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.

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.

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.

The effect of race and health-related factors on naming and memory. The MacArthur Studies of Successful Aging.

OBJECTIVES: The purpose of the analyses was to examine the impact of health-related variables on race differences in neuropsychological functioning (Boston Naming Task). METHODS: Using cross-sectional data from the MacArthur Successful Aging Study, the authors examined the relationship of demographic characteristics, health status, health habits, physical functioning, and speed of performance to naming and incidental recall of items from the Boston Naming Task. Participants were 1,175 healthy African American and European American older persons 70 to 79 years old. RESULTS: Regression analyses indicated that although race differences persisted for confrontational naming after controlling for demographic and health factors, there was no effect due to race for incidental recall scores or for savings scores for recall. DISCUSSION: The racial differences found in test performance may reflect differences in cultural appropriateness of the material rather than differences in ability.

A prospective study of the effect of fracture on measured physical performance: results from the MacArthur Study--MAC.

OBJECTIVE: To examine the impact of fractures on measured physical performance and to assess whether specific fractures have unique sequelae. SUBJECTS: 762 men and women, aged 70 to 79 at baseline, who were part of the MacArthur Study of Successful Aging. DESIGN: A longitudinal case-cohort: those with prevalent fractures at baseline were excluded; cases were persons with a medically diagnosed hip, arm, spine, or wrist fracture during the follow-up period (1988-1995). MEASURES: Eight physical performance tests: turning a circle, walking fast, chair stands, timed tap, tandem stand, grip strength, single leg stand, and balance (average of single leg and tandem stands) measured at baseline and follow-up. ANALYSIS: Two fracture groups were defined: (1) those with incident wrist fractures (n = 7) and (2) those with a fracture of the hip, arm, or spine (combined fractures group, n = 16). Change in physical performance was analyzed using crude, age-adjusted, and multiply-adjusted ANCOVA models. RESULTS: The combined fracture group demonstrated statistically significant (P < .05) declines seven of eight of the performance tests compared with individuals without fractures. In contrast, individuals with wrist fractures did not experience a statistically significant decline in any performance measure compared with the no fracture group. CONCLUSIONS: Relative to those without fractures, individuals with a hip, arm, or clinical spinal fracture show similar global declines in physical performance, whereas those with wrist fracture demonstrate no physical performance decrements.

Successful aging and disease prevention.

Substantial increases in the relative and absolute number of older persons in our society pose a challenge for biology, social and behavioral science, and medicine. Successful aging is multidimensional, encompassing the avoidance of disease and disability, the maintenance of high physical and cognitive function, and sustained engagement in social and productive activities. Research has identified factors predictive of success in these critical domains. Two additional research domains, resilience and wisdom, are suggested, and a national initiative in health promotion and disease prevention is proposed.

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.

The future of aging.

In 1984, the John D. and Catherine T. MacArthur Foundation funded a long-term research program that brought together 16 scientists from various disciplines to study what factors contribute to successful physical and mental aging. Last year, two of those scientists published Successful Aging, in which they discuss the study's generally encouraging findings. In the sections excerpted below, they share some sometimes surprising insights into how people age in America.

Intraindividual variability in perceived control in an older sample: the MacArthur successful aging studies.

Two aspects of perceived control, locus of control (LOC) and perceived competence (COM), command significant attention in personality and aging research. Mainly, these concepts are regarded as stable variables of considerable promise for predicting a range of outcomes. The authors concentrate on week-to-week within-person variability in self-reported LOC and COM. Using data collected over 7 months, the authors first demonstrates that the responses of a panel of older participants are structurally consistent with dominant conceptions of perceived control and that the responses maintain an underlying structure over the frequently repeated protocol. They next show that the within-person variation over weekly measurements is coherent information rather than "noise" and that individual differences in magnitude of week-to-week variability are a relatively stable attribute that predicts mortality status 5 years later. Implications of the findings for both methodological and substantive concerns are discussed.

Price of adaptation--allostatic load and its health consequences. MacArthur studies of successful aging.

BACKGROUND: Exponential growth in the population of older adults presents clinicians with special concerns about factors affecting risks for declines in cognitive and physical functioning. OBJECTIVES: To examine the hypothesis that risks for such declines and for disease outcomes, such as cardiovascular disease, are related to differences in allostatic load, the cumulative physiologic toll exacted on the body over time by efforts to adapt to life experiences. To present an operational definition of allostatic load, along with preliminary evidence of its predictive validity in relation to salient outcomes of aging. METHODS: Data from a longitudinal, community-based study of successful aging were used to develop a measure of allostatic load based on 10 parameters reflecting levels of physiologic activity across a range of important regulatory systems. Allostatic load is the sum of the number of parameters for which the subject was rated in the highest-risk quartile. RESULTS: Higher allostatic load scores were associated with poorer cognitive and physical functioning and predicted larger decrements in cognitive and physical functioning as well as being associated with an increased risk for the incidence of cardiovascular disease, independent of sociodemographic and health status risk factors. CONCLUSIONS: Findings are consistent with the conceptualization of allostatic load as an index of wear and tear on the body, with elevations in allostatic load predicting an increased risk for a decline in cognitive and physical functioning as well as cardiovascular disease in a cohort of older men and women. From a clinical perspective, the concept of allostatic load may provide the basis for a more comprehensive assessment of major risks in the aging process.

Increase in urinary cortisol excretion and memory declines: MacArthur studies of successful aging.

Cortisol production is increased during stress, and the actions of cortisol on receptors in the brain and other body organs are involved in allostasis, the process of adaptation to stress, as well as in allostatic load, the wear and tear associated with excessive exposure to cortisol. Using data from a community-based longitudinal study of older men and women, aged 70-79 yr, we tested the hypothesis that exposure to increasing levels of cortisol is associated with declines in memory performance. Associations between 12-h urinary free cortisol excretion and performance on tests of memory (delayed verbal recall and spatial recognition), abstraction, and spatial ability were examined. Among the women, greater cortisol excretion was associated with poorer baseline memory performance, independent of socio-demographic, health status, health behavior, and psychosocial characteristics. Moreover, women who exhibited increases in cortisol excretion over a 2.5-yr follow-up period were more likely to show declines in memory performance. By contrast, women who experienced declines in cortisol exhibited improvements in memory performance. No significant associations were found among the men. The results for the women suggest that decrements in memory performance associated with increases in cortisol may not represent irreversible effects, as declines in cortisol were associated with improvements in memory.

Successful aging.

Substantial increases in the relative and absolute number of older persons in our society pose a challenge for biology, social and behavioral science, and medicine. Successful aging is multidimensional, encompassing the avoidance of disease and disability, the maintenance of high physical and cognitive function, and sustained engagement in social and productive activities. Research has identified factors predictive of success in these critical domains. The stage is set for intervention studies to enhance the proportion of our population aging successfully.

Health indices as predictors of cognition among older African Americans: MacArthur studies of successful aging.

Using cross-sectional and longitudinal data from the MacArthur Successful Aging Study, this paper examines associations between cognition and indices of health in 224 elderly African Americans 70 to 79 years of age at initial interview. The results indicated that greater average peak expiratory flow was predictive of better cognitive performance at the first interview. One longitudinal analysis showed that gender was the only significant predictor of change (change as a continuous variable) with women tending to slightly improve their cognitive performance over time. When change was treated as a dichotomous variable (e.g., a decline of 6 or more points), lower levels of average peak expiratory flow and education were predictive of decline, and positive self-ratings of current health and changes in health in the past year were important factors in the improvement of cognitive performance. The results indicate that, in addition to education, health is an important predictor of the status and course of cognitive functioning in older African Americans.