The Alternative Healthy Eating Index and Physical Function Impairment in Men.

OBJECTIVES: Physical function is increasingly recognized as integral to healthy aging, in particular as a core component of mobility and independent living in older adults. Thus, it is important to identify strategies for the prevention of physical function decline. DESIGN: Longitudinal cohort study. SETTING AND PARTICIPANTS: A total of 12,658 men from the Health Professionals Follow-Up Study were followed from 2008-2012. MEASUREMENTS: We examined the association between the Alternative Healthy Eating Index-2010 (AHEI), a measure of diet quality combining 11 dietary components (vegetables, fruits, nuts and legumes, red and processed meats, sugar-sweetened beverages and fruit juices, alcohol, whole grains, omega-3 fatty acids, polyunsaturated fatty acids, trans fatty acids, sodium), and impairment in physical function, as measured by the SF-36. Multivariable logistic regression models were used to estimate the odds ratios (OR) and 95% confidence intervals (CI) of impairment in physical function. RESULTS: In the multivariable-adjusted model, each 10-point increase in total AHEI score was associated with a 10% lower odds of impairment in physical function (OR=0.90, 95% CI: 0.86,0.95), and in the categorical analysis, men with AHEI scores in the top quintile had a 26% lower odds (OR=0.74, 95% CI:0.63,0.86) compared with men in the bottom quintile. For individual AHEI components, higher intake of vegetables (p-trend=0.01), nuts and legumes (p-trend<0.01), polyunsaturated fatty acids (p-trend<0.01) and lower intake of red and processed meats (p-trend=0.03) and sugar-sweetened beverages (p-trend=0.01) were significantly associated with lower odds of physical impairment. For specific foods, higher consumption of lettuce, broccoli, blueberries, peanuts, walnuts and other nuts were associated with lower odds of impairment. CONCLUSIONS: In this large cohort of older men, better overall diet quality was significantly associated with a lower odds of impairment in physical function. Given the value of physical function to healthy aging and quality of life, this may represent a particularly compelling public health rationale for older men to improve their diet.

Reduction in physical function in women after venous thromboembolism.

Essentials The association of venous thromboembolism (VTE) with subsequent physical function remains unclear. We prospectively evaluated this relationship among women from the Nurses' Health Studies. We found a decline in physical function over four years in women with incident VTE. This decline was somewhat greater among women specifically reporting a pulmonary embolism. SUMMARY: Background Physical function is integral to healthy aging; however, limited research has examined the association of venous thromboembolism(VTE) with subsequent physical function. Objectives To prospectively evaluate the relationship between VTE and decline in physical function among 80 836 women from the Nurses' Health Study(NHS), ages 46-72 in 1992, and 84 304 women from the Nurses' Health Study II(NHS II), ages 29-48 in 1993. Methods Physical function was measured by the Medical Outcomes Short Form-36 physical function scale, administered every 4 years. We compared change in physical function for women with vs. without an incident VTE in each 4-year follow-up period using multivariable linear regression. Results We observed a decline in physical function over 4 years when comparing women with vs. those without incident VTE in both older (NHS) and younger (NHS II) women (multivariable-adjusted mean difference NHS, -6.5 points [95% CI -7.4, -5.6] per 4 years; NHS II, -3.8 [95% CI -5.6, -2.0]). This difference appeared greater among women specifically reporting a pulmonary embolism (NHS, -7.4 [95% CI -8.7, -6.1]; NHS II, -4.8 [95% CI -6.8, -2.8]), and was equivalent to 6.2 years of aging. Whereas longer-term slopes of physical function decline following a VTE were not different from the slopes of decline in women without a VTE, the absolute level of physical function of women with VTE was worse at the end of follow-up compared to women without VTE. Conclusions In this prospective cohort, incident VTE was strongly associated with an acute decline in physical function. These results suggest it may be clinically important to consider approaches to ameliorating functional deficits shortly after VTE diagnosis.

Mediterranean diet and hip fracture incidence among older adults: the CHANCES project.

The association between adherence to Mediterranean diet (MD) and hip fracture incidence is not yet established. In a diverse population of elderly, increased adherence to MD was associated with lower hip fracture incidence. Except preventing major chronic diseases, adhering to MD might have additional benefits in lowering hip fracture risk. INTRODUCTION: Hip fractures constitute a major public health problem among older adults. Latest evidence links adherence to Mediterranean diet (MD) with reduced hip fracture risk, but still more research is needed to elucidate this relationship. The potential association of adherence to MD with hip fracture incidence was explored among older adults. METHODS: A total of 140,775 adults (116,176 women, 24,599 men) 60 years and older, from five cohorts from Europe and the USA, were followed-up for 1,896,219 person-years experiencing 5454 hip fractures. Diet was assessed at baseline by validated, cohort-specific, food-frequency questionnaires, and hip fractures were ascertained through patient registers or telephone interviews/questionnaires. Adherence to MD was evaluated by a scoring system on a 10-point scale modified to be applied also to non-Mediterranean populations. In order to evaluate the association between MD and hip fracture incidence, cohort-specific hazard ratios (HR), adjusted for potential confounders, were estimated using Cox proportional-hazards regression and pooled estimates were subsequently derived implementing random-effects meta-analysis. RESULTS: A two-point increase in the score was associated with a significant 4% decrease in hip fracture risk (pooled adjusted HR 0.96; 95% confidence interval (95% CI) 0.92-0.99, pheterogeneity = 0.446). In categorical analyses, hip fracture risk was lower among men and women with moderate (HR 0.93; 95% CI 0.87-0.99) and high (HR 0.94; 95% CI 0.87-1.01) adherence to the score compared with those with low adherence. CONCLUSIONS: In this large sample of older adults from Europe and the USA, increased adherence to MD was associated with lower hip fracture incidence.

Association of Long-Term Adherence to the MIND Diet with Cognitive Function and Cognitive Decline in American Women.

OBJECTIVES: There is increasing attention for dietary patterns as a potential strategy to prevent cognitive decline. We examined the association between adherence to a recently developed Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet with cognitive function and cognitive decline, taking into account the interaction between the apolipoprotein E ε4 genotype and the MIND diet. DESIGN: Population-based prospective cohort study. PARTICIPANTS: A total of 16,058 older women aged 70 and over from the Nurses' Health Study. MEASUREMENTS: Dietary intake was assessed five times between 1984 and 1998 with a 116-item Food Frequency Questionnaire. The MIND score includes ten brain-healthy foods and five unhealthy foods. Cognition was assessed four times by telephone from 1995 to 2001 (baseline) with the Telephone Interview for Cognitive Status (TICS) and by calculating composite scores of verbal memory and global cognition. Linear regression modelling and linear mixed modelling were used to examine the associations of adherence to the MIND diet with average cognitive function and cognitive change over six years, respectively. RESULTS: Greater long-term adherence to the MIND diet was associated with a better verbal memory score (multivariable-adjusted mean differences between extreme MIND quintiles=0.04 (95%CI 0.01-0.07), p-trend=0.006), but not with cognitive decline over 6 years in global cognition, verbal memory or TICS. CONCLUSION: Long-term adherence to the MIND diet was moderately associated with better verbal memory in later life. Future studies should address this association within populations at greater risk of cognitive decline.

Excess mortality after hip fracture in elderly persons from Europe and the USA: the CHANCES project.

BACKGROUND: Hip fractures are associated with diminished quality of life and survival especially amongst the elderly. OBJECTIVE: All-cause mortality after hip fracture was investigated to assess its magnitude. METHODS: A total of 122 808 participants from eight cohorts in Europe and the USA were followed up for a mean of 12.6 years, accumulating 4273 incident hip fractures and 27 999 deaths. Incident hip fractures were assessed through telephone interviews/questionnaires or national inpatient/fracture registries, and causes of death were verified with death certificates. Cox proportional hazards models and the time-dependent variable methodology were used to assess the association between hip fracture and mortality and its magnitude at different time intervals after the injury in each cohort. We obtained the effect estimates through a random-effects meta-analysis. RESULTS: Hip fracture was positively associated with increased all-cause mortality; the hazard ratio (HR) in the fully adjusted model was 2.12, 95% confidence interval (CI) 1.76-2.57, after adjusting for potential confounders. This association was stronger amongst men [HR: 2.39, 95% CI: 1.72-3.31] than amongst women [HR: 1.92, 95% CI: 1.54-2.39], although this difference was not significant. Mortality was higher during the first year after the hip fracture [HR: 2.78, 95% CI: 2.12-3.64], but it remained elevated without major fluctuations after longer time since hip fracture [HR (95% CI): 1.89 (1.50-2.37) after 1-4 years; 2.15 (1.81-2.55) after 4-8 years; 1.79 (1.57-2.05) after 8 or more years]. CONCLUSION: In this large population-based sample of older persons across eight cohorts, hip fracture was associated with excess short- and long-term all-cause mortality in both sexes.

Education, marital status, and risk of hip fractures in older men and women: the CHANCES project.

UNLABELLED: The role of socioeconomic status in hip fracture incidence is unclear. In a diverse population of elderly, higher education was found to be associated with lower, whereas living alone, compared to being married/cohabiting, with higher hip fracture risk. Educational level and marital status may contribute to hip fracture risk. INTRODUCTION: The evidence on the association between socioeconomic status and hip fracture incidence is limited and inconsistent. We investigated the potential association of education and marital status with hip fracture incidence in older individuals from Europe and USA. METHODS: A total of 155,940 participants (79 % women) aged 60 years and older from seven cohorts were followed up accumulating 6456 incident hip fractures. Information on education and marital status was harmonized across cohorts. Hip fractures were ascertained through telephone interviews/questionnaires or through record linkage with registries. Associations were assessed through Cox proportional hazard regression adjusting for several factors. Summary estimates were derived using random effects models. RESULTS: Individuals with higher education, compared to those with low education, had lower hip fracture risk [hazard ratio (HR) = 0.84, 95 % confidence interval (CI) 0.72-0.95]. Respective HRs were 0.97 (95 % CI 0.82-1.13) for men and 0.75 (95 % CI 0.65-0.85) for women. Overall, individuals living alone, especially those aged 60-69 years, compared to those being married/cohabiting, tended to have a higher hip fracture risk (HR = 1.12, 95 % CI 1.02-1.22). There was no suggestion for heterogeneity across cohorts (P heterogeneity > 0.05). CONCLUSIONS: The combined data from >150,000 individuals 60 years and older suggest that higher education may contribute to lower hip fracture risk. Furthermore, this risk may be higher among individuals living alone, especially among the age group 60-69 years, when compared to those being married/cohabiting.

Long-term intake of nuts in relation to cognitive function in older women.

OBJECTIVE: Nuts contain nutrients that may benefit brain health; thus, we examined long-term intake of nuts in relation to cognition in older women. DESIGN: Population-based prospective cohort study. SETTING: Academic research using data from the Nurses' Health Study. PARTICIPANTS: Nut intake was assessed in a food-frequency questionnaire beginning in1980, and approximately every four years thereafter. Between 1995-2001, 16,010 women age 70 or older (mean age = 74 years) without a history of stroke were administered 4 repeated telephone-based cognitive interviews over 6 years. Our final sample included 15,467 women who completed an initial cognitive interview and had complete information on nut intake. MAIN OUTCOME MEASURES: The Telephone Interview for Cognitive Status (TICS), a global score averaging the results of all tests (TICS, immediate and delayed verbal recall, category fluency, and attention), and a verbal memory score averaging the results of tests of verbal recall. RESULTS: In multivariable-adjusted linear regression models, higher long-term total nut intake was associated with better average cognitive status for all cognitive outcomes. For the global composite score combining all tests, women consuming at least 5 servings of nuts/week had higher scores than non-consumers (mean difference=0.08 standard units, 95% confidence interval 0.00-0.15; p-trend=0.003). This mean difference of 0.08 is equivalent to the mean difference we find between women 2 years apart in age. Long-term intake of nuts was not associated with rates of cognitive decline. CONCLUSIONS: Higher nut intake may be related to better overall cognition at older ages, and could be an easily-modifiable public health intervention.

Plasma vitamin D levels and cognitive function in aging women: the nurses' health study.

BACKGROUND: Vitamin D may play a role in preserving cognitive function. However, there is a paucity of prospective studies on the relationship between vitamin D and cognition with aging. The aim of this study was to examine the association between plasma levels of vitamin D and subsequent cognitive function. METHODS: This is a prospective study including 1,185 women aged 60-70 years from the Nurses' Health Study, who had plasma 25-hydroxy-vitamin D levels measured in 1989-1990 and completed an initial Telephone Interview of Cognitive Status approximately 9 years later. Subsequently, three follow-up cognitive assessments were conducted at 1.5-2.0 years intervals. We used multivariable-adjusted linear regression to model initial cognitive function, and mixed linear regression to model change in cognitive function over time. RESULTS: Lower vitamin D levels were associated with significantly worse cognitive function 9 years later. For example, the mean global composite score averaging all the cognitive tests was 0.20 lower (95% Confidence Interval (CI):-0.33,-0.08; p-trend=0.009) in women in the lowest quintile (median=14.1 ng/mL) compared with women in the highest quintile of vitamin D (median=38.4 ng/mL). The observed differences were equivalent to the effect estimates we found for women who were approximately 4-6 years apart in age. However, vitamin D levels were not significantly associated with subsequent cognitive decline during 6 years of follow-up. CONCLUSIONS: Higher levels of plasma vitamin D in women aged 60-70 years were associated with better cognitive function about a decade later but were not associated with cognitive decline during 6 years of follow-up.

Dietary fat intake in relation to cognitive change in high-risk women with cardiovascular disease or vascular factors.

BACKGROUND/OBJECTIVES: Dietary fat intake may influence the rate of cognitive change among those at high risk due to vascular disease or risk factors. SUBJECTS/METHODS: Women's Antioxidant Cardiovascular Study began in 1995-1996 as a randomized trial of antioxidants and B vitamin supplementation for secondary prevention in women with cardiovascular disease or ≥3 coronary risk factors. From 1998-1999, eligible participants aged ≥65 years were administered a telephone cognitive battery including five tests of general cognition, memory and category fluency (n=2551). Tests were administered four times over 5.4 years. The primary outcome was a global composite score averaging z-scores of all tests. Multivariable generalized linear models for repeated measures were used to evaluate the difference in cognitive decline rates across tertiles of total fat and various types of fat. RESULTS: Total fat intake or different types of fat were not related to cognitive decline. However, older age significantly modified the association: among the oldest participants, higher intakes of mono- and polyunsaturated fat were inversely related to cognitive decline (P-interaction: 0.06 and 0.04, respectively), and the rate differences between the highest and lowest tertiles were cognitively equivalent to the rate differences observed with being 4-6 years younger. CONCLUSIONS: In women at high risk of cognitive decline due to vascular disease or risk factors, dietary fat intake was not associated with 5-year cognitive change. However, a possible protective relation of unsaturated fats with cognitive decline in the oldest women warrants further study.

Relation of NSAIDs to incident AD, change in cognitive function, and AD pathology.

OBJECTIVE: To examine the relation of nonsteroidal anti-inflammatory drugs (NSAIDs) to incident Alzheimer disease (AD), change in cognition, and AD pathology. METHODS: Participants were 1,019 older Catholic clergy followed up annually for up to 12 years (mean baseline age = 75.0 years, education = 18.1 years, Mini-Mental State Examination score = 28.5), enrolled in the Religious Orders Study, a longitudinal clinical-pathologic study of aging and AD. Clinical evaluations allowed for AD classification and assessment of global cognition and five cognitive domains. NSAIDs were identified by direct medication inspection at baseline and follow-up evaluations. Neuropathologic data were available on 328 deceased participants. AD pathology was summarized as a global measure and as measures of neuritic plaques, diffuse plaques, and neurofibrillary tangles. We used Cox proportional hazards models and mixed models for incident AD and cognitive decline, respectively, and logistic and linear regression for pathologic outcomes, adjusted for age, sex, and education. RESULTS: Overall, we found no apparent relation of NSAIDs to incident AD (n = 209 cases), change in cognition, or AD pathology. The hazard ratio of incident AD was 1.19 (95% CI 0.87-1.62) comparing those using NSAIDs with those not using NSAIDs at baseline, and 0.84 (95% CI 0.63-1.11) for specific use of aspirin. Findings were similar in analyses in which we considered NSAID use during follow-up. NSAIDs were not related to change in cognition (all p values > 0.14). There was no relation of NSAIDs to global AD pathology or plaques or tangles. CONCLUSION: These data do not support a strong relation between nonsteroidal anti-inflammatory drugs and Alzheimer disease or cognition. Consistent findings across clinical and pathologic outcomes provide additional confidence in these results.

Postmenopausal hormone use and secondary prevention of coronary events in the nurses' health study. a prospective, observational study.

BACKGROUND: The Heart and Estrogen/progestin Replacement Study (HERS) was the first randomized clinical trial of combined hormone therapy and secondary prevention of coronary events. The trial had overall null results but reported an unexpected increased risk for recurrent events in the initial year, followed by a decrease during the final years. OBJECTIVE: To provide additional data on a time trend in risk for recurrent heart disease. DESIGN: A prospective, observational cohort study of secondary prevention of coronary heart disease. SETTING: Nurses' Health Study. PATIENTS: 2489 postmenopausal women with previous myocardial infarction or documented atherosclerosis; 213 cases of recurrent nonfatal myocardial infarction or coronary death were identified from 1976 through 1996. MEASUREMENTS: Information on hormone status and on recurrent disease was collected by using biennial questionnaires. Multivariable-adjusted relative risks and 95% CIs were calculated from logistic regression models. RESULTS: A trend of decreasing risk for recurrent major coronary heart disease events with increasing duration of hormone use was observed (P for trend = 0.002). For short-term current users, the multivariate-adjusted relative risk for major coronary heart disease was 1.25 (95% CI, 0.78 to 2.00) compared with never-users. However, after longer-term hormone use, the rate of second events was lower in current users than in never-users (relative risk, 0.38 [CI, 0.22 to 0.66]). No clear differences emerged between users of estrogen alone and users of estrogen combined with progestin. Overall, with up to 20 years of follow-up, the relative risk for a second event among current users of hormone therapy was 0.65 (CI, 0.45 to 0.95) compared with never-users. CONCLUSIONS: The risk for recurrent major coronary events seems to increase among short-term hormone users with previous coronary disease but to decrease with longer-term use.

Type 2 diabetes and cognitive function in community-dwelling elderly women.

OBJECTIVE: To examine the relationship of type 2 diabetes to cognitive function in community-dwelling women. RESEARCH DESIGN AND METHODS: From 1995 to 1999, we administered four tests of cognitive function (Telephone Interview of Cognitive Status [TICS], immediate and delayed recall of the East Boston Memory Test, and verbal fluency) by telephone to 2,374 participants (70-78 years of age) of the Nurses' Health Study. Information on diabetes was collected biennially beginning in 1976; 82 women reported type 2 diabetes before their cognitive testing. We used linear and logistic regression models to calculate multivariate-adjusted mean differences in scores and relative risks of a low score (bottom 10% of the distribution) for diabetic women compared with nondiabetic women. RESULTS: After multivariate adjustment, women with type 2 diabetes scored lower on all our cognitive tests than women without diabetes. On the general test of cognition (TICS), the mean difference in score between women with and without diabetes was -0.60 (95% CI -1.18 to -0.03, P = 0.04) and the relative risk of a low TICS score was 1.98 (95% CI 1.06 to 3.69). On a global score combining results of the four tests, the mean for diabetic women was lower than that among women without diabetes (adjusted difference in score -0.73, 95% CI -1.42 to -0.04, P = 0.04), and the relative risk of a low global score was 2.16 (95% CI 1.10 to 4.21). Relative to women without diabetes, longer duration of diabetes was associated with lower scores. Few diabetic women were pharmacologically treated (n = 31), but those taking medication had scores similar to those of women without diabetes. CONCLUSIONS: In these women, diabetes was related to lower scores on several aspects of cognitive function. Longer duration of diabetes may be associated with poorer scores, but hypoglycemic therapy may ameliorate scores.

A prospective, observational study of postmenopausal hormone therapy and primary prevention of cardiovascular disease.

BACKGROUND: Most primary prevention studies have found that long-term users of postmenopausal hormone therapy are at lower risk for coronary events, but numerous questions remain. An adverse influence of hormone therapy on cardiovascular risk has been suggested during the initial year of use; however, few data are available on short-term hormone therapy. In addition, the cardiovascular effects of daily doses of oral conjugated estrogen lower than 0.625 mg are unknown, and few studies have examined estrogen plus progestin in this regard. OBJECTIVE: To investigate duration, dose, and type of postmenopausal hormone therapy and primary prevention of cardiovascular disease. DESIGN: Prospective, observational cohort study. SETTING: Nurses' Health Study, with follow-up from 1976 to 1996. PATIENTS: 70 533 postmenopausal women, in whom 1258 major coronary events (nonfatal myocardial infarction or fatal coronary disease) and 767 strokes were identified. MEASUREMENTS: Details of postmenopausal hormone use were ascertained by using biennial questionnaires. Cardiovascular disease was established by using a questionnaire and was confirmed by medical record review. Logistic regression models were used to calculate relative risks and 95% CIs, adjusted for confounders. RESULTS: When all cardiovascular risk factors were considered, the risk for major coronary events was lower among current users of hormone therapy, including short-term users, compared with never-users (relative risk, 0.61 [95% CI, 0.52 to 0.71]). Among women taking oral conjugated estrogen, the risk for coronary events was similarly reduced in those currently taking 0.625 mg daily (relative risk, 0.54 [CI, 0.44 to 0.67]) and those taking 0.3 mg daily (relative risk, 0.58 [CI, 0. 37 to 0.92]) compared with never-users. However, the risk for stroke was statistically significantly increased among women taking 0.625 mg or more of oral conjugated estrogen daily (relative risk, 1.35 [CI, 1.08 to 1.68] for 0.625 mg/d and 1.63 [CI, 1.18 to 2.26] for >/=1.25 mg/d) and those taking estrogen plus progestin (relative risk, 1.45 [CI, 1.10 to 1.92]). Overall, little relation was observed between combination hormone therapy and risk for cardiovascular disease (major coronary heart disease plus stroke) (relative risk, 0.91 [CI, 0.75 to 1.11]). CONCLUSIONS: Postmenopausal hormone use appears to decrease risk for major coronary events in women without previous heart disease. Furthermore, 0.3 mg of oral conjugated estrogen daily is associated with a reduction similar to that seen with the standard dose of 0.625 mg. However, estrogen at daily doses of 0.625 mg or greater and in combination with progestin may increase risk for stroke.

Trends in the incidence of coronary heart disease and changes in diet and lifestyle in women.

BACKGROUND: Previous studies have found concurrent declines in blood pressure, serum cholesterol levels, and the incidence of and mortality from coronary disease. However, the effects of changes in diet and lifestyle on trends in coronary disease are largely unknown. METHODS: We followed 85,941 women who were 34 to 59 years old and had no previously diagnosed cardiovascular disease or cancer from 1980 to 1994 in the Nurses' Health Study. Diet and lifestyle variables were assessed at base line and updated during follow-up. RESULTS: After adjustment for the effect of age, the incidence of coronary disease declined by 31 percent from the two-year period 1980-1982 to the two-year period 1992-1994. From 1980 to 1992, the proportion of participants currently smoking declined by 41 percent, the proportion of postmenopausal women using hormone therapy increased by 175 percent, and the prevalence of overweight, defined as a body-mass index (the weight in kilograms divided by the square of the height in meters) of 25 or more, increased by 38 percent. During the study period, diet improved substantially. Statistically, changes in these variables--when considered simultaneously--explained a 21 percent decline in the incidence of coronary disease, representing 68 percent of the overall decline from 1980-1982 to 1992-1994. Taken individually, the reduction in smoking explained a 13 percent decline in the incidence of coronary disease; improvement in diet explained a 16 percent decline; and increase in postmenopausal hormone use explained a 9 percent decline. On the other hand, the increase in body-mass index explained an 8 percent increase in the incidence of coronary disease. CONCLUSIONS: Reduction in smoking, improvement in diet, and an increase in postmenopausal hormone use accounted for much of the decline in the incidence of coronary disease in this group of women. An increasing prevalence of obesity, however, appears to have slowed the decline in the incidence of coronary disease.

Postmenopausal hormone therapy and cognitive function in healthy older women.

OBJECTIVE: Accumulating biologic evidence suggests that estrogen is related to cognitive function. Several epidemiologic investigations have reported that hormone therapy may reduce the risk of Alzheimer's disease. However, fewer studies have examined the relation of postmenopausal hormone use to general cognitive function in nondemented older women. Thus, we examined the association of hormone therapy to performance on four cognitive tests among healthy participants of the Nurses' Health Study. DESIGN: Cohort study. SETTING: The Nurses' Health Study, an ongoing prospective cohort study begun in 1976. PARTICIPANTS: From the Nurses' Health Study, 2138 women aged 70-78 years. MEASUREMENTS: From 1995-1999 we administered four cognitive tests (Telephone Interview for Cognitive Status (TICS), immediate and delayed recall of the East Boston Memory Test (EBMT), and verbal fluency) by telephone. Hormone use was ascertained from biennial questionnaires beginning in 1976. Linear and logistic regression models were used to calculate multivariate-adjusted differences in scores and relative risks of a low score for never users compared to current and past hormone users. RESULTS: After adjustment for confounders, neither current nor long-term hormone users demonstrated better performance on an overall measure of cognition (TICS), or on three tests of verbal memory (immediate and delayed recall of the EBMT, immediate recall of the TICS 10-word list) than never users. On the test of verbal fluency, current hormone users scored significantly better than never users (linear regression estimate of the difference in score = 0.78 points, 95% confidence interval (CI) 0.19-0.38, P = .01 for any current use; and 0.91 points, 95% CI 0.28-1.54, P = .005 for > or = 5 years current use). Current hormone users also had a 30% decrease (RR = 0.70, 95% CI 0.45-1.09) in their risk of a low score on the test of verbal fluency. These results were similar for women taking estrogen alone and estrogen combined with a progestin. CONCLUSIONS: Verbal fluency may be enhanced among women taking postmenopausal hormones, however, there is little support for better overall cognitive function in hormone users than nonusers.

Postmenopausal hormone therapy and risk of cardiovascular disease and hip fracture in a cohort of Swedish women.

Postmenopausal estrogen use is associated with a reduced risk of heart disease and hip fracture; in observational studies, different behaviors among hormone users and nonusers may partially explain these results. We examined risk of cardiovascular disease and hip fracture with medium-potency compared with low-potency or short-term estrogen use, and the effect of added progestin, among 9,236 women in Uppsala, Sweden, who responded to a mailed questionnaire in 1987-1988. Using population registries, we identified 213 cases of myocardial infarction, 289 strokes, and 114 hip fractures from 1987-1995. We found a reduced risk of myocardial infarction for medium-potency compared with low-potency or short-term estrogen use (relative risk = 0.75, 95% confidence interval (CI) = 0.56-0.99), with a similar decrease in the subgroup that took estrogens with progestin (RR = 0.69, 95% CI = 0.45-0.90). There was no relation of medium-potency estrogen to stroke (RR = 0.91, 95% CI = 0.71-1.17, and RR = 0.81, 95% CI = 0.61-1.10 for the subgroup taking progestin), and no effect of duration on either heart disease or stroke. We observed a reduction in hip fractures for medium-potency use (RR = 0.65, 95% CI = 0.45-0.95), and for use of combined estrogen-progestin therapy (RR = 0.64, 95% CI = 0.41-1.00). These data support a decreased risk of heart disease and hip fracture for medium-potency estrogen use alone or with progestin; self-selection to hormone use cannot explain these reductions.

Recreational physical activity and the risk of cholecystectomy in women.

BACKGROUND: Physical activity may be an important determinant of the risk of gallstone disease in women, both independently and as a result of its role in maintaining body weight. METHODS: We prospectively studied recreational physical activity (such as jogging, running, and bicycling) and sedentary behavior (such as spending hours watching television) in relation to the risk of cholecystectomy, a surrogate for symptomatic cholelithiasis, in a cohort of 60,290 women who were 40 to 65 years of age in 1986 and had no history of gallstone disease. As part of the Nurses' Health Study, the women reported on questionnaires mailed to them every two years both their activity level and whether they had undergone cholecystectomy. During a 10-year follow-up period (1986 to 1996), 3257 cases of cholecystectomy were documented. RESULTS: Recreational physical activity was inversely related to the risk of cholecystectomy. The multivariate relative risk for women in the highest as compared with the lowest quintile of physical activity was 0.69 (95 percent confidence interval, 0.61 to 0.78). In contrast, sedentary behavior was independently related to an increased risk of cholecystectomy. As compared with women who spent less than 6 hours per week sitting while at work or driving, women who spent 41 to 60 hours per week sitting had a multivariate relative risk of 1.42 (95 percent confidence interval, 1.06 to 1.89), and women who spent more than 60 hours per week sitting while at work or driving had a multivariate relative risk of 2.32 (95 percent confidence interval, 1.26 to 4.26). These associations persisted after we controlled for body weight and weight change. CONCLUSIONS: In women, recreational physical activity is associated with a decreased risk of cholecystectomy. The association is independent of other risk factors for gallstone disease, such as obesity and recent weight loss.

Age at natural menopause and risk of cardiovascular disease.

BACKGROUND: Early natural menopause has been postulated to increase the risk of cardiovascular disease. OBJECTIVE: To examine the relation of age at natural menopause with risk of coronary heart disease (CHD) and stroke in the Nurses' Health Study. METHODS: Analysis was restricted to 35 616 naturally postmenopausal women who never used estrogen replacement therapy and with no diagnosed cardiovascular disease at baseline, followed up from 1976 to 1994. Information on menopausal status, age at menopause, and other risk factors was obtained in 1976 and updated every 2 years by mailed questionnaires. RESULTS: During 354326 person-years of follow-up, we documented 757 incident cases of CHD and 350 incident cases of stroke. After adjusting for age, smoking status, and other cardiovascular risk factors, the relative risks (RRs) across categories of age at natural menopause (<40, 40-44, 45-49, 50-54, and > or = 55 years) were 1.53, 1.42, 1.10, 1.00 (reference), and 0.95, respectively; the RR for each 1-year decrease in age at natural menopause was 1.03 (95% confidence interval, 1.01-1.05). Elevated risk with younger age at menopause was observed among current smokers (RR, 1.04 [95% CI, 1.01-1.07] for each 1-year decrease in age at natural menopause) but not among never smokers (RR, 1.00; 95% CI, 0.96-1.04). Age at natural menopause was not significantly associated with ischemic stroke (RR, 1.01; 95% CI, 0.97-1.04) or hemorrhagic stroke (RR, 1.03; 95% CI, 0.97-1.10). CONCLUSIONS: We observed an overall significant association between younger age at menopause and higher risk of CHD among women who experienced natural menopause and never used hormone therapy. This increased risk was observed among current smokers but not among never smokers. The apparent elevated risk of CHD with decreased age at natural menopause among smokers might reflect residual confounding by smoking.