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Background: Normal brain aging is associated with dopamine decline, which has been linked to age-related cognitive decline. Factors underlying individual differences in dopamine integrity at older ages remain, however, unclear. Here we aimed at investigating: (i) whether inflammation is associated with levels and 5-year changes of in vivo dopamine D2-receptor (DRD2) availability, (ii) if DRD2-inflammation associations differ between men and women, and (iii) whether inflammation and cerebral small-vessel disease (white-matter lesions) serve as two independent predictors of DRD2 availability.

Methods: Analyses were performed in a sample of healthy adults > 60 years assessed at two measurement occasions separated by 5 years. At both occasions, DRD2 availability was estimated by ¹¹C-raclopride PET, and white-matter lesions by MRI. Inflammation was assessed by two C-reactive protein-associated DNA methylation scores at study baseline.

Results: Individuals with higher DNA methylation scores at baseline showed reduced striatal DRD2 availability. An interaction was found between DNA methylation scores and sex in relation to striatal DRD2 availability, such that associations were found in men but not in women. DNA methylation scores at study entrance were not significantly associated with 5-year striatal DRD2 decline rates. No significant association was found between DNA methylation scores and white-matter lesions, but higher scores as well as higher lesion burden were independently associated with reduced striatal DRD2 availability in men.

Conclusions: These findings suggest negative associations between one proxy of inflammation and DRD2 availability in older adults, selectively for men who had higher DNA methylation scores. Future studies should investigate other inflammatory markers in relation to dopamine integrity.

Background: Chaotic sporting environments require the performance of concurrent cognitive and motor tasks. A reduced capacity for either or both of the tasks when performed concurrently is known as cognitive-motor interference (CMi) and is believed to increase the injury risk. A greater susceptibility to CMi after a rupture of the anterior cruciate ligament (ACL) has been suggested to be caused by central nervous system adaptations, thus possibly contributing to high secondary ACL injury rates.

Purpose: To investigate whether patients after ACL reconstruction (ACLR) demonstrate greater CMi than noninjured controls when adding secondary cognitive tasks to the drop vertical jump (DVJ) and explore the potential influence of sex on CMi.

Study Design: Controlled laboratory study.

Methods: A total of 40 (50% male) sports-active patients who had undergone ACLR (mean, 24.9 ± 16.1 months after surgery) and 40 (50% male) sports-active noninjured controls performed DVJs with and without secondary cognitive tasks targeting short-term memory, attention, fast decision-making, and inhibitory control. Outcomes included a letter position recall task and 3 motor variables: (1) correct action (landing or landing with a subsequent vertical jump), (2) relative jump height (relative between DVJs), and (3) relative peak vertical ground-reaction force (relative between DVJs). Participants also completed isolated cognitive tests (CANTAB) included as covariates in multivariate analysis.

Results: Multivariate analysis of variance revealed that the ACLR group had greater CMi than the control group (P < .001), as manifested by more incorrect answers for the cognitive letter recall task (mean difference [MD], –13.3% [95% CI, –20.8% to –5.9%]; P < .001), more incorrect motor actions (MD, –7.5% [95% CI, −12.4% to –2.6%]; P = .003), and a reduced relative jump height (MD, –4.5% [95% CI, –7.9% to –1.2%]; P = .010). No difference in relative peak vertical ground-reaction force was found (MD, 2.8% [95% CI, –7.7% to 13.3%]; P = .59). Isolated cognitive outcomes did not affect these results, and there were no significant differences between male and female participants.

Conclusion: Patients after ACLR showed greater CMi than noninjured controls, which was unrelated to isolated cognitive outcomes, thus indicating aberrant neurocognitive function.

Clinical Relevance: Clinicians should consider cognitive and dual-task training and screening during ACL rehabilitation to better prepare patients for chaotic and uncontrolled sporting environments in which dual tasking is prevalent. Such interventions may help to reduce the risk of secondary ACL injuries.

Background: Physical activity and exercise are promoted worldwide as effective interventions for healthy ageing. Various exercise initiatives have been developed and evaluated for their efficacy and effectiveness among older populations. However, a deeper understanding of participants’ experiences with these initiatives is crucial to foster long-term activity and exercise among older persons.

Methods: A constructivist grounded theory study was conducted to explore the experiences of older persons participating in a supervised group supramaximal high-intensity training (HIT) programme. Four focus groups were held, involving 28 persons aged 65 to 78. The focus groups were analysed inductively, followed by an iterative process of abstraction, abduction, and theory generation using a constant comparative method. A conceptual framework comprising three theoretical concepts—stereotype embodiment, ageist practices, and self-efficacy—was employed during the abductive phase as an analytical lens.

Results: The core category of our grounded theory, Negotiating a physically active life in tune with ageing, encapsulates the complex processes and actions influencing older persons as they engage in physical activities in their daily lives and in relation to HIT. This core category was created from the conceptual framework and the four categories: Grit in the moment and overall life, Empowered by the training group, Navigating one’s physically active self, and Committing to exercise for duty and pleasure. Participants reported feeling invigorated by the exercise, enjoying the challenge, and valuing the group setup for its social connectedness and structure. The generated theory illustrates how participants’ engagement with physical activity and exercise is shaped by various perspectives accumulated over their lifespan. The findings provide a plausible explanation of how participation in HIT groups can challenge negative age stereotypes and ageist practices while enhancing self-efficacy for high-intensity exercise.

Conclusions: Our grounded theory underscores that physical activity and exercise should be regarded as multifaceted processes, which must be considered when promoting physical activity initiatives for older persons. By considering the older person and societal norms and values, we can gather knowledge to design physical exercise interventions that are not only effective but also enjoyable and capable of transforming how individuals perceive themselves as exercising persons.

This analysis of secondary outcomes investigated the applicability of supramaximal high-intensity interval training (HIT) with individually prescribed external intensity performed on stationary bicycles. Sixty-eight participants with a median (min; max) age of 69 (66; 79), at the time not engaged in regular exercise were randomized to 25 twice-weekly sessions of supramaximal HIT (20-min session with 10 × 6-s intervals) or moderate-intensity training (MIT, 40-min session with 3 × 8-min intervals). The primary aim was outcomes on applicability regarding; adherence to prescribed external interval intensity, participant reported positive and negative events, ratings of perceived exertion (RPE 6–20), and affective state (Feeling Scale, FS -5–5). A secondary aim was to investigate change in exercise-related self-efficacy (Exercise Self-Efficacy Scale) and motivation (Behavioural Regulations in Exercise Questionnaire-2). Total adherence to the prescribed external interval intensity was [median (min; max)] 89 % (56; 100 %) in supramaximal HIT, and 100 % (95; 100 %) in MIT. The supramaximal HIT group reported 60 % of the positive (112 of 186) and 36 % of the negative (52 of 146) events. At the end of the training period, the median (min; max) session RPE was 15 (12; 17) for supramaximal HIT and 14 (9; 15) for MIT. As for FS, the median last within-session rating was 3 (−1; 5) for supramaximal HIT and 3 (1; 5) for MIT. Exercise-related motivation increased (mean difference in Relative Autonomy Index score = 1.54, 95 % CI [0.69; 2.40]), while self-efficacy did not change (mean difference = 0.55, 95 % CI [-0.75; 1.82]), regardless of group. This study provide support for supramaximal HIT in supervised group settings for older adults.

Throughout adulthood and ageing our brains undergo structural loss in an average pattern resembling faster atrophy in Alzheimer’s disease (AD). Using a longitudinal adult lifespan sample (aged 30-89; 2–7 timepoints) and four polygenic scores for AD, we show that change in AD-sensitive brain features correlates with genetic AD-risk and memory decline in healthy adults. We first show genetic risk links with more brain loss than expected for age in early Braak regions, and find this extends beyond APOE genotype. Next, we run machine learning on AD-control data from the Alzheimer’s Disease Neuroimaging Initiative using brain change trajectories conditioned on age, to identify AD-sensitive features and model their change in healthy adults. Genetic AD-risk linked with multivariate change across many AD-sensitive features, and we show most individuals over age ~50 are on an accelerated trajectory of brain loss in AD-sensitive regions. Finally, high genetic risk adults with elevated brain change showed more memory decline through adulthood, compared to high genetic risk adults with less brain change. Our findings suggest quantitative AD risk factors are detectable in healthy individuals, via a shared pattern of ageing- and AD-related neurodegeneration that occurs along a continuum and tracks memory decline through adulthood.

Background: Beyond being a pulmonary disease, chronic obstructive pulmonary disease (COPD) presents with extrapulmonary manifestations including reduced cognitive, cardiovascular, and muscle function. While exercise training is the cornerstone in the non-pharmacological treatment of COPD, there is a need for new exercise training methods due to suboptimal adaptations when following traditional exercise guidelines, often applying moderate-intensity continuous training (MICT). In people with COPD, short-duration high-intensity interval training (HIIT) holds the potential to induce a more optimal stimulus for training adaptations while circumventing the ventilatory burden often associated with MICT in people with COPD. We aim to determine the effects of supramaximal HIIT and MICT on extrapulmonary manifestations in people with COPD compared to matched healthy controls.

Methods: COPD-HIIT is a prospective, multi-centre, randomized, controlled trial with blinded assessors and data analysts, employing a parallel-group designed trial. In phase 1, we will investigate the effects and mechanisms of a 12-week intervention of supramaximal HIIT compared to MICT in people with COPD (n = 92) and matched healthy controls (n = 70). Participants will perform watt-based cycling two to three times weekly. In phase 2, we will determine how exercise training and inflammation impact the trajectories of neurodegeneration, in people with COPD, over 24 months. In addition to the 92 participants with COPD performing HIIT or MICT, a usual care group (n = 46) is included in phase 2. In both phases, the primary outcomes are a change from baseline in cognitive function, cardiorespiratory fitness, and muscle power. Key secondary outcomes include change from baseline exercise tolerance, brain structure, and function measured by MRI, neuroinflammation measured by PET/CT, systemic inflammation, and intramuscular adaptations. Feasibility of the interventions will be comprehensively investigated.

Discussion: The COPD-HIIT trial will determine the effects of supramaximal HIIT compared to MICT in people with COPD and healthy controls. We will provide evidence for a novel exercise modality that might overcome the barriers associated with MICT in people with COPD. We will also shed light on the impact of exercise at different intensities to reduce neurodegeneration. The goal of the COPD-HIIT trial is to improve the treatment of extrapulmonary manifestations of the disease.

OBJECTIVE: This study investigated the effectiveness of supramaximal high-intensity interval training (supramaximal HIT) on muscle capacities and physical function compared to moderate-intensity training (MIT) for older adults.

METHODS: Sixty-eight older adults (66-79 years, 56% women), not engaged in regular exercise, were randomised to 3 months of twice-weekly supramaximal HIT (20 minutes including 10 × 6-second intervals) or MIT (40 minutes including 3 × 8-minute intervals). Both groups performed the training on stationary bicycles in a group setting. Target intensity was watt-controlled, with standardised cadence and individualised resistance. Outcomes analysed with linear-mixed models included leg power (Nottingham Power Rig), hand grip strength (Jamar dynamometer), static and dynamic balance (One leg stance, 30-second step test), chair stand (30-second chair stand), and anaerobic cycling performance (modified Borg Cycle Strength Test).

RESULTS: Baseline values were (supramaximal HIT/MIT, mean ± SD) leg power 198 ± 60/189 ± 53 W, hand grip strength 4.2 ± 1.0/4.3 ± 1.1 N/kg, static balance 64 ± 41/62 ± 41 s, dynamic balance 39 ± 7/38 ± 5 steps, chair stands 22 ± 6/22 ± 6 and anaerobic cycling performance 224 ± 60/217 ± 55 W. At 3-month follow-up, a between-group difference in favour of supramaximal HIT [95% CI] was observed in anaerobic cycling performance of 19[3;35] W. Within-group mean changes for supramaximal HIT/MIT were for leg power 8.4[0.9;15.8]/6.0[-1.3;13.3] W, hand grip strength 0.14[0.00;0.27]/0.13[-0.01;0.26] N/kg, static balance 11[3;20]/10[1;18] s, dynamic balance 1.6[0.3;2.8]/2.3[1.1;3.6] steps, 2.1[1.1;3.1]/1.4[0.4;2.3] chair stands and anaerobic cycling performance 31.3[19.6;43.0]/12.0[0.4;23.5] W.

CONCLUSION: Supramaximal HIT showed superior effect on anaerobic cycling performance when compared to MIT. Additionally, the results indicate that supramaximal HIT is comparably beneficial as MIT in terms of effects on muscle capacity and physical function for older adults.

Background: Sick-leave rates are high due to stress-related illnesses, but little is still known about the process of recovery from these conditions. The aim of this study was to explore the experiences of the recovery process, 6 to 10 years after treatment in people previously diagnosed with exhaustion disorder (ED), focusing on facilitators and barriers for the process of recovery from ED, and recovery activities experienced as helpful during the recovery process.

Method: Thirty-eight participants (average age: 52 years, 32 females) previously diagnosed with ED were interviewed with semi-structured interviews 6–10 years after undergoing treatment. The interviews were analyzed with thematic analysis.

Results: Three themes resulted from the analysis. The first theme, “A long and rocky road”, summarizes the fluctuating path to feeling better and emphasizes barriers and facilitators that affected the process of recovery, with a focus on external life events and the participants’ own behaviors. Facilitators were changing workplace, receiving support, a reduction in stressors, and changed behaviors. Barriers were a poor work environment, caregiver responsibilities, negative life events and lack of support. The second theme “Recovery activities are needed every step of the way” describes how both the need for recovery activities and the types of activities experienced as helpful changed during the recovery process, from low-effort recovery activities for long periods of time to shorter and more active recovery activities. Recovery activities were described as important for self-care but hard to prioritize in everyday life. The last theme, “Reorienting to a new place”, captures the struggle to cope with the remaining impact of ED, and how internal facilitators in terms of understanding and acceptance were important to reorient and adjust to a new way of functioning.

Conclusions: Recovering from ED is a long and ongoing process where recovery activities are needed every step of the way. Our results highlight the importance of supporting personal recovery and long-term behavioral change, addressing individual stressors that may perpetuate the condition, and adjusting recovery activities according to where the person is in the recovery process.

Trial registration: ClinicalTrials.gov: NCT0073772. Registered on March 8, 2017. This study was pre-registered on Open Science Framework (osf.io).

Generalization of training to support the performance on new tasks—transfer—has been much studied. One hypothesis is that transfer occurs if overlapping neuronal circuits are engaged in both training and transfer tasks. Here, we investigated transfer effects in the domain of episodic memory by following 356 participants between 20 and 83 years who downloaded and used a smart phone application to practice the method of loci (MoL) over 3 months. We measured transfer of MoL training to three associative memory tasks with hypothesized neurocognitive overlap (binding in the hippocampus) with the trained task. Transfer tasks were administered at the beginning of training and when two specific proficiency levels in Loci training were reached. Results showed robust transfer effects across the age span at both levels. These results indicate that app-based strategy training can lead to enhancement of episodic memory beyond the specific training task, which may have clinical implementations.

Modifiable lifestyle factors have been shown to promote healthy brain ageing. However, studies have typically focused on a single factor at a time. Given that lifestyle factors do not occur in isolation, multivariable analyses provide a more realistic model of the lifestyle-brain relationship. Here, canonical correlation analyses (CCA) examined the relationship between nine lifestyle factors and seven MRI-derived indices of brain structure. The resulting covariance pattern was further explored with Bayesian regressions. CCA analyses were first conducted on a Danish cohort of older adults (n = 251) and then replicated in a British cohort (n = 668). In both cohorts, the latent factors of lifestyle and brain structure were positively correlated (UK: r =.37, p < 0.001; Denmark: r =.27, p < 0.001). In the cross-validation study, the correlation between lifestyle-brain latent factors was r =.10, p = 0.008. However, the pattern of associations differed between datasets. These findings suggest that baseline characterisation and tailoring towards the study sample may be beneficial for achieving targeted lifestyle interventions.