Urinary cortisol excretion as a predictor of incident cognitive impairment

Elevated glucocorticoid levels have been associated with cognitive impairment, including dementia. However, few longitudinal studies have examined the association between resting cortisol levels and the incidence of cognitive impairment. We measured overnight urinary excretion of cortisol in 538 high-functioning men and women, 70-79 years of age, in 1988, and assessed their cognitive functioning in 1988, 1991, and 1995 using the short portable mental status questionnaire (SPMSQ). Compared to participants in the bottom quartile of urinary cortisol at baseline, those in the top three quartiles had higher risk of incident cognitive impairment over the 7-year follow up (i.e., decline in SPMSQ score to below six out of nine). This association was not affected by adjustment for age, gender, education level, ethnicity, smoking, prevalent cardiovascular disease, and blood pressure (adjusted odds ratio for the highest quartile 2.34, 95% confidence interval, 1.07-5.14). There was no effect modification by gender; the association was equally strong in men and women. We conclude that urinary excretion of cortisol predicts incident cognitive impairment in older men and women.     

Family history of cardiovascular disease is associated with cardiovascular responses to stress in healthy young men and women.

Heightened cardiovascular stress responsivity is associated with cardiovascular disease, but the origins of heightened responsivity are unclear. The present study investigated whether disturbances in cardiovascular responsivity were evident in individuals with a family history of cardiovascular disease risk. Data were collected from 60 women and 31 men with an average age of 21.4 years. Family history of cardiovascular disease risk was defined by the presence of coronary heart disease, hypertension, diabetes or high cholesterol in participants' parents and grandparents; 75 participants had positive, and 16 had negative family histories. Systolic and diastolic blood pressure (BP), heart rate and heart rate variability were measured continuously for 5 min periods at baseline, during two mental stress tasks (Stroop and speech task) and at 10-15 min, 25-30 min and 40-45 min post-stress. Individuals with a positive family history exhibited significantly greater diastolic BP reactivity and poorer systolic and diastolic BP recovery from the stressors in comparison with family history negative individuals. In addition, female participants with a positive family history had heightened heart rate and heart rate variability reactivity to stressors. These effects were independent of baseline cardiovascular activity, body mass index, waist to hip ratio and smoking status. Family history of hypertension alone was not associated with stress responsivity. The findings indicate that a family history of cardiovascular disease risk influences stress responsivity which may in turn contribute to risk of future cardiovascular disorders.     

Loneliness and health: potential mechanisms

OBJECTIVE: Two studies using cross-sectional designs explored four possible mechanisms by which loneliness may have deleterious effects on health: health behaviors, cardiovascular activation, cortisol levels, and sleep. METHODS: In Study 1, we assessed autonomic activity, salivary cortisol levels, sleep quality, and health behaviors in 89 undergraduate students selected based on pretests to be among the top or bottom quintile in feelings of loneliness. In Study 2, we assessed blood pressure, heart rate, salivary cortisol levels, sleep quality, and health behaviors in 25 older adults whose loneliness was assessed at the time of testing at their residence. RESULTS: Total peripheral resistance was higher in lonely than nonlonely participants, whereas cardiac contractility, heart rate, and cardiac output were higher in nonlonely than lonely participants. Lonely individuals also reported poorer sleep than nonlonely individuals. Study 2 indicated greater age-related increases in blood pressure and poorer sleep quality in lonely than nonlonely older adults. Mean salivary cortisol levels and health behaviors did not differ between groups in either study. CONCLUSIONS: Results point to two potentially orthogonal predisease mechanisms that warrant special attention: cardiovascular activation and sleep dysfunction. Health behavior and cortisol regulation, however, may require more sensitive measures and large sample sizes to discern their roles in loneliness and health.     

Cardiovascular and cortisol reactions to acute psychological stress and cognitive ability in the Dutch Famine Birth Cohort Study

Given evidence linking blunted cardiovascular and cortisol reactions to acute stress and a range of adverse behavioral outcomes, the present study examined the associations between cardiovascular and cortisol reactivity and cognitive ability measured independently of the stress task exposure. Cognitive ability was assessed using the Alice Heim-4 test of general intelligence and two memory tasks in 724 men and women who were part of the Dutch Famine Birth Cohort Study. Blood pressure and heart rate, as well as cortisol reactivity, were measured to a battery of three standard acute stress tasks. Poorer cognitive ability was associated with lower cardiovascular reactions to stress and lower cortisol area under the curve. Our results are consistent with recent findings implicating low physiological stress reactivity in a range of adverse behavioral and health outcomes.     

Salivary α‐amylase stress reactivity across different age groups

Salivary α‐amylase (sAA) increases rapidly in response to psychosocial stress in young adults, but no direct comparisons between different age groups across the life span have been made. Secretion of sAA and cortisol was assessed in children, young adults, and older adults after exposure to the Trier Social Stress Test. Additionally, cardiovascular activity was measured in both adult groups. Older adults showed attenuated sAA, heart rate (HR), and heart rate variability (HRV) responses. Furthermore, we found higher sAA but lower cortisol at baseline as well as lower sAA and cortisol responses in children. Age × sex interactions were observed only for cortisol with higher responses in older male participants. No associations between the parameters were found. These results implicate sAA as an alternative or additional sympathetic stress marker throughout the life span, with marked and rapid stress responsiveness in three relevant age groups.     

Differential heart rate reactivity and recovery after psychosocial stress (TSST) in healthy children,younger adults,and elderly adults: The impact of age and gender

In addition to numerous reports about psychophysiological stress responses to acute stressors, there are few data available on gender differences of stress-induced heart rate responses in multiple age groups applying the same psychological stressor. Second, the assessment of poststress recovery appears to be neglected in the empirical literature. For this study, data from 5 independent studies were reanalyzed to investigate the impact of age and gender on heart rate responses and poststress recovery to a standardized psychosocial stress task (Trier Social Stress Test; TSST) in 28 children, 34 younger adults, and 26 older adults. As expected, prestressor baselines correlated significantly with chronological age (r = -.27, p = .01). There was a marked age-related decrease in the heart rate stress response (p = .0003) with children and younger adults showing significantly higher increases than elderly persons. The analysis of gender effects showed that girls had higher heart rate increases during the stress exposure than boys (p = .03). In younger adults, stress responsivity was also higher in women (p = .03). Peak heart rate responses were comparable in older men and women, with only men returning to prestressor baselines during the observation period. In sum, this reanalysis revealed differential heart rate responses and recovery after exposition to the TSST in healthy children, younger adults, and elderly adults.     

Individual differences in alpha rhythm responsivity: Inter-task consistency and relationships to cardiovascular and dispositional variables

Individual differences in EEG alpha rhythm responsivity were examined with respect to: (1) consistency of response across cognitive tasks; (2) relationships to cardiovascular responsivity; and (3) relationships to dispositional variables. Inter-task correlations revealed a significant degree of stability in subjects' alpha responses to four ‘sensory rejection’ tasks: mental arithmetic, time estimation and imagining oneself as cold or warm. Individuals evidencing greater suppression of alpha activity during mental arithmetic also displayed greater heart rate increase and greater digital vasoconstriction, as well as obtaining higher scores on the Activity subscale of the EASI-III Temperament Survey and on the ‘Hard Striving’ subscale of the Jenkins Activity Survey for Health Prediction, a measure of the Coronary-Prone Behavior Pattern. Alpha responsivity in the time estimation and warm imagery tasks was also associated with greater heart rate increase. The results suggest that alpha responsivity is related to individual differences affecting one's attentiveness or involvement in experimental tasks.     

Age- and sex-related disturbance in a battery of sensorimotor and cognitive tasks in Kunming mice

A battery of tasks, i.e. beam walking, open field, tightrope, radial six-arm water maze (RAWM), novel-object recognition and olfactory discrimination, was used to determine whether there was age- and sex-related memory deterioration in Kunming (KM) mice, and whether these tasks are independent or correlated with each other. Two age groups of KM mice were used: a younger group (7-8 months old, 12 males and 11 females) and an older group (17-18 months old, 12 males and 12 females). The results showed that the spatial learning ability and memory in the RAWM were lower in older female KM mice relative to younger female mice and older male mice. Consistent with this, in the novel-object recognition task, a non-spatial cognitive task, older female mice but not older male mice had impairment of short-term memory. In olfactory discrimination, another non-spatial task, the older mice retained this ability. Interestingly, female mice performed better than males, especially in the younger group. The older females exhibited sensorimotor impairment in the tightrope task and low locomotor activity in the open-field task. Moreover, older mice spent a longer time in the peripheral squares of the open-field than younger ones. The non-spatial cognitive performance in the novel-object recognition and olfactory discrimination tasks was related to performance in the open-field, whereas the spatial cognitive performance in the RAWM was not related to performance in any of the three sensorimotor tasks. These results suggest that disturbance of spatial learning and memory, as well as selective impairment of non-spatial learning and memory, existed in older female KM mice.     

Hemodynamic profile of stress-induced anticipation and recovery.

Systolic and diastolic blood pressure, heart rate, stroke volume, cardiac output, and total peripheral resistance were measured in 100 healthy men and women with the aim of investigating hemodynamic profile during anticipation of, and recovery from, exposure to active and passive laboratory stressors. A 5-min anticipatory period preceded two tasks, both of which lasted 2.5 min. The tasks were mental arithmetic ('beta-adrenergic' stress) and the cold pressor test ('alpha-adrenergic' stress). Each task was followed by a 5-min recovery period. Blood pressure and heart rate were measured with a FinaPres 2300e, and stroke volume, cardiac output, and total peripheral resistance were computed from these parameters. Salivary cortisol was measured in relation to both tasks, and participants completed tests of state and trait anxiety, locus of control, and hostility. As expected, mental arithmetic and the cold pressor test elicited myocardial and vascular patterns of reactivity, respectively. However, contrary to expectations, anticipatory and recovery hemodynamic profile involved essentially vascular responding for both stressors. Salivary cortisol increased in response to both tasks but only weakly correlated with hemodynamic changes. None of the subjective measurements was a strong predictor of physiological reactivity. The findings suggest that stress-induced anticipatory and recovery reactivity may be generally vascular rather than myocardial. This could have important implications in light of suggestions that anticipatory and recovery responses may be better predictors of subsequent cardiovascular disease than direct stress-induced reactivity.     

Effects of Working Memory Load on Performance and Cardiovascular Activity in Younger and Older Workers

Background

Working memory (WM) declines with ageing, and this may cause problems in older workers who have to do complex work requiring WM.

Purpose

We tested the assumption that an increase in WM load negatively affects performance and results in impaired cardiovascular adaptation to changing task demands in older workers relative to younger ones.

Method

Thirty-three younger (29?±?3?years) and 32 older (55?±?3?years) workers had to perform a visual 0-back (low WM load) and 2-back (high WM load) task. Heart rate (HR), heart rate variability (HRV), beat-to-beat blood pressure (BP) and baroreflex were registered.

Results

In the high WM load condition, older adults responded more slowly and less accurately than younger adults, while no age effects in the low WM load condition were found. Older workers showed a higher systolic blood pressure (SBP) reactivity to high WM load as well as a diminished post-task recovery of SBP and HRV than younger workers. Factor analysis demonstrated a close relationship between HR, baroreflex and HRV and their modulation by a common factor (??vagal tone??) in the younger group. By contrast, HR was more related to the ??sympathetic?? factor in the older group.

Conclusion

The data suggest that older workers as compared with younger ones are impaired in tasks requiring WM, which is accompanied by enhanced cardiovascular ??costs?? in terms of increased SBP and reduced vagal control over HR.     

The socio-economic status of communities predicts variation in brain serotonergic responsivity

BACKGROUND: We reported previously that the socio-economic status (SES) of individuals predicts variation in brain serotonergic responsivity, as assessed by neuropharmacological challenge in an adult community sample, and that this association is qualified by allelic variation in the serotonin transporter gene-linked polymorphic region (5-HTTLPR). Here we examine whether serotonergic responsivity covaries similarly with the SES of communities, as indexed by US Census data in the same study sample. METHOD: Community SES was defined by levels of income, economic disadvantage, housing costs, and educational attainment of census tracts in which 249 locally recruited study participants (54% male) resided. Serotonergic responsivity was assessed as the baseline-adjusted, peak plasma prolactin (Prl) concentration following acute administration of the serotonin-releasing agent, fenfluramine; tissue for DNA extraction and 5-HTTLPR genotyping was available on 131 participants. RESULTS: Subjects residing in census tracts of lower SES showed a blunted Prl response to fenfluramine (diminished serotonergic responsivity) relative to individuals living in more affluent neighborhoods. When adjusted for personal income and education, SES at the community level continued to predict fenfluramine-stimulated Prl responses and did so independently of 5-HTTLPR genotype. CONCLUSIONS: Area-level indices of relative social and economic disadvantage covary with individual differences in brain serotonergic responsivity, and this association is, in part, independent of individually defined SES. These findings may be relevant to reported effects of low community SES on the prevalence of psychiatric disorders or behaviors associated with dysregulation of central serotonergic function, such as depression, impulsive aggression, and suicide.     

Association between smoking status and cardiovascular and cortisol stress responsivity in healthy young men

Acutely, cigarette smoking stimulates increases in blood pressure (BP). heart rate (HR), and cortisol, but little evidence is available concerning the impact of habitual smoking status on cardiovascular stress responsivity. This relation was assessed in 86 healthy male firefighters, age 19 to 31, comprising 52 nonsmokers and 34 smokers. Measures of BP, HR, salivary free cortisol, breathing pattern, and self-reported stress and alertness were obtained while subjects performed nonverbal mental arithmetic and a socially evaluative speech task. Systolic and diastolic BP were higher at rest in nonsmokers than smokers, and a consistent difference in stress responsivity was also found. BP, HR, and cortisol responses to mental arithmetic were significantly smaller in smokers than nonsmokers, with mean changes in BP (adjusted for body weight) averaging 19.3/1 l.0 mmHg and 28.5/15.4 mmHg in smokers and nonsmokers, respectively. There were no effects of smoking status on task performance or subjective stress responses and no differences between groups in family health history, health-related behaviors, or psychological characteristics that might account for the reactivity difference. Possible explanations of the results are discussed, and methodological implications for cardiovascular stress reactivity studies are outlined. This study was supported by the Medical Research Council, UK     

Salivary alpha-amylase response to acute psychosocial stress: the impact of age

The impact of stress on health varies across the different stages of human life. Aging is associated with psychobiological changes that could limit our ability to cope with stressors. Therefore, it is crucial to clarify the physiological mechanisms that underlie the stress response and the changes that occur in them as we age. Our aim was to investigate age differences in the salivary alpha amylase (sAA) response to stress, and its relationship with other typical stress biomarkers such as cortisol and heart rate (HR). Sixty-two participants divided into two age groups (younger group: N = 31, age range: 18-35 years; older group: N = 31, age range: 54-71 years) were exposed to the Trier Social Stress Test and a control condition in a crossover design. No age differences were found in the sAA or HR responses to stress. However, the sAA global output was higher in older than younger adults. Additionally, in the stress condition, the total amount of cortisol released was positively related to the total sAA released, while the HR increase was positively related to the sAA increase. Our results do not support the existence of an attenuated autonomic nervous system response to stress in older adults, but rather a heightened sympathetic tone. Furthermore, we found further evidence of the coordination between the hypothalamus-pituitary-adrenal system and the autonomic nervous system in their response to acute psychosocial stress.     

The effects of depressive symptoms on cardiovascular and catecholamine responses to the induction of depressive mood

We examined the effects of depressive symptoms on cardiovascular and catecholamine responses to the induction of different mood states. Fifty-five healthy men and women (mean age 23.4 +/- 3 years) were recruited. Depressive symptoms were evaluated using the Center for Epidemiological Studies Depression Scale (CES-D) and participants were classified into high depressive (CES-D*16) or low depressive symptoms (CES-D < 16) groups. Following a baseline period, participants were required to complete two separate speech tasks where they were asked to recall life events that made them feel angry or depressed. The tasks were separated by a 30-min recovery period and the order was randomised between participants using a counterbalanced design. Cardiovascular function was monitored continuously using a Finometer device and saliva was collected for the assessment of 3-methoxy-phenylglycol (MHPG, the major metabolite of norephinephrine). Blood pressure (BP), heart rate, and total peripheral resistance (TPR) were significantly increased in response to both tasks (p = .001). Averaged over conditions, higher diastolic BP and higher MHPG levels were observed in high depressive symptoms participants. MHPG levels did not change in response to mood induction in the low depressive symptoms group. However, the high depression symptoms group showed significantly higher levels of MHPG during recovery from the depressed mood induction task and increased levels immediately after the anger induction task. These findings suggest depressive symptoms are associated with heightened central adrenergic activation during negative mood induction, but that the time course of responses is dependent on the type of emotion elicited.     

Cardiovascular responses to light isometric and aerobic exercise in 21- and 59-year-old males

The effects of aging on the cardiovascular response to continuous light isometric and aerobic exercise remains to be determined. Thus, the purpose of this study was to compare the cardiovascular response of young and older males during light handgrip and cycle ergometry exercise. Blood pressure, heart rate, rate pressure product, as well as pre-ejection period (derived from impedance cardiography) were obtained for 15 young [mean (SE) age: 21?(0.7) years] and 15 older males [59 (0.8) years] during and after light handgrip exercise and cycle ergometry. The parasympathetic influence on the heart was also assessed through a time-series analysis of heart period variability (HPV_ts). Both during and when recovering from the handgrip exercise and cycle ergometry, the older subjects exhibited a significantly higher absolute systolic and diastolic blood pressure, and rate pressure product, and a lower HRV_ts than the young subjects. Relative to baseline, the change in pre-ejection period was lower for the young subjects during the handgrip and cycle ergometry, tasks. These results indicate that although the sympathetic influence on both the myocardium and the vasculature was less pronounced in the older males, the aging cardiovasculature was under greater hemodynamic stress both during rest and during exposure to light isometric and aerobic challenge.     

Age-related differences in brain activation during emotional face processing

Advancing age is associated with significant declines on neurobehavioral tasks that demand substantial mental effort. Functional imaging studies of mental abilities indicate that older adults faced with cognitive challenges tend to activate more regions, particularly frontal, than their younger counterparts, and that this recruitment of additional regions may reflect an attempt to compensate for inefficiency in cortical networks. The neural basis of emotion processing in aging has received little attention, and the goal of the present study was to use functional magnetic resonance imaging (fMRI) to examine the influence of age on facial emotion processing and activation in cortical and limbic regions. Participants (eight old and eight young adults) viewed facial displays of happiness, sadness, anger, fear, disgust, and neutrality in alternating blocks of emotion and age discrimination. We predicted that in response to an emotion discrimination task, older adults would demonstrate increased use of frontal regions relative to younger adults, perhaps combined with diminished use of regions recruited by younger adults, such as temporo-limbic regions. During the emotion discrimination task, young participants activated, visual, frontal and limbic regions, whereas older participants activated parietal, temporal and frontal regions. A direct comparison between emotion and age discrimination revealed that while younger adults activated the amygdala and surrounding temporo-limbic regions, older adults activated left frontal regions. The results of this study suggest that older adults may rely on different cortical networks to perceive emotional facial expressions than do their younger counterparts.     

Age dependence of the response of blood pressure, heart rate and plasma renin activity to captopril in essential hypertension

The acute effects of the converting enzyme inhibitor captopril on blood pressure, heart rate and plasma renin activity were assessed in 53 patients (aged 20-80 years) with mild to moderate essential hypertension under basal conditions. The systolic blood pressure before captopril was elevated in patients in the forties (p less than 0,01) when compared to the younger patients and was positively correlated to the age before (r = 0.32, p less than 0.05) and after (r = 0.32, p less than 0,05) angiotensin converting enzyme inhibition with captopril 25 mg. the drop in systolic (-13%) and diastolic (-10%) blood pressure was significantly greater in patients in the fifties (p less than 0,025 and p less than 0,05 respectively) when compared to younger and older (p less than 0,1) patients. The response of plasma renin activity paralleled the blood pressure response, while heart rate after captopril was not significantly changed in any group. The lack of age dependence of the blood pressure response to captopril and of reflex tachycardia suggests converting enzyme inhibition to be a valuable adjunct for the treatment of essential hypertension in the elderly.     

Sleep duration and cardiovascular responses to stress in undergraduate men

Short sleep has been related to incident cardiovascular disease, but physiological mechanisms accounting for this relationship are largely unknown. This study examines sleep duration and cardiovascular stress responses in 79 healthy, young men. Sleep duration was assessed by wrist actigraphy for seven nights. Participants then completed a series of laboratory stress tasks while heart rate and blood pressure were monitored. Shorter total sleep time was related to a greater reduction in high‐frequency heart rate variability during stress tasks, and to prolonged elevations in heart rate and diastolic pressure following tasks. Associations were independent of age, race, body mass index, caffeine intake, and smoking status. In sum, healthy young men with shorter actigraphy‐assessed sleep exhibit less cardiac vagal activity, and poorer heart rate and diastolic blood pressure recovery, upon encountering stressful stimuli, than those with longer sleep.     

Forced expiratory volume is associated with cardiovascular and cortisol reactions to acute psychological stress

It has been argued that blunted cardiovascular and cortisol reactions to acute psychological stress reflect a dysregulation of the neural system that supports motivation. We examined the association between forced expiratory volume in 1 s, an effort (hence motivation) dependent measure of lung function measured by spirometry, and cardiovascular and cortisol reactions to a battery of standard psychological stress tasks, assessed 7 years later. Irrespective of how it was expressed, low forced expiratory volume was associated with blunted heart rate and cortisol stress reactivity. The association survived adjustment for smoking, a range of anthropometric and sociodemographic covariates, and commitment to the stress tasks, as well as cognitive ability.     

Influence of Age on Sensitivity and Effector Mechanisms of the Carotid Baroreflex

In 30 healthy subjects aged 20–48 years the hemodynamic response to carotid sinus stimulation (neck suction -40 mmHg) was studied. Heart rate, arterial pressure and cardiac output (dye dilution technique) were measured. In order to evaluate the effect of age on carotid sinus function the material was subdivided into two arbitrary subgroups, aged up to 30 years (n = 15) respectively 30 years and above (n = 15). Carotid sinus stimulation induced a significantly greater reduction in mean arterial pressure in the younger group compared to the older group. The heart rate reduction was, on the average, slightly greater in the younger group though the difference was not significant. In both groups a significant decrease in cardiac output contributed to the demonstrated reduction in mean arterial pressure. As the decrease in cardiac output was, on the average, slightly smaller in the younger group, the results indicate that the greater blood pressure response in the younger group was due to a greater reduction in peripheral vascular resistance. This is further supported by the finding of a significant correlation between changes in total peripheral vascular resistance, elicited by carotid sinus stimulation and age.