Is Short Sleep Bad for the Brain? Brain Structure and Cognitive Function in Short Sleepers.

Many sleep less than recommended without experiencing daytime sleepiness. According to prevailing views, short sleep increases risk of lower brain health and cognitive function. Chronic mild sleep deprivation could cause undetected sleep debt, negatively affecting cognitive function and brain health. However, it is possible that some have less sleep need and are more resistant to negative effects of sleep loss. We investigated this using a cross-sectional and longitudinal sample of 47,029 participants of both sexes (20-89 years) from the Lifebrain consortium, Human Connectome project (HCP) and UK Biobank (UKB), with measures of self-reported sleep, including 51,295 MRIs of the brain and cognitive tests. A total of 740 participants who reported to sleep <6 h did not experience daytime sleepiness or sleep problems/disturbances interfering with falling or staying asleep. These short sleepers showed significantly larger regional brain volumes than both short sleepers with daytime sleepiness and sleep problems (n = 1742) and participants sleeping the recommended 7-8 h (n = 3886). However, both groups of short sleepers showed slightly lower general cognitive function (GCA), 0.16 and 0.19 SDs, respectively. Analyses using accelerometer-estimated sleep duration confirmed the findings, and the associations remained after controlling for body mass index, depression symptoms, income, and education. The results suggest that some people can cope with less sleep without obvious negative associations with brain morphometry and that sleepiness and sleep problems may be more related to brain structural differences than duration. However, the slightly lower performance on tests of general cognitive abilities warrants closer examination in natural settings.SIGNIFICANCE STATEMENT Short habitual sleep is prevalent, with unknown consequences for brain health and cognitive performance. Here, we show that daytime sleepiness and sleep problems are more strongly related to regional brain volumes than sleep duration. However, participants sleeping ≤6 h had slightly lower scores on tests of general cognitive function (GCA). This indicates that sleep need is individual and that sleep duration per se is very weakly if at all related brain health, while daytime sleepiness and sleep problems may show somewhat stronger associations. The association between habitual short sleep and lower scores on tests of general cognitive abilities must be further scrutinized in natural settings.

Individual differences in brain aging: heterogeneity in cortico-hippocampal but not caudate atrophy rates.

It is well documented that some brain regions, such as association cortices, caudate, and hippocampus, are particularly prone to age-related atrophy, but it has been hypothesized that there are individual differences in atrophy profiles. Here, we document heterogeneity in regional-atrophy patterns using latent-profile analysis of 1,482 longitudinal magnetic resonance imaging observations. The results supported a 2-group solution reflecting differences in atrophy rates in cortical regions and hippocampus along with comparable caudate atrophy. The higher-atrophy group had the most marked atrophy in hippocampus and also lower episodic memory, and their normal caudate atrophy rate was accompanied by larger baseline volumes. Our findings support and refine models of heterogeneity in brain aging and suggest distinct mechanisms of atrophy in striatal versus hippocampal-cortical systems.

Is it all in the baseline? Trajectories of chair stand performance over 4 years and their association with grey matter structure in older adults.

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.

Subjective cognitive complaints and its associations to response inhibition and neural activation in patients with stress-related exhaustion disorder.

Stress-related exhaustion is associated with cognitive deficits, measured subjectively using questionnaires targeting everyday slips and failures or more objectively as performance on cognitive tests. Yet, only weak associations between subjective and objective cognitive measures in this group has been presented, theorized to reflect recruitment of compensational resources during cognitive testing. This explorative study investigated how subjectively reported symptoms of cognitive functioning and burnout levels relate to performance as well as neural activation during a response inhibition task. To this end, 56 patients diagnosed with stress-related exhaustion disorder (ED; ICD-10 code F43.8A) completed functional magnetic resonance imaging (fMRI) using a Flanker paradigm. In order to investigate associations between neural activity and subjective cognitive complaints (SCCs) and burnout, respectively, scores on the Prospective and Retrospective Memory Questionnaire (PRMQ) and the Shirom-Melamed Burnout Questionnaire (SMBQ) were added as covariates of interest to a general linear model at the whole-brain level. In agreement with previous research, the results showed that SCCs and burnout levels were largely unrelated to task performance. Moreover, we did not see any correlations between these self-report measures and altered neural activity in frontal brain regions. Instead, we observed an association between the PRMQ and increased neural activity in an occipitally situated cluster. We propose that this finding may reflect compensational processes at the level of basic visual attention which could go unnoticed in cognitive testing but still be reflected in the experience of deficits in everyday cognitive functioning.

Multimodal Image Analysis of Apparent Brain Age Identifies Physical Fitness as Predictor of Brain Maintenance.

Maintaining a youthful brain structure and function throughout life may be the single most important determinant of successful cognitive aging. In this study, we addressed heterogeneity in brain aging by making image-based brain age predictions and relating the brain age prediction gap (BAPG) to cognitive change in aging. Structural, functional, and diffusion MRI scans from 351 participants were used to train and evaluate 5 single-modal and 4 multimodal prediction models, based on 7 regression methods. The models were compared on mean absolute error and whether they were related to physical fitness and cognitive ability, measured both currently and longitudinally, as well as study attrition and years of education. Multimodal prediction models performed at a similar level as single-modal models, and the choice of regression method did not significantly affect the results. Correlation with the BAPG was found for current physical fitness, current cognitive ability, and study attrition. Correlations were also found for retrospective physical fitness, measured 10 years prior to imaging, and slope for cognitive ability during a period of 15 years. The results suggest that maintaining a high physical fitness throughout life contributes to brain maintenance and preserved cognitive ability.

The effect of two multi-component behavior change interventions on cognitive functions.

BACKGROUND: We previously reported the effects of two cluster-randomized 6-month multi-component workplace interventions, targeting reducing sedentary behavior or increasing physical activity among office workers, on movement behaviors and cardiorespiratory fitness. The primary aim of this study was to investigate the effects of these interventions on cognitive functions compared to a wait-list control group. The secondary aims were to examine if changes in cognition were related to change in cardiorespiratory fitness or movement behaviors and if age, sex, or cardiorespiratory fitness moderated these associations. METHODS: Both interventions encompassed multi-components acting on the individual, environmental, and organizational levels and aimed to change physical activity patterns to improve mental health and cognitive function. Out of 263 included participants, 139 (mean age 43 years, 76% females) completed a neuropsychological test battery and wore accelerometers at baseline and 6-month follow-up. The intervention effect (aim 1) on cognitive composite scores (i.e., Executive Functions, Episodic Memory, Processing Speed, and Global Cognition) was investigated. Additionally, associations between changes in movement behaviors and cardiorespiratory fitness, and changes in cognition were examined (aim 2). Moreover, age, sex, and cardiorespiratory fitness level were investigated as possible moderators of change associations (aim 3). RESULTS: Overall, cognitive performance improved from baseline to follow-up, but the change did not differ between the intervention groups and the control group. Changes in cardiorespiratory fitness or any movement behavior category did not predict changes in cognitive functions. The association between changes in time in bed and changes in both Executive Function and Global Cognition were moderated by age, such that a more positive relation was seen with increasing age. A less positive association was seen between changes in sedentary behavior and Processing Speed for men vs. women, whereas higher cardiorespiratory fitness was related to a more positive association between changes in moderate-intensity physical activity and Global Cognition. CONCLUSION: The lack of an intervention effect on cognitive functions was expected since the intervention did not change movement behavior or fitness. Age, sex, and cardiorespiratory fitness level might moderate the relationships between movement behaviors and cognitive functions changes. TRIAL REGISTRATION: ISRCTN92968402 . Registered 09/04/2018.

Regional Myo-Inositol, Creatine, and Choline Levels Are Higher at Older Age and Scale Negatively with Visuospatial Working Memory: A Cross-Sectional Proton MR Spectroscopy Study at 7 Tesla on Normal Cognitive Ageing.

Proton MR spectroscopy (1H-MRS) has been used to assess regional neurochemical brain changes during normal ageing, but results have varied. Exploiting the increased sensitivity at ultra-high field, we performed 1H-MRS in 60 healthy human volunteers to asses age-related differences in metabolite levels and their relation to cognitive ageing. Sex was balanced, and participants were assigned to a younger, middle, and older group according to their age, ranging from 18 to 79 years. They underwent 7T 1H-MRS of the ACC, DLPFC, hippocampus, and thalamus and performed a visuospatial working memory task outside the scanner. A multivariate ANCOVA revealed a significant overall effect of age group on metabolite levels in all regions. Higher levels in the middle than the younger group were observed for myo-inositol (mIns) in DLPFC and hippocampus and total choline (tCho) in ACC. Higher levels in the older than the younger group were observed for mIns in hippocampus and thalamus, total creatine (tCr) and tCho in ACC and hippocampus; lower levels of glutamate (Glu) were observed in DLPFC. Higher levels in the older than the middle group were observed for mIns in hippocampus, tCr in ACC and hippocampus, tCho in hippocampus, and total N-acetyl aspartate (tNAA) in hippocampus. Working memory performance correlated negatively with tCr and tCho levels in ACC and mIns levels in hippocampus and thalamus, but not with tNAA or glutamate levels. As NAA and Glu are commonly regarded to reflect neuronal health and function and concentrations of mIns, tCr, and tCho are higher in glia than neurons, the findings of this study suggest a potential in vivo connection between cognitive ageing and higher regional levels of glia-related metabolites.SIGNIFICANCE STATEMENT Neurochemical ageing is an integral component of age-related cognitive decline. Proton MR spectroscopy (1H-MRS) studies of in vivo neurochemical changes across the lifespan have, however, yielded inconclusive results. 1H-MRS at ultra-high field strength can potentially improve the consistency of findings. Using 7T 1H-MRS, we assessed levels of mIns, tCr, and tCho (glia-related metabolites) and tNAA and Glu (neuron-related metabolites) in ACC, DLPFC, hippocampus, and thalamus. We found higher levels of glia-related metabolites in all brain regions in older individuals. Working memory performance correlated negatively with regional levels of glia-related metabolites. This study is the first to investigate normal ageing in these brain regions using 7T 1H-MRS and findings indicate that glia-related metabolites could be valuable in cognitive ageing studies.

Right-left asymmetry in corticospinal tract microstructure and dexterity are uncoupled in late adulthood.

Ageing leads to a decline in white matter microstructure and dexterous function of the hand. In adolescents, it has previously been shown that the degree of right-left asymmetry in the corticospinal tract (CST) is linearly related with right-left asymmetry in dexterity. Here, we tested whether this association is also expressed in older adults. Participants completed a simple circle drawing task with their right and left hand as a measure of dexterity and underwent whole-brain diffusion weighted imaging at 3 Tesla (n = 199; aged 60-72 years). Fractional anisotropy and mean diffusivity of right and left CST were extracted from a manually defined region-of-interest. Linear regression analyses were computed to replicate the analyses in adolescents. Frequentist analyses were complemented with a Bayesian analytical framework. Outcome measures were compared with those previously reported in adolescents (aged 11-16 years). Asymmetries in white matter microstructure of the CST were evident and comparable to the degree of lateralisation observed in adolescence. Similarly, asymmetries in dexterity were evident, but to a lesser degree than in adolescents. Unlike in adolescents, we found no evidence of a linear relationship between asymmetries in CST microstructure and dexterity. Complementary Bayesian regression analysis provided moderate evidence in favour of the null hypothesis, pointing towards a lack of association between the structural and functional measures of right-left asymmetry. Our findings are compatible with the notion that, by late adulthood, a diverging impact of age on white matter structure and dexterous hand function dilutes the structure-function relationship between CST microstructure and manual proficiency that has been reported in adolescents.

Do glia provide the link between low-grade systemic inflammation and normal cognitive ageing? A 1 H magnetic resonance spectroscopy study at 7 tesla.

Low-grade systemic inflammation contributes to ageing-related cognitive decline, possibly by triggering a neuroinflammatory response through glial activation. Using proton magnetic resonance spectroscopy (1 H-MRS) at 7T in normal human individuals from 18 to 79 years in a cross-sectional study, we previously observed higher regional levels of myo-inositol (mIns), total creatine (tCr) and total choline (tCho) in older than younger age groups. Moreover, visuo-spatial working memory (vsWM) correlated negatively with tCr and tCho in anterior cingulate cortex (ACC) and mIns in hippocampus and thalamus. As mIns, tCr and tCho are higher in glia than neurons, this suggest a potential in vivo connection between cognitive ageing and higher regional levels of glia-related metabolites. In the present study, we tested whether these metabolic differences may be related to low-grade systemic inflammation. In the same individuals, plasma concentrations of the proinflammatory markers C-reactive protein (CRP), interleukin 8 (IL-8), and tumour necrosis factor α (TNF-α) were measured on the same day as 1 H-MRS assessments. We tested whether CRP, IL-8, and TNF-α concentrations correlated with the levels of glia-related metabolites. CRP and IL-8, but not TNF-α, were higher in older (69-79 years) than younger (18-26 years) individuals. CRP correlated positively with thalamic mIns and negatively with vsWM. IL-8 correlated positively with ACC tCho and hippocampal mIns, but not with vsWM. Mediation analysis revealed an indirect effect of IL-8 on vsWM via ACC tCho. Together, these findings corroborate the role of glial cells, perhaps via their role in neuroinflammation, as part of the neurobiological link between systemic inflammation and cognitive ageing.

Influence of visual feedback, hand dominance and sex on individuated finger movements.

The ability to perform individual finger movements, highly important in daily activities, involves visual monitoring and proprioception. We investigated the influence of vision on the spatial and temporal control of independent finger movements, for the dominant and non-dominant hand and in relation to sex. Twenty-six healthy middle-aged to old adults (M age = 61 years; range 46-79 years; females n = 13) participated. Participants performed cyclic flexion-extension movements at the metacarpophalangeal joint of one finger at a time while keeping the other fingers as still as possible. Movements were recorded using 3D optoelectronic motion technique (120 Hz). The movement trajectory distance; speed peaks (movement smoothness); Individuation Index (II; the degree a finger can move in isolation from the other fingers) and Stationarity Index (SI; how still a finger remains while the other fingers move) were extracted. The main findings were: (1) vision only improved the II and SI marginally; (2) longer trajectories were evident in the no-vision condition for the fingers of the dominant hand in the female group; (3) longer trajectories were specifically evident for the middle and ring fingers within the female group; (4) females had marginally higher II and SI compared with males; and (5) females had fewer speed peaks than males, particularly for the ring finger. Our results suggest that visual monitoring of finger movements marginally improves performance of our non-manipulative finger movement task. A consistent finding was that females showed greater independent finger control compared with males.

Evaluating a frontostriatal working-memory updating-training paradigm in Parkinson's disease: the iPARK trial, a double-blinded randomized controlled trial.

BACKGROUND: Cognitive decline and dementia are common in Parkinson's disease (PD). Cognitive deficits have been linked to the depletion of dopamine in the nigrostriatal pathway, but pharmacological treatments for PD have little evidence of improving or delaying cognitive decline. Therefore, exploring non-pharmacological treatment options is important. There have been some promising results of cognitive training interventions in PD, especially for improvements in working memory and executive functions. Yet, existing studies are often underpowered, lacking appropriate control condition, long term follow-up, a thorough description of the intervention and characteristics of the participants. Working memory updating training has previously shown to increase striatal activation in healthy young and old participants as well as dopaminergic neurotransmission in healthy young participants. In the light of dopamine dysfunction in PD, with negative effects on both motor and cognitive functions it is of interest to study if an impaired striatal system can be responsive to a non-invasive, non-pharmacological intervention. METHODS AND DESIGN: The iPARK trial is a double-blinded, randomized controlled trial with a parallel-group design that aims to recruit 80 patients with PD (during the period 02/2017-02/2023). Included patients need to have PD, Hoehn and Yahr staging I-III, be between 45 to 75 years of age and not have a diagnosis of dementia. All patients will undergo 30 sessions (6-8 weeks) of web-based cognitive training performed from home. The target intervention is a process-based training program targeting working memory updating. The placebo program is a low dose short-term memory program. A battery of neuropsychological tests and questionnaires will be performed before training, directly after training, and 16 weeks after training. DISCUSSION: We expect that the iPARK trial will provide novel and clinically useful information on whether updating training is an effective cognitive training paradigm in PD. Further, it will hopefully contribute to a better understanding of cognitive function in PD and provide answers regarding cognitive plasticity as well as determining critical factors for a responsive striatal system. TRIAL REGISTRATION: Clinicaltrials.gov registry number: NCT03680170 , registry name: "Cognitive Training in Parkinson's Disease: the iPARK study", retrospectively registered on the 21st of September 2018. The inclusion of the first participant was the 1st of February 2017.

Distinct effects of acute exercise and breaks in sitting on working memory and executive function in older adults: a three-arm, randomised cross-over trial to evaluate the effects of exercise with and without breaks in sitting on cognition.

BACKGROUND: Sedentary behaviour is associated with impaired cognition, whereas exercise can acutely improve cognition. OBJECTIVE: We 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. METHODS: Sedentary 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. RESULTS: Working 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). CONCLUSION: A 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 NUMBER: ACTRN12614000737639.

Hopeful struggling for health: Experiences of participating in computerized cognitive training and aerobic training for persons with stress-related exhaustion disorder.

It is important to understand how people with exhaustion disorder (ED) perceive interventions aiming to facilitate cognitive functioning. Therefore, the overall aim of this study was to explore experiences from persons with ED after participating in a 12-week intervention of either computerized cognitive training or aerobic training. Both interventions were performed in addition to a multimodal rehabilitation programme. Thirteen participants, 11 women and 2 men, were interviewed about pros and cons with participating in the training. The interviews were analysed with Qualitative Content Analysis. The analyses resulted in the theme hopeful struggling for health and the categories support, motivation and sensations. It was hard work recovering from ED. Support from others who are in the same situation, family members, and technology and routines for the training were strongly emphasized as beneficial for recovery. Timing, i.e., matching activities to the rehabilitation programme, getting feedback and perceiving joy in the training were important for motivation. Participants in both interventions experienced positive sensations with improved memory performance, everyday life functioning and increased faith in the prospect of recovery. However, it is important to consider various aspects of support and motivation in both computerized cognitive training and aerobic training to enable participants to pursue their participation.

Higher striatal D2-receptor availability in aerobically fit older adults but non-selective intervention effects after aerobic versus resistance training.

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.

Copenhagen Consensus statement 2019: physical activity and ageing.

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.

Rehabilitation for improved cognition in patients with stress-related exhaustion disorder: RECO - a randomized clinical trial.

Stress-related exhaustion has been associated with selective and enduring cognitive impairments. However, little is known about how to address cognitive deficits in stress rehabilitation and how this influences stress recovery over time. The aim of this open-label, parallel randomized controlled trial (ClinicalTrials.gov: NCT03073772) was to investigate the long-term effects of 12 weeks cognitive or aerobic training on cognitive function, psychological health, and work ability for patients diagnosed with exhaustion disorder (ED). One-hundred-and-thirty-two patients (111 women) participating in multimodal stress rehabilitation were randomized to receive additional cognitive training (n = 44), additional aerobic training (n = 47), or no additional training (n = 41). Treatment effects were assessed before, immediately after and one-year post intervention. The primary outcome was global cognitive function. Secondary outcomes included domain-specific cognition, self-reported burnout, depression, anxiety, fatigue and work ability, aerobic capacity, and sick-leave levels. Intention-to-treat analysis revealed a small but lasting improvement in global cognitive functioning for the cognitive training group, paralleled by a large improvement on a trained updating task. The aerobic training group showed improvements in aerobic capacity and episodic memory immediately after training, but no long-term benefits. General improvements in psychological health and work ability were observed, with no difference between interventional groups. Our findings suggest that cognitive training may be a viable method to address cognitive impairments for patients with ED, whereas the effects of aerobic exercise on cognition may be more limited when performed during a restricted time period. The implications for clinical practice in supporting patients with ED to adhere to treatment are discussed.

Aerobic training for improved memory in patients with stress-related exhaustion: a randomized controlled trial.

BACKGROUND: Patients with stress-related exhaustion suffer from cognitive impairments, which often remain after psychological treatment or work place interventions. It is important to find effective treatments that can address this problem. Therefore, the aim of this study was to investigate the effects on cognitive performance and psychological variables of a 12-week aerobic training program performed at a moderate-vigorous intensity for patients with exhaustion disorder who participated in a multimodal rehabilitation program. METHODS: In this open-label, parallel, randomized and controlled trial, 88 patients diagnosed with exhaustion disorder participated in a 24-week multimodal rehabilitation program. After 12 weeks in the program the patients were randomized to either a 12-week aerobic training intervention or to a control group with no additional training. Primary outcome measure was cognitive function, and secondary outcome measures were psychological health variables and aerobic capacity. RESULTS: In total, 51% patients in the aerobic training group and 78% patients in the control group completed the intervention period. The aerobic training group significantly improved in maximal oxygen uptake and episodic memory performance. No additional improvement in burnout, depression or anxiety was observed in the aerobic group compared with controls. CONCLUSION: Aerobic training at a moderate-vigorous intensity within a multimodal rehabilitation program for patients with exhaustion disorder facilitated episodic memory. A future challenge would be the clinical implementation of aerobic training and methods to increase feasibility in this patient group. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03073772 . Retrospectively registered 21 February 2017.

Physical activity over a decade modifies age-related decline in perfusion, gray matter volume, and functional connectivity of the posterior default-mode network-A multimodal approach.

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.

Is better preservation of eccentric strength after stroke due to altered prefrontal function?

Ventrolateral prefrontal cortex (VLPFC) is part of a network that exerts inhibitory control over the motor cortex (MC). Recently, we demonstrated that VLPFC was more activated during imagined maximum eccentric than during imagined concentric contractions in healthy participants. This was accompanied with lower activation levels within motor regions during imagined eccentric contractions. The aim was to test a novel hypothesis of an involvement of VLPFC in contraction mode-specific modulation of force. Functional magnetic resonance imaging was used to examine differences in VLPFC and motor regions during the concentric and the eccentric phases of imagined maximum contractions in a selected sample of subjects with stroke (n = 4). The subjects were included as they exhibited disturbed modulation of force. The previously demonstrated pattern within VLPFC was evident only on the contralesional hemisphere. On the ipsilesional hemisphere, the recruitment in VLPFC was similar for both modes of contractions. The findings support a hypothesis of the involvement of VLPFC in contraction mode-specific modulation of maximum force production. A disturbance of this system might underlie the lack of contraction mode-specific modulation commonly found among stroke subjects, often expressed as an increased ratio between eccentric and concentric strength.

Effects of a process-based cognitive training intervention for patients with stress-related exhaustion.

Stress-related exhaustion has been linked to a pattern of selective cognitive impairments, mainly affecting executive functioning, attention and episodic memory. Little is known about potential treatments of these cognitive deficits. The purpose of this study was to evaluate the effects of a process-based cognitive training intervention, designed to target the specific cognitive impairments associated with stress-related exhaustion. To this end, patients diagnosed with exhaustion disorder (ED) were randomized to either a multimodal stress rehabilitation program with the addition of a process-based cognitive training intervention (training group, n = 27) or a treatment-as-usual control condition, consisting of multimodal stress rehabilitation with no additional training (control group, n = 32). Treatment effects were evaluated through an extensive cognitive test battery, assessing both near and far transfer effects, as well as self-report forms regarding subjective cognitive complaints and burnout levels. Results showed pronounced training-related improvements on the criterion updating task (p < 0.001). Further, evidence was found of selective near transfer effects to updating (p = 0.01) and episodic memory (p = 0.04). Also, the trained group reported less subjective memory complaints (p = 0.02) and levels of burnout decreased for both groups, but more so for the trained group (p = 0.04), following the intervention. These findings suggest that process-based cognitive training may be a viable method to address the cognitive impairments associated with ED.