Occupational characteristics and cognitive performance among elderly male twins.

OBJECTIVE: To examine the effect of occupational characteristics on cognitive status change in members of the NAS-NRC Twins Registry of World War II veterans. METHODS: Participants completed the modified Telephone Interview for Cognitive Status (TICS-m) on three occasions spanning a period of approximately 7 years. Based on factor analysis, occupational characteristics were interpreted as reflecting general intellectual demands (GI), human interaction and communication (HC), physical exertion (PE), and visual attention (VA). RESULTS: Based on regression analysis of TICS-m change that was dependent on twin pairing and additionally covarying for education, age at each testing event, medical conditions, and initial TICS-m score, higher GI was associated with a modest longitudinal improvement in TICS-m performance, whereas higher PE and VA were both associated with a modest decline. Subsequent analysis revealed that these significant effects were present among dizygotic twins, but not among monozygotic twins. CONCLUSIONS: Previous findings of a relationship between occupational characteristics and cognitive performance in later life may be partially explained by genetic factors; however, until these genes are identified, occupational characteristics may be useful markers.

Age effects of coronary artery bypass graft on cognitive status change among elderly male twins.

BACKGROUND: Research regarding long-term cognitive outcome following coronary artery bypass graft (CABG) is inconsistent, which may be due in part to differential genetic and environmental influences within most study samples. METHODS: The authors examined the effect of CABG on cognitive status change scores in members of the National Academy of Sciences-National Research Council Twins Registry of World War II veterans. Subjects were administered the modified Telephone Interview for Cognitive Status (TICS-m) at approximately 3-year intervals between 1990 and 2002 as part of an epidemiologic study of dementia. RESULTS: Based on co-twin control analyses using a repeated-measures analysis of variance matching twins discordant for CABG within the pair (n = 464 individuals) across three age categories (63 to 70, 71 to 73, 74 to 83), the authors found at follow-up that men who had CABG between ages 63 and 70 showed an increase in TICS-m scores and performed better than their co-twin who did not have the procedure. No significant differences were found within twin pairs for the older two age groups following CABG surgery. This age effect was replicated when comparing individuals positive for CABG surgery with nonfamilial, age- and education-matched controls who were negative for CABG. CONCLUSIONS: In this study of twin pairs who share many genetic and environmental risks for cerebrovascular problems, the results suggest that timing of the CABG procedure may be important to predicting positive cognitive outcomes.

Modulated kinase activities in cells undergoing tumour necrosis factor-induced apoptotic cell death.

Tumour necrosis factor-alpha (TNF) has a variety of cellular effects including apoptotic and necrotic cytotoxicity. TNF activates a range of kinases, but their role in cytotoxic mechanisms is unclear. HeLa cells expressing elevated type II 75 kDa TNF receptor (TNFR2) protein, analysed by flow cytometry and Western analysis, showed altered c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38MAPK; but not MAPK) protein content and activation. There was greater JNK activation, but reduced p38MAPK activation in dying cells compared to those still to enter TNF-induced apoptosis. Moreover, cells displaying more rapid apoptosis possess higher levels of type I 55 kDa TNFR1 receptor isoform, but less TNFR2. These findings reveal differential kinase activation in TNF-induced apoptotic death.

A longitudinal study of gender differences in depressive symptoms from age 50 to 80.

The Obvious Depression Scale was administered to 739 community residents at ages 50, 60, and 80 years, with 151 present at all waves. Although selective attrition influenced the level of depressive symptoms in cross-sectional vs. longitudinal samples, both sets of analyses revealed higher scores in women than in men at ages 50 and 60, but not at age 80. Men showed increases in depressive symptoms from age 60 to 80, but women did not (interaction p < .002). This interaction was not present in somatic symptoms, which increased across time in both genders. Potential explanations include differential changes in social roles with aging.

Central nervous system serotonin function and cardiovascular responses to stress.

OBJECTIVE: The objective of this study was to evaluate the impact of indices of central nervous system (CNS) serotonin function on cardiovascular reactivity to mental stress. METHODS: Lumbar puncture was performed on 54 healthy volunteers to obtain cerebrospinal fluid (CSF) for determination of 5-hydroxyindoleacetic acid (5HIAA) levels. Genotypes were determined with respect to a functional polymorphism of the serotonin transporter gene promoter region (5HTTLPR). Subjects then underwent mental stress testing. RESULTS: Persons with one or two long (l) 5HTTLPR alleles had CSF levels of the major serotonin metabolite, 5HIAA, that were 50% higher than those of persons with the s/s 5HTTLPR genotype. Persons with one or two l alleles or higher CSF 5HIAA levels also exhibited greater blood pressure and heart rate responses to a mental stress protocol. CONCLUSIONS: These findings suggest the 5HTTLPR polymorphism affects CNS serotonin function, and they are consistent with the general hypothesis that CNS serotonin function is involved in the regulation of potentially health-damaging biobehavioral characteristics. In particular, the l allele could contribute, through its association with increased cardiovascular reactivity to stress, to increased risk of cardiovascular disease.

Documented head injury in early adulthood and risk of Alzheimer's disease and other dementias.

BACKGROUND: The association between antecedent head injury and AD is inconsistent. OBJECTIVE: To examine the association between early adult head injury, as documented by military hospital records, and dementia in late life; and to evaluate the interaction between head injury and APOE epsilon4 as risk factors for dementia. METHODS: The study had a population-based prospective historical cohort design. It included men who were World War II Navy and Marine veterans, and were hospitalized during their military service with a diagnosis of either a nonpenetrating head injury or another unrelated condition. In 1996 to 1997, military medical records were abstracted to document the occurrence and details of closed head injury. The entire sample was then evaluated for dementia and AD using a multistage procedure. There were 548 veterans with head injury and 1228 without head injury who completed all assigned stages of the study. The authors estimated risk of dementia, specifically AD, using proportional hazards models. RESULTS: Both moderate head injury (hazard ratio [HR] = 2.32; CI = 1.04 to 5.17) and severe head injury (HR = 4.51; CI = 1.77 to 11.47) were associated with increased risk of AD. Results were similar for dementia in general. The results for mild head injury were inconclusive. When the authors stratified by the number of APOE epsilon4 alleles, they observed a nonsignificant trend toward a stronger association between AD and head injury in men with more epsilon4 alleles. CONCLUSIONS: Moderate and severe head injuries in young men may be associated with increased risk of AD and other dementias in late life. However, the authors cannot exclude the possibility that other unmeasured factors may be influencing this association.

Hostility predicts magnitude and duration of blood pressure response to anger.

The hypothesis that hostile and nonhostile individuals would differ in both magnitude and duration of cardiovascular reactivity to relived anger was tested. Participants were 66 older adults (mean age, 62; 38 women and 28 men; 70% Caucasian American, 30% African American). Each took part in a structured interview scored using the Interpersonal Hostility Assessment Technique. Later each relived a self-chosen anger memory while heart rate and systolic and diastolic blood pressures were measured continuously using an Ohmeda Finapres monitor. Hostile participants had larger and longer-lasting blood pressure responses to anger. African Americans also showed longer-lasting blood pressure reactivity to anger. Health and measurement implications are discussed.

Ambulatory cardiovascular activity in Vietnam combat veterans with and without posttraumatic stress disorder.

The present study investigated the relationship between daily diary affect ratings and ambulatory cardiovascular activity in 117 male Vietnam combat veterans (61 with posttraumatic stress disorder [PTSD] and 56 without PTSD). Participants completed 12-14 hr of ambulatory monitoring and daily diary affect ratings. Compared with veterans without PTSD, veterans with PTSD reported higher negative affect and lower positive affect in daily diary ratings. No differences were detected for mean laboratory initial recordings or mean ambulatory heart rate (HR), systolic blood pressure (SBP), or diastolic blood pressure (DBP). However, compared with veterans without PTSD, veterans with PTSD demonstrated higher SBP and DBP variability and a higher proportion of HR activity (compared with initial recording values) during daily activity. There was a significant Time of Day x Group interaction for mean HR, with a trend for PTSD participants to maintain HR levels during evening hours.

APOE and AD concordance in twin pairs as predictors of AD in first-degree relatives.

OBJECTIVE: To examine the independent effects of the APOE genotype (APOE) and concordance for AD in twin pairs on the occurrence of AD in first-degree relatives. BACKGROUND: Studies of twins have been undertaken to investigate the influence of genes in a variety of conditions, including AD. A previous study, performed before reports linking APOE to AD, demonstrated an increase in AD among first-degree relatives of twins concordant for AD compared with relatives of discordant twins. METHODS: In a sample of 94 twin pairs the authors examined the association between concordance for AD within the twin pair and family history of AD among first-degree relatives of twins. They then examined the extent to which the presence of the APOE epsilon4 allele in the twin pair explains the association between concordance for AD within the twin pair and family history of AD. RESULTS: Concordance among twins was associated with increased risk of AD among relatives (logrank test, chi2 = 12.558; p = 0.0004), and the presence of at least one APOE epsilon4 allele in each member of the twin pair is also associated with increased risk of AD among family members (logrank test, chi2 = 7.712; p = 0.0055). CONCLUSIONS: APOE genotype explains much but not all of the association between concordance among twins and increased familial risk of AD.

Depressive symptoms and survival of patients with coronary artery disease.

OBJECTIVE: Multiple studies have shown that high levels of depressive symptoms increase the mortality risk of patients with established coronary disease. This investigation divided depressive symptoms into groups to assess their relative effectiveness in predicting survival. METHODS: Questionnaires about the presence of depressive symptoms were administered to 1250 patients with significant coronary disease while they were hospitalized for diagnostic coronary angiography. Follow-up for mortality due to cardiac disease was conducted annually for up to 19.4 years. Factor analysis was used to divide items on the Zung Self-Rating Depression Scale into four groups: Well-Being, Negative Affect, Somatic, and Appetite. In addition, responses to a single item regarding feelings of hopelessness were available for 920 patients. RESULTS: Well-Being and Somatic symptoms significantly predicted survival (p < or = .01). Negative Affect items were also related to survival (p = .0001) and interacted with age. A 2-SD difference in the Negative Affect term was associated with a relative risk of 1.29 for patients >50 years old and 1.70 for younger ones. Only Negative Affect remained significant in a model with the other symptom groups. Hopelessness also predicted survival with a relative risk of 1.5. Both the Hopelessness and Negative Affect items remained as independent predictors in the same model. All models controlled for severity of disease and treatment. With one exception (income and Hopelessness), results were essentially unchanged by additional controls for age, gender, and income. CONCLUSIONS: Depressive symptoms differentially predicted survival, with depressive affect and hopelessness being particularly important. These effects were independent of disease severity and somatic symptoms and may be especially important in younger patients.

Cerebrovascular disease and depression symptoms in the cardiovascular health study.

BACKGROUND AND PURPOSE: Evidence is mounting linking cerebrovascular disease with depressive symptoms in the elderly. Lesions in both white and gray matter have been associated with depressive symptoms and major depression. We sought to investigate the relationship between depressive symptoms and white and gray matter lesions in subjects participating in the Cardiovascular Health Study. METHODS: In a sample of 3660 men and women who underwent a standardized interview, physical examination, and MRI scan, we examined the association between number of white and gray matter lesions and white matter grade (a measure of severity) and reported depressive symptoms using a modified version of the Centers for Epidemiologic Studies Depression (CES-D) scale. We controlled for a variety of demographic and medical variables as well as functional status and Modified Mini-Mental State Examination score. RESULTS: The number of small (<3 mm) basal ganglia lesions was significantly associated with reported depressive symptoms, but white matter grade was not. In subsequent logistic regression models, number of basal ganglia lesions remained a significant predictor after controlling for non-MRI variables and severity of white matter lesions. CONCLUSIONS: Our findings extend previous reports that linked cerebrovascular changes to depressive symptoms in clinical populations to a large community-based population. This report provides further evidence of the importance of basal ganglia lesions in geriatric depression.

Symptoms of depression and changes in body weight from adolescence to mid-life.

OBJECTIVE: To investigate the relationship of symptoms of depression to weight changes in healthy individuals of normal weight across a follow-up of over 20 y. PARTICIPANTS AND DESIGN: College students (3885 men and 841 women) were administered a self-report depression measure in the mid-1960s. Their baseline body mass index (BMI) was calculated from their college medical records. Participants were contacted by mail in the late 1980s and asked to report their current height and weight as well as their smoking and exercise habits. Another measure of depressive symptoms was obtained from 3560 individuals at follow-up. Multiple regression models were used to relate changes in weight to depression scores while controlling for background (gender, baseline BMI and the gender by BMI interaction) and behavioral (exercise and smoking) predictors. RESULTS: The relationship between depressive symptoms and body weight change took the form of an interaction with baseline BMI (P < 0.001). Those with high baseline depression scores gained less weight than their nondepressed counterparts if they were initially lean, but more if they were initially heavy. This trend was especially strong in those with high depression scores at both baseline and follow-up. CONCLUSIONS: The findings support the hypothesis that depression exaggerates pre-existing weight change tendencies. This pattern would not have been detected by an examination of main effects alone, illustrating the need to move toward more complicated interactive models in the study of psychological factors and weight.

Measures of hostility as predictors of facial affect during social interaction: evidence for construct validity.

We assessed the construct validity of several self-report measures and an interview-based measure of hostility (Interpersonal Hostility Assessment Technique [IHAT]) by evaluating their associations with a behavioral indicator of hostile emotions (facial expressions during social interaction). Participants in the study were 123 volunteers (44% males and 56% females) who were recruited from local community organizations. Self-report measures (Cook-Medley Hostility Scale, Rotter Interpersonal Trust Scale, Buss-Durkee Hostility Inventory, and Spielberger Anger Expression Scale) were represented by factor scores reflecting Overt Hostility, Covert Hostility, and Hostile Beliefs. A canonical correlation analysis identified significant associations between a set of facial affect scores reflecting animosity and various measures of hostility. Specifically, increases in anger and disgust expressions and decreases in happy facial expressions were associated with high IHAT scores and high scores on self-report measures of Hostile Beliefs and Covert Hostility. Women were more expressive than men, especially concerning positive affect, and women had lower scores on self-report measures of Hostile Beliefs and Overt Hostility. IHAT scores were uncorrelated with any of the self-report factors which suggests the two assessment techniques are tapping different aspects of the hostility construct.

Psychosocial correlates of job strain in a sample of working women.

BACKGROUND: This study identifies potential mediators of job strain effects on health by determining whether psychosocial factors known to predict an increased risk of cardiovascular disease and all-cause mortality are higher among women who report high levels of job strain. METHODS: Measures of job strain and other psychosocial risk factors were obtained in a sample of 152 female employees of a local corporation. Canonical correlation and analyses of covariance were used to assess relationships between job demands and decision latitude and other psychosocial risk factors. RESULTS: A significant (P = .002) solution to the canonical correlation analysis showed that high job demands and low decision latitude were correlated with a pattern of psychosocial factors consisting of (1) increased levels of negative emotions like anxiety, anger, depression, and hostility; (2) reduced levels of social support; and (3) a preponderance of negative compared with positive feelings in dealings with coworkers and supervisors. This pattern was confirmed by analyses of covariance that adjusted for demographic and specific job characteristics. CONCLUSIONS: The canonical correlation analysis results provide empirical support for the job strain construct. The most important finding is that health-damaging psychosocial factors like job strain, depression, hostility, anxiety, and social isolation tend to cluster in certain individuals.

A twin study of late-onset depression and apolipoprotein E epsilon 4 as risk factors for Alzheimer's disease.

A prior history of depression and the epsilon 4 allele of apolipoprotein E (APOE) have each been associated with development of Alzheimer's disease (AD). In a sample of 142 elderly twins from a large study of dementia, we examined the relation of major depression, APOE genotype and AD using time-dependent proportional hazards models. Compared against the risk for AD with no history of depression and no epsilon 4 allele, the risk ratio for AD with two epsilon 4 alleles was 2.87 (C.I. = 1.56-5.28), with one epsilon 4 allele, 1.82 (C.I. = 1.09-3.04) and with late-onset depression and no epsilon 4 allele, 2.95 (C.I. = 1.55-5.62). There was no suggestion of an interaction between prior depression and APOE genotype in their effects on AD risk. Results were similar when the sample was stratified by twin pair, so that a single genetic marker is unlikely to explain the relation among depression, APOE, and dementia. Risk ratios declined substantially with increasing intervals between the onset of depression and AD. Thus, for many individuals, the association of depression and AD may reflect the occurrence of prodromal depressive symptoms rather than a true risk relationship.

Apolipoprotein E epsilon 4 allele and hippocampal volume in twins with normal cognition.

We examined the relation of APOE-epsilon 4, hippocampal volume, and cognitive performance in ten pairs of cognitively normal twins who had a mean age of 62.5 years (SD = 7.8). There were no significant differences in neuropsychological measures of the groups categorized by the presence of an epsilon 4 allele. However, the mean normalized right and left hippocampal volumes were smaller in the epsilon 4 groups compared to the group without epsilon 4. Combined with prior reports, these findings suggest that epsilon 4 is associated with differences in brain morphology that may be evident when no symptoms of dementia are present.

Personality factors differentially predict exercise behavior in men and women.

Personality assessed with the Minnesota Multiphasic Personality Inventory (MMPI) in college was used to predict exercise behavior measured at midlife in 3,630 men and 796 women enrolled in the University of North Carolina Alumni Heart Study. Logistic regression models were fitted for each of the MMPI clinical scales to test the predictive effect of personality, gender, and their interaction on adult exercise behavior. Lower depression, social introversion, and psychopathic deviance scores were associated with increased probability of exercising in midlife for both men and women. Furthermore, better psychological health (indexed by lower hypochondriases and psychasthenia) in college was generally predictive of increased exercise for men, whereas higher scores on these same factors predicted midlife exercise for women. There were two other patterns of gender interactions: (a) for men, lower scores on hysteria and schizophrenia scales were associated with increased probability of exercising at midlife, whereas these factors were unrelated to exercise for women and (b) for women, lower ego strength and higher college scores on paranoia and mania were associated with exercise behavior at midlife. These data suggest that early adulthood personality predictors of exercise behavior at midlife are both gender-neutral and gender-specific; that is, where no gender differences exist, healthier personality traits predict exercise at midlife, and when gender differences do occur, healthier college patterns of personality predict exercise behavior for men and sedentary behavior for women.

Are SSRIs better than TCAs? Comparison of SSRIs and TCAs: a meta-analysis.

In this analysis we examined studies of tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) to compare efficacy and drop-out rates. Frequency of reported side effects was also studied. Using Medline, we located 36 clinical trials of TCAs and SSRIs in a double-blind comparison. We performed a meta-analysis on these studies and on a subgroup of 21 studies that had more uniformly defined outcome criteria. The main outcome measures were efficacy for treatment completers and for the intention-to-treat group; drop-out rates due to adverse reactions and lack of efficacy; and reported side effects. Overall, the response rate to treatment for patients who completed a trial was 63.2% for SSRIs and 68.2% for TCAs (P = 0.038). For the intention-to-treat groups, these rates dropped to 48.0 and 48.6% (P, NS), respectively. Significantly more TCA-treated than SSRI-treated subjects dropped out due to either lack of efficacy or adverse reactions (30.0 vs. 24.7%, P = 0.01). Patients taking SSRIs experienced significantly more gastrointestinal problems and sexual dysfunction, whereas treatment with TCAs produced significantly more complaints of sedation, dizziness, and anticholinergic symptoms.

Depression and long-term mortality risk in patients with coronary artery disease.

Previous research has established that patients with coronary artery disease (CAD) have an increased risk of death if they are depressed at the time of hospitalization. Follow-up periods have been short in these studies; therefore, the present investigation examined this phenomenon over an extended period of time. Patients with established CAD (n = 1,250) were assessed for depression with the Zung Self-Rating Depression Scale (SDS) and followed for subsequent mortality. Follow-up ranged up to 19.4 years. SDS scores were associated with increased risk of subsequent cardiac death (p = 0.002) and total mortality (p < 0.001) after controlling for initial disease severity and treatment. Patients with moderate to severe depression had a 69% greater odds of cardiac death and a 78% greater odds of mortality from all causes than nondepressed patients. Increased risk was not confined to the initial months after hospitalization. Patients with high SDS scores at baseline still had a higher risk of cardiac death > 5 years later (p < 0.005). Compared with the nondepressed, patients with moderate to severe depression had an 84% greater risk 5 to 10 years later and a 72% greater risk after > 10 years. Patients with mild depression had intermediate levels of risk in all models. The heightened long-term risk of depressed patients suggests that depression may be persistent or frequently recurrent in CAD patients and is associated with CAD progression, triggering of acute events, or both.

Interpersonal and self-reported hostility among combat veterans with and without posttraumatic stress disorder.

The present study investigated self-reported and interpersonal hostility in 70 Vietnam combat veterans with and without posttraumatic stress disorder (PTSD) and 60 comparison community volunteer subjects. Veterans were 50 help-seeking, male Vietnam combat veterans with PTSD and 20 non-help-seeking male combat veterans without PTSD. Vietnam veterans with PTSD not only reported more hostility than non-PTSD veterans and healthy community volunteers, but also reacted behaviorally with more hostility during an interpersonal interaction. Compared to veterans without PTSD, veterans with PTSD reported significantly higher levels of hostility and demonstrated significantly greater non-verbal expressions of hostility during an interpersonal task. These results suggest that the level of hostility in PTSD combat veterans may be high as compared to comparison groups. The implications of these results and possible research directions are presented.