Myokines as mediators of exercise-induced cognitive changes in older adults: protocol for a comprehensive living systematic review and meta-analysis

Wouter A J Vints; Evrim Gökçe; Antoine Langeard; Iuliia Pavlova; Özge Selin Çevik; Mohammad Mosaferi Ziaaldini; Jasemin Todri; Orges Lena; Giorgos K Sakkas; Suzanne Jak; Ioanna Zorba Zormpa; Christina Karatzaferi; Oron Levin; Nerijus Masiulis; Yael Netz

doi:10.3389/fnagi.2023.1213057

Myokines as mediators of exercise-induced cognitive changes in older adults: protocol for a comprehensive living systematic review and meta-analysis

Front Aging Neurosci. 2023 Jul 13:15:1213057. doi: 10.3389/fnagi.2023.1213057. eCollection 2023.

Authors

Wouter A J Vints^{1

2

3}, Evrim Gökçe⁴, Antoine Langeard⁵, Iuliia Pavlova⁶, Özge Selin Çevik⁷, Mohammad Mosaferi Ziaaldini⁸, Jasemin Todri⁹, Orges Lena⁹, Giorgos K Sakkas¹⁰, Suzanne Jak¹¹, Ioanna Zorba Zormpa¹², Christina Karatzaferi¹⁰, Oron Levin^{1

13}, Nerijus Masiulis¹, Yael Netz^{1

14}

Affiliations

¹ Department of Health Promotion and Rehabilitation, Lithuanian Sports University, Kaunas, Lithuania.
² Department of Rehabilitation Medicine, Research School Care and Public Health Research Institute (CAPHRI), Maastricht University, Maastricht, Netherlands.
³ Adelante Zorggroep Centre of Expertise in Rehabilitation and Audiology, Hoensbroek, Netherlands.
⁴ Sports Rehabilitation Laboratory, Ankara City Hospital, Ankara, Türkiye.
⁵ COMETE, INSERM, UNICAEN, Normandie Univ, Caen, France.
⁶ Department of Theory and Methods of Physical Culture, Lviv State University of Physical Culture, Lviv, Ukraine.
⁷ Department of Physiology, Mersin University, Mersin, Türkiye.
⁸ Department of Exercise Physiology, Faculty of Sport Sciences, Ferdowsi University of Mashhad, Mashhad, Iran.
⁹ Department of Physiotherapy, Universidad Catolica San Antonio (UCAM), Murcia, Spain.
¹⁰ Lifestyle Medicine and Experimental Physiology and Myology Lab, Department of Physical Education and Sports Science, The Center of Research and Evaluation of Human Performance (CREHP), University of Thessaly, National and Kapodistrian University of Athens (TEFAA) Campus, Karyes, Greece.
¹¹ Research Institute of Child Development and Education, University of Amsterdam, Amsterdam, Netherlands.
¹² Information and Library Centre, University of Ioannina, Ioannina, Greece.
¹³ Movement Control and Neuroplasticity Research Group, Group Biomedical Sciences, Catholic University of Leuven, Heverlee, Belgium.
¹⁴ The Levinsky-Wingate Academic Center, Wingate Campus, Netanya, Israel.

Abstract

Background: The world's population is aging, but life expectancy has risen more than healthy life expectancy (HALE). With respect to brain and cognition, the prevalence of neurodegenerative disorders increases with age, affecting health and quality of life, and imposing significant healthcare costs. Although the effects of physical exercise on cognition in advanced age have been widely explored, in-depth fundamental knowledge of the underlying mechanisms of the exercise-induced cognitive improvements is lacking. Recent research suggests that myokines, factors released into the blood circulation by contracting skeletal muscle, may play a role in mediating the beneficial effect of exercise on cognition. Our goal in this ongoing (living) review is to continuously map the rapidly accumulating knowledge on pathways between acute or chronic exercise-induced myokines and cognitive domains enhanced by exercise.

Method: Randomized controlled studies will be systematically collected at baseline and every 6 months for at least 5 years. Literature search will be performed online in PubMed, EMBASE, PsycINFO, Web of Science, SportDiscus, LILACS, IBECS, CINAHL, SCOPUS, ICTRP, and ClinicalTrials.gov. Risk of bias will be assessed using the Revised Cochrane Risk of Bias tool (ROB 2). A random effects meta-analysis with mediation analysis using meta-analytic structural equation modeling (MASEM) will be performed. The primary research question is to what extent exercise-induced myokines serve as mediators of cognitive function. Secondarily, the pooled effect size of specific exercise characteristics (e.g., mode of exercise) or specific older adults' populations (e.g., cognitively impaired) on the relationship between exercise, myokines, and cognition will be assessed. The review protocol was registered in PROSPERO (CRD42023416996).

Discussion: Understanding the triad relationship between exercise, myokines and cognition will expand the knowledge on multiple integrated network systems communicating between skeletal muscles and other organs such as the brain, thus mediating the beneficial effects of exercise on health and performance. It may also have practical implications, e.g., if a certain myokine is found to be a mediator between exercise and cognition, the optimal exercise characteristics for inducing this myokine can be prescribed. The living review is expected to improve our state of knowledge and refine exercise regimes for enhancing cognitive functioning in diverse older adults' populations.

Registration: Systematic review and meta-analysis protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) on the 24th of April 2023 (registration number CRD42023416996).

Keywords: aged; biomarker; brain; cognition; exercise; muscle; myokine; physical activity.

Grants and funding

A grant was awarded by COST (award number CA20104-dc00d18b-2213e134-470c-11ed-8dfc-06f1f03d9269, date of award 14th of November 2022) in the context of the COST Action CA20104 – Network on evidence-based physical activity in old age (PhysAgeNet) to support young researchers taking a leading role in research projects. The grant was received by WV. The funder was not involved in designing the study or writing of the manuscript, nor in the decision to submit the article for publication.