The association of affective, behavioral, and cognitive components of hostility with telomere length, a marker of biological aging

Variability within species in the rate of biological aging and noticeable differences in susceptibility to diseases of aging suggest ecological factors, such as trait characteristics, may contribute to individual vulnerability. In this regard, some evidence shows a relationship between hostile tendencies and risk for the most prevalent disease of aging, coronary heart disease (CHD). One plausible pathway through which hostility may increase risk for such age-related disease is through premature cellular aging. Recent evidence suggests that the length of telomeres in cells provides a biomarker of biological aging that predicts all-cause mortality and coronary disease morbidity and mortality. The present study examined associations of hostile temperaments with telomere length in a sample of African American (n = 35) and European American (n = 160) men (aged 40-70 years) at increased risk for CHD by virtue of their hypertensive status. In addition, the moderation of this association by race and age was also explored. Results showed no significant associations of hostile affects, behaviors, or cognitions, as measured by the Cook-Medley Hostility (CMH) scale and the Speilberger State Trait Anger Expression Inventory (STAXI), and telomere length. Although race did not moderate any associations between hostility and telomere length, there was a trend towards significant interactions of age with hostile cognitions (β = .87, p = .06), CMH hostile affect (β = .91, p = .057), and STAXI anger-in (β = 1.01, p = .07) in the prediction of telomere length, suggesting an inverse association of hostility with telomere length among younger subjects (40's), which may contribute to increased risk for diseases of aging in this age group. In contrast, older subjects (60's) showed a positive association of hostility with telomere length. In addition, across the whole sample, there was a significant positive association of years of education with telomere length (r = .15, p < .05). This association was independent of a number of demographic and health covariates among European Americans, but not African Americans, suggesting that among European American males with hypertension, those with fewer years of education show greater cellular aging. In contrast, hostility may be protective among older hypertensives

Screening for childhood adversity: the what and when of identifying individuals at risk for lifespan health disparities.

Existing research on childhood adversity and health risk across the lifespan lacks specificity regarding which types of exposures to assess and when. The purpose of this study was to contribute to an empirically-supported framework to guide practitioners interested in identifying youth who may be at greatest risk for a lifelong trajectory of health disparities. We also sought to identify the point in childhood at which screening for adversity exposure would capture the largest group of at risk individuals for triage to prevention and intervention services. Participants (n = 4036) collected as part of the Midlife in the United States study reported their medical status and history including physical (cardiovascular disease, hypertension, obesity, diabetes, cancer) and mental health (depression, substance use problems, sleep problems). Participants indicated whether they were exposed to 7 adversities at any point in childhood and their age of exposure to 19 additional lifetime adversities before the age of 18. Parent drug abuse, dropping out or failing out of school, being fired from a job, and sexual assault during childhood exhibited the largest effect sizes on health in adulthood, which were comparable to the effects of childhood maltreatment. Childhood adversity screening in early adolescence may identify the largest proportion of youth at risk for negative health trajectories. The results of this descriptive analysis provide an empirical framework to guide screening for childhood adversity in pediatric populations. We discuss the implications of these observations in the context of prevention science and practice

Biomarkers of aging associated with past treatments in breast cancer survivors.

Radiation and chemotherapy are effective treatments for cancer, but are also toxic to healthy cells. Little is known about whether prior exposure to these treatments is related to markers of cellular aging years later in breast cancer survivors. We examined whether past exposure to chemotherapy and/or radiation treatment was associated with DNA damage, telomerase activity, and telomere length 3-6 years after completion of primary treatments in breast cancer survivors (stage 0-IIIA breast cancer at diagnosis). We also examined the relationship of these cellular aging markers with plasma levels of Interleukin (IL)-6, soluble TNF-receptor-II (sTNF-RII), and C-reactive protein (CRP). Ninety-four women (36.4-69.5 years; 80% white) were evaluated. Analyses adjusting for age, race, BMI, and years from last treatment found that women who had prior exposure to chemotherapy and/or radiation compared to women who had previously received surgery alone were more likely to have higher levels of DNA damage (P = .02) and lower telomerase activity (P = .02), but did not have differences in telomere length. More DNA damage and lower telomerase were each associated with higher levels of sTNF-RII (P's &lt; .05). We found that exposure to chemotherapy and/or radiation 3-6 years prior was associated with markers of cellular aging, including higher DNA damage and lower telomerase activity, in post-treatment breast cancer survivors. Furthermore, these measures were associated with elevated inflammatory activation, as indexed by sTNF-RII. Given that these differences were observed many years after the treatment, the findings suggest a long lasting effect of chemotherapy and/or radiation exposure

Prediction of cognitive decline in older breast cancer survivors: the Thinking and Living with Cancer study

PURPOSE: Cancer survivors commonly report cognitive declines after cancer therapy. Due to the complex etiology of cancer-related cognitive decline (CRCD), predicting who will be at risk of CRCD remains a clinical challenge. We developed a model to predict breast cancer survivors who would experience CRCD after systematic treatment. METHODS: We used the Thinking and Living with Cancer study, a large ongoing multisite prospective study of older breast cancer survivors with complete assessments pre-systemic therapy, 12 months and 24 months after initiation of systemic therapy. Cognition was measured using neuropsychological testing of attention, processing speed, and executive function (APE). CRCD was defined as a 0.25 SD (of observed changes from baseline to 12 months in matched controls) decline or greater in APE score from baseline to 12 months (transient) or persistent as a decline 0.25 SD or greater sustained to 24 months. We used machine learning approaches to predict CRCD using baseline demographics, tumor characteristics and treatment, genotypes, comorbidity, and self-reported physical, psychosocial, and cognitive function. RESULTS: Thirty-two percent of survivors had transient cognitive decline, and 41% of these women experienced persistent decline. Prediction of CRCD was good: yielding an area under the curve of 0.75 and 0.79 for transient and persistent decline, respectively. Variables most informative in predicting CRCD included apolipoprotein E4 positivity, tumor HER2 positivity, obesity, cardiovascular comorbidities, more prescription medications, and higher baseline APE score. CONCLUSIONS: Our proof-of-concept tool demonstrates our prediction models are potentially useful to predict risk of CRCD. Future research is needed to validate this approach for predicting CRCD in routine practice settings

Pre-treatment psychoneurological symptoms and their association with longitudinal cognitive function and quality of life in older breast cancer survivors

Context Symptoms affect quality of life (QOL), functional status, and cognitive function in cancer survivors, but older survivors are understudied. Objectives To identify prototypical pre-systemic therapy psychoneurological symptom clusters among older breast cancer survivors, and determine whether these symptom clusters predicted cognition and QOL over time. Methods Women with newly diagnosed non-metastatic breast cancer (n=319) and matched non-cancer controls (n=347) aged 60+ completed questionnaires and neuropsychological tests before systemic therapy and 12- and 24-months later. Latent class analysis identified clusters of survivors based upon their pre-therapy depression, anxiety, fatigue, sleep disturbance, and pain. Linear mixed-effects models examined changes in objective cognition, perceived cognition, and functional status (instrumental activities of daily living (IADL) disability, functional well-being, and breast cancer-specific QOL) by group, controlling for covariates. Results Nearly one-fifth of older survivors were classified as having a high pre-therapy symptoms (n=51; 16%); the remainder had a low symptoms (n=268; 84%); both groups improved over time on all outcomes. However, compared to the low symptom group and controls, survivors with high symptoms had lower baseline objective cognition and lower perceived cognition at baseline and 24-months, lower functional well-being at baseline and 12-months, greater IADL disability at baseline, and lower breast cancer-specific QOL at all time points (all p<0.05). Conclusion Nearly one-fifth of older breast cancer survivors had high psychoneurological symptoms at diagnosis, which, predict clinically meaningful decrements in perceived cognition and function in the first 24 months post-diagnosis. Pre-treatment psychoneurological symptom clusters could identify survivors for monitoring or intervention

Symptom burden among older breast cancer survivors: The Thinking and Living With Cancer (TLC) study

Background: Little is known about longitudinal symptom burden and its consequences for well-being, and if lifestyle moderates burden in older survivors. Methods: We report on 36-month data from survivors 60+ with newly diagnosed non-metastatic breast cancer and non-cancer controls recruited August 2010-June 2016. Symptom burden was a sum of self-reported symptoms/diseases: pain (yes/no), fatigue (FACT-fatigue), cognitive (FACT-cog), sleep problems (yes/no), depression (CES-D), anxiety (STAI), and cardiac problems and neuropathy (yes/no). Well-being was measured using the FACT-G, scaled from 0–100. Lifestyle included smoking, alcohol use, BMI, physical activity, and leisure activities. Mixed models assessed relationships between treatment group (chemotherapy +/− hormonal, hormonal only, control) and symptom burden, lifestyle, and covariates. Separate models tested the effects of fluctuations in symptom burden and lifestyle on function. Results: All groups reported high baseline symptoms, and levels remained high over time; survivor-control differences were most notable for cognitive and sleep problems, anxiety, and neuropathy. The adjusted burden score was highest among chemotherapy-exposed survivors, followed by hormonal therapy vs. controls (p<.001). Burden score was related to physical, emotional, and functional well-being (e.g., survivors with lower vs. higher burden scores had 12.4-point higher physical well-being score). The composite lifestyle score was not related to symptom burden or well-being, but physical activity was significantly associated with each outcome (<.005). Conclusions: Cancer and its treatments are associated with a higher level of actionable symptoms and greater loss of well-being over time in older breast cancer survivors than comparable non-cancer populations, suggesting the need for surveillance and opportunities for intervention

Cancer-Related Cognitive Outcomes Among Older Breast Cancer Survivors in the Thinking and Living With Cancer Study

Purpose To determine treatment and aging-related effects on longitudinal cognitive function in older breast cancer survivors. Methods Newly diagnosed nonmetastatic breast cancer survivors (n = 344) and matched controls without cancer (n = 347) 60 years of age and older without dementia or neurologic disease were recruited between August 2010 and December 2015. Data collection occurred during presystemic treatment/control enrollment and at 12 and 24 months through biospecimens; surveys; self-reported Functional Assessment of Cancer Therapy-Cognitive Function; and neuropsychological tests that measured attention, processing speed, and executive function (APE) and learning and memory (LM). Linear mixed-effects models tested two-way interactions of treatment group (control, chemotherapy with or without hormonal therapy, and hormonal therapy) and time and explored three-way interactions of ApoE (ε4+ v not) by group by time; covariates included baseline age, frailty, race, and cognitive reserve. Results Survivors and controls were 60 to 98 years of age, were well educated, and had similar baseline cognitive scores. Treatment was related to longitudinal cognition scores, with survivors who received chemotherapy having increasingly worse APE scores (P = .05) and those initiating hormonal therapy having lower LM scores at 12 months (P = .03) than other groups. These group-by-time differences varied by ApoE genotype, where only ε4+ survivors receiving hormone therapy had short-term decreases in adjusted LM scores (three-way interaction P = .03). For APE, the three-way interaction was not significant (P = .14), but scores were significantly lower for ε4+ survivors exposed to chemotherapy (−0.40; 95% CI, −0.79 to −0.01) at 24 months than ε4+ controls (0.01; 95% CI, 0.16 to 0.18; P < .05). Increasing age was associated with lower baseline scores on all cognitive measures (P < .001); frailty was associated with baseline APE and self-reported decline (P < .001). Conclusion Breast cancer systemic treatment and aging-related phenotypes and genotypes are associated with longitudinal decreases in cognitive function scores in older survivors. These data could inform treatment decision making and survivorship care planning

Supporting genetics in primary care: investigating how theory can inform professional education

Evidence indicates that many barriers exist to the integration of genetic case finding into primary care. We conducted an exploratory study of the determinants of three specific behaviours related to using breast cancer genetics referral guidelines effectively: 'taking a family history', 'making a risk assessment', and 'making a referral decision'. We developed vignettes of primary care consultations with hypothetical patients, representing a wide range of genetic risk for which different referral decisions would be appropriate. We used the Theory of Planned Behavior to develop a survey instrument to capture data on behavioural intention and its predictors (attitude, subjective norm, and perceived behavioural control) for each of the three behaviours and mailed it to a sample of Canadian family physicians. We used correlation and regression analyses to explore the relationships between predictor and dependent variables. The response rate was 96/125 (77%). The predictor variables explained 38-83% of the variance in intention across the three behaviours. Family physicians' intentions were lower for 'making a risk assessment' (perceived as the most difficult) than for the other two behaviours. We illustrate how understanding psychological factors salient to behaviour can be used to tailor professional educational interventions; for example, considering the approach of behavioural rehearsal to improve confidence in skills (perceived behavioural control), or vicarious reinforcement as where participants are sceptical that genetics is consistent with their role (subjective norm)

High-intensity interval training in patients with intermittent claudication

OBJECTIVE: Provision, uptake, adherence, and completion rates for supervised exercise programs (SEP) for intermittent claudication (IC) are low. A shorter, more time-efficient, 6-week, high-intensity interval training (HIIT) program may be an effective alternative that is more acceptable to patients and easier to deliver. The aim of this study was to determine the feasibility of HIIT for patients with IC. METHODS: A single arm proof-of-concept study, performed in secondary care, recruiting patients with IC referred to usual-care SEPs. Supervised HIIT was performed three times per week for 6 weeks. The primary outcome was feasibility and tolerability. Potential efficacy and potential safety were considered, and an integrated qualitative study was undertaken to consider acceptability. RESULTS: A total of 280 patients were screened: 165 (59%) were eligible, and 40 (25%) were recruited. The majority (n = 31; 78%) of participants completed the HIIT program. The remaining nine patients were withdrawn or chose to withdraw. Completers attended 99% of training sessions, completed 85% of sessions in full, and performed 84% of completed intervals at the required intensity. There were no related serious adverse events. Maximum walking distance (+94 m; 95% confidence interval, 66.6-120.8 m) and the SF-36 physical component summary (+2.2; 95% confidence interval, 0.3-4.1) were improved following completion of the program. CONCLUSIONS: Uptake to HIIT was comparable to SEPs in patients with IC, but completion rates were higher. HIIT appears feasible, tolerable, and potentially safe and beneficial for patients with IC. It may provide a more readily deliverable, acceptable form of SEP. Research comparing HIIT with usual-care SEPs appears warranted

High-intensity interval training in patients with intermittent claudication: Presented at the 2022 Vascular Society of Great Britain and Ireland Annual Scientific Meeting, Brighton, United Kingdom, November 23-25, 2022; presented at the 2023 Surgical Research Society Meeting, Nottingham, United Kingdom, March 22-24, 2023; and presented at the 2023 Vascular Annual Meeting of the Society for Vascular Surgery, National Harbor, MD, June 14-17, 2023

Objective: Provision, uptake, adherence, and completion rates for supervised exercise programs (SEP) for intermittent claudication (IC) are low. A shorter, more time-efficient, 6-week, high-intensity interval training (HIIT) program may be an effective alternative that is more acceptable to patients and easier to deliver. The aim of this study was to determine the feasibility of HIIT for patients with IC. Methods: A single arm proof-of-concept study, performed in secondary care, recruiting patients with IC referred to usual-care SEPs. Supervised HIIT was performed three times per week for 6 weeks. The primary outcome was feasibility and tolerability. Potential efficacy and potential safety were considered, and an integrated qualitative study was undertaken to consider acceptability. Results: A total of 280 patients were screened: 165 (59%) were eligible, and 40 (25%) were recruited. The majority (n = 31; 78%) of participants completed the HIIT program. The remaining nine patients were withdrawn or chose to withdraw. Completers attended 99% of training sessions, completed 85% of sessions in full, and performed 84% of completed intervals at the required intensity. There were no related serious adverse events. Maximum walking distance (+94 m; 95% confidence interval, 66.6-120.8 m) and the SF-36 physical component summary (+2.2; 95% confidence interval, 0.3-4.1) were improved following completion of the program. Conclusions: Uptake to HIIT was comparable to SEPs in patients with IC, but completion rates were higher. HIIT appears feasible, tolerable, and potentially safe and beneficial for patients with IC. It may provide a more readily deliverable, acceptable form of SEP. Research comparing HIIT with usual-care SEPs appears warranted