Negative Affect and Mortality in Older Persons

Robert S. Wilson1,2,3 , Julia L. Bienias1,4, Carlos F. Mendes de Leon1,4, Denis A. Evans1,4 and David A. Bennett1,2

1 Rush Alzheimer’s Disease Center and Rush Institute for Healthy Aging, Rush-Presbyterian-St. Luke’s Medical Center, Chicago, IL.
2 Department of Neurological Sciences, Rush-Presbyterian-St. Luke’s Medical Center, Chicago, IL.
3 Department of Psychology, Rush-Presbyterian-St. Luke’s Medical Center, Chicago, IL.
4 Department of Internal Medicine, Rush-Presbyterian-St. Luke’s Medical Center, Chicago, IL.

Received for publication November 19, 2002; accepted for publication May 1, 2003.


    ABSTRACT
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
The authors examined the relation of negative affect to mortality in the Religious Orders Study, a longitudinal cohort study of older persons, between 1994 and 2002. Participants were 851 Catholic clergy members without dementia at baseline (mean age, 75.4 (standard deviation, 6.9) years; 68% women). They completed standard measures of depressive symptoms, proneness to anxiety and anger, and patterns of anger expression at baseline and then underwent annual clinical evaluations for a mean of 4.7 (standard deviation, 2.7) years. The association of each scale with mortality was examined in proportional hazards models adjusted for age, sex, education, measures of cognitive function, lower limb function, chronic illness, smoking, alcohol, and obesity. During follow-up, 164 persons died. Measures of internally experienced negative affect, such as depressive symptoms and suppressed anger, were related to mortality, but measures of externally directed negative affect, such as the tendencies to be angry with others and to express anger overtly, were not. Persons with a high score (90th percentile) on a summary measure of internally experienced negative affect were nearly twice as likely to die as persons with a low score (10th percentile). The results suggest that negative affect in older persons, especially internally experienced distress, is associated with an increased mortality risk.

aging; anger; anxiety; depression; mortality; prospective studies; survival analysis

Abbreviations: Abbreviations: CES-D, Center for Epidemiologic Studies Depression; CI, confidence interval; SD, standard deviation.


    INTRODUCTION
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
In middle-aged persons, negative emotions such as depression, anxiety, and anger have been associated with increased mortality (19). The relation of negative affect to mortality in older persons has not been extensively studied, however. Thus, most studies of the association in community-dwelling older people have focused on one type of negative affect, depressive symptoms, to the exclusion of other forms (1020). It is uncertain, therefore, whether the tendencies to experience anger or anxiety contribute to mortality risk in old age or whether such effects are independent of depressive symptoms.

Although there have been several studies of the association of depressive symptoms with mortality in older persons, results have been conflicting, with symptoms of depression related to mortality in some studies (1012) but with mixed (1317) or no evidence of an association (1820) in other studies. This inconsistency is likely due in part to different methods of controlling for factors that might influence the association of depressive symptoms with mortality. For example, persons in poorer health tend to experience higher levels of depressive affect, which may account for its association with mortality (21, 22). To adjust for the confounding influence of poor health, many studies have relied on self-report measures of disability or global health status (10, 1214, 16, 1820). However, negative appraisal of health and function is a symptom of depression and, as a result, adjustment for such health ratings may obscure the association of depressive symptoms with mortality.

Another challenge is the possibly confounding influence of factors related to socioeconomic status. Persons of low socioeconomic status tend to have higher levels of depressive symptoms and general distress (21–25). Low socioeconomic status itself is a well-established risk factor for mortality in the general population (2628), as well as among older persons (29). Most studies of depressed affect and mortality include statistical control for indicators of socioeconomic status, such as education and income. However, these indicators tend to be relatively crude measures of socioeconomic status, especially among older persons (29, 30), and so may afford only partial control of the confounding influence of socioeconomic status.

In this study, we examine the relation of negative affect to mortality among older adults, addressing these challenges in the following ways. First, we include information on a range of negative affective states, using standardized measures of depressive symptoms, anxiety, and anger. Second, rather than relying on self-report evaluations of overall health, we use performance-based measures of cognitive and physical function, body mass index, and self-report about previously diagnosed medical conditions, smoking, and alcohol use. Third, we examine the association of negative affect with mortality in a cohort of Catholic nuns, priests, and brothers. This cohort is relatively homogeneous in terms of socioeconomic status and related lifestyle factors, which may reduce the influence of these factors on the association of negative affect with mortality.


    MATERIALS AND METHODS
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Participants
Subjects are from the Religious Orders Study, an ongoing longitudinal clinical-pathologic investigation of aging and Alzheimer’s disease in older Catholic clergy members who agreed to annual clinical evaluations and brain donation at death. This study was approved by the Institutional Review Board of Rush-Presbyterian-St. Luke’s Medical Center. Enrollment began in January 1994 and is continuing. In this article, we report the association between measures of negative affect collected at baseline and mortality through July 2002. The years of observation ranged from less than 1 year to more than 8 years (mean, 4.72 (standard deviation (SD), 2.70) years), given the rolling admission and individual differences in survival.

The annual clinical evaluations are highly structured and include a medical history; neurologic examination; assessment of cognitive function, motor function, and other behaviors; and review of a brain scan when available, as previously described (3133). On the basis of this evaluation, an experienced physician clinically classified persons with respect to dementia and Alzheimer’s disease and other common conditions of old age. The diagnosis of dementia followed the criteria of the joint working group of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association that require a history of cognitive decline and impairment in at least two domains of cognitive function (34).

At the time of these analyses, 925 persons had completed the baseline clinical evaluation. We excluded 74 persons who met the clinical criteria for dementia at baseline. Analyses are based on the remaining 851 persons. They had a mean age of 75.4 (SD, 6.9) years, a mean education of 18.2 (SD, 3.4) years, and a mean Mini-Mental State Examination score of 28.4 (SD, 1.7); 580 (68.1 percent) were women, and 763 (89.9 percent) were non-Hispanic White.

Assessment of negative affect
All assessment of negative affect took place at the baseline evaluation. Depressive symptoms were assessed with a 10-item version of the Center for Epidemiologic Studies Depression (CES-D) Scale (3537). Persons were asked whether they had experienced each of 10 symptoms much of the time in the past week. The score was the number of symptoms reported.

We modified each remaining scale by using a binary response option, as on the 10-item CES-D Scale, rather than the original rating format to reduce response burden. We made no other modifications.

Anxiety was assessed with a modified version of the Anxiety Trait Scale from the State-Trait Anxiety Inventory (38). The scale consists of 20 questions (e.g., "I feel nervous and restless.") about feelings of anxiety that are thought to be relatively stable over time. Persons were asked whether each feeling was characteristic, and the score was the number of questions answered in the direction indicative of anxiety.

Anger was assessed with four scales from the State-Trait Anger Expression Inventory (39). "Trait Anger" consists of 10 items that measure a general disposition to experience anger (e.g., "I am a hot-headed person."). "Anger-in" is an eight-item measure of the tendency to internally experience anger (e.g., "I pout or sulk."). "Anger-out" is an eight-item scale of the tendency to outwardly express anger (e.g., "I do things like slam doors."). The score on each scale was the number of items answered in the direction indicative of the trait. "Anger-control" is an eight-item measure of how successfully anger is controlled (e.g., "I am patient with others."). We reversed the scoring of the Anger-control Scale so that higher scores indicated a lack of control, to make it consistent with the other negative affect scales in the study.

Assessment of other clinical features
We gathered data on six indicators of health and function at baseline. Cognitive function was assessed with a set of 19 individual tests in an approximately 1-hour session. To make use of all available data, we formed a composite measure of global cognition by converting raw scores on each test to z scores, using the baseline mean and standard deviation, and averaging the z scores to yield the composite. Detailed information about the 19 individual tests and the formation of the composite measure is published elsewhere (31, 4042).

We assessed lower limb function with five performance-based measures, each scaled from 0 to 5, with higher scores indicating better performance and 0 indicating an inability to perform the task. We asked participants to walk 8 feet (2.438 m) at a normal pace and measured the time and number of steps taken. Each distribution was divided into quintiles, with scores of 5 assigned to the fastest walking speeds and fewest walking steps. Participants were asked to sit up and down five times in a chair. Those who attempted but could not complete the task were given a score of 1. The time taken to successfully complete the task was divided into quartiles, and scores of 2–5 were assigned, with higher scores for more rapid performance. We asked persons to walk an 8-foot line heel to toe. The number of steps off the line was divided into quintiles, with scores of 5 assigned to those with the least steps off the line. To assess standing balance, we asked persons to stand in each of four positions up to 10 seconds: full tandem stand (i.e., heel to toe) with eyes open, semitandem stand (i.e., heel of one foot astride toes of other) with eyes open, and side-by-side stand (i.e., feet aligned and touching) with eyes open and with eyes closed. The total time on the four tasks was divided into quintiles, with 5 assigned to those able to maintain balance the longest. Because the resulting five measures were moderately correlated (median r = 0.39), we averaged them to create a global performance-based measure of lower limb function (43, 44).

Seven medical conditions were present in at least 5 percent of persons at baseline. We classified hypertension, diabetes, heart disease, cancer, thyroid disease, and head injury with loss of consciousness based on self-report that a physician previously identified the condition. A clinical diagnosis of stroke was based on the history plus the neurologic examination. We used the total number of conditions present at baseline as an index of chronic illness, as previously described (41, 45).

Persons were divided into those who ever versus never smoked cigarettes. Current alcohol use was expressed as the number of alcoholic drinks consumed in the past year, log transformed because of the skewed distribution. Weight divided by height squared (kg/m2) was used as an index of body mass.

Ascertainment of vital status
Information on vital status was available for all participants. Because all participants have agreed to brain donation upon death, the Religious Orders Study is organized to ensure that the study coordinator is promptly informed of deaths. In the rare event that the coordinator is not notified, the information is obtained from regular phone contacts intended to update vital status of participants at each study site.

Data analysis
We examined the associations among the negative affect scales with Pearson’s correlations and a principal-components factor analysis with varimax rotation. We computed Cronbach’s coefficient alpha to assess the internal consistency of each scale.

We examined the association of CES-D score with risk of death on follow-up in a Cox proportional hazards model (46) that also included terms for the potentially confounding effects of age, sex, and education. We then repeated the analysis with terms added for global cognition, lower limb function, chronic medical conditions, alcohol use, history of smoking, body mass index, and body mass index squared, to see if these variables influenced the association of the baseline CES-D score with mortality. We repeated the original model with a term added for the interaction of sex with CES-D score and then again with a term for the CES-D score squared.

We evaluated the associations of the measures of anxiety and anger with mortality in separate proportional hazards models adjusted for age, sex, and education. We repeated each analysis with a term for the interaction of sex with the affect scale and again with a quadratic term for the affect scale. We repeated each original model with terms added for the baseline measures of health and function, and then we added a term for the CES-D score to these models in another set of analyses. We constructed a final model with the two composite measures of negative affect, age, sex, education, and the measures of health and function.

All analyses were programmed in SAS software (47). Model assumptions were evaluated graphically and analytically and judged to be adequately met.


    RESULTS
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
During an average of 4.7 years of follow-up, 164 deaths occurred. Compared with survivors, those who died were older and more likely to be male, had higher scores on half of the negative affect scales, and showed some evidence of impaired health and function at baseline (table 1).


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TABLE 1. Baseline characteristics of participants who survived and those who died, Religious Orders Study, 1994–2002*
 
Psychometric properties of negative affect scales
Information on the distributions of the measures of depression, anxiety, and anger is provided in table 2. Each scale had a positively skewed distribution with many people reporting few or no negative emotions. Coefficient alpha ranged from 0.68 to 0.91 (median, 0.82), indicating that each scale had a moderately high level of internal consistency. As shown in table 3, the negative affect measures were positively correlated with one another (median correlation, 0.28) but had generally small to negligible correlations with the measures of health and function. To further examine the associations between the scales, we performed a principal- components factor analysis with varimax rotation (table 3). The CES-D, Trait Anxiety, and Anger-in scales loaded on one factor, and the Trait Anger, Anger-out, and Anger- control scales loaded on a second factor. Guided by the factor analytical results, we created two composite affect measures to reduce floor artifacts and other sources of measurement error. We formed a measure of internally experienced negative affect by adding the CES-D score, Anger-in score, and one half of the Trait Anxiety score (because it has about twice as many items as the other scales). Scores ranged from 0 to 22 (mean, 5.30; SD, 3.93). We formed a measure of externally directed negative affect by adding scores from the Trait Anger, Anger-out, and Anger-control scales. Scores ranged from 0 to 19 (mean, 3.95; SD, 3.35). Each composite measure had an interquartile range of 6.


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TABLE 2. Psychometric information on the measures of negative affect, Religious Orders Study, 1994–2002
 

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TABLE 3. Correlation of negative affect measures with each other and measures of health and function, Religious Orders Study, 1994–2002*
 
Depressive symptoms and mortality
We began analyses with the CES-D Scale because of its extensive use in prior research. We examined the association of CES-D score with mortality in a proportional hazards model adjusted for the potentially confounding effects of age, sex, and education. For each depressive symptom on the CES-D Scale, risk of death increased by 18 percent (hazards ratio = 1.18, 95 percent confidence interval (CI): 1.08, 1.28). Thus, compared with a person without depressive symptoms at baseline, a person with three symptoms (90th percentile) was 62 percent more likely to die on follow-up.

To determine if the association of depressive symptoms with mortality was influenced by level of health or functional ability at baseline, we repeated the analysis with the following covariates added: cognitive function, lower limb function, number of chronic illnesses, number of alcoholic drinks in the past year, history of cigarette use, body mass index, and body mass index squared. The association of depressive symptoms with mortality remained significant in this model (hazards ratio = 1.13, 95 percent CI: 1.04, 1.24).

To determine whether the association of depressive symptoms with mortality differed for men and women, we repeated the original analysis with a term for the interaction of the CES-D score with sex. The interaction was not significant.

To see if the association of depressive symptoms with mortality was linear, we repeated the original model with a quadratic term for depressive symptoms added. It was not significant.

Others forms of negative affect and mortality
We examined the relation of each remaining affect measure to mortality in separate proportional hazards models adjusted for age, sex, and education (table 4, model 1). Higher levels of Trait Anxiety and Anger-in were associated with a significantly increased mortality risk, but no significant association was observed for Trait Anger, Anger-out, or Anger-control. We repeated each analysis with a term for the interaction of the affect scale with sex and again with a quadratic term for the affect scale added. None of these added terms was significant (data not shown).


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TABLE 4. Relative risk of death associated with measures of negative affect adjusted for age, sex, and education, Religious Orders Study, 1994–2002*
 
We then repeated each original analysis with terms added for the indicators of baseline health and function. In these analyses (table 4, model 2), the association of Trait Anxiety with mortality was reduced to a trend (p = 0.09), but the effect of Anger-in was essentially unchanged.

Because of the association of depressive symptoms with anxiety and anger, we constructed another set of models for each anxiety and anger measure that included a term for the CES-D Scale and also controlled for age, sex, education, and the indicators of baseline health and function (table 4, model 3). With depressive symptoms included in the analysis, the effect of Anger-in was reduced somewhat (p = 0.07), and anxiety was no longer related to mortality.

To further examine the differential association of subtypes of negative affect with mortality risk, we constructed another proportional hazards model with the composite measures of internally experienced and externally directed negative affect. The model also included terms for age, sex, education, and the indices of health and function. In this analysis (table 5), internally experienced negative affect was related to mortality, but the measure of externally directed negative affect was not (hazards ratio = 0.98, 95 percent CI: 0.94, 1.03). Thus, a person with a high level of internally experienced negative affect (score = 10.5, 90th percentile) was 91 percent more likely to die than a person with a low level (score = 1.0, 10th percentile).


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TABLE 5. Relative risk of death associated with summary measures of internally experienced negative affect and externally directed negative affect, adjusted for age, sex, education, and indicators of baseline health and function, Religious Orders Study, 1994–2002
 

    DISCUSSION
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
In this cohort of more than 800 older persons without clinical evidence of dementia at baseline, we found that both depressive symptomatology and the tendency to suppress anger were associated with an increased risk of death during an average of 4.7 years of follow-up. Anxiety proneness was also related to mortality, but this effect was mainly due to the association of anxiety with depressive symptoms. The results suggest that negative affect in older persons, especially internally experienced distress, is associated with an increased risk of mortality.

The association of depressive symptoms with mortality in this study is consistent with results from some previous studies of community-dwelling older persons (1012), but as noted above, others have found no or inconsistent evidence of this association (1320). One issue is that some previous studies have treated the number of depressive symptoms as a binary measure (10, 12, 1517, 20), despite evidence from this and previous (1, 11) studies of an approximately linear association between the number of symptoms and the risk of death, resulting in reduced power to detect the association. In addition, because negative appraisal of one’s functional abilities and health is a common symptom of depression, use of self-report measures of disability or global ratings of health as covariates may have obscured the association of depressive symptoms with mortality in some studies (10, 1214, 16, 18, 20).

Little is known about the relation of other negative affective states to mortality in older persons. Prior research has long suggested that chronic anger and hostility (2, 4, 5, 20, 4851) and chronic anxiety (69) are associated with coronary heart disease or mortality. However, with few exceptions (52), these studies have been limited to middle-aged persons or younger adults. In addition, few studies have assessed multiple forms of negative affect, making it hard to examine whether some negative emotions are more strongly related to mortality than others. In this cohort, measures of negative affect were differentially associated with mortality. Anger suppression and anxiety, which like depressive symptoms may be considered indicators of internally experienced distress, were related to mortality, although the effect of anxiety was not independent of depressive symptoms. By contrast, the Anger Trait, Anger-out, and Anger-control scales, which may be seen as indicators of externally expressed hostility, were not related to mortality. One possible explanation for this dissociation is that the low level of angry feelings and outwardly expressed anger in this cohort limited our power to detect an association with mortality. None of the three measures of externally expressed anger was related to mortality, however, and neither was a composite of all three that had a much less skewed distribution, whereas all three of the indicators of internal distress were related to mortality, despite low levels of depressive symptomatology and anxiety. It seems unlikely, therefore, that floor effects can be the sole explanation for the observed dissociation.

The basis of the association of depressive symptoms and anger suppression with mortality is uncertain. Depressed affect and anger may increase mortality risk through their association with cardiovascular disease (15, 11, 17, 5256). There are a number of mechanisms that may account for the link between negative affect and cardiovascular disease. For example, depressed or angry persons tend to have poorer adherence to healthy lifestyles and medical treatment (57). Although unhealthy behaviors may be an important component of the adverse health effects of negative affect (58), these behaviors usually explain only part of the increased risk for cardiovascular disease and mortality (1, 2, 52, 54, 59). Other research has focused on the pathophysiologic effects of negative affect. For example, negative affect has been linked with a series of impaired cardiovascular responses that may explain its association with clinical disease outcomes (57, 6062). Negative affect has also been related to neuroendocrine abnormalities and their metabolic consequences (6365), as well as to impaired immune responses (6668), both of which may contribute to increased risk of morbidity and mortality. Further research is needed on the factors linking negative affect with mortality.

The cohort in this study is unique: older Catholic nuns, priests, and brothers who agreed to annual clinical evaluations and brain autopsy at death. The relative homogeneity of socioeconomic status and access to health care in this cohort may have provided additional control over these confounding influences and thereby enhanced our ability to assess the association of negative affect with death. On the other hand, the selected nature of the cohort, its differences from the US population in education and lifestyle, and its generally low level of negative affect all underscore the importance of replicating these findings in more diverse cohorts and defined populations.

Two additional study limitations should be noted. Our reliance on total rather than cause-specific mortality may have obscured evidence of an association of negative affect with specific mortality outcomes. Although we used psychometrically established measures of negative affect, they are relatively brief and were collected at a single point in time with a binary response format, which may have introduced measurement error and thereby biased findings to the null.


    ACKNOWLEDGMENTS
 
This research was supported by National Institute on Aging grants R01 AG15819 and P30 AG10161.

The authors are indebted to the following groups for their support of the Religious Orders Study: the archdioceses of Chicago, Illinois, Dubuque, Iowa, and Milwaukee, Wisconsin; Benedictines, Lisle, Illinois, Collegeville, Minnesota, and Erie, Pennsylvania; Benedictine Sisters of the Sacred Heart, Lisle, Illinois; Capuchins, Appleton, Wisconsin; Christian Brothers, Chicago, Illinois, and Memphis, Tennessee; the Diocese of Gary, Indiana; Dominicans of River Forest, Illinois; Felician Sisters, Chicago, Illinois; Franciscan Handmaids of Mary, New York, New York; Franciscans, Chicago, Illinois; Holy Spirit Missionary Sisters, Techny, Illinois; Maryknolls, Los Altos, California, and Maryknoll, New York; Norbertines, DePere, Wisconsin; Oblate Sisters of Providence, Baltimore, Maryland; Passionists, Chicago, Illinois; Presentation Sisters, Blessed Virgin Mary, Dubuque, Iowa; Servites, Chicago, Illinois; Sinsinawa Dominican Sisters, Chicago, Illinois, and Sinsinawa, Wisconsin; Sisters of Charity, Blessed Virgin Mary, Chicago, Illinois, and Dubuque, Iowa; Sisters of the Holy Family, New Orleans, Louisiana; Sisters of the Holy Family of Nazareth, DesPlaines, Illinois; Sisters of Mercy of the Americas, Chicago and Aurora, Illinois, and Erie, Pennsylvania; Sisters of St. Benedict, St. Cloud and St. Joseph, Minnesota; Sisters of St. Casimir, Chicago, Illinois; Sisters of St. Francis of Mary Immaculate, Joliet, Illinois; Sisters of St. Joseph of LaGrange, LaGrange Park, Illinois; Society of Divine Word, Techny, Illinois; Trappists, Gethsemane, Kentucky, and Peosta, Iowa; and Wheaton Franciscan Sisters, Wheaton, Illinois. The authors also thank Julie Bach, coordinator of the Religious Orders Study; Liping Gu for programming; George Dombrowski and Greg Klein for data management; and Valerie J. Young for preparing the manuscript.


    NOTES
 
Correspondence to Dr. Robert S. Wilson, Rush Alzheimer’s Disease Center, 1645 West Jackson Boulevard, Suite 675, Chicago, IL 60612 (e-mail: rwilson{at}rush.edu). Back


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 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
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