Cortisol, cognition and the ageing prefrontal cortex

The structural and functional decline of the ageing human brain varies by brain region, cognitive function and individual. The underlying biological mechanisms are poorly understood. One potentially important mechanism is exposure to glucocorticoids (GCs; cortisol in humans); GC production is increasingly varied with age in humans, and chronic exposure to high levels is hypothesised to result in cognitive decline via cerebral remodelling. However, studies of GC exposure in humans are scarce and methodological differences confound cross-study comparison. Furthermore, there has been little focus on the effects of GCs on the frontal lobes and key white matter tracts in the ageing brain. This thesis therefore examines relationships among cortisol levels, structural brain measures and cognitive performance in 90 healthy, elderly community-dwelling males from the Lothian Birth Cohort 1936. Salivary cortisol samples characterised diurnal (morning and evening) and reactive profiles (before and after a cognitive test battery). Structural variables comprised Diffusion Tensor Imaging measures of major brain tracts and a novel manual parcellation method for the frontal lobes. The latter was based on a systematic review of current manual methods in the context of putative function and cytoarchitecture. Manual frontal lobe brain parcellation conferred greater spatial and volumetric accuracy when compared to both single- and multi-atlas parcellation at the lobar level. Cognitive ability was assessed via tests of general cognitive ability, and neuropsychological tests thought to show differential sensitivity to the integrity of frontal lobe sub-regions. The majority of, but not all frontal lobe test scores shared considerable overlap with general cognitive ability, and cognitive scores correlated most consistently with the volumes of the anterior cingulate. This is discussed in light of the diverse connective profile of the cingulate and a need to integrate information over more diffuse cognitive networks according to proposed de-differentiation or compensation in ageing. Individuals with higher morning, evening or pre-test cortisol levels showed consistently negative relationships with specific regional volumes and tract integrity. Participants whose cortisol levels increased between the start and end of cognitive testing showed selectively larger regional volumes and lower tract diffusivity (correlation magnitudes <.44). The significant relationships between cortisol levels and cognition indicated that flatter diurnal slopes or higher pre-test levels related to poorer test performance. In contrast, higher levels in the morning generally correlated with better scores (correlation magnitudes <.25). Interpretation of all findings was moderated by sensitivity to type I error, given the large number of comparisons conducted. Though there were limited candidates for mediation analysis, cortisol-function relationships were partially mediated by tract integrity (but not sub-regional frontal volumes) for memory and post-error slowing. This thesis offers a novel perspective on the complex interplay among glucocorticoids, cognition and the structure of the ageing brain. The findings suggest some role for cortisol exposure in determining age-related decline in complex cognition, mediated via brain structure

Systematic review to identify and appraise outcome measures used to evaluate childhood obesity treatment interventions: evidence of purpose, application, validity, reliability and sensitivity

Background: Lack of uniformity in outcome measures used in evaluations of childhood obesity treatment interventions can impede the ability to assess effectiveness and limits comparisons across trials. Objective: To identify and appraise outcome measures to produce a framework of recommended measures for use in evaluations of childhood obesity treatment interventions. Data sources: Eleven electronic databases were searched between August and December 2011, including MEDLINE; MEDLINE In-Process and Other Non-Indexed Citations; EMBASE; PsycINFO; Health Management Information Consortium (HMIC); Allied and Complementary Medicine Database (AMED); Global Health, Maternity and Infant Care (all Ovid); Cumulative Index to Nursing and Allied Health Literature (CINAHL) (EBSCOhost); Science Citation Index (SCI) [Web of Science (WoS)]; and The Cochrane Library (Wiley) - from the date of inception, with no language restrictions. This was supported by review of relevant grey literature and trial databases. Review methods: Two searches were conducted to identify (1) outcome measures and corresponding citations used in published childhood obesity treatment evaluations and (2) manuscripts describing the development and/or evaluation of the outcome measures used in the childhood intervention obesity evaluations. Search 1 search strategy (review of trials) was modelled on elements of a review by Luttikhuis et al. (Oude Luttikhuis H, Baur L, Jansen H, Shrewsbury VA, O'Malley C, Stolk RP, et al. Interventions for treating obesity in children. Cochrane Database Syst Rev 2009;1:CD001872). Search 2 strategy (methodology papers) was built on Terwee et al.'s search filter (Terwee CB, Jansma EP, Riphagen II, de Vet HCW. Development of a methodological PubMed search filter for finding studies on measurement properties of measurement instruments. Qual Life Res 2009;18:1115-23). Eligible papers were appraised for quality initially by the internal project team. This was followed by an external appraisal by expert collaborators in order to agree which outcome measures should be recommended for the Childhood obesity Outcomes Review (CoOR) outcome measures framework. Results: Three hundred and seventy-nine manuscripts describing 180 outcome measures met eligibility criteria. Appraisal of these resulted in the recommendation of 36 measures for the CoOR outcome measures framework. Recommended primary outcome measures were body mass index (BMI) and dual-energy X-ray absorptiometry (DXA). Experts did not advocate any self-reported measures where objective measurement was possible (e.g. physical activity). Physiological outcomes hold potential to be primary outcomes, as they are indicators of cardiovascular health, but without evidence of what constitutes a minimally importance difference they have remained as secondary outcomes (although the corresponding lack of evidence for BMI and DXA is acknowledged). No preference-based quality-of-life measures were identified that would enable economic evaluation via calculation of quality-adjusted life-years. Few measures reported evaluating responsiveness. Limitations Proposed recommended measures are fit for use as outcome measures within studies that evaluate childhood obesity treatment evaluations specifically. These may or may not be suitable for other study designs, and some excluded measures may be more suitable in other study designs. Conclusions: The CoOR outcome measures framework provides clear guidance of recommended primary and secondary outcome measures. This will enhance comparability between treatment evaluations and ensure that appropriate measures are being used. Where possible, future work should focus on modification and evaluation of existing measures rather than development of tools de nova. In addition, it is recommended that a similar outcome measures framework is produced to support evaluation of adult obesity programmes. Funding: The National Institute for Health Research Health Technology Assessment programme

EFFECTS OF HEART RATE VARIABILITY-GUIDED PRESCRIPTIONS ON THE FITNESS OUTCOMES OF HIGH INTENSITY FUNCTIONAL TRAINING

Nicholas Drake1, Michael J. Carper1, & Derek A. Crawford1 1Pittsburg State University, Pittsburg, KS. High intensity functional training (HIFT) is predicated on individuals giving constant maximum effort/intensity each session; constant maximal effort can result in maladaptation such as overreaching or overtraining. PURPOSE: To determine the effectiveness of heart rate variability (HRV) as a tool to optimize training stimuli and recovery during HIFT. METHODS: Twenty-five recreationally-trained males and females were randomized to either an experimental (EXP; n=10) or control (CON; n=15) group and a 14-day baseline of HRV was established prior to study commencement. Participants then completed a two three-week (5 days/week) HIFT intervention with outcomes assessed pre-, mid (i.e., after week 3), and post-intervention. HRV status was monitored continuously using the root mean square of successive R-R interval deviations (RMSSD7-day)throughout the study duration. Daily training intensity was determined for EXP according to the magnitude of deviation from individuals’ baseline mean RMSSD7-day;resulting in training prescriptions of full effort (within 0.5 standard deviation), moderate effort (±0.51 – 1.0 standard deviation), or active recovery (greater than ±1.0 standard deviation). CON performed every session at maximum effort/intensity. Outcomes of interest were physical work capacity (WC) and the summation of one-repetition maximums for back squat, standing shoulder press, and deadlift exercises (Total). RESULTS: No significant group by time interaction for either outcome variable was observed, however there were significant main effects for time for both. WC increased for CON (F = 9.70; p \u3c 0.01; mean diff. = 15.7 reps; 95% CI = 4.49, 27.07) and EXP (F = 37.18; p \u3c 0.001; mean diff. = 14.2 reps; 95% CI = 8.50, 19.89). Similarly, Total increased within both groups (CON: mean diff. = 13.84 kg, 95% CI = 7.47, 20.20, F = 23.44, p \u3c 0.001; EXP: mean diff. = 14.14 kg, 95% CI = 4.65, 23.63, F = 2.61; p = 0.018). In addition, there was a significant difference in days spent training at full effort/intensity between groups (EXP:15.4 ± 6.75 days; CON: 25.67 ± 2.94 days; F = 27.355, p \u3c 0.001). CONCLUSION: Individualized HIFT prescriptions, based on RMSSD7-day of HRV, resulted in comparable fitness outcomes between EXP and CON groups. However, EXP spent significantly less time training at maximum effort/intensity

THREE WEEKS OF CROSSFIT® TRAINING DOES NOT CONTRIBUTE TO OVERTRAINING SYNDROME IN RECREATIONALLY TRAINED MALES: A PILOT STUDY

Derek. A. Crawford1, Josh. Smeed1, and Michael. J. Carper2 1Applied Movement Science Laboratory, and 2Applied Physiology Laboratory. Department of Health, Human Performance and Recreation, Pittsburg State University, Pittsburg, KS, USA Physical inactivity remains a significant public health concern. CrossFit® (CF) is currently one of the most popular health and fitness activities. However, CF faces strong opposition and criticism claiming it causes injury. PURPOSE: Therefore, the purpose of this study was to investigate if CF participation contributes to overtraining syndrome. A secondary purpose was to determine if there are differences between CF original methodologies and real-world practice. METHODS: Six recreationally trained males (height, 182.8 ± 8.6 cm; weight, 84.3 ± 12.4 kg, and age, 25.0 ± 5.4 years) were randomized into two groups, either theoretical (TH) or real-world (RW) prior to the intervention. Both groups completed pre-testing assessment of body composition, physiological, biochemical, psychological, and performance-based data. Both groups participated in CF training 5 days/week. However, the TH group completed training designed to follow original CF methodology while the RW group followed programming designed by a randomly selected CF affiliate. At the beginning and end of each week blood was collected for serum analyses and select joint range-of-motions (ROM) were measured. Additionally, prior to each training session, resting heart rate (RHR), blood pressure (BP), muscle soreness (DOMS), and select training variables were collected. Following the completion of each training session, HR and perceived exertion (RPE) were collected. RESULTS: There are no significant differences in physiological, biochemical, immunological, psychological, or performance outcome variables assessed in this study for both between groups and pre-post testing (all p \u3e .05). However, there are differences in intervention programming between TR and RW groups. In practice, there were significantly less element priority sessions in practice compared to what is recommended (40% vs 0%; χ2=8.25; p=.016). Further, these element priority sessions had significantly lower associated training heart rates (127.4 vs 167.0, 172.4 bpm; F=8.63; p=.001) and ratings of perceived exertions (9.4 vs 14.8, 14.7; F=15.26; p=.000) than other session designs common in CF. CONCLUSION: These data suggest that short-term CF participation does not contribute to the development of overtraining syndrome in recreationally trained males. Questions still remain on the potential for where CF may have the greatest impact on health and fitness and its implementation in practice. This project was funded through an Independent Faculty Research Award provided by the Council for Research and Discovery at Pittsburg State University

PREDICTING MAXIMAL OXYGEN CONSUMPTION (VO2max) FROM ANAEROBIC TREADMILL TEST TIME

Kylie J. Brown1, Crawford, Derek A. Crawford2, and Michael J. Carper1. 1Applied Physiology Laboratory and 2Applied Movement Science Laboratory, Department of Health, Human Performance, and Recreation, Pittsburg State University, Pittsburg, KS, U.S.A. Maximal oxygen consumption (VO2max) testing is widely used in laboratories and requires expensive pieces of equipment. There are numerous prediction equations used to determine VO2max, but none are based on the anaerobic treadmill test (AnTT). PURPOSE: The purpose of this investigation was to develop a regression model to predict maximal oxygen consumption (VO2max) from anaerobic treadmill test time. METHODS: A total of 30 college-aged males and females participated in this investigation. Subjects reported to the Applied Physiology Laboratory for both VO2max and AnTT. On day 1 and day 2 of testing basic anthropometric data was collected. On day 1 of testing subjects performed a VO2max treadmill (TM) test utilizing the Bruce protocol. Subjects were properly fitted into a safety harness (SH) to ensure subjects reached volitional fatigue in safety. Subjects were fitted with a face mask connected to a metabolic cart (MMC) for collection of expired gases and determination of VO2max. Blood pressure (BP), heart rate (HR), and RPE were recorded at rest, 30s prior to the end of each stage, and at volitional fatigue. On day 2 of testing (≥48h after day 1 testing) subjects performed an AnTT. Subjects were, again, properly fitted into the SH and fitted with a face mask connected to a MMC for determination of VO2max. For this test the treadmill was set at a 20% grade and at a speed of 8mph. Subjects were timed with a standard stop watch from the time they began running until volitional fatigue was reached. Measures of BP and HR were recorded at rest and at termination of the test and RPE was measured at termination of the test. RESULTS: The mean VO2max for the AnTT was 57.1 ml·kg-1·min-1 and the mean VO2max for the aerobic (Bruce) treadmill test was 58.6 ml·kg-1·min-1. Multiple linear regression analysis was used to develop a model for predicting VO2max from AnTT time. The correlation between the aerobic protocol and the AnTT time was significant (p≤0.003; r = 0.603), thus, the regression analysis produced the following predictive model: y = 37.2 + 0.38(x). CONCLUSION: Based on these results, we have demonstrated a model to predict VO2 max from anaerobic treadmill test time. However, the data demonstrate that subjects must complete at least 30 sec on the anaerobic treadmill test for the prediction model to work effectively for the 8mph test. This VO2max prediction equation could be used to shorten the amount of time subjects spend in the laboratory. Follow up studies are currently being conducted with variations in speed and grade and reliability studies are being conducted for the 8mph test in a similar population