Autonomic cardiovascular responses in old age

The effect of age on autonomically mediated cardiovascular responses to certain manoeuvres was studied in 15, healthy, old men and women (60-80 years). The results were compared with groups of healthy young (about 25 years) and middle-aged (about 45 years) subjects. There was no significant reduction in cardiovascular responses between the young and middle-aged groups. Respiratory sinus arrhythmia, and heart rate, blood-pressure and contralateral forearm blood flow increases to isometric hand grip, as well as the heart rate decrease during a dive reflex test, were significantly attenuated in the old age group. The Valsalva ratio, and the heart rate and blood-pressure changes during an 8 min orthostatic test did not differ between the old and the two younger age groups. There seems to be only a moderate attenuation of autonomic cardiovascular responses to about 60 years, after which there is a more rapid decline. The difference in reduction between different responses, even those mediated by the same type of autonomic nerve, suggests that the decreased responses are not due to an isolated impaired function of the peripheral autonomic nerve. The impairment may be due to the receptor organ or a combination of defects in function of several parts of the autonomic nervous system in old age.     

Cytomegalovirus infection and cognitive abilities in old age

Cytomegalovirus infection has been implicated in cognitive impairment in studies using brief clinical assessments though findings are inconsistent. The association between cytomegalovirus infection, measured as serostatus or a semiquantitative assessment of antibody level, and cognitive abilities in a sample of older adults was examined. Cytomegalovirus status was assessed at a mean age of 70 years in 1061 participants of the Lothian Birth Cohort 1936. Cognitive ability scores were available for general cognitive ability, processing speed, memory, and vocabulary. Background demographic and environmental factors included father's social class, years of education, childhood cognitive ability, overcrowding in childhood, and access to indoor toilet facilities. Cytomegalovirus seropositive individuals had lower cognitive ability at age 70: mean IQ was 99.1 (SD, 15.1) versus 102.4 (SD, 13.1) in seronegative individuals (t = 3.65; p < 0.001). The likelihood of contracting cytomegalovirus infection by age 70 was predicted by a number of demographic and environmental factors and, after accounting for these, cytomegalovirus infection (considered as serostatus) was not cognitively detrimental. Within cytomegalovirus seropositive individuals, however, higher cytomegalovirus antibody levels were associated with lower general cognitive ability.     

Cardiovascular responses and plasma catecholamines in old age

Plasma catecholamines and haemodynamic responses to isometric handgrip, orthostatic body position and dynamic cycle exercise were studied in 10 healthy old men (mean age 71 years) and 10 healthy young men (mean age 26 years). At rest, plasma noradrenaline (NA) was significantly higher in the old age group. During handgrip there were greater increases in heart rate and blood-pressure in the young rather than in the old men, while forearm blood-flow increase was similar in the two age groups, and there was no increase in NA in either groups. In the orthostatic position heart rate increased in the young men only, and forearm blood-flow decreased more in the young than in the old men. NA concentration increased similarly in both age groups. During dynamic exercise the increases in both the heart rate and the blood-pressure, at similar relative submaximal as well as maximal loads, were smaller in the old men. At maximal work NA and adrenaline (A) concentrations were higher in the young men, while at the lowest load, NA concentration was higher in the old men. Similar increases in exercise heart rate, blood-pressure or rate of perceived exertion corresponded to lower increases in NA in the old men. It can be concluded that old men, compared with young men, have a reduced maximal capacity to release NA and A upon provocation. In addition, the sensitivity for catecholamines in the target organ is reduced with age, as suggested by the smaller increases in heart rate and blood-pressure for a given increase in NA during exercise. The higher basal NA level and the higher NA level, during moderate provocation, may suggest a compensatory increase in activity.     

Unhappiness, health and cognitive ability in old age

BACKGROUND: To test whether scores on depression inventories on entry to a longitudinal study predict mental ability over the next 4-16 years. METHOD: Associations between scores on the Beck Depression Inventory and on tests of intelligence, vocabulary and memory were analysed in 5070 volunteers aged 49-93 years after differences in prescribed drug consumption, death and drop-out, sex, socio-economic advantage and recruitment cohort effects had also been considered. RESULTS: On all cognitive tasks Beck scores on entry, even in the range 0-7 indicating differences in above average contentment, affected overall levels of cognitive performance but not rates of age-related cognitive decline suggesting effects of differences in life satisfaction rather than in depression. CONCLUSIONS: A new finding is that, in old age, increments in life satisfaction are associated with better cognitive performance. Implications for interpreting associations between depression inventory scores and cognitive performance in elderly samples are discussed.     

Immune responses in the skin in old age

A marked increase in the susceptibility to cutaneous infections and malignancies has been observed in older humans indicating that cutaneous immunity becomes defective with age. In this review we will focus on recent developments in the understanding of age-related changes in immune function of the skin with a particular emphasis on how alterations in the interaction between cells involved in innate and adaptive immunity leads to decreased cutaneous antigen-specific T cell immunosurveillance.     

Rapid neuroendocrine responses evoked at the onset of social challenge

At the onset of agonistic social challenge, individuals must assess the degree of threat the opponent represents in order to react appropriately. We aimed to characterize the neuroendocrine changes accompanying this period of initial social assessment using the lizard Anolis carolinensis. Conveyance of aggressive intent by male A. carolinensis is facilitated by rapid postorbital skin darkening (eyespot), whereas eyespot presence inhibits opponent aggression. By manipulating this visual signal, we also investigated whether differing neuroendocrine changes were evoked by initial presentation of varying levels of social threat. Subjects were painted postorbitally either with black paint (high threat level), green paint (low threat level) or water (controls). Painted animals were presented with a mirror and sampled immediately upon exhibiting aggressive intent towards the reflected simulated opponent, but before producing behaviors such as motor pattern-based displays. Control animals (blank surface presented) were sampled at times derived from averaging response times of painted subjects. Brains and plasma were analyzed for monoamine activity and catecholamine levels using electrochemical HPLC. Social threat evoked increases in plasma catecholamine levels indistinguishable from those caused by brief environmental disturbance. However, brief social challenge caused distinct rapid increases in amygdala and nucleus accumbens (NAc) dopamine and serotonin levels. Amygdalar changes were associated with general social threat presence, but NAc monoamines were affected by both threat level and subject motivation to engage in confrontation. This suggests that specific rapid activity changes in key forebrain limbic nuclei differ according to the degree of social threat perceived at the start of the interaction.     

Opponent recognition and social status differentiate rapid neuroendocrine responses to social challenge

Individual social status discriminates rapid neuroendocrine responses to non-social stress in male Anolis carolinensis, but whether such status-influenced reactions are retained in response to subsequent social stress is unknown. Dominant and subordinate males modify their behavioral responses to social challenge according to familiarity of the opponent, suggesting that accompanying neuroendocrine responses may differ according to opponent recognition despite social rank. We examined endocrine and neurochemical correlates of prior social status and opponent recognition during the opening stages of social challenge. Male pairs interacted and established dominant/subordinate status, followed by 3 days separation. Subsequently, subjects were paired with either the same opponent or an unfamiliar male according to rank (dominant with subordinate). After 90 s of social exposure, subjects were caught and brains and plasma collected for measurement of circulating corticosterone and limbic monoamines. Controls included pairs experiencing just one 90 s encounter plus a group of non-interacting subjects. Opponent recognition differentiated status-influenced responses, such that dominant lizards paired with familiar subordinate opponents had increased hippocampal dopamine and epinephrine, but showed increased plasma corticosterone and ventral tegmental area (VTA) norepinephrine when challenged with an unfamiliar opponent. Subordinate lizards encountering familiar opponents also had increased corticosterone, along with decreased hippocampal dopamine and increased VTA epinephrine, but showed no changes in response to an unfamiliar opponent. Such plasticity in status-influenced rapid neuroendocrine responses according to opponent recognition may be necessary for facilitating production of behavioral responses adaptive for particular social contexts, such as encountering a novel versus familiar opponent.     

Cardiovascular responses in Type A children during a cognitive challenge

The few studies which have examined stress-induced cardiovascular reactivity among Type A children have had equivocal results. In the present study, 41 extreme Type A and 46 extreme Type B children were monitored for heart rate and blood pressure during a challenging cognitive task under clear or ambiguous performance standards. Significant heart-rate and blood-pressure responses were observed, but no effects could be attributed to the behavior pattern or performance standards. Type A's were more self-involved, generally attributing their performance to effort. Under ambiguous performance standards, they perceived themselves more negatively and attributed performance to luck and task difficulty. These results do not support the exaggerated cardiovascular response hypothesis but do suggest that Type A children look toward external cues in the evaluation of both themselves and their performance, particularly when the external standards for performance are ambiguous.Selected data described in this paper were presented as part of a poster session at the American Psychological Association Annual Convention, August 26–30, 1983, Anaheim, California. This work was supported by Grant R01 HL 19877 from the National Heart, Lung, and Blood Institute.     

Parental hypertension, affect, and cardiovascular response to cognitive challenge

This investigation examined the cardiovascular and affective reactions of offspring of hypertensive and normotensive parents on exposure of subjects to a frustrating cognitive task. Subjects were 44 normotensive, male undergraduate volunteers, 22 with and 22 without a parental history of hypertension. Heart rate (HR) and systolic and diastolic blood pressure (SBP, DBP) measurements were recorded under resting (baseline) conditions and during subjects' performance of a 3-min mental arithmetic task. Subjects were also administered state forms of the State-Trait Anxiety and Anger Inventories following baseline measurements and immediately after the experimental task. Results indicated that relative to sons of normotensive parents, offspring of hypertensives showed significantly greater HR and DBP elevations during mental arithmetic. However, neither task performance nor task-related changes on the state measures of anxiety and anger varied reliably with differences in parental status. When subjects were divided into groups of high- and low-affect (i.e., anxiety, anger) responders, the HR reactions of persons having hypertensive and normotensive parents were found to differ significantly only among subjects who reported experiencing the most appreciable anxiety--and to a lesser extent, anger--when performing the mental arithmetic task. This finding suggests that persons at familial risk for hypertension possess a heightened cardiovascular response "potential" which is expressed, in part, in relation to concomitant affective experiences of the individual.     

Secretory immunoglobulin a and cardiovascular responses to acute psychological challenge

Cardiovascular activity and secretory immunoglobulin A (sIgA) in saliva were recorded at rest, during a 30-min computer game task, and during subsequent recovery. Blood pressure (BP) rose and remained elevated during the task and returned to resting levels during recovery. This pressor response was produced by increased total peripheral resistance rather than increased cardiac output. SIgA secretion rate also increased during the task, although the effect proved significant only toward the end of the task. As such, the data provide preliminary indication that sIgA is sensitive to acute psychological challenge in the laboratory. Although correlational analyses revealed that sIgA reactions were stable, they were not significantly correlated with pressor reactions. The influence of task uncertainty was explored by comparing individuals who had previously played the computer game with those who had not. Task-induced increases in BP and sIgA were a feature of individuals new to the computer game. In contrast to these novice players, experienced players showed minimal increases in BP and no increases in sIgA.     

Bupropion and paroxetine differentially influence cardiovascular and neuroendocrine responses to stress in depressed patients

BACKGROUND: There exists a need to identify safe and effective treatments for depression in patients with coronary heart disease (CHD). METHODS: Using a cross-sectional design, 17 depressed patients being treated with bupropion (200-450 mg/day) were compared with 17 depressed patients being treated with paroxetine (10-50 mg/day) and with a group of 15 unmedicated, non-depressed controls for cardiovascular, neuroendocrine and heart rate variability (HRV) measures at rest and in response to mental and physical stressors. RESULTS: Regardless of treatment, both treated groups exhibited blunted plasma cortisol, plasma epinephrine, systolic blood pressure, cardiac output, and pre-ejection period responses to mental stressors relative to controls. Bupropion treated individuals exhibited greater total peripheral resistance (TPR) increases than either the paroxetine or control groups, and greater plasma norepinephrine (NE) increases to mental stressors than the paroxetine group. The bupropion group also displayed reduced HRV at rest relative to the controls and during orthostatic challenge relative to both the control and paroxetine groups. LIMITATIONS: Despite the fact that the treated groups were well matched for depression and other psychiatric histories, lack of randomization into treatment arms may be associated with a selection bias in the two treated groups. CONCLUSIONS: Although both pharmacological treatments were associated with a blunting of some cardiovascular and neuroendocrine responses to stress relative to controls, which may be reflective of their therapeutic mechanisms of action, the results of our study also suggest that bupropion is associated with a more detrimental autonomic profile than paroxetine, as reflected in increased TPR and NE, and reduced HRV. The results of this study may have implications for the pharmacological treatment of depression in CHD patients.     

Estimated maximal and current brain volume predict cognitive ability in old age

Brain tissue deterioration is a significant contributor to lower cognitive ability in later life; however, few studies have appropriate data to establish how much influence prior brain volume and prior cognitive performance have on this association. We investigated the associations between structural brain imaging biomarkers, including an estimate of maximal brain volume, and detailed measures of cognitive ability at age 73 years in a large (N = 620), generally healthy, community-dwelling population. Cognitive ability data were available from age 11 years. We found positive associations (r) between general cognitive ability and estimated brain volume in youth (male, 0.28; females, 0.12), and in measured brain volume in later life (males, 0.27; females, 0.26). Our findings show that cognitive ability in youth is a strong predictor of estimated prior and measured current brain volume in old age but that these effects were the same for both white and gray matter. As 1 of the largest studies of associations between brain volume and cognitive ability with normal aging, this work contributes to the wider understanding of how some early-life factors influence cognitive aging.     

KLOTHO genotype and cognitive ability in childhood and old age in the same individuals

This study examined the influence of a variation in the KLOTHO gene on cognitive ability at age 11 and age 79 in 464 people from the Lothian Birth Cohort 1921 (LBC1921), and at age 11 and age 64 in 451 people in the Aberdeen Birth Cohort 1936 (ABC1936). In the LBC1921, people with the KLOTHO V/V genotype had lower verbal reasoning ability at age 11 and age 79, and lower non-verbal reasoning at age 79, than those with the F/F genotype, or heterozygotes. The effect of the KLOTHO polymorphism on cognition at age 79 was non-significant when adjusted for IQ at age 11. In this sample, KLOTHO V allele status accounts for about 2% of the variance in life-long traits related to verbal and non-verbal reasoning, but not to age-related cognitive change. These results were not replicated in the ABC1936 sample. In a combined analysis of the LBC1921 and the ABC1936 cohorts there was a significant KLOTHOxsex interaction: women with the V/V genotype had lower non-verbal reasoning scores at age 79, after adjustment for cognitive ability at age 11. Variation in the KLOTHO gene is a possible contributor to life-long reasoning differences in humans and/or to the ageing of non-verbal reasoning, especially in women.     

Influences of sex and age on cardiovascular responses during stress

The present investigation examined the influence of sex and age on blood pressure and heart rate responses in 125 women, 93 men, 121 girls, and 96 boys to three standardized stressors: serial subtraction, mirror-image tracing, and isometric handgrip. With baseline measures and body mass index controlled for, analyses of covariance showed that adults had greater systolic blood pressure responses than did children; men had greater blood pressure responses to all stressors than did women; and high school boys had greater systolic blood pressure responses than did high school girls. In addition, adults had smaller heart rate responses during isometric handgrip than did children, and high school students had smaller heart rate responses during all tasks than did the remaining, younger students. These results show that sex and age are important determinants of the magnitude of cardiovascular adjustments during stressors. The implications of these results are discussed in light of sex differences in coronary heart disease morbidity and mortality.     

VDR gene variants associate with cognitive function and depressive symptoms in old age

Vitamin D has been recently implicated in brain function. Our objective was to test whether genetic variance in the vitamin D receptor (VDR) gene is associated with cognitive functioning and depressive symptoms in old age. The study was carried out in the prospective population-based Leiden 85-plus Study. All 563 participants of the study were genotyped for Cdx-2, FokI, BsmI, ApaI and TaqI polymorphisms in the VDR gene. Our data revealed an overall worse performance on tests measuring cognitive functioning for carriers of BsmI (p=0.013) and TaqI (p=0.004) polymorphisms, and of haplotype 2 (BAt) (p=0.004). In contrast, carriers of ApaI variant-allele and of haplotype 1 (baT) had better cognitive functioning together with less depressive symptoms. These associations could not be explained by differences in calcium levels, and by selective survival, since no associations between the VDR gene variants and calcium levels and mortality were observed. In conclusion, our results show that genetic variance in the VDR gene influences the susceptibility to age-related changes in cognitive functioning and in depressive symptoms.     

Effect of arm position on cardiovascular responses during isometric handgrips

Summary Sixteen subjects (eight women and eight men, age 20–25 years) carried out in the seated position, isometric contractions sustained until exhaustion of the digital flexors. The subject's arm was placed in two positions, high and low. The muscle tensions used were 30, 40 and 50% of maximum voluntary contraction (MVC). Under these conditions, for a given relative force, the duration of contraction (limit-time) was not modified by the arm position. In the male subjects, increases in heart rate (HR) and systolic blood pressure (SBP) were slightly more pronounced in the low than the high position, but the differences were not significant. Limit times in the high position were similar to those in the low position, and, in the absence of an increase in HR and SBP, this seemed to be due to an increase in cardiac output consequent upon a transient improvement in venous return together with an increase in the coefficient of oxygen utilization.     

The relationship of age and cardiovascular fitness to cognitive and motor processes

Older and younger aerobically trained and sedentary adults participated in an S1-S2-S3 paradigm designed to elicit event-related potential (ERP) and behavioral responses to determine the influence of cardiovascular fitness on cognitive and motor processes. The paradigm provided warning (S1) as to the difficulty level of an upcoming decision task (S2). Participants had to decide the taller of two bars on presentation of S2 but hold their response until S3, to which they indicated their choice motorically. Results revealed age-related differences for ERP measures as older participants showed increased amplitude of the stimulus preceding negativity (SPN) prior to S2, and longer latencies and equipotentiality of P3 in response to S2. Fitness effects were also observed for the contingent negative variation (CNV) with decreased amplitude for fit relative to sedentary individuals. Age interacted with fitness for P3 latency to S2 as older sedentary individuals showed the longest latency followed by older fit and both younger groups. No significant group differences were observed for reaction time (RT) to S3. Therefore, physical fitness is associated with attenuation of cognitive decline in older individuals and greater economy of motor preparation for both young and older participants.     

Serum lipids, neuroendocrine and cardiovascular responses to stress in healthy Type A men.

This study examined the relationship between serum lipid activity in healthy Type A men and cardiovascular and neuroendocrine responses to a behavioral stressor, mental arithmetic. Assessment of blood lipids included measures of total cholesterol (TC), low density lipoprotein cholesterol (LDLC), high density lipoprotein cholesterol (HDLC), and serum triglycerides. Cardiovascular (blood pressure and heart rate) and neuroendocrine (epinephrine, norepinephrine and cortisol) responses were recorded before (rest), during (stress) and after (recovery) the mental arithmetic test. Diastolic blood pressure, mean arterial pressure and, to a lesser extent, systolic blood pressure levels at rest, during stress, and at recovery correlated positively with TC levels. In addition, both diastolic and mean arterial pressure were positively correlated with the ratio of TC to HDLC and with triglycerides during stress and recovery. Heart rate did not correlate with any lipid measure. Cardiovascular stress-reactivity calculated as change from rest to stress did not correlate significantly with any lipid measure. Plasma norepinephrine during stress correlated positively with triglycerides; a similar trend was observed for the TC/HDLC ratio. Plasma cortisol at rest and during stress correlated positively with the TC/HDLC ratio and serum triglycerides, and negatively with HDLC. Plasma norepinephrine reactivity calculated as change from rest to stress correlated negatively with HDLC and positively with triglycerides. In addition, cortisol reactivity was positively correlated with triglycerides. It is suggested that the mechanisms mediating Type A behavior and coronary heart disease may include increased cardiovascular and neuroendocrine responses as well as unfavorable lipid profiles.     

Cancer vaccination: manipulation of immune responses at old age

The incidence of cancer has increased over the last decade, mainly due to an increase in the elderly population. Vaccine therapy for cancer is less toxic than chemotherapy or radiation and could be, therefore, especially effective in older, more frail cancer patients. However, it has been shown that older individuals do not respond to vaccine therapy as well as younger adults. This has been attributed to T-cell unresponsiveness, a phenomenon also observed in cancer patients per se. This review summarizes the current knowledge of impaired T-cell responses in cancer patients and the elderly, and the results of cancer vaccination in preclinical models at young and old age. Finally, various approaches how to manipulate immune responses against cancer by vaccination at older age will be proposed.