Cardiorespiratory Fitness Moderates the Age-Related Association Between Executive Functioning and Mobility: Evidence From Remote Assessments.

Background and Objectives: In older adults, executive functions are important for daily-life function and mobility. Evidence suggests that the relationship between cognition and mobility is dynamic and could vary according to individual factors, but whether cardiorespiratory fitness reduces the age-related increase of interdependence between mobility and cognition remains unexplored. Research Design and Methods: One hundred eighty-nine participants (aged 50-87) were divided into 3 groups according to their age: middle-aged (MA; <65), young older adults (YOA; 65-74), and old older adults (OOA; ≥75). Participants performed Timed Up and Go and executive functioning assessments (Oral Trail Making Test and Phonologic verbal fluency) remotely by videoconference. Participants completed the Matthews questionnaire to estimate their cardiorespiratory fitness (VO2 max in ml/min/kg). A 3-way moderation was used to address whether cardiorespiratory fitness interacts with age to moderate the relationship between cognition and mobility. Results: Results showed that the cardiorespiratory fitness × age interaction moderated the association between executive functioning and mobility (ß = -0.05; p = .048; R 2 = 17.6; p < .001). At lower levels of physical fitness (<19.16 ml/min/kg), executive functioning significantly influenced YOA's mobility (ß = -0.48, p = .004) and to a greater extent OOA's mobility (ß = -0.96, p = .002). Discussion and Implications: Our results support the idea of a dynamic relationship between mobility and executive functioning during aging and suggest that physical fitness could play a significant role in reducing their interdependency.

Cardiopulmonary Rehabilitation in Long-COVID-19 Patients with Persistent Breathlessness and Fatigue: The COVID-Rehab Study.

(1) Background: Cardiopulmonary and brain functions are frequently impaired after COVID-19 infection. Exercise rehabilitation could have a major impact on the healing process of patients affected by long COVID-19. (2) Methods: The COVID-Rehab study will investigate the effectiveness of an eight-week cardiopulmonary rehabilitation program on cardiorespiratory fitness (V˙O2max) in long-COVID-19 individuals. Secondary objectives will include functional capacity, quality of life, perceived stress, sleep quality (questionnaires), respiratory capacity (spirometry test), coagulation, inflammatory and oxidative-stress profile (blood draw), cognition (neuropsychological tests), neurovascular coupling and pulsatility (fNIRS). The COVID-Rehab project was a randomised clinical trial with two intervention arms (1:1 ratio) that will be blindly evaluated. It will recruit a total of 40 individuals: (1) rehabilitation: centre-based exercise-training program (eight weeks, three times per week); (2) control: individuals will have to maintain their daily habits. (3) Conclusions: Currently, there are no specific rehabilitation guidelines for long-COVID-19 patients, but preliminary studies show encouraging results. Clinicaltrials.gov (NCT05035628).

Videoconference version of the Montreal Cognitive Assessment: normative data for Quebec-French people aged 50 years and older.

BACKGROUND: The COVID-19 pandemic forced health professionals to rapidly develop and implement telepractice and remote assessments. Recent reviews appear to confirm the validity of a wide range of neuropsychological tests for teleneuropsychology and among these, the Montreal Cognitive Assessment (MoCA), a cognitive screening test widely used in clinical settings. The normative data specific to the context of videoconference administration is essential, particularly that consider sociodemographic characteristics. AIMS: This study had for objective to develop French-Quebec normative data for videoconference-administration of the MoCA that consider sociodemographic characteristics. METHODS: A total of 230 community-dwelling adults aged 50 years and older taking part in clinical trials completed the MoCA by videoconference. Regression analyses were run with sex, education, and age as predictors of the total MoCA scores, based on previously published norms. As an exploratory analysis, a second regression analysis was also run with cardiovascular disease as a predictor. RESULTS: Regression analyses revealed that older age and lower education were associated with poorer total MoCA scores, for medium effect size (p < 0.001, R2 = 0.17). Neither sex nor cardiovascular disease, were significant predictors in our analyses. For clinicians, a regression equation was proposed to calculate Z scores. DISCUSSION: This study provides normative data for the MoCA administered via videoconference in Quebec-French individuals aged 50 years and over. CONCLUSIONS: The present normative data will not only allow clinicians to continue to perform assessments remotely in this pandemic period but will also allow them to perform cognitive assessments to patients located in remote areas.

Investigation of the Effects of Home-Based Exercise and Cognitive Training on Cognitive and Physical Functions in Cardiac Patients: The COVEPICARDIO Study Protocol of a Randomized Clinical Trial.

Introduction: During the COVID-19 pandemic, confinement measures are likely to produce collateral damage to health (stress, confusion, anxiety), especially in frail individuals and those living with cardiovascular disease (CVD). In cardiac patients in particular, these measures dramatically increase the level of physical inactivity and sedentary lifestyle, which can decrease cardiorespiratory capacity and increase the risk of acute events, rehospitalization, and depressive syndromes. Maintaining a minimum level of physical activity and cognitive stimulation during the COVID-19 crisis is essential for cardiac patients. This study is designed to document the effects of 6 months of home-based physical exercise alone or combined with cognitive training on cognitive and physical functions in patients with CVD over 50 years old. Methods and Analysis: 122 patients (>50 years old) with stable CVD and no contraindication to perform physical exercise training will be recruited and randomly assigned to one of the 2 following arms: (1) Home-based physical exercise alone, (2) Home-based physical exercise combined with cognitive training. The intervention lasts 6 months, with remote assessments performed prior to, mid and post-training. A follow-up 6 months after the end of the intervention (12 month) is also proposed. The primary outcome is cognition, including general functioning (Montreal Cognitive Assessment (MoCA) score), as well as performances on measures of executive functions, processing speed, and episodic memory. The secondary outcome is physical performance, including balance, gait and mobility, leg muscle strength and estimated cardiorespiratory fitness. Tertiary outcomes include mood, anxiety, and health-related quality of life as assessed by self-reported online questionnaires. Discussion: With the COVID-19 crisis, there is a critical need for remote exercise and cognitive training, and to further investigate this topic, in particular for cardiac patients. The present context can be viewed as an opportunity to perform a major shift from center-based programs to home-based physical exercise. This is especially important to reach out to older adults living in remote areas, where access to such interventions is limited. ClinicalTrials.gov: [https://clinicaltrials.gov/ct2/show/NCT04661189], NCT04661189.

COVEPIC (Cognitive and spOrt Virtual EPIC training) investigating the effects of home-based physical exercise and cognitive training on cognitive and physical functions in community-dwelling older adults: study protocol of a randomized single-blinded clinical trial.

BACKGROUND: In the context of the COVID-19 pandemic, lockdown and social distancing measures are applied to prevent the spread of the virus. It is well known that confinement and social isolation can have a negative impact on physical and mental health, including cognition. Physical activity and cognitive training can help enhance older adults' cognitive and physical health and prevent the negative collateral impacts of social isolation and physical inactivity. The COVEPIC study aims to document the effects of 6 months of home-based physical exercise alone versus home-based physical exercise combined with cognitive training on cognitive and physical functions in adults 50 years and older. METHODS: One hundred twenty-two healthy older adults (> 50 years old) will be recruited from the community and randomized to one of the two arms for 6 months: (1) home-based physical exercises monitoring alone and (2) combined physical exercises monitoring with home-based cognitive training. The primary outcome is cognition, including general functioning (Montreal Cognitive Assessment (MoCA) score), as well as executive functions, processing speed, and episodic memory (composite Z-scores based on validated neuropsychological tests and computerized tasks). The secondary outcome is physical functions, including balance (one-leg stance test), gait and mobility performance (Timed Up and Go, 4-meter walk test), leg muscle strength (5-time sit-to-stand), and estimated cardiorespiratory fitness (Matthews' questionnaire). Exploratory outcomes include mood, anxiety, and health-related quality of life as assessed by self-reported questionnaires (i.e., Geriatric depression scale-30 items, Perceived stress scale, State-trait anxiety inventory-36 items, Perseverative thinking questionnaire, Connor-Davidson Resilience Scale 10, and 12-item Short Form Survey). DISCUSSION: This trial will document the remote monitoring of home-based physical exercise alone and home-based physical combined with cognitive training to enhance cognitive and physical health of older adults during the COVID-19 pandemic period. Remote interventions represent a promising strategy to help maintain or enhance health and cognition in seniors, and potentially an opportunity to reach older adults in remote areas, where access to such interventions is limited. TRIAL REGISTRATION: Clinical trial Identifier NCT04635462 . COVEPIC was retrospectively registered on November 19, 2020.

High-intensity interval training vs. hydrochlorothiazide on blood pressure, cardiovascular health and cognition: Protocol of a non-inferiority trial.

BACKGROUND: While the number of people with hypertension (HBP) continues to increase, the therapeutic target for optimal blood pressure (BP) has been revised to a lower level. Studies have suggested that High-Intensity Interval Training (HIIT) could be as efficient as BP-lowering drugs, but no study has compared their efficacy in a randomized trial. The aim of this protocol is to determine if HIIT is as efficient as Hydrochlorothiazide (HCTZ) in lowering 24 h ambulatory BP in prehypertensive older adults. Moreover, the secondary aim is to determine if HIIT is associated with greater cardiovascular and cognitive benefits than HCTZ. METHODS: This study is an interventional, single-center, non-inferiority trial, with two randomized parallel groups of prehypertensive participants aged 60 years or more. One group will be prescribed daily doses of 12.5 mg of HCTZ for 12 weeks, and the other group will follow thrice-weekly HIIT for 12 weeks. Each group will be composed of 30 participants. The primary outcome is 24 h ambulatory BP. Secondary outcomes are scores on neuropsychological assessments, balance and gait performances, maximal oxygen uptake, peripheral endothelial function, and arterial stiffness. Non-inferiority tests will be performed on the primary outcome, and secondary outcomes will be compared using independent t-tests. CONCLUSION: This study will determine if HIIT is at least as efficient as HCTZ in lowering BP in prehypertensive older adults. This study will also determine if HIIT provides greater benefits in terms of cardiovascular and cognitive status (NCT04103411).

Gross Motor Skills Training Leads to Increased Brain-Derived Neurotrophic Factor Levels in Healthy Older Adults: A Pilot Study.

Exercise is recognized as a promising approach to counteract aging-associated declines in cognitive functions. However, the exact molecular pathways involved remain unclear. Aerobic training interventions and improvements in peak oxygen uptake (VO2peak) have been associated with increases in the peripheral concentration of brain-derived neurotrophic factor (BDNF) and better cognitive performances. However, other training interventions such as resistance training and gross motor skills programs were also linked with improvements in cognitive functions. Thus far, few studies have compared different types of physical exercise training protocols and their impact on BDNF concentrations, especially in participants over 60 years old. The main objective of this study was to compare the effects of three exercise protocols on plasma BDNF concentrations at rest in healthy older adults. Thirty-four older adults were randomized into three interventions: (1) lower body strength and aerobic training (LBS-A), (2) upper body strength and aerobic training (UBS-A), or (3) gross motor activities (GMA). All interventions were composed of 3 weekly sessions over a period of 8 weeks. Physical, biochemical, and cognitive assessments were performed pre and post-intervention. All interventions resulted in improved cognitive functions but the GMA intervention induced a larger increase in plasma BDNF concentrations than LBS-A. No correlation was observed between changes in BDNF concentrations and cognitive performances. These findings suggest that a program of GMA could lead to enhancements in plasma BDNF concentrations. Moreover, cognition improvement could occur without concomitant detectable changes in BDNF, which highlights the multifactorial nature of the exercise-cognition relationship in older adults.

RNA-Sequencing Reveals Unique Transcriptional Signatures of Running and Running-Independent Environmental Enrichment in the Adult Mouse Dentate Gyrus.

Environmental enrichment (EE) is a powerful stimulus of brain plasticity and is among the most accessible treatment options for brain disease. In rodents, EE is modeled using multi-factorial environments that include running, social interactions, and/or complex surroundings. Here, we show that running and running-independent EE differentially affect the hippocampal dentate gyrus (DG), a brain region critical for learning and memory. Outbred male CD1 mice housed individually with a voluntary running disk showed improved spatial memory in the radial arm maze compared to individually- or socially-housed mice with a locked disk. We therefore used RNA sequencing to perform an unbiased interrogation of DG gene expression in mice exposed to either a voluntary running disk (RUN), a locked disk (LD), or a locked disk plus social enrichment and tunnels [i.e., a running-independent complex environment (CE)]. RNA sequencing revealed that RUN and CE mice showed distinct, non-overlapping patterns of transcriptomic changes versus the LD control. Bio-informatics uncovered that the RUN and CE environments modulate separate transcriptional networks, biological processes, cellular compartments and molecular pathways, with RUN preferentially regulating synaptic and growth-related pathways and CE altering extracellular matrix-related functions. Within the RUN group, high-distance runners also showed selective stress pathway alterations that correlated with a drastic decline in overall transcriptional changes, suggesting that excess running causes a stress-induced suppression of running's genetic effects. Our findings reveal stimulus-dependent transcriptional signatures of EE on the DG, and provide a resource for generating unbiased, data-driven hypotheses for novel mediators of EE-induced cognitive changes.

Endogenous neural stem cell responses to stroke and spinal cord injury.

Stroke and spinal cord injury (SCI) are among the most frequent causes of central nervous system (CNS) dysfunction, affecting millions of people worldwide each year. The personal and financial costs for affected individuals, their families, and the broader communities are enormous. Although the mammalian CNS exhibits little spontaneous regeneration and self-repair, recent discoveries have revealed that subpopulations of glial cells in the adult forebrain subventricular zone and the spinal cord ependymal zone possess neural stem cell properties. These endogenous neural stem cells react to stroke and SCI by contributing a significant number of new neural cells to formation of the glial scar. These findings have raised hopes that new therapeutic strategies can be designed based on appropriate modulation of endogenous neural stem cell responses to CNS injury. Here, we review the responses of forebrain and spinal cord neural stem cells to stroke and SCI, the role of these responses in restricting injury-induced tissue loss, and the possibility of directing these responses to promote anatomical and functional repair of the CNS.

Central canal ependymal cells proliferate extensively in response to traumatic spinal cord injury but not demyelinating lesions.

The adult mammalian spinal cord has limited regenerative capacity in settings such as spinal cord injury (SCI) and multiple sclerosis (MS). Recent studies have revealed that ependymal cells lining the central canal possess latent neural stem cell potential, undergoing proliferation and multi-lineage differentiation following experimental SCI. To determine whether reactive ependymal cells are a realistic endogenous cell population to target in order to promote spinal cord repair, we assessed the spatiotemporal dynamics of ependymal cell proliferation for up to 35 days in three models of spinal pathologies: contusion SCI using the Infinite Horizon impactor, focal demyelination by intraspinal injection of lysophosphatidylcholine (LPC), and autoimmune-mediated multi-focal demyelination using the active experimental autoimmune encephalomyelitis (EAE) model of MS. Contusion SCI at the T9-10 thoracic level stimulated a robust, long-lasting and long-distance wave of ependymal proliferation that peaked at 3 days in the lesion segment, 14 days in the rostral segment, and was still detectable at the cervical level, where it peaked at 21 days. This proliferative wave was suppressed distal to the contusion. Unlike SCI, neither chemical- nor autoimmune-mediated demyelination triggered ependymal cell proliferation at any time point, despite the occurrence of demyelination (LPC and EAE), remyelination (LPC) and significant locomotor defects (EAE). Thus, traumatic SCI induces widespread and enduring activation of reactive ependymal cells, identifying them as a robust cell population to target for therapeutic manipulation after contusion; conversely, neither demyelination, remyelination nor autoimmunity appears sufficient to trigger proliferation of quiescent ependymal cells in models of MS-like demyelinating diseases.

Untangling the influences of voluntary running, environmental complexity, social housing and stress on adult hippocampal neurogenesis.

Environmental enrichment (EE) exerts powerful effects on brain physiology, and is widely used as an experimental and therapeutic tool. Typical EE paradigms are multifactorial, incorporating elements of physical exercise, environmental complexity, social interactions and stress, however the specific contributions of these variables have not been separable using conventional housing paradigms. Here, we evaluated the impacts of these individual variables on adult hippocampal neurogenesis by using a novel "Alternating EE" paradigm. For 4 weeks, adult male CD1 mice were alternated daily between two enriched environments; by comparing groups that differed in one of their two environments, the individual and combinatorial effects of EE variables could be resolved. The Alternating EE paradigm revealed that (1) voluntary running for 3 days/week was sufficient to increase both mitotic and post-mitotic stages of hippocampal neurogenesis, confirming the central importance of exercise; (2) a complex environment (comprised of both social interactions and rotated inanimate objects) had no effect on neurogenesis itself, but enhanced depolarization-induced c-Fos expression (attributable to social interactions) and buffered stress-induced plasma corticosterone levels (attributable to inanimate objects); and (3) neither social isolation, group housing, nor chronically increased levels of plasma corticosterone had a prolonged impact on neurogenesis. Mouse strain, handling and type of running apparatus were tested and excluded as potential confounding factors. These findings provide valuable insights into the relative effects of key EE variables on adult neurogenesis, and this "Alternating EE" paradigm represents a useful tool for exploring the contributions of individual EE variables to mechanisms of neural plasticity.