NEURO-FRAIL

Aging is associated with several interconnected conditions, such as sarcopenia, mild cognitive impairment (MCI), frailty, and falls, all of which share common biological mechanisms, including chronic inflammation, hormonal changes, and metabolic dysfunction. Sarcopenia compromises muscle mass and function, while MCI affects cognition, and both conditions increase the risk of frailty and falls in older adults. Recent research highlights the potential of physical activity to enhance cognitive function and promote neuroplasticity. Regular exercise has been shown to reduce inflammation, improve metabolic health, and stimulate neurogenesis and synaptic plasticity—processes that are essential for maintaining cognitive function. Additionally, physical activity can mitigate the physical decline associated with MCI frailty and sarcopenia condition (Chupel et al., 2018), leading to improvements in muscle strength and overall physical performance. Given that both sarcopenia, frailty and MCI share common inflammatory and metabolic pathways, exercise has the unique ability to target these underlying mechanisms, offering a dual benefit for physical and cognitive health. The relationship between exercise dosage and its effects on health outcomes is complex, with evidence suggesting that different intensities, durations, and frequencies of exercise can lead to distinct yet synergistic benefits. For instance, moderate-intensity aerobic exercises have been linked to significant improvements in cardiovascular health and cognitive function, while resistance training has been shown to specifically improve muscle strength and mass, crucial for combating sarcopenia. Furthermore, low-frequency, high-intensity interval training may promote neuroplasticity more effectively than traditional steady-state exercise by eliciting more robust neurochemical responses. However, evidence regarding more contemporary exercise protocols, such as co-designed exercise programs and "exercise snacks", remains limited. This is a line of research involving interventional studies with multidimensional assessments, which will explore the impact of more contemporary exercise prescription approaches on neuroplasticity, physical fitness, and biochemical markers of immune-inflammatory function in older adults with different outcomes. To achieve this, we will use a randomized controlled trial (RCT) design with short, medium, and long-term interventions. Participants will be recruited from local community centers and healthcare institutions. Eligible participants will be involved in the following interventions: (1) Structured Exercise Group; (2) Co-Designed Physical Activity Program; (3) Exercise Snack Protocol. Assessments will be conducted at baseline, 3, 6, 12, and 18 months. Key indicators will include: (a) physical-functional fitness; (b) Neuroendocrine Function: Cortisol, DHEA, testosterone, and insulin-like growth factor 1 (IGF-1) from saliva and blood samples; (c) Immune Function: Cytokines (IL-6, TNF-alpha, IL-10); (d) Cardiovascular Health (ECG and Heart-Brain Coupling), with analysis of resting heart rate, heart rate variability (HRV), blood pressure, and ECG readings, along with coupling with brain imaging—ECG readings synchronized with brain images (fMRI/EEG) during exercise and at rest. It is expected that participants in all intervention groups will show significant improvements in muscle strength and cognitive function compared to baseline measurements. Additionally, changes in biological markers are expected to reflect the neuroplastic and metabolic benefits of physical activity.

Keywords:Brain Health; Physical Activity; Muscle mass

Objective:

• To investigate the impact of contemporary exercise prescription approaches on neuroplasticity, physical fitness, and biochemical markers of immune-inflammatory function in older adults with different clinical outcomes that share common biological mechanisms (sarcopenia, mild cognitive impairment, fallers, and frailty).

Specific objectives:

• To evaluate the impact ofdifferent physical exercise interventions on muscle strength, overall physical fitness, and the reduction of sarcopenia in older adults.
• To examine the effects of exercise interventions on cognitive function and neuroplasticity in older adults with different clinical outcomes.
• To analyze changes in biochemical markers of immune3 inflammatory and neuroendocrine function (cytokines, cortisol, DHEA, IGF-1) in response to exercise interventions over time.

References

• Caldo-Silva, A., Furtado, G. E., Chupel, M. U., Letieri, R. V., Valente, P. A., Farhang, M., Barros, M. P., Bachi, A. L. L., Marzetti, E., Teixeira, A. M., & Massart, A. (2021). Effect of a 40-weeks multicomponent exercise program and branched chain amino acids supplementation on functional fitness and mental health in frail older persons. In Experimental gerontology (Vol. 155). Experimental Gerontology. https://doi.org/10.1016/j.exger.2021.111592
• Chupel, M. U., Minuzzi, L. G., Furtado, G. E., Santos, M. L., Hogervorst, E., Filaire, E., & Teixeira, A. M. (2018). Exercise and taurine in inflammation, cognition, and peripheral markers of blood-brain barrier integrity in older women. Applied Physiology, Nutrition, and Metabolism, 43(351), apnm-2017-0775. https://doi.org/10.1139/apnm-2017-0775
• Barros, M. P. de, Bachi, A. L. L., Santos, J. de M. B. dos, Lambertucci, R. H., Ishihara, R., Polotow, T. G., Caldo-Silva, A., Valente, P. A., Hogervorst, E., & Furtado, G. E. (2021). The poorly conducted orchestra of steroid hormones, oxidative stress and inflammation in frailty needs a maestro: Regular physical exercise. Experimental Gerontology, 155, 111562. https://doi.org/10.1016/j.exger.2021.111562
• Furtado, G. E., Letieri, R. V., Silva-Caldo, A., Trombeta, J. C. S., Monteiro, C., Rodrigues, R. N., Vieira-Pedrosa, A., Barros, M. P., Cavaglieri, C. R., Hogervorst, E., Teixeira, A. M., & Ferreira, J. P. (2021). Combined Chair-Based Exercises Improve Functional Fitness, Mental Well-Being, Salivary Steroid Balance, and Anti-microbial Activity in Pre-frail Older Women. Frontiers in Psychology, 12(March), 1–13. https://doi.org/10.3389/fpsyg.2021.564490
• Furtado, G. E., Caldo, A., Vieira-Pedrosa, A., Letieri, R. V., Hogervorst, E., Teixeira, A. M., & Ferreira, J. P. (2020). Emotional Well-Being and Cognitive Function Have Robust Relationship With Physical Frailty in Institutionalized Older Women. Frontiers in Psychology, 11(July), 1–11. https://doi.org/10.3389/fpsyg.2020.01568
• Farhang, M., Miranda-Castillo, C., Rubio, M., & Furtado, G. (2019). Impact of mind-body interventions in older adults with mild cognitive impairment: A systematic review. International Psychogeriatrics, 31(5), 643–666. https://doi.org/10.1017/S1041610218002302
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MSc/PhD students:

• 3 Master's Students
• 3 PhD students

Related Projects:

• IND&GATE
• BIO4CARTILAGE
• RO-HMESCI
• RECOVERY BIO4CARTILAGE
• RO-HMESCI

Sponsors

• Sensing Future -Thecnology of Health Care
• Sociedade Portuguesa de Neurosciência
• INOPOL-IPC - entrepreneurship academy
• Diagnostic and Technology Department, Neuroradiology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta Milan, Italy (Sara Palermo: https://scholar.google.it/citations?hl=it&user=-ztgib8AAAAJ
• Loughborough University (Eef Hogervorst): https://scholar.google.it/citations?hl=it&user=4iTclmIAAAAJ