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

Neurocognitive profile of the post-COVID condition in adults in Catalonia. A mixed method prospective cohort and nested case-control study: Study Protocol

The diagnosis of the post-COVID condition is usually achieved by excluding other diseases; however, cognitive changes are often found in the post-COVID disorder. Therefore, monitoring and treating the recovery from the post-COVID condition is necessary to establish biomarkers to guide the diagnosis of symptoms, including cognitive impairment. Our study employs a prospected cohort and nested case-control design with mixed methods, including statistical analyses, interviews, and focus groups. Our main aim is to identify biomarkers (functional and structural neural changes, inflammatory and immune status, vascular and vestibular signs and symptoms) easily applied in primary care to detect cognitive changes in post-COVID cases. The results will open up a new line of research to inform diagnostic and therapeutic decisions with special considerations for cognitive impairment in the post-COVID condition

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

Kinetics of humoral immune response over 17 months of COVID-19 pandemic in a large cohort of healthcare workers in Spain : the ProHEpiC-19 study

Understanding the immune response to the SARS-CoV-2 virus is critical for efficient monitoring and control strategies. The ProHEpic-19 cohort provides a fine-grained description of the kinetics of antibodies after SARS-CoV-2 infection with an exceptional resolution over 17 months. We established a cohort of 769 healthcare workers including healthy and infected with SARS-CoV-2 in northern Barcelona to determine the kinetics of the IgM against the nucleocapsid (N) and the IgG against the N and spike (S) of SARS-CoV-2 in infected healthcare workers. The study period was from 5 May 2020 to 11 November 2021.We used non-linear mixed models to investigate the kinetics of IgG and IgM measured at nine time points over 17 months from the date of diagnosis. The model included factors of time, gender, and disease severity (asymptomatic, mild-moderate, severe-critical) to assess their effects and their interactions. 474 of the 769 participants (61.6%) became infected with SARS-CoV-2. Significant effects of gender and disease severity were found for the levels of all three antibodies. Median IgM(N) levels were already below the positivity threshold in patients with asymptomatic and mild-moderate disease at day 270 after the diagnosis, while IgG(N and S) levels remained positive at least until days 450 and 270, respectively. Kinetic modelling showed a general rise in both IgM(N) and IgG(N) levels up to day 30, followed by a decay with a rate depending on disease severity. IgG(S) levels remained relatively constant from day 15 over time. IgM(N) and IgG(N, S) SARS-CoV-2 antibodies showed a heterogeneous kinetics over the 17 months. Only the IgG(S) showed a stable increase, and the levels and the kinetics of antibodies varied according to disease severity. The kinetics of IgM and IgG observed over a year also varied by clinical spectrum can be very useful for public health policies around vaccination criteria in adult population. Regional Ministry of Health of the Generalitat de Catalunya (Call COVID19-PoC SLT16_04; NCT04885478). The online version contains supplementary material available at 10.1186/s12879-022-07696-6

Neurocognitive Profile of the Post-COVID Condition in Adults in Catalonia-A Mixed Method Prospective Cohort and Nested Case-Control Study : Study Protocol

Altres ajuts: This study is also supported in part by grants from the CIBER-Consorcio Centro de Investigación Biomédica en Red-(CB 2021), Ministerio de Ciencia e Innovación and Unión Europea, NextGenerationEU.The diagnosis of the post-COVID condition is usually achieved by excluding other diseases; however, cognitive changes are often found in the post-COVID disorder. Therefore, monitoring and treating the recovery from the post-COVID condition is necessary to establish biomarkers to guide the diagnosis of symptoms, including cognitive impairment. Our study employs a prospected cohort and nested case-control design with mixed methods, including statistical analyses, interviews, and focus groups. Our main aim is to identify biomarkers (functional and structural neural changes, inflammatory and immune status, vascular and vestibular signs and symptoms) easily applied in primary care to detect cognitive changes in post-COVID cases. The results will open up a new line of research to inform diagnostic and therapeutic decisions with special considerations for cognitive impairment in the post-COVID condition

Factores implicados en el envejecimiento cognitivo

Programa de Doctorat en Psicologia Clínica i de la Salut[spa] El declive cognitivo y funcional asociado a la edad es un proceso biológico continuo con diferentes trayectorias cognitivas. Las complejas interacciones entre genes, variables ambientales y cognición en el proceso de envejecimiento han sido destacados como factores clave para entender las diferencias interindividuales y generar estrategias específicas para un envejecimiento saludable y exitoso. Entre otros factores, las diferencias genéticas explican alrededor del 15-25% de la variación de la esperanza de vida. Uno de los genes más relevantes implicados en la cognición es la Apolipoproteína E (APOE). Este gen está implicado en varias vías que afectan directa e indirectamente a la cognición. Además, presenta interacciones complejas con otros genes como el factor neurotrófico derivado del cerebro (BDNF) y variables ambientales como son las sociodemográficas y características del estilo de vida. Nuestra principal hipótesis fue que, en una cohorte de individuos cognitivamente sanos mayores de cincuenta años, los genotipos APOE y BDNF estarían implicados en las diferencias interindividuales en el envejecimiento cognitivo y que la edad, el sexo, las interacciones gen-gen y el perfil lipídico serían factores clave para entender esta compleja relación. Al inicio del estudio, encontramos que los portadores del alelo E2 del gen APOE se desempeñaron notablemente mejor en los dominios de la memoria verbal y la fluidez, pero este efecto estaba presente sólo entre mujeres y fue parcialmente mediada por factores inflamatorios y metabólicos. Cuando la cohorte fue analizada longitudinalmente, también observamos efectos interactivos gen-sexo sobre el cambio en cognición, pero la dirección de los efectos fue sustancialmente diferente. Nuestros resultados destacan la importancia del genotipo APOE sobre el envejecimiento cognitivo y como el sexo, las interacciones gen-gen y el perfil de lípidos están implicados y modifican el efecto del genotipo sobre la cognición.[eng] Age-related cognitive and functional decline is a continuous biological process with different cognitive trajectories. Complex interactions between genes, environmental variables, and cognition in the aging process have been highlighted as key factors to understand interindividual differences and to generate specific strategies for a successful and healthy aging across the lifespan. Among other factors, genetic differences explain around 15–25% of the variance in life expectancy. One of the most relevant genes involved in cognition is the Apolipoprotein E (APOE). This gene is implicated in several pathways that directly and indirectly affect cognition. Furthermore, it has complex interactions with other genes as the Brain-derived neurotrophic factor (BDNF) and environmental variables such as sociodemographics and lifestyle. Our main hypothesis was that, in a cohort of cognitively healthy individuals older than fifty, APOE and BDNF genotypes are implicated in interindividual differences in the cognitive aging process and that age, sex, gene-gene interactions and lipidic profile are key factors to understand this relationship. At baseline, we found that carriers of the e2 allele of the APOE gene performed remarkably better in the verbal memory and fluency domains, but this effect was present only among women and was partially mediated by inflammatory and metabolic factors. When the cohort was analyzed longitudinally, we also observed gene-sex interactive effects on the change in cognition, but the direction of the effects was substantially different. Our results highlight the importance of the APOE genotype over cognitive aging and how sex, gene-gene interactions and lipid profile are implicated and modify the genotype effect over cognition

Factores implicados en el envejecimiento cognitivo

[spa] El declive cognitivo y funcional asociado a la edad es un proceso biológico continuo con diferentes trayectorias cognitivas. Las complejas interacciones entre genes, variables ambientales y cognición en el proceso de envejecimiento han sido destacados como factores clave para entender las diferencias interindividuales y generar estrategias específicas para un envejecimiento saludable y exitoso. Entre otros factores, las diferencias genéticas explican alrededor del 15-25% de la variación de la esperanza de vida. Uno de los genes más relevantes implicados en la cognición es la Apolipoproteína E (APOE). Este gen está implicado en varias vías que afectan directa e indirectamente a la cognición. Además, presenta interacciones complejas con otros genes como el factor neurotrófico derivado del cerebro (BDNF) y variables ambientales como son las sociodemográficas y características del estilo de vida. Nuestra principal hipótesis fue que, en una cohorte de individuos cognitivamente sanos mayores de cincuenta años, los genotipos APOE y BDNF estarían implicados en las diferencias interindividuales en el envejecimiento cognitivo y que la edad, el sexo, las interacciones gen-gen y el perfil lipídico serían factores clave para entender esta compleja relación. Al inicio del estudio, encontramos que los portadores del alelo E2 del gen APOE se desempeñaron notablemente mejor en los dominios de la memoria verbal y la fluidez, pero este efecto estaba presente sólo entre mujeres y fue parcialmente mediada por factores inflamatorios y metabólicos. Cuando la cohorte fue analizada longitudinalmente, también observamos efectos interactivos gen-sexo sobre el cambio en cognición, pero la dirección de los efectos fue sustancialmente diferente. Nuestros resultados destacan la importancia del genotipo APOE sobre el envejecimiento cognitivo y como el sexo, las interacciones gen-gen y el perfil de lípidos están implicados y modifican el efecto del genotipo sobre la cognición.[eng] Age-related cognitive and functional decline is a continuous biological process with different cognitive trajectories. Complex interactions between genes, environmental variables, and cognition in the aging process have been highlighted as key factors to understand interindividual differences and to generate specific strategies for a successful and healthy aging across the lifespan. Among other factors, genetic differences explain around 15–25% of the variance in life expectancy. One of the most relevant genes involved in cognition is the Apolipoprotein E (APOE). This gene is implicated in several pathways that directly and indirectly affect cognition. Furthermore, it has complex interactions with other genes as the Brain-derived neurotrophic factor (BDNF) and environmental variables such as sociodemographics and lifestyle. Our main hypothesis was that, in a cohort of cognitively healthy individuals older than fifty, APOE and BDNF genotypes are implicated in interindividual differences in the cognitive aging process and that age, sex, gene-gene interactions and lipidic profile are key factors to understand this relationship. At baseline, we found that carriers of the e2 allele of the APOE gene performed remarkably better in the verbal memory and fluency domains, but this effect was present only among women and was partially mediated by inflammatory and metabolic factors. When the cohort was analyzed longitudinally, we also observed gene-sex interactive effects on the change in cognition, but the direction of the effects was substantially different. Our results highlight the importance of the APOE genotype over cognitive aging and how sex, gene-gene interactions and lipid profile are implicated and modify the genotype effect over cognition