review and meta-analysis. DATA IDENTIFICATION AND ANALYSIS: Literature search of English-language studies reported from January 1966 to October 31, 1993, using MEDLINE, manual literature review, and consultation with experts. A total of 13 studies were selected, and their results were combined using meta-analytic techniques based on the assumption of fixed effects. MAIN RESULTS: The overall summary relative risk (RR) estimate for breast cancer mortality for women aged 50 to 74 years undergoing screening mammography compared with those who did not was 0.74 (95% confidence interval [CI], 0.66 to 0.83). The magnitude of the benefit in this age group was similar regardless of number of mammographic views per screen, screening interval, or duration of follow-up. In contrast, none of the summary RR estimates for women aged 40 to 49 years was significantly less than 1.0, irrespective of screening intervention or duration of follow-up. The overall summary RR estimate in women aged 40 to 49 years was 0.93 (95% CI, 0.76 to 1.13); the summary RR estimate for those studies that used two-view mammography was 0.87 (95% CI, 0.68 to 1.12) compared with 1.02 (95% CI, 0.73 to 1.44) for those studies that used one-view mammography, and for those studies with 7 to 9 years of follow-up, the summary RR estimate was 1.02 (95% CI, 0.82 to 1.27) compared with 0.83 (95% CI, 0.65 to 1.06) for those studies with 10 to 12 years of follow-up. CONCLUSION: Screening mammography significantly reduces breast cancer mortality in women aged 50 to 74 years after 7 to 9 years of follow-up, regardless of screening interval or number of mammographic views per screen. There is no reduction in breast cancer mortality in women aged 40 to 49 years after 7 to 9 years of follow-up. Screening mammography may be effective in reducing breast cancer mortality in women aged 40 to 49 years after 10 to 12 years of follow-up, but the same benefit could probably be achieved by beginning screening at menopause or 50 years of age.

Increasing the completion of the durable power of attorney for health care. A randomized, controlled trial.

OBJECTIVE: Wider use of written advance directives may prevent many ethical dilemmas about life-sustaining interventions for patients who have lost decision-making capacity. We investigated whether a simple educational intervention increased patient completion of the durable power of attorney for health care. DESIGN: A randomized, controlled trial. SETTING: A health maintenance organization. SUBJECTS: All patients aged 65 years and older and discharged from a hospital between January 1991 and May 1991 (n = 1101) were randomized to either an intervention group or a control group. INTERVENTION: An educational pamphlet on the durable power of attorney for health care and a durable power of attorney for health care form were mailed to all patients in the intervention group. The control group received conventional care only. MAIN OUTCOME MEASURE: Completion of the durable power of attorney for health care form. RESULTS: There were no significant baseline differences between the intervention group and the control group. Following our intervention, 18.5% of the subjects in the experimental group completed a durable power of attorney for health care form, compared with 0.4% of the control group (P < .0001). CONCLUSIONS: A simple educational intervention significantly increased the completion of the durable power of attorney for health care. Our findings should stimulate further efforts to empower patients to make informed decisions about their health care.

Hormone therapy to prevent disease and prolong life in postmenopausal women.

PURPOSE: To critically review the risks and benefits of hormone therapy for asymptomatic postmenopausal women who are considering long-term hormone therapy to prevent disease or to prolong life. DATA SOURCES: Review of the English-language literature since 1970 on the effect of estrogen therapy and estrogen plus progestin therapy on endometrial cancer, breast cancer, coronary heart disease, osteoporosis, and stroke. We used standard meta-analytic statistical methods to pool estimates from studies to determine summary relative risks for these diseases in hormone users and modified lifetable methods to estimate changes in lifetime probability and life expectancy due to use of hormone regimens. RESULTS: There is evidence that estrogen therapy decreases risk for coronary heart disease and for hip fracture, but long-term estrogen therapy increases risk for endometrial cancer and may be associated with a small increase in risk for breast cancer. The increase in endometrial cancer risk can probably be avoided by adding a progestin to the estrogen regimen for women who have a uterus, but the effects of combination hormones on risk for other diseases has not been adequately studied. We present estimates for changes in lifetime probabilities of disease and life expectancy due to hormone therapy in women who have had a hysterectomy; with coronary heart disease; and at increased risk for coronary heart disease, hip fracture, and breast cancer. CONCLUSIONS: Hormone therapy should probably be recommended for women who have had a hysterectomy and for those with coronary heart disease or at high risk for coronary heart disease. For other women, the best course of action is unclear.

Mortality following unilateral twin interstitial ectopic pregnancy. A case report.

Twin ectopic pregnancy is an uncommon event, usually occurring as simultaneous intrauterine and tubal gestations. Interstitial implantation of an ectopic pregnancy is also a rare event, associated with a high mortality rate. Twin interstitial pregnancy has been previously reported only three times in the English literature. We report a recent case of unilateral twin interstitial ectopic pregnancy that resulted in maternal death and review the literature with regard to both ectopic pregnancy and factors associated with mortality from interstitial implantation.

Results of bone densitometry affect women's decisions about taking measures to prevent fractures.

OBJECTIVE: To describe how the results of bone densitometry affect women's decisions about measures to prevent fractures and to determine whether labeling women as having below-normal bone density has adverse effects. DESIGN: Mail survey of a random sample of women. SETTING: Four community hospitals in the San Francisco Bay area. PATIENTS: A total of 261 women (response rate, 81.3%) who had undergone bone densitometry. MEASUREMENTS: Bone densitometry and self-report of changes in attitude and behaviors. RESULTS: Fifty-three percent of the women reported that their first bone density measurements were below normal, and 44% said that they were diagnosed as having osteoporosis on the basis of their test results. Women who reported that their bone density measurements were below normal were much more likely than women with normal results to begin some type of measure to prevent fractures (94% compared with 56%; P less than 0.01), to start hormone therapy (38% compared with 8%; P less than 0.01), and to take precautions to avoid falling (50% compared with 9%; P less than 0.01). Women reporting low bone density, however, also became more fearful of falling (38% compared with 2%; P less than 0.01) and limited their activities to avoid falling (24% compared with 2%; P less than 0.01). CONCLUSIONS: The results of bone densitometry substantially influence women's decisions about beginning estrogen replacement therapy and other preventive measures for osteoporotic fractures. The potential effects of labeling a woman as having below-normal bone density need to be considered before densitometry is widely used for unselective screening of women.

Management of the pregnant patient with a cerebral venous angioma: a report of two cases.

Though there is a large body of knowledge regarding the management of pregnant women with arterial lesions in the central nervous system, little information is available on venous malformations. We report our experience with two pregnant patients with cerebral venous angiomas. These lesions are usually asymptomatic and only rarely cause seizures or subarachnoid hemorrhage. Based on our experience and literature review, we suggest that patients with venous angiomas without a history of hemorrhage can safely undergo labor and vaginal delivery.

High blood cholesterol in elderly men and the excess risk for coronary heart disease.

OBJECTIVE: To determine whether high blood cholesterol is an important risk factor for mortality from coronary heart disease in elderly men. DESIGN: Cohort study with a mean follow-up of 10.1 years. SETTING: A health maintenance organization. PATIENTS: The cohort included 2746 white men 60 to 79 years of age who had no self-reported history of coronary heart disease. MEASUREMENT AND MAIN RESULTS: A total of 260 deaths occurred during 27,842 person-years of follow-up. The relative risk for mortality from coronary heart disease in men 60 to 79 years of age in the highest serum cholesterol quartile was 1.5 (95% CI, 1.2 to 2.0) compared with those in the three lower quartiles combined. The relative risk did not change greatly with age, ranging from 1.4 in men 60 to 64 years of age to 1.7 in men 75 to 79 years of age. However, because mortality from coronary heart disease increased with age, the excess risk for such mortality attributable to elevated serum cholesterol levels increased fivefold over these 20 years, from 2.2 deaths per 1000 person-years to 11.3 deaths per 1000 person-years. CONCLUSIONS: Our results support those of other observational studies in elderly men. If treatment of high blood cholesterol is as effective in reducing cholesterol-related risk for coronary heart disease after 65 years of age as it is in middle-aged men, it might actually produce greater reductions in mortality due to coronary heart disease. A clinical trial is needed to confirm this extrapolation.

The future of hip fractures in the United States. Numbers, costs, and potential effects of postmenopausal estrogen.

Because of the increasing number of elderly people in the United States, the total number of hip fractures in persons 50 years and older will rise from 238,000 to 512,000 by the year 2040, with a concomitant increase in avoidable deaths, disability, and medical costs. The total annual cost of hip fractures (in 1984 dollars) will increase from approximately 7.2 billion dollars currently to 16 billion dollars in the year 2040. Universal use of estrogen therapy by postmenopausal white women may slow but not prevent this rise in hip fractures. New, effective, and widely applicable strategies to prevent hip fractures are urgently needed.

Lifetime risks of hip, Colles', or vertebral fracture and coronary heart disease among white postmenopausal women.

Lifetime risk is a useful way to estimate and compare the risk of various conditions. Hip fractures, Colles' fractures, and coronary heart disease, and breast and endometrial cancers are important conditions in postmenopausal women that might be influenced by the use of hormone replacement therapy. We used population-based data to estimate a woman's lifetime risk of suffering a hip, Colles', or vertebral fracture and her risk of dying of coronary heart disease. A 50-year-old white woman has a 16% risk of suffering a hip fracture, a 15% risk of suffering a Colles' fracture, and a 32% risk of suffering a vertebral fracture during her remaining lifetime. These risks exceed her risk of developing breast or endometrial cancer. She has a 31% risk of dying of coronary heart disease, which is about 10 times greater than her risk of dying of hip fractures or breast cancer. These lifetime risks provide a useful description of the comparative risks of conditions that might be influenced by postmenopausal hormone therapy.

The cost-effectiveness of counseling smokers to quit.

Cigarette smoking is the most important preventable cause of death in the United States. Surveys of patients, however, suggest that many physicians do not routinely counsel smokers to quit. Because physicians may not consider counseling against smoking to be as worthwhile as other medical practices, we examined its cost-effectiveness. We based our estimates of the effectiveness of physician counseling on published reports of randomized trials and our estimates of its cost on average charges for physician office visits. Our results indicate that the cost-effectiveness of brief advice during routine office visits ranges from $705 to $988 per year of life saved for men and from $1204 to $2058 for women. Follow-up visits about smoking appear to be similarly cost-effective. Physician counseling against smoking, therefore, is at least as cost-effective as several other preventive medical practices and should be a routine part of health care for patients who smoke.