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.

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.

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.

Effect of exercise training for five years on all cause mortality in older adults-the Generation 100 study: randomised controlled trial.

OBJECTIVE: To evaluate the effect of five years of supervised exercise training compared with recommendations for physical activity on mortality in older adults (70-77 years). DESIGN: Randomised controlled trial. SETTING: General population of older adults in Trondheim, Norway. PARTICIPANTS: 1567 of 6966 individuals born between 1936 and 1942. INTERVENTION: Participants were randomised to two sessions weekly of high intensity interval training at about 90% of peak heart rate (HIIT, n=400), moderate intensity continuous training at about 70% of peak heart rate (MICT, n=387), or to follow the national guidelines for physical activity (n=780; control group); all for five years. MAIN OUTCOME MEASURE: All cause mortality. An exploratory hypothesis was that HIIT lowers mortality more than MICT. RESULTS: Mean age of the 1567 participants (790 women) was 72.8 (SD 2.1) years. Overall, 87.5% of participants reported to have overall good health, with 80% reporting medium or high physical activity levels at baseline. All cause mortality did not differ between the control group and combined MICT and HIIT group. When MICT and HIIT were analysed separately, with the control group as reference (observed mortality of 4.7%), an absolute risk reduction of 1.7 percentage points was observed after HIIT (hazard ratio 0.63, 95% confidence interval 0.33 to 1.20) and an absolute increased risk of 1.2 percentage points after MICT (1.24, 0.73 to 2.10). When HIIT was compared with MICT as reference group an absolute risk reduction of 2.9 percentage points was observed (0.51, 0.25 to 1.02) for all cause mortality. Control participants chose to perform more of their physical activity as HIIT than the physical activity undertaken by participants in the MICT group. This meant that the controls achieved an exercise dose at an intensity between the MICT and HIIT groups. CONCLUSION: This study suggests that combined MICT and HIIT has no effect on all cause mortality compared with recommended physical activity levels. However, we observed a lower all cause mortality trend after HIIT compared with controls and MICT. TRIAL REGISTRATION: ClinicalTrials.gov NCT01666340.