Changes in cardiovascular health and white matter integrity with aerobic exercise, cognitive and combined training in physically inactive healthy late‑middle‑aged adults: the “Projecte Moviment” randomized controlled trial

Introduction This is a 12-weeks randomized controlled trial examining the effects of aerobic exercise (AE), computerized cognitive training (CCT) and their combination (COMB). We aim to investigate their impact on cardiovascular health and white matter (WM) integrity and how they contribute to the cognitive benefits. Methods 109 participants were recruited and 82 (62% female; age = 58.38 ± 5.47) finished the intervention with > 80% adherence. We report changes in cardiovascular risk factors and WM integrity (fractional anisotropy (FA); mean diffusivity (MD)), how they might be related to changes in physical activity, age and sex, and their potential role as mediators in cognitive improvements. Results A decrease in BMI (SMD = − 0.32, p = 0.039), waist circumference (SMD = − 0.42, p = 0.003) and diastolic blood pressure (DBP) (SMD = − 0.42, p = 0.006) in the AE group and a decrease in BMI (SMD = − 0.34, p = 0.031) and DBP (SMD = − 0.32, p = 0.034) in the COMB group compared to the waitlist control group was observed. We also found decreased global MD in the CCT group (SMD = − 0.34; p = 0.032) and significant intervention-related changes in FA and MD in the frontal and temporal lobes in the COMB group. Conclusions We found changes in anthropometric measures that suggest initial benefits on cardiovascular health after only 12 weeks of AE and changes in WM microstructure in the CCT and COMB groups. These results add evidence of the clinical relevance of lifestyle interventions and the potential benefits when combining them. Clinical Trial Registration ClinicalTrials.gov NCT031123900.CRUE-CSIC agreement with Springer NatureSpanish Ministry of Economy and Competitiveness: Neuroplasticity in the adulthood: physical exercise and cognitive training (PSI2013- 47724-P)Integrative omics study on the neurobiological effects of physical activity and cognitive stimulation (PSI2016-77475-R)Catalan Institution for Research and Advanced Studies under the ICREA Academia program to MM(FPU014/01460, FI-2016, and FI-2018

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

Vies a un envelliment saludable: Exercici Físic, Entrenament Cognitiu i la seva Combinació

[cat] Les intervencions en l’estil de vida són estratègies eficaces per promoure un envelliment saludable. L’exercici físic i l’entrenament cognitiu poden tenir efectes positius en la cognició, així com en el benestar psicològic i la salut cardiovascular i cerebral de les persones grans. La combinació d’aquestes intervencions podria estar relacionada amb beneficis cognitius potencialment més grans. La literatura actual reclama evidència en RCTs que detallin la metodologia per identificar els paràmetres de les intervencions més idonis que maximitzin els efectes neuroprotectors, el rol de les variables individuals com l’edat i el sexe i les vies implicades en aquests beneficis. Per tant, els objectius principals d’aquesta tesi són: 1) Descriure en una publicació open access el protocol del Projecte Moviment en detall; 2) Examinar els efectes de 12 setmanes d’AE, CCT i COMB en la cognició, el benestar psicològic i les activitats de la vida diària en adults grans sans; 3) Explorar si l’AE i el COMB incrementen la PA i el CRF, i milloren la salut cardiovascular dels participants; 4) Avaluar si l’AE, el CCT i el COMB tenen un impacte positiu en la integritat de la WM; 5) Examinar el rol moderador de l’edat i el sexe en els beneficis relacionats amb les intervencions; 6) Avaluar si els canvis en PA, CRF, benestar psicològic, salut cardiovascular i integritat de WM medien els beneficis cognitius associats amb les intervencions. El Projecte Moviment és un assaig multicèntric, controlat, aleatoritzat, de cec simple, descrit a l’Article 1, que estudia els efectes neuroprotectors de les intervencions d’AE, CCT i COMB i dels mecanismes subjacents en adults grans sans físicament inactius. Es van reclutar un total de 109 participants d’entre 50-70 anys que van ser assignats a un dels tres grups d’intervenció o al grup control de llista d’espera. Abans i després de les intervencions es va aplicar un protocol d’avaluació que incloïa una bateria de proves neuropsicològiques, proves físiques, qüestionaris sobre el benestar psicològic i les activitats de la vida diària, factors de risc cardiovascular, analítica de sang i proves de neuroimatge. Els resultats consten a l’Article 2 i 3 d’aquesta tesi i les troballes principals són: 1) L’AE i el COMB tenen un impacte positiu en les Funcions Executives i l’Atenció- Velocitat; 2) L’AE, el CCT i el COMB no generen canvis significatius a les nostres mesures de benestar psicològic i paràmetres del son; 3) Un increment de la S-PA i del nivell de CRF en els grups d’AE i COMB en comparació amb el grup control; 4) Una disminució del BMI i de la pressió arterial en els grups d’AE i COMB, i també una reducció de la circumferència de la cintura en el grup d’AE; 5) Una disminució de la mesura global de MD en el grup de CCT en comparació amb el grup control, i canvis significatius en els valors locals de FA i MD en àrees dels lòbuls frontal i temporal en el grup COMB; 6) L’edat no modera els canvis cognitius relacionats amb les intervencions en la nostra mostra, però el sexe sí que té un rol moderador en els canvis en la salut cardiovascular; 7) Els canvis en S-PA, però no en salut cardiovascular, CRF, salut cerebral i benestar psicològic, medien significativament les millores en cognició observades en els grups d’AE i COMB. Aquesta tesi, en el marc del Projecte Moviment, aporta evidència sobre els beneficis en cognició i salut cardiovascular d’intervencions de curta durada i alta freqüència d’AE i COMB, i sobre els efectes positius del CCT i el COMB en la microestructura de WM, emfatitzant el rol important del sexe, i subratllant la importància de continuar investigant els mecanismes subjacents en estudis de major durada i en mostres més grans i/o envellides.[eng] Les intervencions en l’estil de vida són estratègies eficaces per promoure un envelliment saludable. L’exercici físic i l’entrenament cognitiu poden tenir efectes positius en la cognició, així com en el benestar psicològic i la salut cardiovascular i cerebral de les persones grans. La combinació d’aquestes intervencions podria estar relacionada amb beneficis cognitius potencialment més grans. La literatura actual reclama evidència en RCTs que detallin la metodologia per identificar els paràmetres de les intervencions més idonis que maximitzin els efectes neuroprotectors, el rol de les variables individuals com l’edat i el sexe i les vies implicades en aquests beneficis. Per tant, els objectius principals d’aquesta tesi són: 1) Descriure en una publicació open access el protocol del Projecte Moviment en detall; 2) Examinar els efectes de 12 setmanes d’AE, CCT i COMB en la cognició, el benestar psicològic i les activitats de la vida diària en adults grans sans; 3) Explorar si l’AE i el COMB incrementen la PA i el CRF, i milloren la salut cardiovascular dels participants; 4) Avaluar si l’AE, el CCT i el COMB tenen un impacte positiu en la integritat de la WM; 5) Examinar el rol moderador de l’edat i el sexe en els beneficis relacionats amb les intervencions; 6) Avaluar si els canvis en PA, CRF, benestar psicològic, salut cardiovascular i integritat de WM medien els beneficis cognitius associats amb les intervencions. El Projecte Moviment és un assaig multicèntric, controlat, aleatoritzat, de cec simple, descrit a l’Article 1, que estudia els efectes neuroprotectors de les intervencions d’AE, CCT i COMB i dels mecanismes subjacents en adults grans sans físicament inactius. Es van reclutar un total de 109 participants d’entre 50-70 anys que van ser assignats a un dels tres grups d’intervenció o al grup control de llista d’espera. Abans i després de les intervencions es va aplicar un protocol d’avaluació que incloïa una bateria de proves neuropsicològiques, proves físiques, qüestionaris sobre el benestar psicològic i les activitats de la vida diària, factors de risc cardiovascular, analítica de sang i proves de neuroimatge. Els resultats consten a l’Article 2 i 3 d’aquesta tesi i les troballes principals són: 1) L’AE i el COMB tenen un impacte positiu en les Funcions Executives i l’Atenció- Velocitat; 2) L’AE, el CCT i el COMB no generen canvis significatius a les nostres mesures de benestar psicològic i paràmetres del son; 3) Un increment de la S-PA i del nivell de CRF en els grups d’AE i COMB en comparació amb el grup control; 4) Una disminució del BMI i de la pressió arterial en els grups d’AE i COMB, i també una reducció de la circumferència de la cintura en el grup d’AE; 5) Una disminució de la mesura global de MD en el grup de CCT en comparació amb el grup control, i canvis significatius en els valors locals de FA i MD en àrees dels lòbuls frontal i temporal en el grup COMB; 6) L’edat no modera els canvis cognitius relacionats amb les intervencions en la nostra mostra, però el sexe sí que té un rol moderador en els canvis en la salut cardiovascular; 7) Els canvis en S-PA, però no en salut cardiovascular, CRF, salut cerebral i benestar psicològic, medien significativament les millores en cognició observades en els grups d’AE i COMB. Aquesta tesi, en el marc del Projecte Moviment, aporta evidència sobre els beneficis en cognició i salut cardiovascular d’intervencions de curta durada i alta freqüència d’AE i COMB, i sobre els efectes positius del CCT i el COMB en la microestructura de WM, emfatitzant el rol important del sexe, i subratllant la importància de continuar investigant els mecanismes subjacents en estudis de major durada i en mostres més grans i/o envellides

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