Effect of aerobic exercise on cognition in younger adults: A randomized clinical trial.

OBJECTIVE: To determine efficacy of aerobic exercise for cognitive function in younger healthy adults. METHODS: In a randomized, parallel-group, observer-masked, community-based clinical trial, 132 cognitively normal individuals aged 20-67 with below median aerobic capacity were randomly assigned to one of two 6-month, 4-times-weekly conditions: aerobic exercise and stretching/toning. Efficacy measures included aerobic capacity; cognitive function in several domains (executive function, episodic memory, processing speed, language, and attention), everyday function, body mass index (BMI), and cortical thickness. RESULTS: Aerobic capacity increased significantly (ß = 2.718; p = 0.003), and BMI decreased significantly (ß = -0.596; p = 0.013) in the aerobic exercise but not in the stretching/toning condition. Executive function improved significantly in the aerobic exercise condition; this effect was moderated by age (ß = 0.018 SD/y; p = 0.028). At age 40, the executive function measure increased by 0.228 SD (95% confidence interval [CI] 0.007-0.448), and by 0.596 SD (95% CI 0.219-0.973) at age 60. Cortical thickness increased significantly in the aerobic exercise group in a left frontal region and did not interact with age. Controlling for age and baseline performance, individuals with at least one APOE ε4 allele showed less improvement in executive function with aerobic exercise (ß = 0.5129, 95% CI 0.0381-0.988; p = 0.0346). CONCLUSIONS: This randomized clinical trial demonstrates the efficacy of aerobic exercise for cognition in adults age 20-67. The effect of aerobic exercise on executive function was more pronounced as age increased, suggesting that it may mitigate age-related declines. Increased cortical thickness suggests that aerobic exercise contributes to brain health in individuals as young as age 20. CLINICALTRIALSGOV IDENTIFIER: NCT01179958. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for adults age 20-67 with below median aerobic capacity, aerobic exercise significantly improves executive function but not other measures of cognitive function.

Preference option randomized design (PORD) for comparative effectiveness research: Statistical power for testing comparative effect, preference effect, selection effect, intent-to-treat effect, and overall effect.

Comparative effectiveness research trials in real-world settings may require participants to choose between preferred intervention options. A randomized clinical trial with parallel experimental and control arms is straightforward and regarded as a gold standard design, but by design it forces and anticipates the participants to comply with a randomly assigned intervention regardless of their preference. Therefore, the randomized clinical trial may impose impractical limitations when planning comparative effectiveness research trials. To accommodate participants' preference if they are expressed, and to maintain randomization, we propose an alternative design that allows participants' preference after randomization, which we call a "preference option randomized design (PORD)". In contrast to other preference designs, which ask whether or not participants consent to the assigned intervention after randomization, the crucial feature of preference option randomized design is its unique informed consent process before randomization. Specifically, the preference option randomized design consent process informs participants that they can opt out and switch to the other intervention only if after randomization they actively express the desire to do so. Participants who do not independently express explicit alternate preference or assent to the randomly assigned intervention are considered to not have an alternate preference. In sum, preference option randomized design intends to maximize retention, minimize possibility of forced assignment for any participants, and to maintain randomization by allowing participants with no or equal preference to represent random assignments. This design scheme enables to define five effects that are interconnected with each other through common design parameters-comparative, preference, selection, intent-to-treat, and overall/as-treated-to collectively guide decision making between interventions. Statistical power functions for testing all these effects are derived, and simulations verified the validity of the power functions under normal and binomial distributions.

Aerobic Exercise Training and Inducible Inflammation: Results of a Randomized Controlled Trial in Healthy, Young Adults.

Background Consensus panels regularly recommend aerobic exercise for its health-promoting properties, due in part to presumed anti-inflammatory effects, but many studies show no such effect, possibly related to study differences in participants, interventions, inflammatory markers, and statistical approaches. This variability makes an unequivocal determination of the anti-inflammatory effects of aerobic training elusive. Methods and Results We conducted a randomized controlled trial of 12 weeks of aerobic exercise training or a wait list control condition followed by 4 weeks of sedentary deconditioning on lipopolysaccharide (0, 0.1, and 1.0 ng/mL)-inducible tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and on toll-like receptor 4 in 119 healthy, sedentary young adults. Aerobic capacity by cardiopulmonary exercise testing was measured at study entry (T1) and after training (T2) and deconditioning (T3). Despite a 15% increase in maximal oxygen consumption, there were no changes in inflammatory markers. Additional analyses revealed a differential longitudinal aerobic exercise training effect by lipopolysaccharide level in inducible TNF -α ( P=0.08) and IL-6 ( P=0.011), showing T1 to T2 increases rather than decreases in inducible (lipopolysaccharide 0.1, 1.0 versus 0.0 ng/mL) TNF- α (51% increase, P=0.041) and IL-6 (42% increase, P=0.11), and significant T2 to T3 decreases in inducible TNF- α (54% decrease, P=0.007) and IL-6 (55% decrease, P<0.001). There were no significant changes in either group at the 0.0 ng/mL lipopolysaccharide level for TNF- α or IL-6. Conclusions The failure to support the primary hypotheses and the unexpected post hoc findings of an exercise-training-induced proinflammatory response raise questions about whether and under what conditions exercise training has anti-inflammatory effects. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 01335737.

The Association of Cigarette Smoking With High-Frequency Heart Rate Variability: An Ecological Momentary Assessment Study.

OBJECTIVE: Evidence from both laboratory and observational studies suggests that acute and chronic smoking leads to reduced high-frequency heart rate variability (HF-HRV), a measure of cardiac vagal regulation. We used ecological momentary assessment (EMA) to study the effect of smoking on concurrent HF-HRV in a trial measuring the effects of hostility reduction and compared 24-hour HF-HRV in smokers and nonsmokers. METHOD: Ambulatory electrocardiogram data were collected before randomization from 149 healthy individuals with high hostility levels (20-45 years, body mass index ≤ 32 kg/m) and paired with concurrent EMA ratings of smoking and physical position during waking hours. A multilevel mixed model was estimated associating ln(HF-HRV) from smoking status (between-person factor) and person-centered momentary smoking (within-person factor, treated as a random effect), adjusting for momentary physical position, medication use, and consumption of alcohol and caffeine. RESULTS: Thirty-five smokers and 114 nonsmokers provided both EMA and HF-HRV data. Within smokers, ln HF-HRV was reduced by 0.31 millisecond (p = .04) when participants reported having recently smoked cigarettes, compared with when they had not. The 24-hour HF-HRV was significantly lower in smokers (M [SD] = 5.24 [0.14] milliseconds) than nonsmokers (5.63 ± 0.07 milliseconds, p = .01). CONCLUSIONS: In healthy smokers with high hostility levels used as their own controls during daily living, smoking acutely reduced HF-HRV. HF-HRV was also reduced in smokers as compared with nonsmokers. Although limited by a small sample of individuals with high hostility levels, these findings nonetheless provide additional evidence that cardiac vagal regulation is lowered by cigarette smoking, which may be one of the numerous pathophysiological effects of smoking.

Vagally-mediated heart rate variability and indices of well-being: Results of a nationally representative study.

OBJECTIVE: High frequency (HF) heart rate variability (HRV) has long been accepted as an index of cardiac vagal control. Recent studies report relationships between HF-HRV and indices of positive and negative affect, personality traits and well-being but these studies generally are based on small and selective samples. METHOD: These relationships were examined using data from 967 participants in the second Midlife in the U.S. (MIDUS II) study. Participants completed survey questionnaires on well-being and affect. HF-HRV was measured at rest. A hierarchical series of regression analyses examined relationships between these various indices and HF-HRV before and after adjustment for relevant demographic and biomedical factors. RESULTS: Significant inverse relationships were found only between indices of negative affect and HF-HRV. Relationships between indices of psychological and hedonic well-being and positive affect failed to reach significance. CONCLUSIONS: These findings raise questions about relationships between cardiac parasympathetic modulation, emotion regulation, and indices of well-being. (PsycINFO Database Record

Sleep Duration and Quality in Relation to Autonomic Nervous System Measures: The Multi-Ethnic Study of Atherosclerosis (MESA).

STUDY OBJECTIVES: Short sleep duration and poor sleep quality are associated with adverse cardiovascular outcomes. Potential pathophysiological mechanisms include sleep-associated alterations in the autonomic nervous system. The objective of this study was to examine the associations of shorter sleep duration and poorer sleep quality with markers of autonomic tone: heart rate (HR), high-frequency HR variability (HF-HRV) and salivary amylase. METHODS: Cross-sectional analysis of data from actigraphy-based measures of sleep duration and efficiency and responses to a challenge protocol obtained from 527 adult participants in the Multi-Ethnic Study of Atherosclerosis. RESULTS: Participants who slept fewer than 6 h per night (compared to those who slept 7 h or more per night) had higher baseline HR (fully adjusted model 0.05 log beats/min, 95% confidence interval [CI] 0.01, 0.09) and greater HR orthostatic reactivity (fully adjusted model 0.02 log beats/min, 95% CI 0.002, 0.023). Participants who slept 6 to less than 7 h/night (compared to those who slept 7 h or more per night) had lower baseline HF-HRV (fully adjusted model -0.31 log msec2, 95% CI -0.60, -0.14). Participants with low sleep efficiency had lower baseline HF-HRV than those with higher sleep efficiency (fully adjusted model -0.59 log msec2, 95% CI -1.03, -0.15). Participants with low sleep efficiency had higher baseline levels of amylase than those with higher sleep efficiency (fully adjusted model 0.45 log U/mL, 95% CI 0.04, 0.86). CONCLUSIONS: Short sleep duration, low sleep efficiency, and insomnia combined with short sleep duration were associated with markers of autonomic tone that indicate lower levels of cardiac parasympathetic (vagal) tone and/or higher levels of sympathetic tone.

The Effect of Hostility Reduction on Autonomic Control of the Heart and Vasculature: A Randomized Controlled Trial.

OBJECTIVE: Hostility is associated with coronary artery disease. One candidate mechanism may be autonomic nervous system (ANS) dysregulation. In this study, we report the effect of cognitive behavioral treatment on ANS regulation. METHODS: Participants were 158 healthy young adults, high in hostility measured by the Cook-Medley Hostility and Spielberger Trait Anger scales. Participants were also interviewed using the Interpersonal Hostility Assessment Technique. They were randomized to a 12-week cognitive behavioral treatment program for reducing hostility or a wait-list control group. The outcome measures were preejection period, low-frequency blood pressure variability, and high-frequency heart rate variability measured at rest and in response to and recovery from cognitive and orthostatic challenge. Linear-mixed models were used to examine group by session and group by session by period interactions while controlling for sex and age. Contrasts of differential group and session effects were used to examine reactivity and recovery from challenge. RESULTS: After Bonferroni correction, two-way and three-way interactions failed to achieve significance for preejection period, low-frequency blood pressure variability, or high-frequency heart rate variability (p > .002), indicating that hostility reduction treatment failed to influence ANS indices. CONCLUSIONS: Reduction in anger and hostility failed to alter ANS activity at rest or in response to or recovery from challenge. These findings raise questions about whether autonomic dysregulation represents a pathophysiological link between hostility and heart disease.

Linking Daily Stress Processes and Laboratory-Based Heart Rate Variability in a National Sample of Midlife and Older Adults.

OBJECTIVE: This study evaluates the associations between people's trait-like patterns of stress in daily life (stressor frequency, perceived stressor severity, affective reactivity to stressors, and negative affect) and laboratory-assessed heart rate variability (HRV). METHODS: Data were collected from 909 participants aged 35 to 85 years in the Midlife in the United States Study. Participants reported negative affect and minor stressful events during telephone interviews on 8 consecutive evenings. On a separate occasion, HRV was measured from electrocardiograph recordings taken at rest during a laboratory-based psychophysiology protocol. Regression models were used to evaluate the associations between daily stress processes and three log-transformed HRV indices: standard deviation of R-R intervals (SDRR), root mean square of successive differences (RMSSD), and high-frequency power (high-frequency HRV [HF-HRV]). Analyses were adjusted for demographics, body mass index, comorbid conditions, medications, physical activity, and smoking. RESULTS: Stressor frequency was unrelated to HRV (r values ranging from -0.04 to -0.01, p values >.20). However, people with greater perceived stressor severity had lower resting SDRR (fully adjusted B [standard error {SE}] = -0.05 [0.02]), RMSSD (-0.08 [0.03]), and HF-HRV (-0.16 [0.07]). Individuals with more pronounced affective reactivity to stressors also had lower levels of all three HRV indices (SDRR: B [SE] = -0.28 [0.14]; RMSSD: -0.44 [0.19]; HF-HRV: -0.96 [0.37]). Furthermore, aggregated daily negative affect was linked to reduced RMSSD (B [SE] = -0.16 [0.08]) and HF-HRV (-0.35 [0.15]). CONCLUSIONS: In a national sample, individual differences in daily negative affect and responses to daily stressors were more strongly related to cardiovascular autonomic regulation than the frequency of such stressors.

Vagal Recovery From Cognitive Challenge Moderates Age-Related Deficits in Executive Functioning.

Decline in executive functioning (EF) is a hallmark of cognitive aging. We have previously reported that faster vagal recovery from cognitive challenge is associated with better EF. This study examined the association between vagal recovery from cognitive challenge and age-related differences in EF among 817 participants in the Midlife in the U.S. study (aged 35-86). Cardiac vagal control was measured as high-frequency heart rate variability. Vagal recovery moderated the association between age and EF (ß = .811, p = .004). Secondary analyses revealed that older participants (aged 65-86) with faster vagal recovery had superior EF compared to their peers who had slower vagal recovery. In contrast, among younger (aged 35-54) and middle-aged (aged 55-64) participants, vagal recovery was not associated with EF. We conclude that faster vagal recovery from cognitive challenge is associated with reduced deficits in EF among older, but not younger individuals.

Beat-to-beat heart rate and blood pressure variability and hypertensive disease in pregnancy.

OBJECTIVE: The aim of this study is to determine the relationship between heart rate and/or blood pressure variability, measured at 28 weeks' gestation, and the incidence of pregnancy-induced hypertension or preeclampsia. STUDY DESIGN: Secondary analysis of data from a prospectively enrolled cohort of 385 active military women in whom spectral analysis of continuous heart rate and variability was measured at 28 weeks' gestation. The primary outcome was the predictive value of spectral analysis of heart rate and blood pressure for hypertensive diseases of pregnancy. RESULTS: High-frequency heart rate variability was reduced and low-frequency variability of systolic and diastolic blood pressure increased in women who would develop pregnancy-induced hypertension but not preeclampsia. Low-frequency variability of diastolic blood pressure remained a significant predictor of pregnancy-induced hypertension but not preeclampsia after adjustment for age, weight, and blood pressure in a multivariate model. CONCLUSION: Early identification of pregnancy-induced hypertension can facilitate treatment to avoid maternal morbidity. Understanding the physiological underpinnings of the two very different diseases may lead to improved treatment and prevention. If proven effective in a broader population, the ability to differentiate pregnancy-induced hypertension from preeclampsia may reduce unnecessary iatrogenic interventions or inappropriate preterm delivery.

A longitudinal study of depression, fatigue, and sleep disturbances as a symptom cluster in women with breast cancer.

CONTEXT: Depression, fatigue, and sleep disturbances have been identified as a symptom cluster among breast cancer patients. However, few longitudinal studies have examined the temporal relations between these symptoms surrounding diagnosis and treatment. OBJECTIVES: The present study investigated the co-occurrence of and interrelations between nonsomatic depressive symptoms, fatigue, and sleep disturbances in breast cancer patients at three time points: before, after, and six to eight months following adjuvant chemotherapy treatment. METHODS: Separate samples of premenopausal (n = 67) and postmenopausal (n = 67) breast cancer patients completed self-report measures of depression, fatigue, and sleep disturbances at all three time points. Path analysis was used to explore within- and cross-symptom paths across time. RESULTS: Depression, fatigue, and sleep disturbances were correlated within each time point. Continuity paths, whereby prior levels of symptom severity tended to predict subsequent severity of the same symptom at the subsequent time point, were significant in both samples, except for depression in the premenopausal sample. Instead, significant cross-symptom paths emerged whereby baseline fatigue predicted postchemotherapy depression, and postchemotherapy fatigue predicted depression at follow-up in the premenopausal patients. No significant cross-symptom paths emerged for the postmenopausal sample. CONCLUSION: Findings supported the notion that depression, fatigue, and sleep disturbances manifest as a symptom cluster. Fatigue may precede nonsomatic symptoms of depression among premenopausal breast cancer patients and represents a potential intervention target.

Heart rate variability predicts levels of inflammatory markers: Evidence for the vagal anti-inflammatory pathway.

Evidence from numerous animal models shows that vagal activity regulates inflammatory responses by decreasing cytokine release. Heart rate variability (HRV) is a reliable index of cardiac vagal regulation and should be inversely related to levels of inflammatory markers. Inflammation is also regulated by sympathetic inputs, but only one previous paper controlled for this. In a larger and more representative sample, we sought to replicate those results and examine potential sex differences in the relationship between HRV and inflammatory markers. Using data from the MIDUS II study, we analyzed the relationship between 6 inflammatory markers and both HF-HRV and LF-HRV. After controlling for sympathetic effects measured by urinary norepinephrine as well as a host of other factors, LF-HRV was found to be inversely associated with fibrinogen, CRP and IL-6, while HF-HRV was inversely associated with fibrinogen and CRP. We did not observe consistent sex differences. These results support the existence of the vagal anti-inflammatory pathway and suggest that it has similar effects in men and women.

Race differences in age-trends of autonomic nervous system functioning.

OBJECTIVE: The objective of this study was to consider race differences in age-trends of autonomic nervous system functioning, using a national data set with a broad age range. METHODS: Measures of baseline heart rate variability (HRV) and HRV reactivity were derived from electrocardiograph (ECG) recordings taken at rest and during cognitive stress tasks. Age-trends in HRV and HRV reactivity were compared among 204 African Americans and 833 Whites ages 34 to 83 years (M = 53.7, SD = 11.4), before and after controlling for socioeconomic status (SES). RESULTS: For HRV-reactivity, age-trends were steeper among African Americans and lower SES participants than Whites and higher SES participants. For baseline HRV, age-trends varied by SES but not race. DISCUSSION: Results relating to HRV-reactivity (but not baseline HRV) were consistent with hypotheses suggesting that African Americans are exposed to higher levels of stress and experience accelerated declines in health across the life span. The relevance of the findings to research on social stress and health disparities is discussed.

Aerobic exercise and strength training effects on cardiovascular sympathetic function in healthy adults: a randomized controlled trial.

OBJECTIVE: Exercise has widely documented cardioprotective effects, but the mechanisms underlying these effects are not entirely known. Previously, we demonstrated that aerobic but not strength training lowered resting heart rate and increased cardiac vagal regulation, changes that were reversed by sedentary deconditioning. Here, we focus on the sympathetic nervous system and test whether aerobic training lowers levels of cardiovascular sympathetic activity in rest and that deconditioning would reverse this effect. METHODS: We conducted a randomized controlled trial contrasting the effects of aerobic (A) versus strength (S) training on indices of cardiac (preejection period, or PEP) and vascular (low-frequency blood pressure variability, or LF BPV) sympathetic regulation in 149 young, healthy, and sedentary adults. Participants were studied before and after conditioning, as well as after 4 weeks of sedentary deconditioning. RESULTS: As previously reported, aerobic capacity increased in response to conditioning and decreased after deconditioning in the aerobic, but not the strength, training group. Contrary to prediction, there was no differential effect of training on either PEP (A: mean [SD] -0.83 [7.8] milliseconds versus S: 1.47 [6.69] milliseconds) or LF BPV (A: mean [SD] -0.09 [0.93] ln mm Hg(2) versus S: 0.06 [0.79] ln mm Hg(2)) (both p values > .05). CONCLUSIONS: These findings, from a large randomized controlled trial using an intent-to-treat design, show that moderate aerobic exercise training has no effect on resting state cardiovascular indices of PEP and LF BPV. These results indicate that in healthy, young adults, the cardioprotective effects of exercise training are unlikely to be mediated by changes in resting sympathetic activity. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT00358137.

A pilot randomized controlled trial of a commercial diet and exercise weight loss program in minority breast cancer survivors.

OBJECTIVE: Obesity is associated with poorer breast cancer outcomes and losing weight postdiagnosis may improve survival. As Hispanic and black women have poorer breast cancer prognosis than non-Hispanic whites diagnosed at similar age and stage, and have higher rates of obesity, effective weight loss strategies are needed. We piloted a randomized, waitlist-controlled, crossover study to examine the effects and feasibility of the commercial Curves weight loss program among Hispanic, African American and Afro-Caribbean breast cancer survivors. DESIGN AND METHODS: Women with stage 0-IIIa breast cancer ≥ 6 months posttreatment, sedentary, and BMI ≥ 25 kg/m(2) were randomized to the immediate arm (IA): 6 months of the Curves program followed by 6 months of observation; or the waitlist control arm (WCA): 6 months of observation followed by 6 months of the Curves program. The Curves program uses a 30-min exercise circuit and a high-vegetable/low-fat/calorie-restricted diet. RESULTS: A total of 42 women enrolled (79% Hispanic, 21% black), mean age 51 (range 32-69) and mean BMI 33.2(± 5.9) kg/m(2); 91% were retained at month 12. At month 6, women in the IA lost an average 3.3% (± 3.5%) of body weight (range: 1.7% gain to 10.6% loss), as compared with 1.8% (± 2.9%) weight loss in the WCA (P = 0.04). At month 12, on average women in the IA regained some but not all of the weight lost during the first 6 months (P = 0.02). CONCLUSIONS: Minority breast cancer survivors were recruited and retained in a weight loss study. Six months of the Curves program resulted in moderate weight loss, but weight loss was not maintained postintervention. Future interventions should identify methods to increase uptake and maintenance of weight loss behaviors.

The interactive effect of change in perceived stress and trait anxiety on vagal recovery from cognitive challenge.

The present study tested the hypothesis that the change in state negative affect (measured as perceived stress) after cognitive challenge moderates the relationship of trait anxiety and anger to vagal recovery from that challenge. Cardiac vagal control (assessed using heart rate variability) and respiratory rate were measured in a sample of 905 participants from the Midlife in the United States Study. Cognitive challenges consisted of computerized mental arithmetic and Stroop color-word matching tasks. Multiple regression analyses controlling for the effects of the demographic, lifestyle, and medical factors influencing cardiac vagal control showed a significant moderating effect of change in perceived stress on the relationship of trait anxiety to vagal recovery from cognitive challenges (Beta=.253, p=.013). After adjustment for respiratory rate, this effect became marginally significant (Beta=.177, p=.037). In contrast, for the relationship of trait anger to vagal recovery, this effect was not significant either before (Beta=.141, p=.257) or after (Beta=.186, p=.072) adjusting for respiratory rate. Secondary analyses revealed that among the individuals with higher levels of trait anxiety, greater reductions in perceived stress were associated with greater increases in cardiac vagal control after the challenge. In contrast, among the individuals with lower levels of trait anxiety, changes in perceived stress had no impact on vagal recovery. Therefore, change in perceived stress moderates the relationship of trait anxiety, but not trait anger, to vagal recovery from cognitive challenge.

Impact of aerobic training on cardiovascular reactivity to and recovery from challenge.

OBJECTIVE: To test the hypothesis that aerobic, but not strength, training would lead to attenuated reactivity to and more rapid recovery from cognitive and orthostatic challenge and that deconditioning would reverse this effect. METHODS: We conducted a randomized controlled trial contrasting the effects of aerobic versus strength training on heart rate, four indices of RR interval variability, and blood pressure reactivity to and recovery from psychological and orthostatic challenge in 149 healthy, young, sedentary adults. Subjects were randomized to 12-week aerobic or strength training programs and studied before and after training and again after 4 weeks of sedentary deconditioning. The data were analyzed by performing a Group (aerobic versus strength) by Session (study entry, post training, and deconditioning), by Period (baseline, speech, Stroop, math, tilt) three-way analysis of variance with prespecified contrasts of the effect of group assignment on reactivity and recovery. RESULTS: Aerobic capacity increased in response to conditioning and decreased after deconditioning in the aerobic, but not the strength, training group. However, the two groups did not differ on heart rate, RR interval variability, or blood pressure reactivity to or recovery from laboratory challenge. CONCLUSIONS: These findings, from the largest randomized controlled trial to address this matter to date, raise doubts about attenuation of reactivity or enhancement of recovery as a putative mechanism underlying the cardioprotective effects of aerobic exercise. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00365196.

The cognitive effects of chemotherapy in post-menopausal breast cancer patients: a controlled longitudinal study.

Studies suggest that adjuvant chemotherapy for early stage breast cancer (BC) is associated with cognitive impairment related to attention, memory, and visuospatial functioning. However, other studies have failed to confirm that relationship. We report one of the first longitudinal, controlled studies of cognitive effects of chemotherapy in older post-menopausal women. Sixty-one post-menopausal women with non-metastatic BC were administered neuropsychological tests before adjuvant therapy (Time1), six months after treatment (Time2), and at a final 6-month follow-up (Time3). Thirty women were treated with chemotherapy; thirty-one women who received no chemotherapy were controls. Cognitive domains measured included motor, language, attention/concentration/working memory, visuospatial, and memory (verbal and visual). Time-by-treatment interaction was significant in the motor domain (P = 0.007) with poorer performance in women treated with chemotherapy. For the other domains, scores did not significantly vary over time by group. In post-menopausal women, chemotherapy was not associated with changes in cognitive function in areas reported by BC survivors: attention, memory, and information processing. Motor slowing in women treated with chemotherapy could be secondary to peripheral neuropathy rather than an indication of more general declines in cognitive processing. Future studies should control for the independent effects of slowed motor functioning when looking to study possible chemotherapy related cognitive processing deficits.

Heart rate recovery after cognitive challenge is preserved with age.

OBJECTIVE: To investigate the effect of age on heart rate recovery (HRR) from cognitive challenge. BACKGROUND: Aging is an independent risk factor for the development of cardiovascular disease. HRR from exercise is an established predictor of cardiac morbidity and mortality, and evidence suggests that HRR from cognitive challenge is predictive of cardiac morbidity as well. Aging is associated with delayed HRR from exercise stress, but little is known about the effect of aging on HRR from psychological stress. We tested the hypothesis that age would be related to delayed HRR from psychological stress. METHODS: HRR post exposure to cognitive challenge (mental arithmetic and Stroop) was investigated in a sample of 436 participants aged 35 to 84 years in MIDUS II, a national study of health and well-being. HRR was measured as 1) the amount of change from the stress level; 2) time to recover; and 3) the area under the curve. The analyses were controlled for medical comorbidities and medications that influence HR, such as body mass index, smoking, sex, menopausal status, and amount of physical activity/exercise. RESULTS: There was no effect for age on HRR as evaluated by all three recovery assessment methods. CONCLUSIONS: Contrary to expectation and in contrast to findings concerning HRR from exercise, HRR from cognitive challenge was preserved with age. These findings require further inquiry into differential mechanism(s) underlying HRR from psychological versus exercise stress, including any role for improved emotion regulation with greater age.