Adult bone strength of children from single-parent families: the Midlife in the United States Study.

UNLABELLED: Bone health may be negatively impacted by childhood socio-environmental circumstances. We examined the independent associations of single-parent childhood and parental death or divorce in childhood with adult bone strength indices. Longer exposure to a single-parent household in childhood was associated with lower bone strength in adulthood. INTRODUCTION: Because peak bone mass is acquired during childhood, bone health may be negatively impacted by childhood socio-environmental disadvantage. The goal of this study was to determine whether being raised in a single-parent household is associated with lower bone strength in adulthood. METHODS: Using dual-energy X-ray absorptiometry data from 708 participants (mean age 57 years) in the Midlife in the United States Biomarker Project, we examined the independent associations of composite indices of femoral neck bone strength relative to load (in three failure modes: compression, bending, and impact) in adulthood with the experience of single-parent childhood and parental death or divorce in childhood. RESULTS: After adjustment for gender, race, menopause transition stage, age, and body mass index, each additional year of single-parent childhood was associated with 0.02 to 0.03 SD lower indices of adult femoral neck strength. In those with 9-16 years of single-parent childhood, the compression strength index was 0.41 SD lower, bending strength index was 0.31 SD lower, and impact strength index was 0.25 SD lower (all p values < 0.05). In contrast, parental death or divorce during childhood was not by itself independently associated with adult bone strength indices. The magnitudes of these associations were unaltered by additional adjustment for lifestyle factors and socioeconomic status in childhood and adulthood. CONCLUSIONS: Independent of parental death or divorce, growing up in a single-parent household is associated with lower femoral neck bone strength in adulthood, and this association is not entirely explained by childhood or adult socioeconomic conditions or lifestyle choices.

The association of cardiac vagal control and executive functioning--findings from the MIDUS study.

Cardiac vagal control (CVC), an index of parasympathetic contribution to cardiac regulation, has been linked to enhanced executive functioning (EF). However, findings to date have been based on small or unique samples. Additionally, previous studies assessed the CVC-EF link only during rest or recovery period from a cognitive challenge, but not during both states. In the present study, data on 817 socioeconomically diverse participants were obtained from the Midlife Development in the United States (MIDUS) study. As part of this study, participants completed cognitive tests, including EF, along with laboratory-based measures of CVC during rest and following recovery from a cognitive challenge. Regression analyses adjusting for respiratory rate revealed no effect of CVC at rest or during recovery on a global index of EF. However, exploratory post-hoc analyses of the components of the global EF index revealed a significant association between faster vagal recovery and better attention-switching and response inhibition abilities, as indexed by faster reaction time to the mixed SGST. This association remained significant after controlling for demographic, clinical (BMI, diseases and medications altering cardiac autonomic functioning, etc.), and health behavior covariates (Beta = .148, p = .010). Our findings suggest that future studies may need to investigate the links of CVC to specific EF abilities, rather than global measures of EF. Additionally, our results highlight the importance of assessing CVC during both rest and recovery from a cognitive challenge. The authors discuss the putative neurobiological underpinning of this link, as well as suggestions for future basic and clinical research.

Associations of salivary cortisol levels with inflammatory markers: the Multi-Ethnic Study of Atherosclerosis.

Socioeconomic and psychosocial factors have been found to be associated with systemic inflammation. Although stress is often proposed as a contributor to these associations, no population studies have investigated the links between inflammation and biomarkers of stress. The current study examines associations between daily cortisol profiles and inflammatory markers interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor (TNF-a) in a population-based sample of 869 adults with repeat measures of cortisol over multiple days. Persons with higher levels of IL-6 had a less pronounced cortisol awakening response, a less steep daily decline, and higher cortisol area under the curve for the day with associations persisting after controls for risk factors and other cytokines. Persons with higher levels of TNF-a had lower cortisol levels upon waking, and flatter daily decline, although associations with decline were attenuated when controlling for inflammatory risk factors. Higher levels of IL-10 were associated with marginally flatter daily cortisol decline (p<.10). This study is the first to identify associations of basal cortisol activity and inflammatory markers in a population based sample. Findings are consistent with the possibility that HPA axis activity may mediate associations between psychosocial stressors and inflammatory processes. Additional prospective data are necessary to clarify the directionality of associations between cortisol and inflammatory markers.

Socioeconomic status, race, and bone turnover in the Midlife in the US Study.

UNLABELLED: Among a group of 940 US adults, economic adversity and minority race status were associated with higher serum levels of markers of bone turnover. These results suggest that higher levels of social stress may increase bone turnover. INTRODUCTION: To determine socioeconomic status (SES) and race differences in levels of bone turnover. METHODS: Using data from the Biomarker Substudy of the Midlife in the US (MIDUS) study (491 men, 449 women), we examined cross-sectional associations of SES and race with serum levels of bone turnover markers (bone-specific alkaline phosphatase [BSAP], procollagen type I N-terminal propeptide [PINP], and N-telopeptide [Ntx]) separately in men and women. Linear multivariable regression was used to control for body weight, menopausal transition stage, and age. RESULTS: Among men, low family poverty-to-income ratio (FPIR) was associated with higher turnover, but neither education nor race was associated with turnover. Men with FPIR <3 had 1.808 nM BCE higher Ntx (P = 0.05), 3.366 U/L higher BSAP (P = 0.02), and 7.066 higher PINP (P = 0.02). Among women, neither education nor FPIR was associated with bone turnover, but Black women had 3.688 nM BCE higher Ntx (P = 0.001), 5.267 U/L higher BSAP (P = 0.005), and 11.906 µg/L higher PINP (P = 0.008) compared with non-Black women. CONCLUSIONS: Economic adversity was associated with higher bone turnover in men, and minority race status was associated with higher bone turnover in women, consistent with the hypothesis that higher levels of social stresses cause increased bone turnover. The magnitude of these associations was comparable to the effects of some osteoporosis medications on levels of turnover.

Associations of salivary cortisol levels with metabolic syndrome and its components: the multi-ethnic study of atherosclerosis.

CONTEXT: Prior research has identified associations between social-environmental factors and metabolic syndrome (MetS) components. The physiological mechanisms underlying these associations are not fully understood, but alterations in activity of the hypothalamic-pituitary-adrenal axis, a stress-responsive biological system, have been hypothesized to play a role. OBJECTIVE: The aim of the study was to determine whether MetS diagnosis and specific clusters of MetS components (waist circumference, high-density lipoproteins, glucose, and blood pressure) are associated with cortisol levels. DESIGN AND SETTING: We conducted cross-sectional analyses of data from the Multi-Ethnic Study of Atherosclerosis (MESA) study in the general community. PATIENTS OR OTHER PARTICIPANTS: We studied a population-based sample of 726 adults (ages 48 to 89 yr) who do not have clinical diabetes. INTERVENTION(S): There were no interventions. MAIN OUTCOME MEASURE(S): Cortisol awakening response, cortisol decline across the waking day, and total cortisol output were analyzed (using 18 timed measures of salivary cortisol over 3 d). RESULTS: Overall, we found little evidence that the presence of MetS or its components is related to cortisol output or patterns. Contrary to expectation, the presence of MetS was associated with lower rather than higher area under the curve, and no consistent pattern was observed when MetS components or subsets of components were examined in relation to cortisol. CONCLUSIONS: Our findings do not support the hypothesis that differences in level or diurnal pattern of salivary cortisol output are associated with MetS among persons without clinical diabetes.

The role of APOE-epsilon4 in longitudinal cognitive decline: MacArthur Studies of Successful Aging.

BACKGROUND: While a genetic risk factor for late-onset AD, the effects of the epsilon4 allele of the APOE gene on cognitive functioning more generally remain unclear. OBJECTIVE: To assess the role of the epsilon4 allele of the APOE gene in longitudinal cognitive decline. METHODS: Multiple measures of cognitive function were assessed longitudinally in the MacArthur Successful Aging Study, a population-based cohort free of frank impairment at baseline. Subjects were 965 Caucasian and African American men and women from Durham NC, East Boston, MA, and New Haven, CT, aged 70 to 79 years, recruited in 1988 through 1989, who completed two follow-up evaluations, one at 3 years and another at 7 years. RESULTS: At the first follow-up, modest but significant declines in naming and spatial ability were associated with the APOE-epsilon4 genotype. By the second follow-up, more pronounced and significant associations were noted between the APOE-epsilon4 genotype and cognitive decline from six of the eight cognitive outcomes. After 7 years, APOE-epsilon4 allele carriers were twice as likely to have declined on a global cognitive score (odds ratio = 2.0; 95% CI: 1.1, 3.6) as noncarriers. CONCLUSIONS: APOE-epsilon4 is associated with cognitive decline among a high-functioning elderly cohort, with effects most pronounced after 7 years of follow-up. Hence, the epsilon4 allele either may function as a risk factor for cognitive impairment in normal aging across a broad spectrum of domains or may exert detectable effects early in a long prodromal AD trajectory.

Interleukin-6 and risk of cognitive decline: MacArthur studies of successful aging.

OBJECTIVE: To investigate whether plasma interleukin-6 (IL-6) is cross-sectionally related to poorer cognitive function and whether a baseline plasma IL-6 measurement can predict risk for decline in cognitive function in longitudinal follow-up of a population-based sample of nondisabled elderly people. METHODS: A prospective cohort study of 779 high-functioning men and women aged 70 to 79 from the MacArthur Study of Successful Aging was conducted. Regression modeling was used to investigate whether baseline IL-6 levels (classified by tertiles) were associated with initial cognitive function and whether IL-6 levels predicted subsequent declines in cognitive function from 1988 to 1991 (2.5-year follow-up) and from 1988 to 1995 (7-year follow-up). RESULTS: Subjects in the highest tertile for plasma IL-6 were marginally more likely to exhibit poorer baseline cognitive function (i.e., scores below the median), independent of demographic status, social status, health and health behaviors, and other physiologic variables (odds ratio [OR] = 1.46; 95% CI: 0.97, 2.20). At 2.5 years, those in both the second tertile of IL-6 (OR = 2.21; 95% CI: 1.44, 3.42) and the third tertile (OR = 2.03; 95% CI: 1.30, 3.19) were at increased risk of cognitive decline even after adjusting for all confounders. At 7 years of follow-up, only those in the highest IL-6 tertile were significantly more likely to exhibit declines in cognition (OR = 1.90; 95% CI: 1.14, 3.18) after adjustment for all confounders. CONCLUSIONS: The results suggest a relationship between elevated baseline plasma IL-6 and risk for subsequent decline in cognitive function. These findings are consistent with the hypothesized relationship between brain inflammation, as measured here by elevated plasma IL-6, and neuropathologic disorders.

Social relationships, social support, and patterns of cognitive aging in healthy, high-functioning older adults: MacArthur studies of successful aging.

This study examines the relationship of social ties and support to patterns of cognitive aging in the MacArthur Studies of Successful Aging (see L. F. Berkman et al., 1993), a cohort study of 1,189 initially high-functioning older adults. Baseline and longitudinal data provide information on initial levels as well as changes in cognitive performance over a 7.5-year period. Linear regression analyses revealed that participants receiving more emotional support had better baseline performance, as did those who were unmarried and those reporting greater conflict with network members. Greater baseline emotional support was also a significant predictor of better cognitive function at the 7.5-year follow-up, controlling for baseline cognitive function and known sociodemographic, behavioral, psychological, and health status predictors of cognitive aging. The findings suggest the potential value of further research on the role of the social environment in protecting against cognitive declines at older ages.

Allostatic load as a marker of cumulative biological risk: MacArthur studies of successful aging.

Allostatic load (AL) has been proposed as a new conceptualization of cumulative biological burden exacted on the body through attempts to adapt to life's demands. Using a multisystem summary measure of AL, we evaluated its capacity to predict four categories of health outcomes, 7 years after a baseline survey of 1,189 men and women age 70-79. Higher baseline AL scores were associated with significantly increased risk for 7-year mortality as well as declines in cognitive and physical functioning and were marginally associated with incident cardiovascular disease events, independent of standard socio-demographic characteristics and baseline health status. The summary AL measure was based on 10 parameters of biological functioning, four of which are primary mediators in the cascade from perceived challenges to downstream health outcomes. Six of the components are secondary mediators reflecting primarily components of the metabolic syndrome (syndrome X). AL was a better predictor of mortality and decline in physical functioning than either the syndrome X or primary mediator components alone. The findings support the concept of AL as a measure of cumulative biological burden.

Gender differences in age-related changes in HPA axis reactivity.

Possible differences between men and women in age-related patterns of hypothalamic-pituitary-adrenal (HPA) axis response to challenge were examined to test the hypothesis that women show greater age-related increase in HPA axis reactivity to challenge. Twenty-six younger subjects, 9 men and 17 women, ages 22-26 and 14 older subjects, 7 men and 7 women, ages 67-88 participated in the study. Patterns of change in salivary "free" cortisol were measured in response to a standardized, 30-minute cognitive challenge, administered individually to each subject beginning at 1600 h. Consistent with previous research, there was a significant main effect for age with respect to baseline cortisol: older age was associated with higher baseline cortisol (P = <0.001). Results also provide support for the hypothesized age-by-gender interaction with respect to patterns of response to challenge. There was a significant interaction with respect to maximum percentage increase over baseline (P < 0.002): among younger adults, the men exhibited greater increases whereas among the older adults, the women exhibited greater increases. A similar, though only marginally significant pattern was seen for total area under the response curve (P = 0.07). Repeated measures ANOVA confirmed the gender-by-age differences in the patterns of response (P = 0.01 for time*age*gender interaction).

Is serum uric acid level associated with all-cause mortality in high-functioning older persons: MacArthur studies of successful aging?

OBJECTIVES: To explore the effect of serum uric acid level on subsequent all-cause mortality in high-functioning community-dwelling older persons. It is controversial whether high serum uric acid level is a true independent risk factor for cardiovascular and total mortality or the association is due to other confounding variables. Furthermore, it remains unclear whether the predictive value of uric acid level on mortality observed in younger cohorts can be extended to older people. DESIGN: Prospective cohort study. SETTING: A sample of community-dwelling older people. PARTICIPANTS: A cohort of 870 participants from the MacArthur Studies of Successful Aging. MEASUREMENTS: Baseline information was obtained for serum uric acid level, C-reactive protein (CRP), interleukin-6 (IL-6), prevalent medical conditions, and health behaviors. Crude and multivariate logistic regression analyses were used to examine the association between serum uric acid levels and 7-year all-cause mortality, while adjusting for potential confounders. RESULTS: In men, the multiply adjusted risk ratios for 7-year total mortality were 1.07 (95% CI=0.61-1.88) for the mid tertile of uric acid level and 1.24 (95% CI=0.70-2.20) for the top tertile. In women, the multiply adjusted risk ratios were 0.58 (95% CI=0.29-1.18) and 0.47 (95% CI=0.22-0.99), for the mid and top tertiles respectively. CRP and IL-6 were important confounders in the relationship between serum uric acid and overall mortality. CONCLUSIONS: High serum uric acid level is not independently associated with increased total mortality in high-functioning older men and women. When evaluating the association between serum uric acid and mortality, the potential confounding effect of underlying inflammation and other risk factors must be considered.

Social environment effects on health and aging: integrating epidemiologic and demographic approaches and perspectives.

This paper provides an overview of epidemiological and demographic research linking social characteristics of both individuals and communities to differences in both morbidity and mortality risks. Evidence is presented linking three broad aspects of the social environment to health--the network of personal social relationships within which most of us live our lives, individual socioeconomic status (SES), and community-level social characteristics. Large and consistent bodies of literature from both epidemiology and demography provide clear evidence for the generally health-promoting effects of personal social relationships and SES. The bulk of the evidence relates to mortality although both fields have begun to examine other health outcomes, including aspects of physical and cognitive functioning as well as disease outcomes. A smaller but growing body of community-level data, reflecting both the socioeconomic/resource characteristics of these broader communities and, more specifically, social features of these environments, also point to health impacts from these more macro level social environment characteristics. Much remains to be elucidated, however, concerning the actual mechanisms through which something as complex and multifaceted as SES "gets under the skin." This necessarily includes consideration of external characteristics of the environments (both physical and sociocultural) where people live and work, and individual characteristics, as well as possible interactions between these in producing the observed SES gradients in health and mortality. These questions concerning links between social environment conditions and health may be a particularly fruitful area of future collaboration, drawing on the shared interest of demographers and epidemiologists in understanding how different social conditions promote variation in distributions of better versus worse health outcomes within a population.

Cross-sectional and prospective relationships of interleukin-6 and C-reactive protein with physical performance in elderly persons: MacArthur studies of successful aging.

BACKGROUND: Chronic inflammation has been proposed as a biological mechanism underlying the decline in physical function that occurs with aging. The purpose of this investigation was to examine the cross-sectional and prospective relationships between markers of inflammation, interleukin-6 (IL-6) and C-reactive protein (CRP), with several measures of physical performance in older persons aged 70 to 79 years. METHODS: Subjects were 880 high-functioning men and women participating in the MacArthur Study of Successful Aging (n = 1189), a subset of the Established Populations for Epidemiologic Studies of the Elderly (n = 4030). Plasma IL-6 and CRP levels were determined by enzyme-linked immunosorbent assay and log transformed to normalize the distributions. Physical function measures included handgrip strength, signature time, chair stands (time to complete five repetitions), and 6-m walk time. RESULTS: Women had lower (p < .05) IL-6 levels than men, but there was no significant difference between blacks and whites. IL-6 and CRP levels were higher (p < .05) in current smokers than in nonsmokers and in those with a greater body mass index (BMI). Hours per year undertaking moderate and strenuous physical activity were also related to inflammatory markers with higher (p < .001) IL-6 and CRP levels in less active individuals. After adjusting for age, sex, race, BMI, smoking status, use of nonsteroidal anti-inflammatory drugs, and prevalence of morbidity, those in the top two quartiles for walking speed had lower (p = .012) IL-6 levels than those in the bottom quartile. In addition, there was a trend (p = .038) for lower CRP levels in those with higher walking speed. CRP levels were also lower (p = .04) in individuals in the top quartile for grip strength. No significant differences were noted for chair stands or signature time performance. Repeat performance measures obtained on 405 subjects (67% of those eligible at baseline) obtained 7 years later had declined significantly (grip strength, 18%; signature time, 21%; walking speed, 31%; p < .001), except for the chair rise; however, baseline IL-6 and CRP were not associated with a change in performance. However, those who died or who were unable to undergo testing had higher baseline IL-6 and CRP levels (p < .01) and slower walking speed (p < .05). CONCLUSIONS: Although IL-6 has been shown to predict onset of disability in older persons and both IL-6 and CRP are associated with mortality risk, these markers of inflammation have only limited associations with physical performance, except for walking measures and grip strength at baseline, and do not predict change in performance 7 years later in a high-functioning subset of older adults.

Health promoting effects of friends and family on health outcomes in older adults.

OBJECTIVE: To highlight the significant impact of social relationships on health and illness and suggest implications of these effects for health promotion efforts among older adults. DATA SOURCES: Published studies on social relationships and health (or health behaviors) for the period 1970-1998 were identified through MEDLINE by using the key words social relationships, social support, and health, as well as review of health-related journals such as the American Journal of Epidemiology, Annals of Epidemiology, American Journal of Public Health, Journal of Health and Social Behavior, Social Science and Medicine, and the Journals of Gerontology. STUDY SELECTION: Major published original research was considered. Where published research was too extensive for full discussion of all studies, preference was given to studies focusing on older adults and those using stronger methodology (i.e., representative samples, longitudinal data, or multivariate analyses controlling for potential confounders). DATA EXTRACTION: Reported findings were organized in terms of three major categories: (1) results related to major health outcomes such as mortality, CHD, and depression; (2) findings related to health behaviors; and (3) findings related to potential biological pathways for observed health effects of social relationships. DATA SYNTHESIS: Protective effects of social integration with respect to mortality risk among older adults are the most thoroughly documented, although protective effects have also been documented with respect to risks for mental and physical health outcomes and for better recovery after disease onset. There is also now a growing awareness of the potential for negative health effects from social relationships that are characterized by more negative patterns of critical and/or demanding interactions, including increased risks for depression and angina. Biological pathways are suggested by evidence that more negative social interactions are associated with physiological profiles characterized by elevated stress hormones, increased cardiovascular activity, and depressed immune function, whereas more positive, supportive social interactions are associated with the opposite profile. CONCLUSIONS: Available data clearly indicate that social relationships have the potential for both health promoting and health damaging effects in older adults, and that there are biologically plausible pathways for these effects. Such evidence suggests that aspects of the social environment could play an important role in future health promotion efforts for older adults, although careful consideration of both potentially positive as well as negative social influences is needed.

High urinary catecholamine excretion predicts mortality and functional decline in high-functioning, community-dwelling older persons: MacArthur Studies of Successful Aging.

PURPOSE: Catecholamine release is a marker of stress, and high plasma norepinephrine levels have been associated with increased mortality. The predictive value of high urinary catecholamine excretion for functional decline and mortality in healthier older persons has not been determined. SUBJECTS AND METHODS: We used data from the MacArthur Studies of Successful Aging to determine the effects of high urinary catecholamine excretion on 3- and 7-year mortality and functional decline. In 1988, 765 high-functioning older subjects provided complete overnight urine samples for norepinephrine and epinephrine, and 199 of these provided repeat samples in 1991. Subjects who were in the top tertile of urinary norepinephrine or epinephrine excretion in 1988 were considered high excreters; those in the top tertile in both 1988 and 1991 were considered sustained high excreters. We used bivariate and multivariate analysis to examine the relations between high catecholamine excretion and mortality and Rosow-Breslau functional decline in 1991 and 1995. RESULTS: In multivariate analyses, subjects with high baseline urinary excretion of epinephrine, norepinephrine, or either catecholamine were at higher risk for mortality and functional decline at 3 and 7 years, although the magnitude of risk (adjusted odds-ratios ranged from 1.1 to 3.1) varied depending upon specific catecholamine and outcome measure. Subjects who had sustained high urinary norepinephrine excretion were also at increased risk for 4-year mortality or functional decline. CONCLUSIONS: High urinary catecholamine excretion in high-functioning, community-dwelling older persons likely reflects subclinical sympathetic stimulation and is a marker of increased risk for functional decline and mortality.

From social integration to health: Durkheim in the new millennium.

It is widely recognized that social relationships and affiliation have powerful effects on physical and mental health. When investigators write about the impact of social relationships on health, many terms are used loosely and interchangeably including social networks, social ties and social integration. The aim of this paper is to clarify these terms using a single framework. We discuss: (1) theoretical orientations from diverse disciplines which we believe are fundamental to advancing research in this area; (2) a set of definitions accompanied by major assessment tools; and (3) an overarching model which integrates multilevel phenomena. Theoretical orientations that we draw upon were developed by Durkheim whose work on social integration and suicide are seminal and John Bowlby, a psychiatrist who developed attachment theory in relation to child development and contemporary social network theorists. We present a conceptual model of how social networks impact health. We envision a cascading causal process beginning with the macro-social to psychobiological processes that are dynamically linked together to form the processes by which social integration effects health. We start by embedding social networks in a larger social and cultural context in which upstream forces are seen to condition network structure. Serious consideration of the larger macro-social context in which networks form and are sustained has been lacking in all but a small number of studies and is almost completely absent in studies of social network influences on health. We then move downstream to understand the influences network structure and function have on social and interpersonal behavior. We argue that networks operate at the behavioral level through four primary pathways: (1) provision of social support; (2) social influence; (3) on social engagement and attachment; and (4) access to resources and material goods.

Social conditions and distress in elderly persons: findings from the MacArthur Studies of Successful Aging.

The purpose of this study was to determine separate and joint associations of race/ethnicity and socioeconomic status (SES) with psychological distress among older high-functioning adults and to examine 2 psychosocial resources that may explain these associations. Participants were 70-79-year-old individuals (n = 1,189) participating in the MacArthur Studies of Successful Aging program, a 3-site study of community-dwelling men and women. Participants represented the top third of their peers in terms of functional ability in 1988. Additive and interactive models were used to examine cross-sectional associations among race/ethnicity, SES, and distress. Although decreases in distress generally occur with aging, findings suggest that social structural factors can influence distress even among elderly people. Blacks were less distressed than Whites when SES was controlled. There was a gradient between education and distress among Whites but not among Blacks. Measures of social support and control did not mediate effects of race/ethnicity on distress. These results differ from those of previous studies and indicate that age and functional status should be considered in examinations of relationships among race/ethnicity, SES, and distress.

Evidence for an interaction between apolipoprotein E genotype, gender, and Alzheimer disease.

Carriers of the apolipoprotein E (APOE) epsilon4 allele show significantly higher risk of Alzheimer disease (AD). The aim of this present study was to test the hypothesis that a significant interaction exists between APOE genotype and gender on AD. Interactions of epsilon4 by gender, although indicated in the literature, require further verification. A total of 195 past or current control or AD participants in an ongoing longitudinal study of aging and dementia were genotyped. All subjects were at least 60 years old; demented subjects met clinical or pathologic criteria for late-onset AD. Logistic regression analysis and proportional hazard models were used to evaluate joint effects of APOE and gender. A significant statistical interaction between APOE and gender was shown (p = 0.04) in logistic regression analysis. Women carrying one or more APOE-epsilon4 allele were more likely to develop AD [odds ratio (OR) = 7.8, 95% confidence interval (CI) = 3.2-19. 1]. For men, the presence of the APOE-epsilon4 allele was not associated with a statistically significant increased risk (OR = 1.6, 95% CI = 0.5-5.3). The interaction term in the proportional hazards model neared (p = 0.07) statistical significance, and a similar but reduced gender effect was shown. The analysis suggests that the presence of one or more APOE-epsilon4 allele confers a substantially greater risk of AD to women than to men. These findings in part may account for reports of increased risk of AD faced by women.

The relation between cortisol excretion and fractures in healthy older people: results from the MacArthur studies-Mac.

BACKGROUND: In persons with depression, higher urinary cortisol is associated with lower bone mineral density. OBJECTIVE: To examine the relation between urinary free cortisol (UFC) and fractures. SETTING: Community-based samples from Durham, NC, East Boston, MA, and New Haven, CT. PARTICIPANTS: 684 men and women, aged 70 to 79 at baseline, who were part of the MacArthur Study of Successful Aging. DESIGN: Cohort study. Participants with previous history of fractures at baseline were excluded. MEASURES: The primary exposure variable was overnight (8:00 p.m. to 8:00 a.m.) UFC (microg/g creatinine) at baseline (1988). Outcomes were self-reported hip, arm, spine, wrist, or other fracture during the follow-up period (1988-1995). Covariates were baseline age, gender, race, body mass index, current physical activity, lower extremity strength, depression subscale of the Hopkins Symptom Checklist, and current use of cigarettes and alcohol. ANALYSIS: Logistic regression was used to predict the occurrence of incident fractures (1988-1995) as a function of quartiles of baseline UFC. Models were adjusted for age, gender, and race and were also multiply adjusted for the remaining covariates listed above. Gender-stratified models and models that excluded corticosteroid users were also run. RESULTS: In multiply adjusted models, higher baseline levels of UFC were significantly associated with incident fractures. Odds of fracture (95% Confidence Intervals) for increasing quartiles of baseline UFC, multiply adjusted, were: 2.28 (.91, 5.77); 3.40 (1.33, 8.69); 5.38 (1.68, 17.21). Results were not materially influenced by exclusion of persons using corticosteroids. CONCLUSIONS: Higher baseline UFC is an independent predictor of future fracture.

Social networks and disability transitions across eight intervals of yearly data in the New Haven EPESE.

OBJECTIVES: There is considerable evidence that social networks are strongly related to survival and other health outcomes. However, findings regarding the effect of social networks on disability outcomes have been inconsistent. This study examines this relationship with respect to the risk of developing disability and recovering from disability. METHODS: Data come from a community-based sample of the New Haven population aged 65 years and older, with nine annual interviews conducted between 1982 and 1991. Disability was measured by a 6-item index of activities of daily living (ADL), and a 3-item Rosow-Breslau index, with disability defined as impairment in one or more tasks on each measure. Social network variables were constructed for each of four domains of ties: children, relatives, friends, and a confidant, and a summary measure of total social networks. A Markov model was used to estimate one-year disability transitions averaged across all 8 intervals, after controlling for sociodemographic and health-related variables. RESULTS: Total social networks was associated with a significantly reduced risk of developing ADL disability (beta = -0.009, p < .01), and a significantly increased likelihood of ADL recovery (beta = 0.017, p < .01). Emotional and instrumental support did not affect the protective effect of social networks against disability, but partially accounted for their effect on enhanced recovery. Network variables related to relatives and friends were significantly associated with disability and recovery risks, but those related to children or a confidant were not. The associations with disability transitions as measured by the Rosow-Breslau index were generally smaller and nonsignificant. DISCUSSION: The findings lend further support for the role of social relationships in important health outcomes in old age. They suggest that being "embedded" in a social network of relatives and friends reduces risk for ADL disability, and enhances recovery from ADL disability.