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One step toward healthy brain aging may be to entertain a physically active lifestyle. Studies investigating physical activity effects on brain integrity have, however, mainly been based on single brain markers, and few used a multimodal imaging approach. In the present study, we used cohort data from the Betula study to examine the relationships between scores reflecting current and accumulated physical activity and brain health. More specifically, we first examined if physical activity scores modulated negative effects of age on seven resting state networks previously identified by Salami, Pudas, and Nyberg (2014). The results revealed that one of the most age-sensitive RSN was positively altered by physical activity, namely, the posterior default-mode network involving the posterior cingulate cortex (PCC). Second, within this physical activity-sensitive RSN, we further analyzed the association between physical activity and gray matter (GM) volumes, white matter integrity, and cerebral perfusion using linear regression models. Regions within the identified DMN displayed larger GM volumes and stronger perfusion in relation to both current and 10-years accumulated scores of physical activity. No associations of physical activity and white matter integrity were observed. Collectively, our findings demonstrate strengthened PCC–cortical connectivity within the DMN, larger PCC GM volume, and higher PCC perfusion as a function of physical activity. In turn, these findings may provide insights into the mechanisms of how long-term regular exercise can contribute to healthy brain aging. •Higher physical activity score is related to stronger connectivity in the posterior DMN.•Higher physical activity score is related to larger GM volume of the PCC.•Higher physical activity score is related to higher perfusion rate within the PCC.

From 19th to 22nd November 2018, 26 researchers representing nine countries and a variety of academic disciplines met in Snekkersten, Denmark, to reach evidence-based consensus about physical activity and older adults. It was recognised that the term ‘older adults’ represents a highly heterogeneous population. It encompasses those that remain highly active and healthy throughout the life-course with a high intrinsic capacity to the very old and frail with low intrinsic capacity. The consensus is drawn from a wide range of research methodologies within epidemiology, medicine, physiology, neuroscience, psychology and sociology, recognising the strength and limitations of each of the methods. Much of the evidence presented in the statements is based on longitudinal associations from observational and randomised controlled intervention studies, as well as quantitative and qualitative social studies in relatively healthy community-dwelling older adults. Nevertheless, we also considered research with frail older adults and those with age-associated neurodegenerative diseases, such as Alzheimer’s and Parkinson’s disease, and in a few cases molecular and cellular outcome measures from animal studies. The consensus statements distinguish between physical activity and exercise. Physical activity is used as an umbrella term that includes both structured and unstructured forms of leisure, transport, domestic and work-related activities. Physical activity entails body movement that increases energy expenditure relative to rest, and is often characterised in terms of intensity from light, to moderate to vigorous. Exercise is defined as a subset of structured physical activities that are more specifically designed to improve cardiorespiratory fitness, cognitive function, flexibility balance, strength and/or power. This statement presents the consensus on the effects of physical activity on older adults’ fitness, health, cognitive functioning, functional capacity, engagement, motivation, psychological well-being and social inclusion. It also covers the consensus on physical activity implementation strategies. While it is recognised that adverse events can occur during exercise, the risk can be minimised by carefully choosing the type of activity undertaken and by consultation with the individual’s physician when warranted, for example, when the individual is frail, has a number of co-morbidities, or has exercise-related symptoms, such as chest pain, heart arrhythmia or dizziness. The consensus was obtained through an iterative process that began with the presentation of the state-of-the-science in each domain, followed by group and plenary discussions. Ultimately, the participants reached agreement on the 30-item consensus statements.

Studies have shown that aerobic exercise has the potential to improve cognition and reduce brain atrophy in older adults. However, the literature is equivocal with regards to the specificity or generality of these effects. To this end, we report results on cognitive function and brain structure from a 6-month training intervention with 60 sedentary adults (64-78 years) randomized to either aerobic training or stretching and toning control training. Cognitive functions were assessed with a neuropsychological test battery in which cognitive constructs were measured using several different tests. Freesurfer was used to estimate cortical thickness in frontal regions and hippocampus volume. Results showed that aerobic exercisers, compared to controls, exhibited a broad, rather than specific, improvement in cognition as indexed by a higher \"Cognitive score,\" a composite including episodic memory, processing speed, updating, and executive function tasks ( = 0.01). There were no group differences in cortical thickness, but additional analyses revealed that aerobic fitness at baseline was specifically related to larger thickness in dorsolateral prefrontal cortex (dlPFC), and hippocampus volume was positively associated with increased aerobic fitness over time. Moreover, \"Cognitive score\" was related to dlPFC thickness at baseline, but changes in \"Cognitive score\" and dlPFC thickness were associated over time in the aerobic group only. However, aerobic fitness did not predict dlPFC change, despite the improvement in \"Cognitive score\" in aerobic exercisers. Our interpretation of these observations is that potential exercise-induced changes in thickness are slow, and may be undetectable within 6-months, in contrast to change in hippocampus volume which in fact was predicted by the change in aerobic fitness. To conclude, our results add to a growing literature suggesting that aerobic exercise has a broad influence on cognitive functioning, which may aid in explaining why studies focusing on a narrower range of functions have sometimes reported mixed results.

BackgroundSedentary behaviour is associated with impaired cognition, whereas exercise can acutely improve cognition.ObjectiveWe compared the effects of a morning bout of moderate-intensity exercise, with and without subsequent light-intensity walking breaks from sitting, on cognition in older adults.MethodsSedentary overweight/obese older adults with normal cognitive function (n=67, 67±7 years, 31.2±4.1 kg/m2) completed three conditions (6-day washout): SIT (sitting): uninterrupted sitting (8 hours, control); EX+SIT (exercise + sitting): sitting (1 hour), moderate-intensity walking (30 min), uninterrupted sitting (6.5 hours); and EX+BR (exercise + breaks): sitting (1 hour), moderate-intensity walking (30 min), sitting interrupted every 30 min with 3 min of light-intensity walking (6.5 hours). Cognitive testing (Cogstate) was completed at four time points assessing psychomotor function, attention, executive function, visual learning and working memory. Serum brain-derived neurotrophic growth factor (BDNF) was assessed at six time points. The 8-hour net area under the curve (AUC) was calculated for each outcome.ResultsWorking memory net AUC z-score·hour (95% CI) was improved in EX+BR with a z-score of +28 (−26 to +81), relative to SIT, −25 (−79 to +29, p=0.04 vs EX+BR). Executive function net AUC was improved in EX+SIT, −8 (− 71 to +55), relative to SIT, −80 (−142 to −17, p=0.03 vs EX+SIT). Serum BDNF net AUC ng/mL·hour (95% CI) was increased in both EX+SIT, +171 (−449 to +791, p=0.03 vs SIT), and EX+BR, +139 (−481 to +759, p=0.045 vs SIT), relative to SIT, −227 (−851 to +396).ConclusionA morning bout of moderate-intensity exercise improves serum BDNF and working memory or executive function in older adults, depending on whether or not subsequent sitting is also interrupted with intermittent light-intensity walking.Trial registration numberACTRN12614000737639.

There is much evidence that dopamine is vital for cognitive functioning in aging. Here we tested the hypothesis that aerobic exercise and fitness influence dopaminergic neurotransmission in the striatum, and in turn performance on offline working-memory updating tasks. Dopaminergic neurotransmission was measured by positron emission tomography (PET) and the non-displacable binding potential (BPND) of [11C]raclopride, i.e. dopamine (DA) D2-receptor (D2R) availability. Fifty-four sedentary older adults underwent a six-months exercise intervention, performing either aerobic exercise or stretching, toning, and resistance active control training. At baseline, higher aerobic fitness levels (VO2peak) were associated with higher BPND in the striatum, providing evidence of a link between an objective measure of aerobic fitness and D2R in older adults. BPND decreased substantially over the intervention in both groups but the intervention effects were non-selective with respect to exercise group. The decrease was several times larger than any previously estimated annual decline in D2R, potentially due to increased endogenous DA. Working-memory was unrelated to D2R both at baseline and following the intervention. To conclude, we provide partial evidence for a link between physical exercise and DA. Utilizing a PET protocol able to disentangle both D2R and DA levels could shed further light on whether, and how, aerobic exercise impacts the dopaminergic system in older adults. •Aerobic fitness in older adults predicts D2-receptor availability in striatum.•No direct link between increased VO2peak and change in D2-receptor was observed.•[11C]raclopride binding was significantly reduced, but was non-selective with respect to exercise group.•Changes in [11C]raclopride binding did not predict improved working memory.

Understanding individual variability in response to physical activity is key to developing more effective and personalised interventions for healthy ageing. Here, we aimed to unpack individual differences by using longitudinal data from a randomised‐controlled trial of a 12‐month muscle strengthening intervention in older adults. Physical function of the lower extremities was collected from 247 participants (66.3 ± 2.5 years) at four time‐points. At baseline and at year 4, participants underwent 3 T MRI brain scans. K‐means longitudinal clustering was used to identify patterns of change in chair stand performance over 4 years, and voxel‐based morphometry was applied to map structural grey matter volume at baseline and year 4. Results identified three groups showing trajectories of poor (33.6%), mid (40.1%), and high (26.3%) performance. Baseline physical function, sex, and depressive symptoms significantly differed between trajectory groups. High performers showed greater grey matter volume in the motor cerebellum compared to the poor performers. After accounting for baseline chair stand performance, participants were re‐assigned to one of four trajectory‐based groups: moderate improvers (38.9%), maintainers (38.5%), improvers (13%), and decliners (9.7%). Clusters of significant grey matter differences were observed between improvers and decliners in the right supplementary motor area. Trajectory‐based group assignments were unrelated to the intervention arms of the study. In conclusion, patterns of change in chair stand performance were associated with greater grey matter volumes in cerebellar and cortical motor regions. Our findings emphasise that how you start matters, as baseline chair stand performance was associated with cerebellar volume 4 years later. The LIve active Successful Ageing study conducted a 12‐month muscle strengthening randomised‐controlled trial in older adults. Three years after the end of the intervention, intervention group assignment did not predict grey matter volume (GMV). In contrast, groups derived based on trajectories of physical function over 4 years were associated with GMV in cerebellar and cortical motor regions.

Studies indicate that brain response during proprioceptive tasks predominates in the right hemisphere. A right hemisphere lateralization for proprioception may help to explain findings that right-limb dominant individuals perform position matching tasks better with the non-dominant left side. Evidence for proprioception-related brain response and side preference is, however, limited and based mainly on studies of the upper limbs. Establishing brain response associated with proprioceptive acuity for the lower limbs in asymptomatic individuals could be useful for understanding the influence of neurological pathologies on proprioception and locomotion. We assessed brain response during an active unilateral knee joint position sense (JPS) test for both legs of 19 right-limb dominant asymptomatic individuals (females/males = 12/7; mean ± SD age = 27.1 ± 4.6 years). Functional magnetic resonance imaging (fMRI) mapped brain response and simultaneous motion capture provided real-time instructions based on kinematics, accurate JPS errors and facilitated extraction of only relevant brain images. Significantly greater absolute (but not constant nor variable) errors were seen for the dominant right knee (5.22° ± 2.02°) compared with the non-dominant left knee (4.39° ± 1.79°) ( = 0.02). When limbs were pooled for analysis, significantly greater responses were observed mainly in the right hemisphere for, e.g., the precentral gyrus and insula compared with a similar movement without position matching. Significant response was also observed in the left hemisphere for the inferior frontal gyrus pars triangularis. When limbs were assessed independently, common response was observed in the right precentral gyrus and superior frontal gyrus. For the right leg, additional response was found in the right middle frontal gyrus. For the left leg, additional response was observed in the right rolandic operculum. Significant positive correlations were found between mean JPS absolute errors for the right knee and simultaneous brain response in the right supramarginal gyrus ( = 0.464, = 0.040). Our findings support a general right brain hemisphere lateralization for proprioception (knee JPS) of the lower limbs regardless of which limb is active. Better proprioceptive acuity for the non-dominant left compared with the dominant right knee indicates that right hemisphere lateralization may have meaningful implications for motor control.

Knee proprioception deficits and neuroplasticity have been indicated following injury to the anterior cruciate ligament (ACL). Evidence is however scarce regarding brain response to knee proprioception tasks and the impact of ACL injury. This study aimed to identify brain regions associated with the proprioceptive sense of joint position at the knee and whether the related brain response of individuals with ACL reconstruction differed from that of asymptomatic controls. Twenty-one persons with unilateral ACL reconstruction (mean 23 months post-surgery) of either the right (n = 10) or left (n = 11) knee, as well as 19 controls (CTRL) matched for sex, age, height, weight and current activity level, performed a knee joint position sense (JPS) test during simultaneous functional magnetic resonance imaging (fMRI). Integrated motion capture provided real-timerecorded knee kinematics to activate test instructions, as well as accurate knee angles for JPS outcomes. Recruited brain regions during knee angle reproduction included somatosensory cortices, prefrontal cortex and insula. Neither brain response nor JPS errors differed between groups, but across groups significant correlations revealed that greater errors were associated with greater ipsilateral response in the anterior cingulate (r = 0.476, P = 0.009), supramarginal gyrus (r = 0.395, P = 0.034) and insula (r = 0.474, P = 0.008). This is the first study to capture brain response using fMRI in relation to quantifiable knee JPS. Activated brain regions have previously been associated with sensorimotor processes, body schema and interoception. Our innovative paradigm can help to guide future research investigating brain response to lower limb proprioception.

Premenstrual dysphoric disorder (PMDD) is a debilitating disorder characterized by severe mood symptoms in the luteal phase of the menstrual cycle. PMDD symptoms are hypothesized to be linked to an altered sensitivity to normal luteal phase levels of allopregnanolone (ALLO), a GABAA-modulating progesterone metabolite. Moreover, the endogenous 3β-epimer of ALLO, isoallopregnanolone (ISO), has been shown to alleviate PMDD symptoms through its selective and dose-dependent antagonism of the ALLO effect. There is preliminary evidence showing altered recruitment of brain regions during emotion processing in PMDD, but whether this is associated to serum levels of ALLO, ISO or their relative concentration is unknown. In the present study, subjects with PMDD and asymptomatic controls underwent functional magnetic resonance imaging (fMRI) in the mid-follicular and the late-luteal phase of the menstrual cycle. Brain responses to emotional stimuli were investigated and related to serum levels of ovarian steroids, the neurosteroids ALLO, ISO, and their ratio ISO/ALLO. Participants with PMDD exhibited greater activity in brain regions which are part of emotion-processing networks during the late-luteal phase of the menstrual cycle. Furthermore, activity in key regions of emotion processing networks - the parahippocampal gyrus and amygdala - was differentially associated to the ratio of ISO/ALLO levels in PMDD subjects and controls. Specifically, a positive relationship between ISO/ALLO levels and brain activity was found in PMDD subjects, while the opposite was observed in controls. In conclusion, individuals with PMDD show altered emotion-induced brain responses in the late-luteal phase of the menstrual cycle which may be related to an abnormal response to physiological levels of GABAA-active neurosteroids.

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.