Intrinsic functional brain connectivity changes following aerobic exercise, computerized cognitive training, and their combination in physically inactive healthy late-middle-aged adults: the Projecte Moviment

Lifestyle interventions have positive neuroprotective effects in aging. However, there are still open questions about how changes in resting-state functional connectivity (rsFC) contribute to cognitive improvements. The Projecte Moviment is a 12-week randomized controlled trial of a multimodal data acquisition protocol that investigated the effects of aerobic exercise (AE), computerized cognitive training (CCT), and their combination (COMB). An initial list of 109 participants was recruited from which a total of 82 participants (62% female; age¿=¿58.38¿±¿5.47) finished the intervention with a level of adherence¿>¿80%. Only in the COMB group, we revealed an extended network of 33 connections that involved an increased and decreased rsFC within and between the aDMN/pDMN and a reduced rsFC between the bilateral supplementary motor areas and the right thalamus. No global and especially local rsFC changes due to any intervention mediated the cognitive benefits detected in the AE and COMB groups. Projecte Moviment provides evidence of the clinical relevance of lifestyle interventions and the potential benefits when combining them.Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. Projecte Moviment is a project funded by the Spanish Ministry of Economy and Competitiveness under two grants: Neuroplasticity in the adulthood: physical exercise and cognitive training (PSI2013-47724-P) and Integrative omics study on the neurobiological effects of physical activity and cognitive stimulation (PSI2016-77475-R). It has also been rewarded with three pre-doctoral fellowships (FPU014/01460, FI-2016, and FI-2018). It was supported by the ICREA Academia Program to MM.SID is supported by a Beatriu de Pinós fellowship (2020 BP 00116). This work was supported by the Spanish Ministry of Economy and Competitiveness (www. mineco.gob.es) PID2021-122952OB-I00, Networking Biomedical Research Centre in the subject area of Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), initiatives of Instituto de Investigación Carlos III (ISCIII), and Share4Rare project (Grant Agreement 780262).Peer ReviewedPostprint (published version

Effects of Aerobic Exercise, Cognitive and Combined Training on Cognition in Physically Inactive Healthy Late-Middle-Aged Adults: The Projecte Moviment Randomized Controlled Trial

Background: Lifestyle interventions are promising strategies to promote cognitive health in aging. Projecte Moviment examines if aerobic exercise (AE), computerized cognitive training (CCT), and their combination (COMB) improves cognition, psychological health, and physical status compared to a control group. We assessed the moderating role of age and sex and the mediating effects of cardiorespiratory fitness (CRF), physical activity (PA), and psychological health on intervention-related cognitive benefits. Methods: This was a 12-week multi-domain, single-blind, proof-of-concept randomized controlled trial (RCT). 96 healthy adults aged 50-70 years were assigned to AE, CCT, COMB, and a wait-list control group. The per protocol sample, which completed the intervention with a level of adherence > 80%, consisted of 82 participants (62% female; age = 58.38 ± 5.47). We assessed cognition, psychological health, CRF, and energy expenditure in PA at baseline and after the intervention. We regressed change in each outcome on the treatment variables, baseline score, sex, age, and education. We used PROCESS Macro to perform the mediation and moderation analyses. Results: AE benefited Working Memory (SMD = 0.29, p = 0.037) and Attention (SMD = 0.33, p = 0.028) including the Attention-Speed (SMD = 0.31, p = 0.042) domain, compared to Control. COMB improved Attention (SMD = 0.30, p = 0.043), Speed (SMD = 0.30, p = 0.044), and the Attention-Speed (SMD = 0.30, p = 0.041) domain. CTT group did not show any cognitive change compared to Control. Sportive PA (S-PA) and CRF increased in AE and COMB. Age and sex did not moderate intervention-related cognitive benefits. Change in S-PA, but not in CRF, significantly mediated improvements on Attention-Speed in AE. Conclusion: A 12-week AE program improved Executive Function and Attention-Speed in healthy late-middle-aged adults. Combining it with CCT did not provide further benefits. Our results add support to the clinical relevance of even short-term AE as an intervention to enhance cognition and highlight the mediating role of change in S-PA in these benefits

Effects of Aerobic Exercise, Cognitive and Combined Training on Cognition in Physically Inactive Healthy Late-Middle-Aged Adults : The Projecte Moviment Randomized Controlled Trial

Lifestyle interventions are promising strategies to promote cognitive health in aging. Projecte Moviment examines if aerobic exercise (AE), computerized cognitive training (CCT), and their combination (COMB) improves cognition, psychological health, and physical status compared to a control group. We assessed the moderating role of age and sex and the mediating effects of cardiorespiratory fitness (CRF), physical activity (PA), and psychological health on intervention-related cognitive benefits. This was a 12-week multi-domain, single-blind, proof-of-concept randomized controlled trial (RCT). 96 healthy adults aged 50-70 years were assigned to AE, CCT, COMB, and a wait-list control group. The per protocol sample, which completed the intervention with a level of adherence > 80%, consisted of 82 participants (62% female; age = 58.38 ± 5.47). We assessed cognition, psychological health, CRF, and energy expenditure in PA at baseline and after the intervention. We regressed change in each outcome on the treatment variables, baseline score, sex, age, and education. We used PROCESS Macro to perform the mediation and moderation analyses. AE benefited Working Memory (SMD = 0.29, p = 0.037) and Attention (SMD = 0.33, p = 0.028) including the Attention-Speed (SMD = 0.31, p = 0.042) domain, compared to Control. COMB improved Attention (SMD = 0.30, p = 0.043), Speed (SMD = 0.30, p = 0.044), and the Attention-Speed (SMD = 0.30, p = 0.041) domain. CTT group did not show any cognitive change compared to Control. Sportive PA (S-PA) and CRF increased in AE and COMB. Age and sex did not moderate intervention-related cognitive benefits. Change in S-PA, but not in CRF, significantly mediated improvements on Attention-Speed in AE. A 12-week AE program improved Executive Function and Attention-Speed in healthy late-middle-aged adults. Combining it with CCT did not provide further benefits. Our results add support to the clinical relevance of even short-term AE as an intervention to enhance cognition and highlight the mediating role of change in S-PA in these benefits

Exercise and fitness neuroprotective effects: molecular, brain volume and psychological correlates and their mediating role in healthy late-middle-aged women and men

Background: Although exercise is known to have a neuroprotective effect in aging, the mediators underlying the exercise-cognition association remain poorly understood. In this paper we aimed to study the molecular, brain, and behavioral changes related to physical activity and their potential role as mediators. Methods: We obtained demographic, physical activity outcomes [sportive physical activity and cardiorespiratory fitness (CRF)], plasma biomarkers (TNF-a, ICAM-1, HGF, SDF1-a, and BDNF), structural-MRI (brain volume areas), psychological and sleep health (mood, depressive and distress symptoms, and sleep quality), and multi-domain cognitive data from 115 adults aged 50-70 years. We conducted linear regression models and mediation analyses stratifying results by sex in a final sample of 104 individuals [65 women (age = 56.75 ± 4.96) and 39 men (age = 58.59 ± 5.86)]. Results: Women engaging in greater amounts of exercising showed lower TNF-a levels and greater dorsolateral prefrontal cortex and temporal lobe volumes. Men engaging in greater amounts of exercise showed greater temporal lobe volumes. CRF levels were not related to any of the analyzed outcomes in women but inmen higher CRF was associated with lower TNF-a, HGF and ventricle volumes, greater volume of temporal and parietal lobes and fewer depressive symptoms and better mood. In men, reduced TNF-a and HGF levels mediated brain and cognitive CRF-related benefits. Conclusion: Our results show that exercise is a promising approach for influencing inflammation and brain volume and also contributes to ongoing discussions about the physiological mediators for the association between CRF and cognition in men

Effects and Mechanisms of Cognitive, Aerobic Exercise, and Combined Training on Cognition, Health, and Brain Outcomes in Physically Inactive Older Adults: The Projecte Moviment Protocol

Introduction: Age-related health, brain, and cognitive impairment is a great challenge in current society. Cognitive training, aerobic exercise and their combination have been shown to benefit health, brain, cognition and psychological status in healthy older adults. Inconsistent results across studies may be related to several variables. We need to better identify cognitive changes, individual variables that may predict the effect of these interventions, and changes in structural and functional brain outcomes as well as physiological molecular correlates that may be mediating these effects. Projecte Moviment is a multi-domain randomized trial examining the effect of these interventions applied 5 days per week for 3 months compared to a passive control group. The aim of this paper is to describe the sample, procedures and planned analyses. Methods: One hundred and forty healthy physically inactive older adults will be randomly assigned to computerized cognitive training (CCT), aerobic exercise (AE), combined training (COMB), or a control group. The intervention consists of a 3 month home-based program 5 days per week in sessions of 45 min. Data from cognitive, physical, and psychological tests, cardiovascular risk factors, structural and functional brain scans, and blood samples will be obtained before and after the intervention. Results: Effects of the interventions on cognitive outcomes will be described in intention-to-treat and per protocol analyses. We will also analyze potential genetic, demographic, brain, and physiological molecular correlates that may predict the effects of intervention, as well as the association between cognitive effects and changes in these variables using the per protocol sample. Discussion: Projecte Moviment is a multi-domain intervention trial based on prior evidence that aims to understand the effects of CCT, AE, and COMB on cognitive and psychological outcomes compared to a passive control group, and to determine related biological correlates and predictors of the intervention effects.Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT03123900

Active Aging, Healthy Aging? A Molecular, Brain Volume and Behavioral Approach

[eng] Aging is a normal biological process characterized by a decline at molecular, brain and behavioral level with consequences on cognition and daily functioning. Lifestyle behaviors such as physical activity or stimulating brain activities might enhance neuroprotective benefits when applied single or in combination in healthy adults. Current literature also focuses on understanding the role of physical activity and cardiorespiratory fitness in those benefits as well as better describing the cascade of changes related to exercise. Therefore, the main aims of this dissertation are: 1) To examine the role of physical activity, grouped as exercise and non-exercise, in the promotion of molecular, brain, psychological health and cognitive benefits; 2) To examine the role of cardiorespiratory fitness in the promotion of these neuroprotective benefits as well as in the exercise-cognition relationship; 3) To identify potential sex-differences in the role of physical activity and cardiorespiratory fitness; 4) To examine the effect of 12-weeks 5 days per week of aerobic exercise, computerized cognitive training and their combination on molecular and brain health and assess their role in the intervention-related cognitive benefits. Projecte Moviment consists of a 12 weeks 5 days randomized controlled trial, which allowed us to identify intervention-related changes in physically inactive healthy older adults as well as the role of other variables of interest. We recruited 109 participants and assessed them within 2 weeks before and after the intervention; 82 showed >80% adherence out of the 92 who finished the intervention. Moreover, we designed a cross-sectional strategy to describe the physical activity-cognition relationship in a sample that included 115 low to high fit participants. The assessment protocol included a battery of neuropsychogical and psychological health tests, physical activity questionnaries and fitness test, antropometric measures and cardiovascular risk factors, blood test, and neuroimaging. Results were reported in 3 different papers and the main findings are: 1) We specifically related sportive physical activity, and not non-sportive physical activity, to benefits on cognitive performance as well as markers of inflammation, brain volume and psychological health. 2) We determined that cardiovascular health might be a key factor in the exercise-related benefits, specifically in men. 3) We identified that sex matters in the understanding of exercise and cardiorespiratory fitness benefits. 4) Cardiorespiratory fitness-related benefits in brain volume, executive function and sleep quality in men might be mediated by inflammatory markers. 5) Although after 12-weeks of aerobic exercise and combined training we did not detect significant changes in the targeted molecular and brain volume outcomes that might explain the detected cognitive benefits, significant increases in physical activity outcomes were negatively related to changes in SDF1-α and ICAM-1 levels. 6) We identified that 12-weeks, 5 days per week of home-based multimodal computerized cognitive training enhanced the volume of the precuneus, despite the lack of transfer to our cognitive assessment. Projecte Moviment adds crucial evidence for research and clinical practice to better understand how lifestyle behaviors enhance neuroprotective benefits at late-life.[cat] L’envelliment és un procés biològic normal caracteritzat per un deteriorament a nivell molecular, cerebral i conductual amb conseqüències en la cognició i el funcionament quotidià. Els comportaments relacionats amb l’estil de vida com l’activitat física o activitats d’estimulació cognitiva podrien tenir beneficis neuroprotectors quan s’apliquen individualment o en combinació en adults sans. La literatura actual també se centra en entendre el paper de l’activitat física i la capacitat cardiorespiratòria en aquests beneficis, així com en descriure millor la cascada de canvis relacionats amb l’exercici. Per tant, els principals objectius d’aquesta tesi són: 1) Examinar el paper de l’activitat física, agrupada com a exercici i no exercici, en la promoció de beneficis cognitius i de salut molecular, cerebral i psicològica; 2) Examinar el paper del fitness en la promoció d’aquests beneficis neuroprotectors, així com en la relació exercici- cognició; 3) Identificar les possibles diferències de sexe en el paper de l'activitat física i el fitness; 4) Examinar l’efecte de 12 setmanes, 5 dies per setmana d’exercisi aeròbic, entrenament cognitiu computeritzat i la seva combinació en els nivells de factor de creixement cerebral, marcadors inflamació i volum cerebral i avaluar el seu paper en els beneficis cognitius relacionats amb la intervenció. El Projecte Moviment consisteix en un assaig controlat aleatoritzat de 12 setmanes i 5 dies per setmana que ens va permetre identificar els canvis relacionats amb aquestes intervencions en adults sans físicament inactius. Vam reclutar 109 participants i els vam avaluar durant les dues setmanes d’abans i després de la intervenció; dels 92 que van acabar la intervenció, 82 van mostrar >80% d'adherència. A més, vam dissenyar una estratègia transversal per descriure la relació activitat física-cognició en una mostra que incloïa 115 participants de baix i alt estat físic. El protocol d’avaluació incloïa una bateria de proves neuropsicològiques i de salut psicològica, qüestionaris d’activitat física i proves de condició física, mesures antropomètriques i factors de risc cardiovascular, anàlisi de sang i exploracions de neuroimatge. Els resultats es van informar en 3 articles diferents i les principals troballes són: 1) Vam relacionar específicament l’activitat física esportiva, i no la no esportiva, amb beneficis en el rendiment cognitiu, així com amb marcadors d’inflamació, volum cerebral i salut psicològica. 2) Vam identificar que la salut cardiovascular podria ser un factor clau en els beneficis relacionats amb l’exercici, específicament en els homes. 3) Vam identificar que el sexe és important en la comprensió dels beneficis relacionats amb l'exercici i la capacitat cardiorespiratòria. 4) Els beneficis relacionats amb la salut cardiorespiratòria en el volum del cervell, la funció executiva i la qualitat del son en homes podrien estar mediats per marcadors inflamatoris. 5) Tot i que després de 12 setmanes d’exercici aeròbic i d’entrenament combinat no vam detectar canvis significatius en les variables moleculars i cerebrals analitzades que podrien explicar els beneficis cognitius detectats, els augments significatius en les variables d’activitat física es van relacionar negativament amb els canvis en nivells de SDF1-α i ICAM-1. 6) Es va identificar que 12 setmanes, 5 dies a la setmana d’entrenament cognitiu computerizat multimodal des de casa van millorar el volum del precuneus, tot i la manca de transferència dels beneficis cognitius. El Projecte Moviment aporta evidència rellevant per a la investigació i la pràctica clínica en relació als beneficis neuroprotectors que comportaments relacionats amb l’estil de vida poden tenir en l’envellimen

Effects and mechanisms of cognitive, aerobic exercise, and combined training on cognition, health, and brain outcomes in physically inactive older adults: the projecte moviment protocol

Age-related health, brain, and cognitive impairment is a great challenge in current society. Cognitive training, aerobic exercise and their combination have been shown to benefit health, brain, cognition and psychological status in healthy older adults. Inconsistent results across studies may be related to several variables. We need to better identify cognitive changes, individual variables that may predict the effect of these interventions, and changes in structural and functional brain outcomes as well as physiological molecular correlates that may be mediating these effects. Projecte Moviment is a multi-domain randomized trial examining the effect of these interventions applied 5 days per week for 3 months compared to a passive control group. The aim of this paper is to describe the sample, procedures and planned analyses.Peer Reviewe

Effects and mechanisms of cognitive, aerobic exercise, and combined training on cognition, health, and brain outcomes in physically inactive older adults: the projecte moviment protocol

Age-related health, brain, and cognitive impairment is a great challenge in current society. Cognitive training, aerobic exercise and their combination have been shown to benefit health, brain, cognition and psychological status in healthy older adults. Inconsistent results across studies may be related to several variables. We need to better identify cognitive changes, individual variables that may predict the effect of these interventions, and changes in structural and functional brain outcomes as well as physiological molecular correlates that may be mediating these effects. Projecte Moviment is a multi-domain randomized trial examining the effect of these interventions applied 5 days per week for 3 months compared to a passive control group. The aim of this paper is to describe the sample, procedures and planned analyses.Peer Reviewe

Molecular and Brain Volume Changes Following Aerobic Exercise, Cognitive and Combined Training in Physically Inactive Healthy Late-Middle-Aged Adults: The Projecte Moviment Randomized Controlled Trial

Behavioral interventions have shown promising neuroprotective effects, but the cascade of molecular, brain and behavioral changes involved in these benefits remains poorly understood. Projecte Moviment is a 12-week (5 days per week-45 min per day) multi-domain, single-blind, proof-of-concept randomized controlled trial examining the cognitive effect and underlying mechanisms of an aerobic exercise (AE), computerized cognitive training (CCT) and a combined (COMB) groups compared to a waitlist control group. Adherence was > 80% for 82/109 participants recruited (62% female; age = 58.38 ± 5.47). In this study we report intervention-related changes in plasma biomarkers (BDNF, TNF-α, HGF, ICAM-1, SDF1-α) and structural-MRI (brain volume) and how they related to changes in physical activity and individual variables (age and sex) and their potential role as mediators in the cognitive changes. Our results show that although there were no significant changes in molecular biomarker concentrations in any intervention group, changes in ICAM-1 and SDF1-α were negatively associated with changes in physical activity outcomes in AE and COMB groups. Brain volume changes were found in the CCT showing a significant increase in precuneus volume. Sex moderated the brain volume change in the AE and COMB groups, suggesting that men may benefit more than women. Changes in molecular biomarkers and brain volumes did not significantly mediate the cognitive-related benefits found previously for any group. This study shows crucial initial molecular and brain volume changes related to lifestyle interventions at early stages and highlights the value of examining activity parameters, individual difference characteristics and using a multi-level analysis approach to address these questions