Effect of 5 years of exercise training on the cardiovascular risk profile of older adults: the Generation 100 randomized trial.

AIMS: The aim of this study was to compare the effects of 5 years of supervised exercise training (ExComb), and the differential effects of subgroups of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT), with control on the cardiovascular risk profile in older adults. METHODS AND RESULTS: Older adults aged 70-77 years from Trondheim, Norway (n = 1567, 50% women), able to safely perform exercise training were randomized to 5 years of two weekly sessions of HIIT [∼90% of peak heart rate (HR), n = 400] or MICT (∼70% of peak HR, n = 387), together forming ExComb (n = 787), or control (instructed to follow physical activity recommendations, n = 780). The main outcome was a continuous cardiovascular risk score (CCR), individual cardiovascular risk factors, and peak oxygen uptake (VO2peak). CCR was not significantly lower [-0.19, 99% confidence interval (CI) -0.46 to 0.07] and VO2peak was not significantly higher (0.39 mL/kg/min, 99% CI -0.22 to 1.00) for ExComb vs. control. HIIT showed higher VO2peak (0.76 mL/kg/min, 99% CI 0.02-1.51), but not lower CCR (-0.32, 99% CI -0.64 to 0.01) vs. control. MICT did not show significant differences compared to control or HIIT. Individual risk factors mostly did not show significant between-group differences, with some exceptions for HIIT being better than control. There was no significant effect modification by sex. The number of cardiovascular events was similar across groups. The healthy and fit study sample, and contamination and cross-over between intervention groups, challenged the possibility of detecting between-group differences. CONCLUSIONS: Five years of supervised exercise training in older adults had little effect on cardiovascular risk profile and did not reduce cardiovascular events. REGISTRATION: ClinicalTrials.gov: NCT01666340.

Longitudinal study of the effect of a 5-year exercise intervention on structural brain complexity in older adults. A Generation 100 substudy.

Physical inactivity has been identified as an important risk factor for dementia. High levels of cardiorespiratory fitness (CRF) have been shown to reduce the risk of dementia. However, the mechanism by which exercise affects brain health is still debated. Fractal dimension (FD) is an index that quantifies the structural complexity of the brain. The purpose of this study was to investigate the effects of a 5-year exercise intervention on the structural complexity of the brain, measured through the FD, in a subset of 105 healthy older adults participating in the randomized controlled trial Generation 100 Study. The subjects were randomized into control, moderate intensity continuous training, and high intensity interval training groups. Both brain MRI and CRF were acquired at baseline and at 1-, 3- and 5-years follow-ups. Cortical thickness and volume data were extracted with FreeSurfer, and FD of the cortical lobes, cerebral and cerebellar gray and white matter were computed. CRF was measured as peak oxygen uptake (VO2peak) using ergospirometry during graded maximal exercise testing. Linear mixed models were used to investigate exercise group differences and possible CRF effects on the brain's structural complexity. Associations between change over time in CRF and FD were performed if there was a significant association between CRF and FD. There were no effects of group membership on the structural complexity. However, we found a positive association between CRF and the cerebral gray matter FD (p < 0.001) and the temporal lobe gray matter FD (p < 0.001). This effect was not present for cortical thickness, suggesting that FD is a more sensitive index of structural changes. The change over time in CRF was associated with the change in temporal lobe gray matter FD from baseline to 5-year follow-up (p < 0.05). No association of the change was found between CRF and cerebral gray matter FD. These results demonstrated that entering old age with high and preserved CRF levels protected against loss of structural complexity in areas sensitive to aging and age-related pathology.

The association of change in peak oxygen uptake with use of psychotropics in community-dwelling older adults - The Generation 100 study.

BACKGROUND: The use of psychotropics is high among the older population and may have detrimental effects on their physical and mental health. Cardiorespiratory fitness (CRF) is a strong and modifiable measure of health and declines with age. We aimed to study the association of change in CRF with use of psychotropics in community-dwelling older adults. METHODS: We analyzed longitudinal data from 1531 older adults from the Generation 100 study, aged 70-77 years at inclusion, and with a permanent address in Trondheim, Norway. Data on objectively measured peak oxygen uptake (VO2peak) were linked with register data from the Norwegian Prescription Database on prescribed psychotropics. The included psychotropics were antidepressants (N06A), antipsychotics (N05A), anxiolytics (N05B), hypnotics and sedatives (N05C), and N03AE (benzodiazepine derivatives). Analyses were done on any psychotropics as one group, and on the following separate groups: antidepressants (N06A), benzodiazepines (N05BA, N05CD, and N03AE), and z-hypnotics (N05CF). Peak oxygen uptake was measured four times over a five-year period and corresponding medication use was measured as defined daily doses (DDD). A random effects estimator was applied to investigate the association of change in VO2peak with the use of psychotropics. RESULTS: We found a statistically significant curvilinear association of change in VO2peak with use of any psychotropics and antidepressants. For VO2peak up to ~ 40 ml/kg/min, each 1 ml/kg/min increase was associated by a 3.3 DDD and 2.5 DDD decrease in use of any psychotropics and antidepressants, respectively. A bottoming-out effect was found and increases in VO2peak above ~ 40 ml/kg/min showed increased use of any psychotropics and antidepressants. However, the association of change in VO2peak with use was stronger for changes in the lower continuum of VO2peak levels and decreased with increasing VO2peak. No statistically significant association of change in VO2peak with use of benzodiazepines and z-hypnotics were found. However, because of a non-randomized design, we cannot rule out the possibility of confounding by indication. CONCLUSIONS: The results of this study show a curvilinear association of change in VO2peak with use of any psychotropics and antidepressants in older adults. This relationship adds a new viewpoint on the adverse effects of psychotropic use and should be considered in interventions and policies aimed at reducing psychotropic medication use among the older population.

Genome wide association study of response to interval and continuous exercise training: the Predict-HIIT study.

BACKGROUND: Low cardiorespiratory fitness (V̇O2peak) is highly associated with chronic disease and mortality from all causes. Whilst exercise training is recommended in health guidelines to improve V̇O2peak, there is considerable inter-individual variability in the V̇O2peak response to the same dose of exercise. Understanding how genetic factors contribute to V̇O2peak training response may improve personalisation of exercise programs. The aim of this study was to identify genetic variants that are associated with the magnitude of V̇O2peak response following exercise training. METHODS: Participant change in objectively measured V̇O2peak from 18 different interventions was obtained from a multi-centre study (Predict-HIIT). A genome-wide association study was completed (n = 507), and a polygenic predictor score (PPS) was developed using alleles from single nucleotide polymorphisms (SNPs) significantly associated (P < 1 × 10-5) with the magnitude of V̇O2peak response. Findings were tested in an independent validation study (n = 39) and compared to previous research. RESULTS: No variants at the genome-wide significance level were found after adjusting for key covariates (baseline V̇O2peak, individual study, principal components which were significantly associated with the trait). A Quantile-Quantile plot indicates there was minor inflation in the study. Twelve novel loci showed a trend of association with V̇O2peak response that reached suggestive significance (P < 1 × 10-5). The strongest association was found near the membrane associated guanylate kinase, WW and PDZ domain containing 2 (MAGI2) gene (rs6959961, P = 2.61 × 10-7). A PPS created from the 12 lead SNPs was unable to predict V̇O2peak response in a tenfold cross validation, or in an independent (n = 39) validation study (P > 0.1). Significant correlations were found for beta coefficients of variants in the Predict-HIIT (P < 1 × 10-4) and the validation study (P < × 10-6), indicating that general effects of the loci exist, and that with a higher statistical power, more significant genetic associations may become apparent. CONCLUSIONS: Ongoing research and validation of current and previous findings is needed to determine if genetics does play a large role in V̇O2peak response variance, and whether genomic predictors for V̇O2peak response trainability can inform evidence-based clinical practice. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR), Trial Id: ACTRN12618000501246, Date Registered: 06/04/2018, http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374601&isReview=true .

Exercise patterns in older adults instructed to follow moderate- or high-intensity exercise protocol - the generation 100 study.

BACKGROUND: Making older adults exercise and keeping them in exercise programs is a major challenge. Understanding how older adults prefer to exercise may help developing tailored exercise programs and increase sustained exercise participation in ageing populations. We aimed to describe exercise patterns, including frequency, intensity, type, location and social setting of exercise, in older adults instructed to follow continuous moderate-intensity training (MCT) or high-intensity interval training (HIIT) over a one-year period. METHODS: Frequency, intensity, type, location and social setting (alone vs. together with others) of exercise were assessed using exercise logs from 618 older adults (aged 70-77 years) randomized to MCT or HIIT. All participants completed exercise logs after each exercise session they performed during one year. Pearson Chi-square tests were run to assess the association between intensity, type, location and social setting of exercise with training group. RESULTS: Both groups performed 2.2 ± 1.3 exercise sessions per week during the year. Walking was the most common exercise type in both groups, but MCT had a higher proportion of walking sessions than HIIT (54.2% vs. 41.1%, p < 0.01). Compared to MCT, HIIT had a higher proportion of sessions with cycling (14.2% vs. 9.8%, p < 0.01), combined endurance and resistance training (10.3% vs. 7.5%, p < 0.01), jogging (6.5% vs. 3.2%, p < 0.01) and swimming (2.6% vs. 1.7%, p < 0.01). Outdoors was the most common exercise location in both training groups (67.8 and 59.1% of all sessions in MCT and HIIT, respectively). Compared to MCT, HIIT had a higher proportion of sessions at a gym (21.4% vs. 17.5%, p < 0.01) and sports facility (9.8% vs. 7.6%, p < 0.01). Both groups performed an equal amount of sessions alone and together with others, but women had a higher proportion of sessions together with others compared to men (56% vs. 44%, p < 0.01). CONCLUSION: This is the first study that has followed older adults instructed to perform MCT or HIIT over a one-year period, collected data from each exercise session they performed and provided important knowledge about their exercise patterns. This novel information may help researchers and clinicians to develop tailored exercise programs in an ageing population.

Absolute and relative accelerometer thresholds for determining the association between physical activity and metabolic syndrome in the older adults: The Generation-100 study.

BACKGROUND: When assessing population adherence to physical activity (PA) recommendation using accelerometers, absolute intensity threshold definition is applied despite having limited validity in those with low cardiorespiratory fitness (CRF), who are unable to reach them (e.g older adults). Thus, PA thresholds relative to CRF may be an alternative approach. We compared the proportion of the older adults meeting the PA recommendation when PA is assessed using absolute versus sex-and-CRF-adjusted (relative) accelerometer thresholds and determined the association between relative versus absolute moderate PA (MPA), vigorous PA (VPA) and moderate-to-vigorous PA (MVPA) and metabolic syndrome (MetS). METHODS: Cross-sectional study of 509 men and 567 women aged 70-77. Accelerometer assessed MPA, VPA and MVPA were analyzed using absolute and relative thresholds. Meeting the PA-recommendation was defined as amounting ≥150 min/week in MPA/MVPA or 75 min/week in VPA, respectively. CRF was directly measured as peak oxygen uptake (VO2peak). MetS was defined as 3 or more of the following: elevated waist circumference, fasting glucose, hypertension, triglycerides, decreased HDL-cholesterol or diabetes, dyslipidemia or hypertension medication. RESULTS: Higher proportion of the population met the recommendation when PA was assessed with relative compared to absolute thresholds: VPA (72.4% vs. 1.7%) and MVPA (75.2% vs. 33.8%). Logistic regression analysis revealed that men and women not meeting the relative-MVPA or VPA recommendation had higher likelihood of MetS (Men: MVPA OR: 1.59, 95% CI: 1.08-2.33. VPA OR: 1.81, 95%CI: 1.23-2.67 and Women: MVPA OR: 2.12, 95% CI: 1.36-3.31; VPA OR: 1.95, 95% CI: 1.29-2.95), compared to men and women meeting the relative MVPA or VPA recommendation. There was no significant association between MetS and absolute MVPA, MPA or VPA recommendations in the fully adjusted model. CONCLUSIONS: The association between meeting/not meeting the PA recommendation and MetS differed with method. Not meeting relative MVPA and VPA recommendation was associated with significantly higher likelihood for presence of MetS. Since relative intensity is part of the current PA recommendation, it should be considered when assessing population PA and associated health risks in the older adults. TRIAL REGISTRATION: Clinical Trial Registration: NCT01931111 (Date of trial registration: July 19, 2013).

Fatigue Alters the Pattern of Physical Activity Behavior in Older Adults: Observational Analysis of Data from the Generation 100 Study.

Fatigue has been associated with reductions in daily activity of older people. Summary measures of daily physical activity provide limited understanding of how fatigue affects physical activity behavior. This study examined the hour-by-hour energy expenditure estimated from accelerometry data to provide insight into physical activity behaviors of older people experiencing fatigue. Fatigued participants were matched to 'not fatigued' participants by age, sex, and BMI. Each group consisted of 86 people with a mean age 73.8 years (SD 2.0), BMI 26.5 kg⋅m-2 (SD 3.9) and 61% female. The phase-space plot, constructed to express rate of change of average vertical axis counts per hour as a time series, showed fatigued participants deviated from the not fatigued participants during the morning period, when hour-by-hour activity was increasing. Older people who feel fatigued have a different morning activity pattern, which appears to lead to the lower overall levels of physical activity.

Correlates of Objectively Measured Physical Activity Among Norwegian Older Adults: The Generation 100 Study.

The aim of this study was to identify how demographics, physical activity (PA) history, and environmental and biological correlates are associated with objectively measured PA among older adults. PA was assessed objectively in 850 older adults (70-77 years, 48% females) using the ActiGraph GT3X+ activity monitor. Hierarchical multiple regression analysis was used to identify important PA correlates. The included correlates explained 27.0% of the variance in older adult's PA. Cardiorespiratory fitness (CRF), gender, and season were the most important correlates, explaining 10.1%, 3.9%, and 2.7% of the variance, respectively. PA was positively associated with CRF, females were more physically active than males, and PA increased in warmer months compared with colder months. This is, to our knowledge, the largest study of PA correlates in older adults that has combined objectively measured PA and CRF. Our findings provide new knowledge about how different correlates are associated with PA.

Association between pulmonary function and peak oxygen uptake in elderly: the Generation 100 study.

BACKGROUND: Although reduced function of the respiratory system limits peak oxygen uptake in diseases affecting the lungs or airways, the healthy respiratory system is thought to have a spare capacity for oxygen transport and uptake, and is not considered a limiting factor for peak oxygen uptake in healthy people. However, lung function declines with age and could theoretically limit peak oxygen uptake in elderly. We examined the association between peak oxygen uptake and lung function indices in an elderly population with the hypothesis that lung function indices would be associated with VO2peak up to a threshold value situated above the lower limits of normal lung function for our population. METHODS: Spirometry, gas diffusion tests and incremental work tests were performed in 1443 subjects (714 women) aged 69-77 years. Association between lung function indices and peak oxygen uptake was studied with hockey-stick regression. RESULTS: Forced expiratory volume in 1 s (FEV1) had a positive association with peak oxygen uptake up to, but not above, a threshold value of 2.86 l for men, and 2.13 l for women (lower limit of normal 2.73 and 1.77 l respectively). A corresponding threshold was found for diffusing capacity of the lung for carbon monoxide (DLCO) for men at 9.18 mmol/min/kPa (lower limit of normal 6.84 mmol/min/kPa). DLCO for women and DLCO divided by alveolar volume (DLCO/VA) for both sexes had a significant linear relationship to VO2peak (p < 0.05), but no significant threshold value was found in these associations. CONCLUSIONS: Threshold values for FEV1 for both sexes and DLCO for men were identified. These lung function indices had a positive association with VO2peak up to these threshold values, but not above. The identified threshold values were above lower limits of normal for FEV1 and DLCO.

New relative intensity ambulatory accelerometer thresholds for elderly men and women: the Generation 100 study.

BACKGROUND: Public health initiatives world-wide recommend increasing physical activity (PA) to improve health. However, the dose and the intensity of PA producing the most benefit are still debated. Accurate assessment of PA is necessary in order to 1) investigate the dose-response relationship between PA and health, 2) shape the most beneficial public health initiatives and 3) test the effectiveness of such initiatives. Actigraph accelerometer is widely used to objectively assess PA, and the raw data is given in counts per unit time. Count-thresholds for low, moderate and vigorous PA are mostly based on absolute intensity. This leads to largely inadequate PA intensity assessment in a large proportion of the elderly, who due to their declining maximal oxygen uptake (VO2max) cannot reach the moderate/vigorous intensity as defined in absolute terms. To resolve this issue, here we report relative Actigraph intensity-thresholds for the elderly. METHODS: Submaximal-oxygen-uptake, VO2max and maximal heart rate (HRmax) were measured in 111 70-77 year olds, while wearing an Actigraph-GT3X+. Relationship between VO2max percentage (%), counts-per-minute (CPM) and gender (for both the vertical-axis (VA) and vector-magnitude (VM)) and VO2max% and HRmax% was established using a mixed-regression-model. VM-and VA-models were tested against each other to see which model predicts intensity of PA better. RESULTS: VO2max and gender significantly affected number of CPM at different PA intensities (p < 0.05). Therefore, intensity-thresholds were created for both men and women of ranging VO2max values (low, medium, high). VM-model was found to be a better predictor of PA-intensity than VA-model (p < 0.05). Established thresholds for moderate intensity (46-63 % of VO2max) ranged from 669-3367 and 834-4048 CPM and vigorous intensity (64-90 % of VO2max) from 1625-4868 and 2012-5423CPM, for women and men, respectively. Lastly, we used this evidence to derive a formula that predicts customized relative intensity of PA (either VO2max% or HRmax%) using counts-per-minute values as input. CONCLUSION: Intensity-thresholds depend on VO2max, gender and Actigraph-axis. PA intensity-thresholds that take all these factors into account allow for more accurate relative intensity PA assessment in the elderly and will be useful in future PA research. TRIAL REGISTRATION: (ClinicalTrials.gov Identifier: NCT02017847, registered 17. December 2013).

The effects of high intensity interval training in women with rheumatic disease: a pilot study.

PURPOSE: Rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) are inflammatory diseases which involve increased risk of cardiovascular disease (CVD). High intensity interval training (HIIT) is known to be effective in improving cardiovascular health. The aim of this study was to investigate whether 10 weeks of HIIT at 85-95% of HRmax would improve important risk factors of CVD in rheumatic patients, and if these patients would tolerate exercise intensities above today's recommendations. METHODS: Seven women with RA and eleven with adult-JIA, 20-50 years, were recruited to this cross-over study. Participants performed HIIT, consisting of 4 × 4 min intervals at 85-95% of HRmax twice a week for 10 weeks on spinning bikes. Maximal oxygen uptake (VO2max), heart rate recovery, blood pressure, body composition, and blood variables were measured before and after the exercise and control period. Disease activity was determined and questionnaire data were collected. RESULTS: HIIT resulted in 12.2% increase in VO2max and 2.9% improvement in heart rate recovery (p < 0.05). BMI, body fat, and waist circumference decreased 1.2, 1.0, and 1.6%, respectively, whereas muscle mass increased 0.6% (p < 0.05). A trend toward decreased CRP was detected after HIIT (p = 0.08). No changes were detected in disease activity or pain. CONCLUSION: Despite rigorous high intensity exercise, no increase was detected in disease activity or pain, indicating that HIIT was well tolerated by these patients. Furthermore, HIIT had positive effects on several CVD risk factors. In light of this pilot study, HIIT seems like a promising non-pharmacological treatment strategy for patients with RA and adult-JIA.

Hippocampal neurochemicals are associated with exercise group and intensity, psychological health, and general cognition in older adults.

Based on the premise that physical activity/exercise impacts hippocampal structure and function, we investigated if hippocampal metabolites for neuronal viability and cell membrane density (i.e., N-acetyl aspartate (NAA), choline (Cho), creatine (Cr)) were higher in older adults performing supervised exercise compared to following national physical activity guidelines. Sixty-three participants (75.3 ± 1.9 years after 3 years of intervention) recruited from the Generation 100 study (NCT01666340_date:08.16.2012) were randomized into a supervised exercise group (SEG) performing twice weekly moderate- to high-intensity training, and a control group (CG) following national physical activity guidelines of ≥ 30-min moderate physical activity ≥ 5 days/week. Hippocampal body and head volumes and NAA, Cho, and Cr levels were acquired at 3T with magnetic resonance imaging and spectroscopic imaging. Sociodemographic data, peak oxygen uptake (VO2peak), exercise characteristics, psychological health, and cognition were recorded. General linear models were used to assess group differences and associations corrected for age, sex, education, and hippocampal volume. Both groups adhered to their training, where SEG trained at higher intensity. SEG had significantly lower NAA/Cr in hippocampal body than CG (p = 0.04). Across participants, higher training intensity was associated with lower Cho/Cr in hippocampal body (p < 0.001). Change in VO2peak, increasing VO2peak from baseline to 3 years, or VO2peak at 3 years were not associated with hippocampal neurochemicals. Lower NAA/Cr in hippocampal body was associated with poorer psychological health and slightly higher cognitive scores. Thus, following the national physical activity guidelines and not training at the highest intensity level were associated with the best neurochemical profile in the hippocampus at 3 years.

Effects of a 5-Year Exercise Intervention on White Matter Microstructural Organization in Older Adults. A Generation 100 Substudy.

Aerobic fitness and exercise could preserve white matter (WM) integrity in older adults. This study investigated the effect on WM microstructural organization of 5 years of exercise intervention with either supervised moderate-intensity continuous training (MICT), high-intensity interval training (HIIT), or following the national physical activity guidelines. A total of 105 participants (70-77 years at baseline), participating in the randomized controlled trial Generation 100 Study, volunteered to take part in this longitudinal 3T magnetic resonance imaging (MRI) study. The HIIT group (n = 33) exercised for four intervals of 4 min at 90% of peak heart rate two times a week, the MICT group (n = 24) exercised continuously for 50 min at 70% peak heart rate two times a week, and the control group (n = 48) followed the national guidelines of ≥30 min of physical activity almost every day. At baseline and at 1-, 3-, and 5-year follow-ups, diffusion tensor imaging (DTI) scans were performed, cardiorespiratory fitness (CRF) was measured as peak oxygen uptake (VO2peak) with ergospirometry, and information on exercise habits was collected. There was no group*time or group effect on any of the DTI indices at any time point during the intervention. Across all groups, CRF was positively associated with fractional anisotropy (FA) and axial diffusivity (AxD) at the follow-ups, and the effect became smaller with time. Exercise intensity was associated with mean diffusivity (MD)/FA, with the greatest effect at 1-year and no effect at 5-year follow-up. There was an association between exercise duration and FA and radial diffusivity (RD) only after 1 year. Despite the lack of group*time interaction or group effect, both higher CRF and exercise intensity was associated with better WM microstructural organization throughout the intervention, but the effect became attenuated over time. Different aspects of exercising affected the WM metrics and WM tracts differently with the greatest and most overlapping effects in the corpus callosum. The current study indicates not only that high CRF and exercise intensity are associated with WM microstructural organization in aging but also that exercise's positive effects on WM may decline with increasing age.

Five years of exercise intervention at different intensities and development of white matter hyperintensities in community dwelling older adults, a Generation 100 sub-study.

We investigated if a five-year supervised exercise intervention with moderate-intensity continuous training (MICT) or high-intensity interval training (HIIT) versus control; physical activity according to national guidelines, attenuated the growth of white matter hyperintensities (WMH). We hypothesized that supervised exercise, in particular HIIT, reduced WMH growth. Older adults from the general population participating in the RCT Generation 100 Study were scanned at 3T MRI at baseline (age 70-77), and after 1-, 3- and 5-years. At each follow-up, cardiorespiratory fitness was measured with ergospirometry, and physical activity plus clinical data collected. Manually delineated total WMH, periventricular (PWMH), deep (DWMH), and automated total white matter hypointensity volumes were obtained. No group by time interactions were present in linear mixed model analyses with the different WMH measurements as outcomes. In the combined exercise (MICT&HIIT) group, a significant group by time interaction was uncovered for PWMH volume, with a larger increase in the MICT&HIIT group. Cardiorespiratory fitness at the follow-ups or change in cardiorespiratory fitness over time were not associated with any WMH measure. Contrary to our hypothesis, taking part in MICT or HIIT over a five-year period did not attenuate WMH growth compared to being in a control group following national physical activity guidelines.

Effects of 5 Years Aerobic Exercise on Cognition in Older Adults: The Generation 100 Study: A Randomized Controlled Trial.

OBJECTIVE: The objective of this study was to investigate whether a 5-year exercise intervention and change in peak oxygen uptake ([Formula: see text]) is associated with cognitive function in older adults. METHODS: Nine hundred and forty-five participants (48% women, mean age at study end 78.2 ± 2.02 years) from the Generation 100 Study were randomized 2:1:1 to a control group, moderate-intensity continuous training or high-intensity interval training twice weekly for 5 years. Peak oxygen uptake was measured using ergospirometry at baseline and after 5 years. Global cognition and mild cognitive impairment (MCI) were assessed with the Montreal Cognitive Assessment scale (MoCA) after 5 years. RESULTS: Compared to the control group, the combined moderate-intensity continuous training plus high-intensity interval training (ExComb) group did not have significantly different cognitive scores (beta value 0.26, 95% confidence interval [CI] - 0.17, 0.69) or odds of MCI (odds ratio 0.86, 95% CI 0.66, 1.13). Men in the ExComb group had 0.80 points higher MoCA (95% CI 0.21, 1.40) and 32% lower odds of MCI compared with male controls (95% CI 0.47, 0.99), with no such findings in women. In the total sample, each 1 metabolic equivalent of task increase in [Formula: see text] corresponded to 0.46 points higher MoCA (95% CI 0.25, 0.67) and 27% lower odds of MCI (95% CI 0.63, 0.85). Compared to [Formula: see text] stable, participants whose [Formula: see text] increased did not have significantly different cognitive scores (beta value 0.24, CI - 0.68, 1.15) or odds of MCI (odds ratio 0.70, 95% CI 0.36, 1.34), whereas participants whose [Formula: see text] decreased had 0.64 points lower MoCA (95% CI - 1.15, - 0.14) and 35% higher odds of MCI (95% CI 0.98, 1.87). CONCLUSIONS: Overall, exercise was not significantly associated with cognition among older adults. However, maintaining or increasing [Formula: see text] appeared to benefit cognition. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01666340.

Association Between Personal Activity Intelligence and Mortality: Population-Based China Kadoorie Biobank Study.

OBJECTIVE: To prospectively investigate the association between personal activity intelligence (PAI) - a novel metabolic metric which translates heart rate during physical activity into a simple weekly score - and mortality in relatively healthy participants in China whose levels and patterns of physical activity in addition to other lifestyle factors are different from those in high-income countries. PATIENTS AND METHODS: From the population-based China Kadoorie Biobank study, 443,792 healthy adults were recruited between June 2004 and July 2008. Participant's weekly PAI score was estimated and divided into four groups (PAI scores of 0, ≤50, 51-99, or ≥100). Using Cox proportional hazard analyses, we calculated adjusted hazard ratios (AHRs) for cardiovascular disease (CVD) and all-cause mortality related to PAI scores. RESULTS: During a median follow-up of 8.2 (interquartile range, 7.3 to 9.1) years, there were 21,901 deaths, including 9466 CVD deaths. Compared with the inactive group (0 PAI score), a baseline weekly PAI score greater than or equal to 100 was associated with a lower risk of CVD mortality, an AHR of 0.87 (95% CI, 0.81 to 0.94) in men, and an AHR of 0.84 (95% CI, 0.78 to 0.92) in women, after adjusting for multiple confounders. Participants with a weekly PAI score greater than or equal to 100 also had a lower risk of all-cause mortality (AHR, 0.93; 95% CI, 0.89 to 0.97 in men, and AHR, 0.93; 95%, 0.88 to 0.98 in women). Moreover, this subgroup gained 2.7 (95% CI, 2.4 to 3.0) years of life, compared with the inactive cohort. CONCLUSION: Among relatively healthy Chinese adults, the PAI metric was inversely associated with CVD and all-cause mortality, highlighting the generalizability of the score in different races, ethnicities, and socioeconomic strata.

Study protocol for the BRAIN Training Trial: a randomised controlled trial of Balance, Resistance, And INterval training on cognitive function in older adults with mild cognitive impairment.

INTRODUCTION: Epidemiological evidence suggests that both poor cardiovascular fitness and low muscle mass or strength markedly increase the rate of cognitive decline and incident dementia in older adults. Results from exercise trials for the improvement of cognition in older adults with mild cognitive impairment (MCI) have reported mixed results. This is possibly due to insufficient exercise intensities. The aim of the Balance, Resistance, And INterval (BRAIN) Training Trial is to determine the effects of two forms of exercise, high-intensity aerobic interval training (HIIT) and high-intensity power training (POWER) each compared with a sham exercise control group on cognition in older adults with MCI. METHODS AND ANALYSIS: One hundred and sixty community-dwelling older (≥ 60 years) people with MCI have been randomised into the trial. Interventions are delivered supervised 2-3 days per week for 12 months. The primary outcome measured at baseline, 6 and 12 months is performance on a cognitive composite score measuring the executive domain calculated from a combination of computerised (NeuroTrax) and paper-and-pencil tests. Analyses will be performed via repeated measures linear mixed models and generalised linear mixed models of baseline, 6-month and 12-month time points, adjusted for baseline values and covariates selected a priori. Mixed models will be constructed to determine the interaction of GROUP × TIME. ETHICS AND DISSEMINATION: Ethical approval was obtained from the University of Sydney (HREC Ref.2017/368), University of Queensland (HREC Ref. 2017/HE000853), University of British Columbia (H16-03309), and Vancouver Coastal Health Research Institute (V16-03309) Human Research Ethics. Dissemination will be via publications, conference presentations, newsletter articles, social media, talks to clinicians and consumers and meetings with health departments/managers.It is expected that communication of results will allow for the development of more effective evidence-based exercise prescription guidelines in this population while investigating the benefits of HIIT and POWER on subclinical markers of disease. TRIAL REGISTRATION NUMBER: ACTRN12617001440314 Australian New Zealand Clinical Trials Registry.

Even low level of physical activity is associated with reduced mortality among people with metabolic syndrome, a population based study (the HUNT 2 study, Norway).

BACKGROUND: Low levels of physical activity may increase the risk of developing metabolic syndrome, a cluster of metabolic factors that are associated with the risk of premature death. It has been suggested that physical activity may reduce the impact of factors associated with metabolic syndrome, but it is not known whether physical activity may reduce mortality in people with metabolic syndrome. METHODS: In a prospective study of 50,339 people, 13,449 had metabolic syndrome at baseline and were followed up for ten years to assess cause-specific mortality. The population was divided into two age groups: those younger than 65 years of age and those older than age 65. Information on their physical activity levels was collected at baseline. RESULTS: Metabolic syndrome was associated with higher mortality from all causes (hazard ratio (HR) 1.35, 95% confidence interval (95% CI) 1.20 to 1.52) and from cardiovascular causes (HR 1.78, 95% CI 1.39 to 2.29) in people younger than 65 years old than among other populations. In older people, there was no overall association of metabolic syndrome with mortality. People with metabolic syndrome who reported high levels of physical activity at baseline were at a reduced risk of death from all causes compared to those who reported no physical activity, both in the younger age group (HR 0.52, 95% CI 0.37 to 0.73) and in the older age group (HR 0.59, 95% CI 0.47 to 0.74). CONCLUSION: Among people with metabolic syndrome, physical activity was associated with reduced mortality from all causes and from cardiovascular causes. Compared to inactivity, even low levels of physical activity were associated with reduced mortality.

5 Years of Exercise Intervention Did Not Benefit Cognition Compared to the Physical Activity Guidelines in Older Adults, but Higher Cardiorespiratory Fitness Did. A Generation 100 Substudy.

Background: Aerobic exercise is proposed to attenuate cognitive decline in aging. We investigated the effect of different aerobic exercise interventions and cardiorespiratory fitness (CRF) upon cognition throughout a 5-year exercise intervention in older adults. Methods: 106 older adults (52 women, age 70-77 years) were randomized into high-intensity interval training (HIIT; ∼90% peak heart rate), moderate-intensity continuous training (MICT; ∼70% peak heart rate), or control for 5 years. The HIIT and MICT groups performed supervised training twice weekly, while the control group was asked to follow the national physical activity guidelines (30 min of physical activity/day). At baseline, 1-, 3-, and 5-year follow-up, participants partook in cognitive testing (spatial memory, verbal memory, pattern separation, processing speed, working memory, and planning ability), underwent clinical testing, and filled out health-related questionnaires. Linear mixed models were used to assess the effects of the exercise group and CRF (measured as peak and max oxygen uptake) on each cognitive test. The effects of changes in CRF on changes in each cognitive test score throughout the intervention were also assessed. The associations between baseline CRF and cognitive abilities at the follow-ups were investigated using linear regressions. Results: There was no group-by-time interaction on the cognitive measures, and neither HIIT nor MICT participation was associated with better cognitive performance than control at any time point during the 5-year intervention. All groups increased their CRF similarly during the 1st year and subsequently declined back to baseline levels after 5 years. A higher CRF was associated with higher processing speed throughout the intervention while increasing CRF during the intervention was associated with better working memory and worse pattern separation. Higher CRF at baseline predicted consistently better processing speed and verbal memory performance. Conclusion: In this first 5-year randomized controlled trial investigating the effects of HIIT, MICT, and physical activity according to national guidelines on cognition, we observed no effect of exercise intervention group on cognition when compared to following the national physical activity guidelines. Still, the results showed that higher CRF and increasing CRF benefited multiple, but not all, cognitive abilities in older adults. Clinical Trial Registration: www.ClinicalTrials.gov, identifier [NCT01666340].

Effect of 5 Years of Exercise Intervention at Different Intensities on Brain Structure in Older Adults from the General Population: A Generation 100 Substudy.

PURPOSE: The aim was to examine the effect of a 5-year exercise intervention at different intensities on brain structure in older adults from the general population partaking in the randomized controlled trial Generation 100 Study. PARTICIPANTS AND METHODS: Generation 100 Study participants were invited to a longitudinal neuroimaging study before randomization. A total of 105 participants (52 women, 70-77 years) volunteered. Participants were randomized into supervised exercise twice a week performing high intensity interval training in 4×4 intervals at ~90% peak heart rate (HIIT, n = 33) or 50 minutes of moderate intensity continuous training at ~70% of peak heart rate (MICT, n = 24). The control group (n = 48) followed the national physical activity guidelines of ≥30 min physical activity daily. Brain MRI at 3T, clinical and cardiorespiratory fitness (CRF), measured as peak oxygen uptake, were collected at baseline, and after 1, 3, and 5 years of intervention. Brain volumes and cortical thickness were derived from T1 weighted 3D MRI data using FreeSurfer. The effect of HIIT or MICT on brain volumes over time was investigated with linear mixed models, while linear regressions examined the effect of baseline CRF on brain volumes at later time points. RESULTS: Adherence in each group was between 79 and 94% after 5 years. CRF increased significantly in all groups during the first year. Compared to controls, the HIIT group had significantly increased hippocampal atrophy located to CA1 and hippocampal body, though within normal range, and the MICT group greater thalamic atrophy. No other effects of intervention group were found. CRF across the intervention was not associated with brain structure, but CRF at baseline was positively associated with cortical volume at all later time points. CONCLUSION: Higher baseline CRF reduced 5-year cortical atrophy rate in older adults, while following physical activity guidelines was associated with the lowest hippocampal and thalamic atrophy rates.