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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Physiol.</journal-id>
<journal-title>Frontiers in Physiology</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Physiol.</abbrev-journal-title>
<issn pub-type="epub">1664-042X</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="publisher-id">1638590</article-id>
<article-id pub-id-type="doi">10.3389/fphys.2025.1638590</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Physiology</subject>
<subj-group>
<subject>Original Research</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>Functional training improves cognitive function, functional fitness, and BDNF levels in older women with mild cognitive impairment: a randomized controlled trial</article-title>
<alt-title alt-title-type="left-running-head">Resende-Silva et al.</alt-title>
<alt-title alt-title-type="right-running-head">
<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.3389/fphys.2025.1638590">10.3389/fphys.2025.1638590</ext-link>
</alt-title>
</title-group>
<contrib-group>
<contrib contrib-type="author" corresp="yes">
<name>
<surname>Resende-Silva</surname>
<given-names>Salviano</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<xref ref-type="corresp" rid="c001">&#x2a;</xref>
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<contrib contrib-type="author">
<name>
<surname>de Resende-Neto</surname>
<given-names>Ant&#xf4;nio Gomes</given-names>
</name>
<xref ref-type="aff" rid="aff2">
<sup>2</sup>
</xref>
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<contrib contrib-type="author">
<name>
<surname>Vasconcelos</surname>
<given-names>Alan Bruno Silva</given-names>
</name>
<xref ref-type="aff" rid="aff3">
<sup>3</sup>
</xref>
<uri xlink:href="https://loop.frontiersin.org/people/1030531/overview"/>
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<contrib contrib-type="author">
<name>
<surname>Pereira-Monteiro</surname>
<given-names>Marcos Raphael</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<uri xlink:href="https://loop.frontiersin.org/people/2087385/overview"/>
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<contrib contrib-type="author">
<name>
<surname>Pantoja-Cardoso</surname>
<given-names>Alan</given-names>
</name>
<xref ref-type="aff" rid="aff4">
<sup>4</sup>
</xref>
<uri xlink:href="https://loop.frontiersin.org/people/3184445/overview"/>
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<contrib contrib-type="author">
<name>
<surname>Santana Santos</surname>
<given-names>La&#xed;za Ellen</given-names>
</name>
<xref ref-type="aff" rid="aff2">
<sup>2</sup>
</xref>
<uri xlink:href="https://loop.frontiersin.org/people/3184295/overview"/>
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<contrib contrib-type="author">
<name>
<surname>Carvalho Lima</surname>
<given-names>Newton Benites</given-names>
</name>
<xref ref-type="aff" rid="aff2">
<sup>2</sup>
</xref>
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<contrib contrib-type="author">
<name>
<surname>Jesus Santos</surname>
<given-names>Jos&#xe9; Lucas de</given-names>
</name>
<xref ref-type="aff" rid="aff5">
<sup>5</sup>
</xref>
<role content-type="https://credit.niso.org/contributor-roles/methodology/"/>
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<contrib contrib-type="author">
<name>
<surname>Arag&#xe3;o-Santos</surname>
<given-names>Jos&#xe9; Carlos</given-names>
</name>
<xref ref-type="aff" rid="aff6">
<sup>6</sup>
</xref>
<xref ref-type="aff" rid="aff7">
<sup>7</sup>
</xref>
<xref ref-type="aff" rid="aff8">
<sup>8</sup>
</xref>
<xref ref-type="aff" rid="aff9">
<sup>9</sup>
</xref>
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<contrib contrib-type="author">
<name>
<surname>Schimieguel</surname>
<given-names>Dulce Marta</given-names>
</name>
<xref ref-type="aff" rid="aff5">
<sup>5</sup>
</xref>
<uri xlink:href="https://loop.frontiersin.org/people/3184336/overview"/>
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<contrib contrib-type="author">
<name>
<surname>Santos</surname>
<given-names>Jos&#xe9; Ronaldo dos</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff10">
<sup>10</sup>
</xref>
<uri xlink:href="https://loop.frontiersin.org/people/23313/overview"/>
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<contrib contrib-type="author">
<name>
<surname>Da Silva-Grigoletto</surname>
<given-names>Marzo Edir</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff2">
<sup>2</sup>
</xref>
<xref ref-type="aff" rid="aff11">
<sup>11</sup>
</xref>
<uri xlink:href="https://loop.frontiersin.org/people/631430/overview"/>
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<aff id="aff1">
<sup>1</sup>
<institution>Postgraduate Program in Physiological Sciences, Federal University of Sergipe</institution>, <addr-line>S&#xe3;oCrist&#xf3;v&#xe3;o</addr-line>, <country>Brazil</country>
</aff>
<aff id="aff2">
<sup>2</sup>
<institution>Postgraduate Program in Health Sciences, Federal University of Sergipe</institution>, <addr-line>S&#xe3;o Crist&#xf3;v&#xe3;o</addr-line>, <country>Brazil</country>
</aff>
<aff id="aff3">
<sup>3</sup>
<institution>Department of Health Education, Federal University of Sergipe</institution>, <addr-line>Lagarto</addr-line>, <addr-line>Sergipe</addr-line>, <country>Brazil</country>
</aff>
<aff id="aff4">
<sup>4</sup>
<institution>Department of Physical Education, State University of Par&#xe1;</institution>, <addr-line>Altarmira</addr-line>, <addr-line>Par&#xe1;</addr-line>, <country>Brazil</country>
</aff>
<aff id="aff5">
<sup>5</sup>
<institution>Postgraduate Program in Pharmaceutical Sciences, Federal University of Sergipe</institution>, <addr-line>S&#xe3;o Crist&#xf3;v&#xe3;o</addr-line>, <country>Brazil</country>
</aff>
<aff id="aff6">
<sup>6</sup>
<institution>Graduate Program in Physical Education</institution>, <institution>Physical Education Department, Santa Cruz State University</institution>, <addr-line>Ilh&#xe9;us</addr-line>, <addr-line>Bahia</addr-line>, <country>Brazil</country>
</aff>
<aff id="aff7">
<sup>7</sup>
<institution>Physical Education Department</institution>, <institution>Federal University of Sergipe</institution>, <addr-line>S&#xe3;o Crist&#xf3;v&#xe3;o</addr-line>, <addr-line>Sergipe</addr-line>, <country>Brazil</country>
</aff>
<aff id="aff8">
<sup>8</sup>
<institution>Graduate Program in Physiological Sciences/Physical Education Department</institution>, <institution>Federal University of Sergipe</institution>, <addr-line>S&#xe3;o Crist&#xf3;v&#xe3;o</addr-line>, <addr-line>Sergipe</addr-line>, <country>Brazil</country>
</aff>
<aff id="aff9">
<sup>9</sup>
<institution>Graduate Program in Health Sciences, Physical Education Department</institution>, <institution>Federal University of Sergipe</institution>, <addr-line>S&#xe3;o Crist&#xf3;v&#xe3;o</addr-line>, <addr-line>Sergipe</addr-line>, <country>Brazil</country>
</aff>
<aff id="aff10">
<sup>10</sup>
<institution>Department of bioscience, Federal University of Sergipe</institution>, <addr-line>Itabaiana</addr-line>, <addr-line>Sergipe</addr-line>, <country>Brazil</country>
</aff>
<aff id="aff11">
<sup>11</sup>
<institution>Department of Physical Education, Federal University of Sergipe</institution>, <addr-line>S&#xe3;o Crist&#xf3;v&#xe3;o</addr-line>, <country>Brazil</country>
</aff>
<author-notes>
<fn fn-type="edited-by">
<p>
<bold>Edited by:</bold> <ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/1228916/overview">M&#xe1;rio Cunha Espada</ext-link>, Instituto Politecnico de Setubal (IPS), Portugal</p>
</fn>
<fn fn-type="edited-by">
<p>
<bold>Reviewed by:</bold> <ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/2730514/overview">Carolina Alexandra Cabo</ext-link>, University of Evora, Portugal</p>
<p>
<ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/3020717/overview">Ella Fauziah</ext-link>, Yogyakarta State University, Indonesia</p>
<p>
<ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/3095330/overview">Angelica Stein</ext-link>, Federal University of Paran&#xe1;, Brazil</p>
</fn>
<corresp id="c001">&#x2a;Correspondence: Salviano Resende-Silva, <email>salvianoresende77@hotmail.com</email>
</corresp>
</author-notes>
<pub-date pub-type="epub">
<day>11</day>
<month>09</month>
<year>2025</year>
</pub-date>
<pub-date pub-type="collection">
<year>2025</year>
</pub-date>
<volume>16</volume>
<elocation-id>1638590</elocation-id>
<history>
<date date-type="received">
<day>31</day>
<month>05</month>
<year>2025</year>
</date>
<date date-type="accepted">
<day>18</day>
<month>08</month>
<year>2025</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#xa9; 2025 Resende-Silva, de Resende-Neto, Vasconcelos, Pereira-Monteiro, Pantoja-Cardoso, Santana Santos, Carvalho Lima, Jesus Santos, Arag&#xe3;o-Santos, Schimieguel, Santos and Da Silva-Grigoletto.</copyright-statement>
<copyright-year>2025</copyright-year>
<copyright-holder>Resende-Silva, Gomes de Resende-Neto, Vasconcelos, Pereira-Monteiro, Pantoja-Cardoso, Santana Santos, Carvalho Lima, Jesus Santos, Arag&#xe3;o-Santos, Schimieguel, Santos and Da Silva-Grigoletto</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/">
<p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</p>
</license>
</permissions>
<abstract>
<sec>
<title>Introduction</title>
<p>To oppose the aging-related cognitive and functional decline, the efficacy of different training methods has been tested, aiming body multisystemic adaptations. In this sense, Functional Training (FT) has shown relevant results in the physical fitness of older adults. However, little is known about its impact on older women with mild cognitive impairment (MCI).</p>
</sec>
<sec>
<title>Objective</title>
<p>To compare the effects of functional and aerobic training on cognitive function and functional fitness in older women with mild cognitive impairment.</p>
</sec>
<sec>
<title>Methods</title>
<p>Sixty-eight older women completed a 16-week intervention through three groups: 1) Functional Training (FT: n &#x3d; 28; mean age &#x3d; 67.5 &#xb1; 4.8 years), 2) Aerobic Training (AT: n &#x3d; 22; mean age &#x3d; 66.3 &#xb1; 4.6 years), and 3) Control Group (CG: n &#x3d; 18; mean age &#x3d; 67.5 &#xb1; 4.6 years). The training sessions did occur three times per week, with a duration of 50 min per session for both exercised groups. The training load was quantified daily in the FT group. Cognitive function, serum levels of Brain-Derived Neurotrophic Factor (BDNF), and functional fitness were assessed pre- and post-intervention.</p>
</sec>
<sec>
<title>Results</title>
<p>FT and AT groups showed improvements in cognitive status (FT: d &#x3d; 0.99, p &#x2264; 0.001; AT: d &#x3d; 0.97, p &#x2264; 0.001) and semantic memory (FT: d &#x3d; 0.95, p &#x3c; 0.001; AT: d &#x3d; 0.97, p &#x3c; 0.001); however, only FT led to improvements in executive function (d &#x3d; 0.63, p &#x3d; 0.043) and increased serum BDNF levels (d &#x3d; 0.95, p &#x3d; 0.011). Regarding functional fitness, both groups showed improvements in gait and stand up ability, as well as cardiorespiratory fitness. However, only FT improved dexterity and upper limb strength. No statistically significant differences were observed between the FT and AT groups in the measured outcomes.</p>
</sec>
<sec>
<title>Conclusion</title>
<p>Both FT and AT improve cognitive function and functional fitness in older women with mild cognitive impairment. However, in addition to eliciting a greater magnitude of effects on some outcomes, FT was the only intervention to modulate peripheral BDNF concentration.</p>
</sec>
</abstract>
<kwd-group>
<kwd>ageing</kwd>
<kwd>exercise</kwd>
<kwd>health</kwd>
<kwd>functional status</kwd>
<kwd>personal autonomy</kwd>
</kwd-group>
<custom-meta-wrap>
<custom-meta>
<meta-name>section-at-acceptance</meta-name>
<meta-value>Exercise Physiology</meta-value>
</custom-meta>
</custom-meta-wrap>
</article-meta>
</front>
<body>
<sec id="s1">
<title>1 Introduction</title>
<p>Mild Cognitive Impairment (MCI) is an intermediate state between normal cognitive aging and dementia, characterized by changes that do not significantly affect daily activities. In turn, it hinders the cognitive functions involved in the acquisition, processing, storage, and use of information, with an annual conversion to dementia of approximately 15% (<xref ref-type="bibr" rid="B35">Gure et al., 2013</xref>). This cognitive decline is associated with a reduction in brain density and volume of approximately 2.82% over a 6-month period (<xref ref-type="bibr" rid="B89">Teixeira et al., 2018</xref>), which impairs the connectivity and expression of neurotrophins involved in neuroplasticity, such as Brain-Derived Neurotrophic Factor (BDNF) (<xref ref-type="bibr" rid="B50">Leal et al., 2014</xref>; <xref ref-type="bibr" rid="B53">Li et al., 2021</xref>), compromising cognitive function (<xref ref-type="bibr" rid="B91">Tolea et al., 2015</xref>; <xref ref-type="bibr" rid="B112">Zahodne et al., 2013</xref>). This condition is prevalent in older women due to their longer life expectancy and the reduction in sex hormone production during the post-menopausal period (<xref ref-type="bibr" rid="B36">H&#xe4;gg and Jylh&#xe4;v&#xe4;, 2021</xref>). Furthermore, this decline can be accelerated by factors such as arterial hypertension, obesity, and physical inactivity (<xref ref-type="bibr" rid="B28">Erickson et al., 2022</xref>; <xref ref-type="bibr" rid="B84">Smid et al., 2022</xref>).</p>
<p>Physical exercise stands as the foremost non-pharmacological strategy to counteract physical inactivity (<xref ref-type="bibr" rid="B28">Erickson et al., 2022</xref>; <xref ref-type="bibr" rid="B26">Van Dyck et al., 2023</xref>). Exposure to aerobic exercise enhances cardiorespiratory capacity and cerebral vascularization (<xref ref-type="bibr" rid="B42">Huang et al., 2024</xref>), thereby increasing the supply of oxygen and nutrients to neural cells (<xref ref-type="bibr" rid="B19">Crichton et al., 2014</xref>). This, in turn, leads to greater cerebral connectivity (<xref ref-type="bibr" rid="B40">Holzschneider et al., 2012</xref>), improving learning (<xref ref-type="bibr" rid="B100">Voss et al., 2024</xref>) and decelerating cognitive decline (<xref ref-type="bibr" rid="B14">Brinke et al., 2015</xref>; <xref ref-type="bibr" rid="B63">Norling et al., 2024</xref>). In parallel, neuromuscular stimuli continuously activate areas involved in motor planning and execution (<xref ref-type="bibr" rid="B51">Lee et al., 2024</xref>), consequently impacting cerebral connectivity (<xref ref-type="bibr" rid="B34">Gr&#xe9;goire et al., 2019</xref>; <xref ref-type="bibr" rid="B38">Hewston et al., 2021</xref>). Both types of stimuli promote the release of myokines, interleukins, and neurotrophins, fostering positive adaptations from exercise practice (<xref ref-type="bibr" rid="B44">Islam et al., 2021</xref>; <xref ref-type="bibr" rid="B29">Ferrer-Uris et al., 2022</xref>; <xref ref-type="bibr" rid="B5">Andronie-Cioara et al., 2023</xref>; <xref ref-type="bibr" rid="B37">Herold et al., 2019</xref>; <xref ref-type="bibr" rid="B10">Azevedo et al., 2023</xref>; <xref ref-type="bibr" rid="B24">Duarte Martins et al., 2024</xref>; <xref ref-type="bibr" rid="B99">Vints et al., 2024</xref>). The integration of physical and motor components demonstrably improves global cognition, language, executive function, attention, and concentration (<xref ref-type="bibr" rid="B41">Huang et al., 2022</xref>; <xref ref-type="bibr" rid="B74">Rond&#xe3;o et al., 2022</xref>; <xref ref-type="bibr" rid="B87">Suzuki et al., 2012</xref>; <xref ref-type="bibr" rid="B96">Vaughan et al., 2014</xref>; <xref ref-type="bibr" rid="B115">Zhu et al., 2018</xref>). In healthy older adults, a positive association exists between physical activity levels and cognitive function, alongside enhanced task performance. These benefits can be further amplified in older adults with MCI (<xref ref-type="bibr" rid="B104">Xu et al., 2024</xref>; <xref ref-type="bibr" rid="B103">Wang et al., 2024</xref>).</p>
<p>Among various modalities, functional training (FT) is a multicomponent, multiplanar, and multiarticular approach that emphasizes activities of daily living and leverages the principle of specificity (<xref ref-type="bibr" rid="B83">Silva-Grigoletto et al., 2020</xref>). This is achieved by applying stimuli that develop muscular strength and power in basic functional patterns, such as pushing, pulling, carrying, and squatting. Additionally, the session incorporates acceleration and deceleration exercises, typically organized into blocks (<xref ref-type="bibr" rid="B83">Silva-Grigoletto et al., 2020</xref>; Antonio Gomes De and Marzo). FT demonstrates significant effects on physical fitness, with effect sizes ranging from moderate to large (<xref ref-type="bibr" rid="B73">Rocha et al., 2023</xref>; <xref ref-type="bibr" rid="B8">Arag&#xe3;o-Santos et al., 2020</xref>). However, its impacts on the cognitive function of older adults with MCI are not yet fully elucidated (<xref ref-type="bibr" rid="B67">Pantoja-Cardoso et al., 2023</xref>). Prospective studies suggest incorporating motor complexity and dose control into FT protocols as an alternative to induce cognitive adaptations (<xref ref-type="bibr" rid="B117">Da Silva-Grigoletto et al., 2024</xref>).</p>
<p>On the other hand, Aerobic Training (AT) is considered an effective intervention in the prevention and treatment of cognitive impairments by stimulating the release of myokines and increasing cerebral blood flow. Different types of AT demonstrate promising effects on cognition in older adults with MCI, such as continuous walking (<xref ref-type="bibr" rid="B46">Khan et al., 2023</xref>; <xref ref-type="bibr" rid="B62">Nocera et al., 2017</xref>), high-intensity interval training (HIIT) (<xref ref-type="bibr" rid="B59">Mekari et al., 2020</xref>)), and rhythmic training (<xref ref-type="bibr" rid="B116">Zhu et al., 2022</xref>). However, these protocols show a smaller magnitude of effect on the physical fitness of older adults when compared to neuromuscular training methods (<xref ref-type="bibr" rid="B35">Gure et al., 2013</xref>; <xref ref-type="bibr" rid="B4">Altieri et al., 2021</xref>). Furthermore, it is believed that appropriate levels of muscle strength and power are associated with better overall cognitive performance and in its subdomains (<xref ref-type="bibr" rid="B58">Mavros et al., 2017</xref>).</p>
<p>Therefore, our study compared the effects of functional and aerobic training on cognitive function, serum BDNF levels, and functional fitness in older women with mild cognitive impairment. Additionally, the present intervention proposal has novel characteristics not yet evidenced and a precise quantification of the training load throughout the intervention period. Our initial hypothesis was that FT is as effective as AT to improve the cognitive function; however, it provides greater effects on functional fitness and in increasing peripheral BDNF levels.</p>
</sec>
<sec sec-type="materials|methods" id="s2">
<title>2 Materials and methods</title>
<sec id="s2-1">
<title>2.1 Study design</title>
<p>This was a 22-week randomized controlled trial. Physical and cognitive assessments were conducted over a 4-week period: 2 weeks before the intervention and 2 weeks after the intervention, to collect pre- and post-intervention data. Additionally, 2 weeks were dedicated to familiarizing the participants with the exercises, and 16 weeks were allocated for the implementation of the training protocols (<xref ref-type="fig" rid="F1">Figure 1</xref>).</p>
<fig id="F1" position="float">
<label>FIGURE 1</label>
<caption>
<p>Experimental design.</p>
</caption>
<graphic xlink:href="fphys-16-1638590-g001.tif">
<alt-text content-type="machine-generated">Timeline graphic illustrating a study process. Weeks 01-02 involve cognitive and functional assessments and blood collection. Weeks 03-04 are for familiarization. Weeks 05-20 focus on interventions. Weeks 21-22 return to assessments and blood collection. Icons represent each phase, including brains, tests, and exercise figures.</alt-text>
</graphic>
</fig>
</sec>
<sec id="s2-2">
<title>2.2 Participants</title>
<p>The participants were recruited from the community using leaflets and flyers distributed around the Federal University of Sergipe, through a non-probability sampling method (<xref ref-type="fig" rid="F2">Figure 2</xref>). To detect between-group differences with an alpha level of 0.05 and assuming a large effect size, we would need a total of 45 participants in our study to achieve a power of 0.80. Notably, we considered a 20% sample loss during the intervention, totaling 54 participants. We randomized the participants based on the residual value of the means of all performed tests, which were organized in ascending order for every three values using Microsoft Excel software.</p>
<fig id="F2" position="float">
<label>FIGURE 2</label>
<caption>
<p>Schematic representation of the screening, allocation, and intervention processes of the study.</p>
</caption>
<graphic xlink:href="fphys-16-1638590-g002.tif">
<alt-text content-type="machine-generated">Flowchart showing the enrollment and allocation in a study. Initially, 153 participants were enrolled; 60 did not meet inclusion criteria, and 4 withdrew, leaving 89 randomized. These were allocated into three groups: Functional Training (30), Aerobic Training (30), and Control Group (29). After assessments, exclusions due to adherence issues or non-attendance led to the final analysis with Functional Training (28), Aerobic Training (22), and Control Group (18).</alt-text>
</graphic>
</fig>
<p>The selection process for participants followed several inclusion criteria: 1) female sex; 2) physically independence; 3) being literate; 4) not involved in any hormone replacement therapy; 5) scoring &#x3e;8 and &#x3c;26 points on the Montreal Cognitive Assessment (MoCA) (<xref ref-type="bibr" rid="B56">Malek-Ah et al., 2024</xref>); 6) reporting complaints of memory problems (<xref ref-type="bibr" rid="B33">Gifford et al., 2014</xref>); and 7) without diagnosed neurological diseases (dementia, Parkinson&#x2019;s disease, Alzheimer&#x2019;s disease, multiple sclerosis, and depression), recent surgeries, vision, hearing, musculoskeletal, and cardiorespiratory problems that would prevent the practice of high-intensity physical exercise. Participants with an attendance rate below 70% in the training sessions and those who did not attend the final assessment were excluded from the study analyses.</p>
<p>After the application of the eligibility criteria, the participants signed the Free and Informed Consent Form. This study was conducted in accordance with the Declaration of Helsinki and approved by the institution&#x2019;s Research Ethics Committee (CAAE: 76026223.4.0000.5546; No. 6,598,301). Furthermore, it is registered in the Brazilian Registry of Clinical Trials under protocol RBR-89svjw3 (available at <ext-link ext-link-type="uri" xlink:href="https://ensaiosclinicos.gov.br/rg/RBR-89svjw3">https://ensaiosclinicos.gov.br/rg/RBR-89svjw3</ext-link>).</p>
</sec>
<sec id="s2-3">
<title>2.3 Physical training protocols</title>
<p>Three weekly sessions were conducted, each lasting approximately 50 min, over a period of 16 weeks, totaling 48 trainings sessions, with a minimum interval of 48 h between sessions. Both training protocols were supervised by experienced physical training professionals for older adults. There was one professional for every five participants to ensure safety and correct exercise execution.</p>
<sec id="s2-3-1">
<title>2.3.1 Functional training</title>
<p>The sessions were composed of three parts: 1) preparation for movement with joint mobility exercises (glenohumeral, thoracic, hip, and ankle) and muscle activation (static marching and squats); 2) stimuli directed at speed, coordination, agility, and muscle power; and 3) exercises focused on muscle strength in basic functional patterns of pushing, pulling, carrying, and squatting, which reflect activities of daily living. Both blocks, 2 and 3, were performed in a circuit format (<xref ref-type="table" rid="T1">Table 1</xref>).</p>
<table-wrap id="T1" position="float">
<label>TABLE 1</label>
<caption>
<p>Description of the session structure and progressions implemented during the 16 weeks of Functional Training.</p>
</caption>
<table>
<thead valign="top">
<tr>
<th align="center"/>
<th colspan="3" align="center">Session structure</th>
</tr>
</thead>
<tbody valign="top">
<tr>
<td rowspan="6" align="center">Mobility and activation</td>
<td colspan="3" align="center">(Cervical) &#x2013; Frontal flexion and extension, abduction and adduction</td>
</tr>
<tr>
<td colspan="3" align="center">(Glenohumeral) &#x2013; Horizontal flexion, extension and shoulder flexion, rotation</td>
</tr>
<tr>
<td colspan="3" align="center">(Thorax/Hip) &#x2013; Shoulder protraction and retraction, unilateral thorax abduction; Trunk flexion, alternating leg raises, hip circumduction</td>
</tr>
<tr>
<td colspan="3" align="center">(Knee/Ankle) &#x2013; Forward step, dorsiflexion and plantarflexion, squat</td>
</tr>
<tr>
<td colspan="3" align="center">(Coordination) &#x2013; Knee raises with contralateral hand touches, adding counting rhythm and pause</td>
</tr>
<tr>
<td colspan="3" align="center">(Muscle and Cognitive Activation) &#x2013; Simple multidirectional movement patterns with term correlation</td>
</tr>
<tr>
<td align="center">Total time</td>
<td colspan="3" align="center">10 min total, 01 set with 10 repetitions per exercise</td>
</tr>
</tbody>
</table>
<table>
<thead valign="top">
<tr>
<th colspan="4" align="center">Exercise progression</th>
</tr>
<tr>
<th align="center">Sessions</th>
<th align="center">01&#x2013;16</th>
<th align="center">17&#x2013;32</th>
<th align="center">33&#x2013;48</th>
</tr>
</thead>
<tbody valign="top">
<tr>
<td rowspan="6" align="center">Neuromuscular 01 (Circuit Format)</td>
<td align="center">Parallel stance and straight throw against the wall</td>
<td align="center">Parallel stance and throw to the ground</td>
<td align="center">Parallel stance and upward throw with jump</td>
</tr>
<tr>
<td align="center">Forward jump</td>
<td align="center">Jump with diagonal entry</td>
<td align="center">Lateral jump (gallop)</td>
</tr>
<tr>
<td align="center">Forward entry with one foot in each square at a time</td>
<td align="center">Forward stepping with lateral displacement</td>
<td align="center">Forward entry and bilateral exit with forward jumps (Hopscotch)</td>
</tr>
<tr>
<td align="center">Forward displacement with cone touch</td>
<td align="center">Lateral displacement with change of direction touching the cone with a jump</td>
<td align="center">Lateral and forward displacement with jumps over cones</td>
</tr>
<tr>
<td align="center">Vertical waves with the battle rope</td>
<td align="center">Horizontal waves with the battle rope</td>
<td align="center">Alternating vertical waves with the battle rope</td>
</tr>
<tr>
<td align="center">5-m forward sprint</td>
<td align="center">Bipedal jump with 10-m sprint</td>
<td align="center">Asymmetrical foot jumps with 10-m sprint</td>
</tr>
<tr>
<td align="center">Total time</td>
<td colspan="3" align="center">15 min total, 06 exercises, 2 rounds, 75 s per station, work-to-rest ratio 1/2</td>
</tr>
<tr>
<td rowspan="7" align="center">Neuromuscular 02 (circuit format)</td>
<td align="center">Front Squat (Load)</td>
<td align="center">Front Squat (Load)</td>
<td align="center">Front Squat (Load)</td>
</tr>
<tr>
<td align="center">Neutral Grip Suspension Trainer Row</td>
<td align="center">Alternating Grip (Neutral and Supinated) Row</td>
<td align="center">Alternating Grip (Pronated and Supinated) Row</td>
</tr>
<tr>
<td align="center">Bilateral Hip Thrust</td>
<td align="center">Bilateral Hip Thrust with Simultaneous Bilateral Push-Off</td>
<td align="center">Unilateral Hip Thrust</td>
</tr>
<tr>
<td align="center">Pull-up</td>
<td align="center">Pull-up with Alternating Knee Raise on the Eccentric Phase</td>
<td align="center">Pull-up with Leg Extension and Ipsilateral Touch on the Supporting Leg</td>
</tr>
<tr>
<td align="center">Bilateral Deadlift (Load)</td>
<td align="center">Bilateral Deadlift (Load)</td>
<td align="center">Bilateral Deadlift (Load)</td>
</tr>
<tr>
<td align="center">
<italic>Bilateral Farmer&#x2019;s Walk</italic>
</td>
<td align="center">
<italic>Bilateral Loaded Farmer&#x2019;s Walk in Zig-Zag Pattern</italic>
</td>
<td align="center">
<italic>Unilateral Loaded Farmer&#x2019;s Walk in Zig-Zag Pattern</italic>
</td>
</tr>
<tr>
<td align="center">Supinated Grip Resistance Band Pull-down</td>
<td align="center">Bilateral Pull-down with Squat on the Eccentric Phase</td>
<td align="center">Bilateral Pull-down with Contralateral Leg Flexion</td>
</tr>
<tr>
<td align="center">Total time</td>
<td colspan="3" align="center">25 min total, 07 exercises, 2 rounds of 8 to 12 repetitions, 100 s per station, work-to-rest ratio 2/1</td>
</tr>
</tbody>
</table>
</table-wrap>
<p>Exercises complexity progressions occurred every 16 sessions. In the second part, this was achieved through variations in planes (sagittal, frontal, and transverse) and direction of movement (vertical, horizontal, and diagonal). In the third part, progression explored motor complexity by altering the number of segments and planes, with dual motor tasks associated with increments in movement speed (<xref ref-type="bibr" rid="B77">La Scala Teixeira et al., 2019</xref>; <xref ref-type="bibr" rid="B75">Saeterbakken et al., 2011</xref>). The participants underwent supervised and progressive training, with daily quantification of the load (Volume load &#x3d; sets x repetitions x load) for the eight exercises of the neuromuscular part (<xref ref-type="bibr" rid="B16">Buskard et al., 2018</xref>; <xref ref-type="bibr" rid="B32">Genner and Weston, 2014</xref>).</p>
</sec>
<sec id="s2-3-2">
<title>2.3.2 Aerobic training</title>
<p>The applied systematization possesses particularities not yet evidenced in scientific literature, such as the combination of three training methods within the same session, aiming for improvements in agility, balance, coordination, speed, and cardiorespiratory fitness. Thus, the session was divided into four parts: 1) preparation for movement with joint mobility exercises (glenohumeral, thoracic, hip, and ankle) and muscle activation (static marching and squats); 2) continuous running (50% and 70% of heart rate reserve; HRR); 3) rhythmic movements; and 4) high-intensity interval running (<xref ref-type="bibr" rid="B21">Delgado-Floody et al., 2015</xref>).</p>
<p>There were no progressions during the weeks; however, the intensity of the session was prescribed between 50% and 80% of HRR, being monitored throughout the session, allowing for the tracking of the average HRR behavior during the parts of the sessions (<xref ref-type="bibr" rid="B45">Karvonen et al., 1957</xref>) (<xref ref-type="table" rid="T2">Table 2</xref>).</p>
<table-wrap id="T2" position="float">
<label>TABLE 2</label>
<caption>
<p>Description of the Aerobic Training session.</p>
</caption>
<table>
<thead valign="top">
<tr>
<th align="center">Session structure</th>
<th colspan="3" align="center">Exercises</th>
</tr>
</thead>
<tbody valign="top">
<tr>
<td rowspan="6" align="center">Mobility And Activation</td>
<td colspan="3" align="center">(Cervical) &#x2013; Frontal flexion and extension, abduction and adduction</td>
</tr>
<tr>
<td colspan="3" align="center">(Glenohumeral) &#x2013; Horizontal flexion, extension and shoulder flexion, rotation</td>
</tr>
<tr>
<td colspan="3" align="center">(Thorax/Hip) &#x2013; Shoulder protraction and retraction, unilateral thorax abduction; Trunk flexion, alternating leg raises, hip circumduction</td>
</tr>
<tr>
<td colspan="3" align="center">(Knee/Ankle) &#x2013; Forward step, dorsiflexion and plantarflexion, squat</td>
</tr>
<tr>
<td colspan="3" align="center">(Coordination) &#x2013; Knee raises with contralateral hand touches, adding counting rhythm and pause</td>
</tr>
<tr>
<td colspan="3" align="center">(Muscle and Cognitive Activation) &#x2013; Simple multidirectional movement patterns with term correlation</td>
</tr>
<tr>
<td align="center">Total time</td>
<td colspan="3" align="center">10 min total, 01 set with 10 repetitions per exercise</td>
</tr>
<tr>
<td align="center">Continuous part</td>
<td colspan="3" align="center">Continuous running in a corridor</td>
</tr>
<tr>
<td align="center">Total time</td>
<td colspan="3" align="center">10 min total, 70-m course (70m &#xb1;20 s)</td>
</tr>
<tr>
<td colspan="4" align="center">Movements performed</td>
</tr>
<tr>
<td rowspan="5" align="center">Rhythmic part</td>
<td align="center">Backward step</td>
<td align="center">Forward step</td>
<td align="center">Lateral step</td>
</tr>
<tr>
<td align="center">Backward kick</td>
<td align="center">Forward kick</td>
<td align="center">Lateral kick</td>
</tr>
<tr>
<td colspan="3" align="center">Knee flexion</td>
</tr>
<tr>
<td colspan="3" align="center">Leg curl</td>
</tr>
<tr>
<td align="center">Arm flexion</td>
<td colspan="2" align="center">Leg flexion</td>
</tr>
<tr>
<td align="center">Total time</td>
<td colspan="3" align="center">10 min, 10 sets of 8 repetitions per movement</td>
</tr>
<tr>
<td align="center">Interval part</td>
<td colspan="3" align="center">30 Sprints &#x2013; 12 m</td>
</tr>
<tr>
<td align="center">Total time</td>
<td colspan="3" align="center">10 min, 12 m (01 sprint &#xb1;03 s), work-to-rest ratio 1/4</td>
</tr>
<tr>
<td colspan="4" align="center">130, 140 and 150 &#x2d; Beats Per Minute (Music) (Rhythmic Part)</td>
</tr>
<tr>
<td colspan="4" align="center">05 to 08 &#x2013; Rating of Perceived Exertion (Session)</td>
</tr>
<tr>
<td colspan="4" align="center">50&#x25;&#x2013;70&#x25; Heart Rate Reserve (Session)</td>
</tr>
</tbody>
</table>
</table-wrap>
</sec>
<sec id="s2-3-3">
<title>2.3.3 Control group</title>
<p>The control group performed static and dynamic stretching exercises. The exercises began with the muscles of the neck and progressed down to the dorsum of the feet. The session duration was approximately 40 min, with 10 min dedicated to preparation for movement with joint mobility exercises (glenohumeral, thoracic, hip, and ankle) and 30 min devoted to the practice of submaximal stretches, respecting the comfort levels of the participants.</p>
</sec>
</sec>
<sec id="s2-4">
<title>2.4 Data collection procedures</title>
<p>Initially, the participants underwent an eligibility assessment, and information such as age, body weight, height, address, motivation, medication use, and chronic diseases was recorded. For the cognitive and physical tests, all measurements were performed by trained and experienced professionals in the data collection procedures, which always occurred in the morning period. The assessors were blinded to the physical training protocols previously performed by the participants.</p>
<sec id="s2-4-1">
<title>2.4.1 Categorization instruments</title>
<p>The participants were functionally classified based on the Montreal Cognitive Assessment (MoCA) questionnaire (<xref ref-type="bibr" rid="B61">Nasreddine et al., 2005</xref>), the Geriatric Depression Scale and Anxiety Scale (GDS-15) (<xref ref-type="bibr" rid="B107">Yesavage et al., 1982</xref>), and the Lawton-Brody Instrumental Activities of Daily Living Scale (<xref ref-type="bibr" rid="B49">Lawton, 1969</xref>).</p>
</sec>
<sec id="s2-4-2">
<title>2.4.2 Cognitive assessment</title>
<p>The tests were administered at pre- and post-intervention time points in a closed room, free from visual or auditory distractions, with controlled temperature (23 &#xb0;C &#xb1; 2 &#xb0;C), and with a single investigator in the room to provide instructions and evaluate the participants. The application of the cognitive tests lasted approximately 30 min, following a pre-established order of administration. To assess the impact of the intervention on cognitive function, the following cognitive tests were administered at pre- and post-intervention time points:</p>
<p>The Montreal Cognitive Assessment (MoCA), with a maximum score of 30 points, was used to evaluate overall cognitive status. The MoCA was also used for screening mild cognitive impairment (MCI), demonstrating a high intraclass correlation coefficient (ICC &#x3d; 0.88). Reference values for classifying cognitive impairment are scores above 8 points and below 26 points, with a sensitivity exceeding 80% (<xref ref-type="bibr" rid="B56">Malek-Ah et al., 2024</xref>; <xref ref-type="bibr" rid="B48">Langa and Levine, 2014</xref>).</p>
<p>Animal category verbal fluency was employed to assess semantic memory, language, and executive function. This test is widely used in neuropsychological assessments due to its recognized sensitivity for screening MCI and dementia (<xref ref-type="bibr" rid="B15">Brucki et al., 1997</xref>; <xref ref-type="bibr" rid="B60">Mirandez et al., 2017</xref>). The verbal fluency test is validated for the Brazilian population, exhibiting moderate to high intraclass correlation coefficients (ICC &#x3e;0.8) and a sensitivity greater than 79% (<xref ref-type="bibr" rid="B68">Paulsen et al., 1995</xref>; <xref ref-type="bibr" rid="B70">Radanovic et al., 2009</xref>).</p>
<p>Finally, the Digit Span Forward (DSF) test was administered to assess short-term memory. In contrast, the Digit Span Backward (DSB) test evaluated working memory, where participants had to repeat numerical sequences in reverse order (<xref ref-type="bibr" rid="B78">Schroeder et al., 2012</xref>). Both versions demonstrated a high intraclass correlation coefficient (ICC &#x3d; 0.88) and a sensitivity above 70% (<xref ref-type="bibr" rid="B22">Dell&#x2019;Oro de Oliveira et al., 2014</xref>). These tests have proven efficacy in detecting declines in short-term memory and working memory, respectively (<xref ref-type="bibr" rid="B110">Yoshimura et al., 2023</xref>).</p>
</sec>
<sec id="s2-4-3">
<title>2.4.3 Functional fitness assessment</title>
<p>The tests comprising the functional fitness assessment were performed in a randomized order on the same day for all participants. Each test included a familiarization trial followed by three recorded attempts, with a 2-min rest interval between attempts. The investigators provided verbal encouragement during the execution of the tests and additional explanations when necessary. Participants were instructed to perform all tests with maximum effort to select the best value among the three attempts. The tests comprising the functional fitness assessment were time-based and recorded using a digital stopwatch.</p>
<sec id="s2-4-3-1">
<title>2.4.3.1 Stand up ability</title>
<p>Two tests were used to assess chair-rise ability: 1) Five Times Sit-to-Stand Test (FSTS), which indirectly evaluated lower limb power, with participants sitting down and standing up from a 45 cm high chair for five consecutive repetitions (<xref ref-type="bibr" rid="B90">Teo et al., 2013</xref>); 2) Floor Rise Test (FRT), which evaluated overall functionality with high demand on core muscles, with the participant rising from a prone position to a standing position without swaying (<xref ref-type="bibr" rid="B76">Santana et al., 2021</xref>).</p>
</sec>
<sec id="s2-4-3-2">
<title>2.4.3.2 Gait ability</title>
<p>Two tests were used to assess gait ability: 1) Timed Up and Go (TUG), which evaluated agility and dynamic balance, where the participant stood up from a chair, walked 3 m, turned around a cone, and returned to the seat (<xref ref-type="bibr" rid="B69">Podsiadlo and Richardson, 1991</xref>); 2) 10-m Walk Test (10MWT), which evaluated gait speed, with the participant walking 10 m of a 14-m course, excluding the acceleration and deceleration areas (<xref ref-type="bibr" rid="B55">Lusardi et al., 2003</xref>).</p>
</sec>
<sec id="s2-4-3-3">
<title>2.4.3.3 Dexterity ability</title>
<p>Two tests were used to assess dexterity ability: 1) Gallon Jug Shelf Transfer (GJST), which evaluated upper limb strength and coordination by transferring five gallons of 3.9 kg between a lower and an upper shelf, transferring 1 gallon at a time (<xref ref-type="bibr" rid="B81">Signorile et al., 2007</xref>); and 2) Dressing on and taking off a t-shirt (DTTS), which evaluated upper limb mobility and coordination, with the participant donning and doffing a shirt as quickly as possible (<xref ref-type="bibr" rid="B93">Vale et al., 2006</xref>).</p>
</sec>
<sec id="s2-4-3-4">
<title>2.4.3.4 Upper limb strength</title>
<p>Handgrip strength (HGS), which assessed the muscular strength of the upper limbs, was measured using a handgrip dynamometer (Jamar Hydraulic Hand Dynamometer; Homecraft Ltd., ghamshire, United Kingdom), in conjunction with the functional fitness tests (<xref ref-type="bibr" rid="B101">Wang and Chen, 2010</xref>). The participant was seated in a chair and applied progressive maximal force with the dominant arm flexed at 90&#xb0;. The highest value in kilogram-force (kgf) was selected for analysis.</p>
</sec>
<sec id="s2-4-3-5">
<title>2.4.3.5 Cardiorespiratory capacity</title>
<p>The 6-Minute Walk Test (6MWT), which assessed the cardiorespiratory capacity of the participants, was administered separately from the other tests in a covered and ventilated multi-sport court marked with 30-m lanes. Upon the command (&#x201c;Go&#x201d;), the participant walked as fast as possible for 6 min, with only one attempt performed. At the end, the distance covered was recorded in meters (<xref ref-type="bibr" rid="B13">Bittner et al., 1993</xref>).</p>
</sec>
<sec id="s2-4-3-6">
<title>2.4.3.6 Blood collection and BDNF measurement</title>
<p>Blood samples were collected after a 12-h overnight fast and 72 h of exercise abstinence. Samples were drawn from the antecubital vein (4 mL) into vacuum blood collection tubes (Vacutainer&#xae;; Becton Dickinson&#xae;, Franklin Lakes, United States), centrifuged (3,000 rpm, 10 min at 4 &#xb0;C), and stored at &#x2212;80 &#xb0;C. Serum BDNF levels were measured using a sandwich enzyme-linked immunosorbent assay (ELISA) with a detection range of 0.066&#x2013;16 ng/mL (Human BDNF ELISA kit - cat&#x23; EH42RB, Thermo Fisher Scientific Company, United States) according to the manufacturer&#x2019;s instructions.</p>
</sec>
</sec>
<sec id="s2-4-4">
<title>2.4.4 Statistical analysis</title>
<p>The sample size calculation was performed using the G&#x2a;Power software (Erdfelder, Faul and Buchner, 1996; Kiel, Germany - version 3.1.9.2) based on the main dependent variables: 1) cognitive function - semantic memory and cognitive status (<xref ref-type="bibr" rid="B65">de Oliveira Silva et al., 2019</xref>; <xref ref-type="bibr" rid="B109">Yoon et al., 2017</xref>); 2) functional fitness&#x2013;dynamic balance and cardiorespiratory capacity (<xref ref-type="bibr" rid="B71">de Resende-Neto et al., 2021</xref>). Thus, a statistical power of 0.80 and an alpha of 0.05 were considered, in addition to an anticipated sample loss of 20% during the intervention.</p>
<p>The data were tabulated and analyzed using JAMOVI software (version 2.4.11). Descriptive statistics were used to summarize the general characteristics of the study participants. The normality of the data was confirmed using the Shapiro-Wilk test, and homogeneity of variances was verified using Levene&#x2019;s test.</p>
<p>Repeated measures analysis of variance (ANOVA) was used to verify the differences between the interventions. The Bonferroni <italic>post hoc</italic> test was used to identify where the significance occurred. All tests were two-tailed, and the effect size (ES) was calculated according to the equation proposed by Cohen (1988), as well as the classification of each result (trivial: 0.00-0.19; small: 0.20-0.49; moderate: 0.5-0.79; large: 0.8-1.33; and very large: &#x3e;1.33). The significance level adopted for all tests was p &#x3c; 0.05.</p>
</sec>
</sec>
<sec id="s2-5">
<title>2.5 Results</title>
<p>The initial sample consisted of 89 older women (mean age &#x3d; 67.1 &#xb1; 4.7 years; BMI &#x3d; 29.29 &#xb1; 4.94 kg/m<sup>2</sup>) at risk for MCI (MoCA: 19.32 &#xb1; 3.73 points), independent in activities of daily living (IADL: 20.61 &#xb1; 0.86 points), and with a low indicative risk of depression (GDS-15: 2.46 &#xb1; 1.39). Of these, 68 completed all stages of the intervention, and the experimental groups showed a 91% adherence rate to the training sessions (<xref ref-type="table" rid="T3">Table 3</xref>).</p>
<table-wrap id="T3" position="float">
<label>TABLE 3</label>
<caption>
<p>Baseline Characteristics of participants in the Functional Training (FT), Aerobic (AT), and Control (CG) groups.</p>
</caption>
<table>
<thead valign="top">
<tr>
<th rowspan="2" align="center">Varibles</th>
<th align="center">FT<break/> (n &#x3d; 28)</th>
<th align="center">AT<break/> (n &#x3d; 22)</th>
<th align="center">CG <break/>(n &#x3d; 18)</th>
<th rowspan="2" align="center">p</th>
</tr>
<tr>
<th align="center">M &#xb1; SD</th>
<th align="center">M &#xb1; SD</th>
<th align="center">M &#xb1; SD</th>
</tr>
</thead>
<tbody valign="top">
<tr>
<td align="left">Age (years)</td>
<td align="center">67.5 &#xb1; 4.8</td>
<td align="center">66.4 &#xb1; 4.6</td>
<td align="center">67.5 &#xb1; 4.6</td>
<td align="center">0.680</td>
</tr>
<tr>
<td align="left">Body weight (Kg)</td>
<td align="center">68.2 &#xb1; 11.3</td>
<td align="center">66.0 &#xb1; 14.4</td>
<td align="center">67.9 &#xb1; 15.6</td>
<td align="center">0.845</td>
</tr>
<tr>
<td align="left">Height (meters)</td>
<td align="center">1.53 &#xb1; 6.88</td>
<td align="center">1.50 &#xb1; 4.91</td>
<td align="center">1.50 &#xb1; 5.05</td>
<td align="center">0.171</td>
</tr>
<tr>
<td align="left">BMI (Kg/m<sup>3</sup>)</td>
<td align="center">29.29 &#xb1; 4.39</td>
<td align="center">28.71 &#xb1; 4.68</td>
<td align="center">29.07 &#xb1; 6.13</td>
<td align="center">0.775</td>
</tr>
<tr>
<td align="left">MoCA</td>
<td align="center">18.64 &#xb1; 3.69</td>
<td align="center">19.95 &#xb1; 3.75</td>
<td align="center">19.61 &#xb1; 3.79</td>
<td align="center">0.446</td>
</tr>
<tr>
<td align="left">IADL</td>
<td align="center">20.52 &#xb1; 0.96</td>
<td align="center">20.79 &#xb1; 0.53</td>
<td align="center">20.56 &#xb1; 0.98</td>
<td align="center">0.428</td>
</tr>
<tr>
<td align="left">GDS-15</td>
<td align="center">2.50 &#xb1; 1.58</td>
<td align="center">2.52 &#xb1; 1.12</td>
<td align="center">2.33 &#xb1; 1.45</td>
<td align="center">0.899</td>
</tr>
<tr>
<td align="left">Years of education</td>
<td align="center">7.5 &#xb1; 3.2</td>
<td align="center">8.6 &#xb1; 3.8</td>
<td align="center">7.6 &#xb1; 4.7</td>
<td align="center">0.659</td>
</tr>
<tr>
<td colspan="5" align="left">Medical History</td>
</tr>
<tr>
<td align="left">Diabetes</td>
<td align="center">13 (46%)</td>
<td align="center">08 (40%)</td>
<td align="center">09 (50%)</td>
<td align="center">0.624</td>
</tr>
<tr>
<td align="left">Hypertension</td>
<td align="center">18 (64%)</td>
<td align="center">13 (65%)</td>
<td align="center">13 (72%)</td>
<td align="center">0.738</td>
</tr>
<tr>
<td align="left">Dyslipidemia</td>
<td align="center">20 (71%)</td>
<td align="center">12 (60%)</td>
<td align="center">13 (72%)</td>
<td align="center">0.270</td>
</tr>
<tr>
<td colspan="5" align="left">Medications</td>
</tr>
<tr>
<td align="left">0</td>
<td align="center">03 (10%)</td>
<td align="center">03 (13%)</td>
<td align="center">00 (00%)</td>
<td align="center">0.180</td>
</tr>
<tr>
<td align="left">&#x2264; 3</td>
<td align="center">15 (53%)</td>
<td align="center">12 (54%)</td>
<td align="center">7 (38%)</td>
<td align="center">0.560</td>
</tr>
<tr>
<td align="left">&#x3e; 3</td>
<td align="center">10 (35%)</td>
<td align="center">07 (31%)</td>
<td align="center">11 (61%)</td>
<td align="center">0.151</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn>
<p>Note: Values are presented as mean and standard deviation (M &#xb1; SD). MoCA, Montreal Cognitive Assessment; GDS15 &#x2013; Geriatric Depression Scale; IADL, Instrumental Activities of Daily Living; BMI, Body Mass Index. One-way ANOVA.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<p>In FT, the volume-load demonstrates that the training load was progressive throughout the 16 weeks (<xref ref-type="fig" rid="F3">Figure 3A</xref>). Conversely, the monitoring of HRres demonstrates that an intensity between 50% and 80% was maintained during the AT sessions (<xref ref-type="fig" rid="F3">Figure 3B</xref>).</p>
<fig id="F3" position="float">
<label>FIGURE 3</label>
<caption>
<p>Quantification of training load and monitoring of training intensity. <bold>(A)</bold> Volume load (repetitions x sets x intensity); <bold>(B)</bold> Mean and standard deviation of heart rate reserve. MOB: Mobility; CON: Continuous; RHY: Rhythmic; INT: Interval.</p>
</caption>
<graphic xlink:href="fphys-16-1638590-g003.tif">
<alt-text content-type="machine-generated">A line graph on the left shows volume load in arbitrary units increasing from week 1 to week 16, with error bars. A bar chart on the right depicts heart rate reserve percentages for four groups: MOB, CON, RHY, and INT, each with error bars.</alt-text>
</graphic>
</fig>
<p>Following the 16-week intervention period, we observed a significant group&#x2a;time interaction for cognitive status (MoCA) (F (2, 65) &#x3d; 3.16; &#x3b7;<sup>2</sup> &#x3d; 0.010; p &#x3d; 0.035), with no significant group effect (F (2, 65) &#x3d; 0.910; &#x3b7;<sup>2</sup> &#x3d; 0.020; p &#x3d; 0.408) but a significant time effect (F (2, 65) &#x3d; 89.68; &#x3b7;<sup>2</sup> &#x3d; 0.143; p &#x2264; 0.001). Upon comparing time points, we detected a large effect size increase in both the FT and AT groups compared to baseline values (FT: <italic>d</italic> &#x3d; 0.99; p &#x2264; 0.001/AT: <italic>d</italic> &#x3d; 0.97; p &#x2264; 0.001). However, the CG showed no significant difference despite a moderate effect size (<italic>d</italic> &#x3d; 0.51; p &#x3e; 0.05) (<xref ref-type="fig" rid="F4">Figure 4A</xref>).</p>
<fig id="F4" position="float">
<label>FIGURE 4</label>
<caption>
<p>Effects of functional and aerobic training on cognitive status <bold>(A)</bold> and plasma BDNF concentration <bold>(B)</bold> in older women with Mild Cognitive Impairment. FT: Functional Training; AT: Aerobic Training; CG: Control Group.</p>
</caption>
<graphic xlink:href="fphys-16-1638590-g004.tif">
<alt-text content-type="machine-generated">Bar graphs display MoCA and BDNF scores pre- and post-intervention for FT, AT, and CG groups. The top graph shows increasing MoCA scores with large effect sizes for FT and AT. The bottom graph depicts increased BDNF levels post-intervention with notable effect sizes for FT and AT, but less change in CG. Data points are connected, highlighting individual changes.</alt-text>
</graphic>
</fig>
<p>Regarding the peripheral quantification of BDNF, we found a significant group&#x2a;time interaction (F (2, 37) &#x3d; 9.07; &#x3b7;<sup>2</sup> &#x3d; 0.102; p &#x2264; 0.001), with no significant group effect (F (2, 37) &#x3d; 0.518; &#x3b7;<sup>2</sup> &#x3d; 0.018; p &#x3d; 0.606) and no significant time effect (F (2, 37) &#x3d; 0.079; &#x3b7;<sup>2</sup> &#x3d; 0.002; p &#x3d; 0.790). Upon further exploration of the results, we only detected a large effect size increase in the FT group compared to baseline values (<italic>d</italic> &#x3d; 0.95; p &#x3c; 0.011). Furthermore, when comparing post-test time points, we observed a difference with a large effect size between the FT and CG groups (<italic>d</italic> &#x3d; 0.96; p &#x3d; 0.026) (<xref ref-type="fig" rid="F4">Figure 4B</xref>).</p>
<p>Regarding cognitive function, for which the analyzed variables may influence performance, we observed no significant differences between the groups for short-term memory (DSF), working memory (DSB), semantic memory (FV_QAni), and executive function (FV_QAgru). However, FT showed an improvement with a moderate to large effect size compared to baseline values in semantic memory (<italic>d</italic> &#x3d; 0.95; p &#x3c; 0.001) and executive function (<italic>d</italic> &#x3d; 0.63; p &#x3d; 0.043). In contrast, AT demonstrated an improvement with a large effect size compared to baseline values only for semantic memory (<italic>d</italic> &#x3d; 0.97; p &#x3c; 0.001). The CG showed no adaptations for any of the cognitive variables (<xref ref-type="table" rid="T4">Table 4</xref>).</p>
<table-wrap id="T4" position="float">
<label>TABLE 4</label>
<caption>
<p>Effects of functional and aerobic training on short-term memory, working memory, semantic memory, and executive function in older women with mild cognitive impairment.</p>
</caption>
<table>
<thead valign="top">
<tr>
<th align="center">Variables<break/>
<italic>Assessment Time Points</italic>
</th>
<th align="center">FT (n &#x3d; 28)</th>
<th align="center">AT (n &#x3d; 22)</th>
<th align="center">CG (n &#x3d; 18)</th>
<th align="center">
<italic>p-value</italic>
<break/>Interaction<break/>Group-time</th>
<th align="center">FT vs<italic>.</italic> CG</th>
<th align="center">At vs<italic>.</italic> CG</th>
<th align="center">FT vs<italic>.</italic> AT</th>
</tr>
</thead>
<tbody valign="top">
<tr>
<td colspan="8" align="left">Digit Span - Forward (DSF)</td>
</tr>
<tr>
<td align="left">
<italic>Baseline (pre)</italic>
</td>
<td align="left">16.68 &#xb1; 3.97</td>
<td align="left">16.00 &#xb1; 3.45</td>
<td align="left">16.06 &#xb1; 2.99</td>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
</tr>
<tr>
<td align="left">
<italic>Post_16_week</italic>
</td>
<td align="left">16.50 &#xb1; 4.38</td>
<td align="left">17.64 &#xb1; 4.11</td>
<td align="left">14.88 &#xb1; 3.12</td>
<td align="center">0.009</td>
<td align="center">1.00</td>
<td align="center">1.00</td>
<td align="center">1.00</td>
</tr>
<tr>
<td align="left">
<italic>&#x394;% - ES</italic>
</td>
<td align="left">&#x2212;1.08 &#x2013; 0.05<sup>T</sup>
</td>
<td align="left">&#x2b;10.25&#x2013;0.43<sup>S</sup>
</td>
<td align="left">&#x2212;7.35 &#x2013; 0.39<sup>S</sup>
</td>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
</tr>
<tr>
<td align="left">
<italic>CI (95%)</italic>
</td>
<td align="left">(15.05&#x2013;18.15)</td>
<td align="left">(15.05&#x2013;18.60)</td>
<td align="left">(14.90&#x2013;18.80)</td>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
</tr>
<tr>
<td colspan="8" align="left">Digit Span &#x2013; Backward (DSB)</td>
</tr>
<tr>
<td align="left">
<italic>Baseline (pre)</italic>
</td>
<td align="left">6.89 &#xb1; 2.48</td>
<td align="left">7.14 &#xb1; 3.18</td>
<td align="left">6.89 &#xb1; 3.08</td>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
</tr>
<tr>
<td align="left">
<italic>Post_16_week</italic>
</td>
<td align="left">8.00 &#xb1; 2.68</td>
<td align="left">8.41 &#xb1; 3.36</td>
<td align="left">7.22 &#xb1; 2.98</td>
<td align="center">0.424</td>
<td align="center">0.82</td>
<td align="center">1.00</td>
<td align="center">1.00</td>
</tr>
<tr>
<td align="left">
<italic>&#x394;% - ES</italic>
</td>
<td align="left">&#x2b;16.11&#x2013;0.43<sup>S</sup>
</td>
<td align="left">&#x2b;17.79&#x2013;0.39<sup>S</sup>
</td>
<td align="left">&#x2b;4.78&#x2013;0.11<sup>T</sup>
</td>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
</tr>
<tr>
<td align="left">
<italic>CI (95%)</italic>
</td>
<td align="left">(6.33&#x2013;8.55)</td>
<td align="left">(6.52&#x2013;9.02)</td>
<td align="left">(5.67&#x2013;8.44)</td>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
</tr>
<tr>
<td colspan="8" align="left">Verbal Fluency &#x2013; category animals (number of animals) &#x2013; VF_Nani</td>
</tr>
<tr>
<td align="left">
<italic>Baseline (pre)</italic>
</td>
<td align="left">13.64 &#xb1; 4.04</td>
<td align="left">14.73 &#xb1; 4.70</td>
<td align="left">14.11 &#xb1; 4.68</td>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
</tr>
<tr>
<td align="left">
<italic>Post_16_week</italic>
</td>
<td align="left">17.57 &#xb1; 4.20&#x2a;</td>
<td align="left">19.14 &#xb1; 4.37&#x2a;</td>
<td align="left">16.06 &#xb1; 4.37</td>
<td align="center">0.173</td>
<td align="center">1.00</td>
<td align="center">1.00</td>
<td align="center">1.00</td>
</tr>
<tr>
<td align="left">
<italic>&#x394;% - ES</italic>
</td>
<td align="left">&#x2b;28.81&#x2013;0.95<sup>L</sup>
</td>
<td align="left">&#x2b;29.94&#x2013;0.97<sup>L</sup>
</td>
<td align="left">&#x2b;13.82&#x2013;0.43<sup>S</sup>
</td>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
</tr>
<tr>
<td align="left">
<italic>CI (95%)</italic>
</td>
<td align="left">(13.95&#x2013;17.30)</td>
<td align="left">(15.00&#x2013;18.85)</td>
<td align="left">(13.90&#x2013;18.15)</td>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
</tr>
<tr>
<td colspan="8" align="left">Verbal Fluency &#x2013; category animals (number of clusters) &#x2013; VF_NClus</td>
</tr>
<tr>
<td align="left">
<italic>Baseline (pre)</italic>
</td>
<td align="left">1,39 &#xb1; 1.34</td>
<td align="left">1.68 &#xb1; 1.32</td>
<td align="left">1.50 &#xb1; 1.34</td>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
</tr>
<tr>
<td align="left">
<italic>Post_16_week</italic>
</td>
<td align="left">2.25 &#xb1; 1.40&#x2a;</td>
<td align="left">2.32 &#xb1; 1.46</td>
<td align="left">2.06 &#xb1; 1.21</td>
<td align="center">0.822</td>
<td align="center">1.00</td>
<td align="center">1.00</td>
<td align="center">1.00</td>
</tr>
<tr>
<td align="left">
<italic>&#x394;% - ES</italic>
</td>
<td align="left">&#x2b;65.25&#x2013;0.63<sup>M</sup>
</td>
<td align="left">&#x2b;38.10&#x2013;0.46<sup>S</sup>
</td>
<td align="left">&#x2b;37.33&#x2013;0.44<sup>S</sup>
</td>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
</tr>
<tr>
<td align="left">
<italic>CI (95%)</italic>
</td>
<td align="left">(1.31&#x2013;2.33)</td>
<td align="left">(1.41&#x2013;2.57)</td>
<td align="left">(1.13&#x2013;2.41)</td>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn>
<p>Note: Values are presented as mean and standard deviation (M &#xb1; SD); p &#x2264; 0.05 (pre/post). &#x394;%: Percentage change between Baseline (pre) and Post_16. wks: Weeks. ES: Effect Size (<sup>T</sup>Trivial: 0.0-0.19; <sup>S</sup>Small: 0.2-0.49; <sup>M</sup>Moderate: 0.5-0.79; <sup>L</sup>Large: 0.8-1.32; <sup>VL</sup>Very, Large: &#x3e;1.33). CI &#x2013; Confidence Interval.</p>
</fn>
<fn>
<p>The &#x2a; indicates the statistical difference when the p-value &#x2264; 0.05 in the pre- and post-values. The # indicates the statistical difference between the post-time points.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<p>Regarding cardiorespiratory fitness (6MWT), we observed differences between the groups (FT/CG: p &#x3d; 0.008; AT/CG: p &#x3d; 0.041). When compared to baseline, we found an increase in the distance covered for both the FT and AT groups with a moderate effect size (FT: <italic>d</italic> &#x3d; 0.66; p &#x3d; 0.002/AT: <italic>d</italic> &#x3d; 0.56; p &#x3d; 0.036). In the CG, we observed a non-significant reduction with a small effect size (<italic>d</italic> &#x3d; 0.35; p &#x3d; 0.464). Regarding upper limb strength (ULS), we observed no significant differences between the groups. However, when considering changes from baseline, only the FT group showed an increase in handgrip strength in kilogram-force with a moderate effect size (<italic>d</italic> &#x3d; 0.64; p &#x2264; 0.001) (<xref ref-type="table" rid="T5">Table 5</xref>).</p>
<table-wrap id="T5" position="float">
<label>TABLE 5</label>
<caption>
<p>Effects of Functional and Aerobic Training on Functional Fitness for activities of daily living in older women with mild cognitive impairment.</p>
</caption>
<table>
<thead valign="top">
<tr>
<th align="center">Variables<break/>
<italic>Assessment Time Points</italic>
</th>
<th align="center">FT (n &#x3d; 28)</th>
<th align="center">AT (n &#x3d; 22)</th>
<th align="center">CG (n &#x3d; 18)</th>
<th align="center">
<italic>p-value</italic>
<break/>Interaction<break/>Group-time</th>
<th align="center">FT vs<italic>.</italic> CG</th>
<th align="center">At vs<italic>.</italic> CG</th>
<th align="center">FT vs<italic>.</italic> AT</th>
</tr>
</thead>
<tbody valign="top">
<tr>
<td colspan="8" align="left">Six-Minute Walk Test - 6MWT (meters)</td>
</tr>
<tr>
<td align="left">
<italic>Baseline (pre)</italic>
</td>
<td align="left">481.27 &#xb1; 61.56</td>
<td align="left">479.43 &#xb1; 73.31</td>
<td align="left">474.94 &#xb1; 78.16</td>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
</tr>
<tr>
<td align="left">
<italic>Post_16_week</italic>
</td>
<td align="left">525.37 &#xb1; 71.77&#x2a;</td>
<td align="left">517.05 &#xb1; 58.98&#x2a;</td>
<td align="left">445.87 &#xb1; 85.58</td>
<td align="center">0.001</td>
<td align="center">0.008</td>
<td align="center">0.041</td>
<td align="center">1.00</td>
</tr>
<tr>
<td align="left">
<italic>&#x394;% - ES</italic>
</td>
<td align="left">&#x2b;9.16&#x2013;0.66<sup>M</sup>
</td>
<td align="left">&#x2b;7.85&#x2013;0.56<sup>M</sup>
</td>
<td align="left">&#x2212;6.12 &#x2013; 0.35<sup>S</sup>
</td>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
</tr>
<tr>
<td align="left">
<italic>CI (95%)</italic>
</td>
<td align="left">(476.00 &#x2013; 530.50)</td>
<td align="left">(468.00&#x2013;528.50)</td>
<td align="left">(427.00&#x2013;494.00)</td>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
</tr>
<tr>
<td colspan="8" align="left">Five Times Sit-to-Stand Test &#x2013; FTSST (seconds)</td>
</tr>
<tr>
<td align="left">
<italic>Baseline (pre)</italic>
</td>
<td align="left">8.26 &#xb1; 1.97</td>
<td align="left">8.00 &#xb1; 1.71</td>
<td align="left">7.91 &#xb1; 2.37</td>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
</tr>
<tr>
<td align="left">
<italic>Post_16_week</italic>
</td>
<td align="left">7.12 &#xb1; 1.77&#x2a;</td>
<td align="left">7.33 &#xb1; 1.55&#x2a;</td>
<td align="left">8.14 &#xb1; 2.26</td>
<td align="center">0.001</td>
<td align="center">1.00</td>
<td align="center">1.00</td>
<td align="center">1.00</td>
</tr>
<tr>
<td align="left">
<italic>&#x394;% - ES</italic>
</td>
<td align="left">&#x2b;13.80&#x2013;0.61<sup>M</sup>
</td>
<td align="left">&#x2b;8.37&#x2013;0.41<sup>S</sup>
</td>
<td align="left">&#x2212;8.14 &#x2013; 0.10<sup>T</sup>
</td>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
</tr>
<tr>
<td align="left">
<italic>CI (95%)</italic>
</td>
<td align="left">(6.97&#x2013;8.42)</td>
<td align="left">(6.85&#x2013;8.49)</td>
<td align="left">(7.12&#x2013;8.93)</td>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
</tr>
<tr>
<td colspan="8" align="left">Floor Rise Test &#x2013; FRT (seconds)</td>
</tr>
<tr>
<td align="left">
<italic>Baseline (pr&#xe9;)</italic>
</td>
<td align="left">3.81 &#xb1; 0.96</td>
<td align="left">3.91 &#xb1; 1.00</td>
<td align="left">3.77 &#xb1; 0.86</td>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
</tr>
<tr>
<td align="left">
<italic>P&#xf3;s_16_sem</italic>
</td>
<td align="left">3.03 &#xb1; 0.60&#x2a;</td>
<td align="left">3.33 &#xb1; 0.97&#x2a;</td>
<td align="left">4.04 &#xb1; 0.97</td>
<td align="center">0.001</td>
<td align="center">0.003</td>
<td align="center">0.161</td>
<td align="center">1.00</td>
</tr>
<tr>
<td align="left">
<italic>&#x394;% - ES</italic>
</td>
<td align="left">&#x2b;20.47&#x2013;0.97<sup>L</sup>
</td>
<td align="left">&#x2b;14.83&#x2013;0.59<sup>M</sup>
</td>
<td align="left">&#x2212;7.16 &#x2013; 0.29<sup>S</sup>
</td>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
</tr>
<tr>
<td align="left">
<italic>CI (95%)</italic>
</td>
<td align="left">(3.08&#x2013;3.76)</td>
<td align="left">(3.23&#x2013;4.01)</td>
<td align="left">(3.48&#x2013;4.33)</td>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
</tr>
<tr>
<td colspan="8" align="left">Timed Up and Go &#x2013; TUG (seconds)</td>
</tr>
<tr>
<td align="left">
<italic>Baseline (pre)</italic>
</td>
<td align="left">7.57 &#xb1; 1.00</td>
<td align="left">7.36 &#xb1; 0.72</td>
<td align="left">7.52 &#xb1; 0.91</td>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
</tr>
<tr>
<td align="left">
<italic>Post_16_week</italic>
</td>
<td align="left">6.92 &#xb1; 0.88&#x2a;</td>
<td align="left">6.95 &#xb1; 0.80&#x2a;</td>
<td align="left">7.68 &#xb1; 1.07</td>
<td align="center">0.001</td>
<td align="center">0.114</td>
<td align="center">0.210</td>
<td align="center">1.00</td>
</tr>
<tr>
<td align="left">
<italic>&#x394;% - ES</italic>
</td>
<td align="left">&#x2b;8.58&#x2013;0.69<sup>M</sup>
</td>
<td align="left">&#x2b;5.57&#x2013;0.54<sup>M</sup>
</td>
<td align="left">&#x2212;2.12 &#x2013; 0.16<sup>T</sup>
</td>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
</tr>
<tr>
<td align="left">
<italic>CI (95%)</italic>
</td>
<td align="left">(6.91&#x2013;7.59)</td>
<td align="left">(6.77&#x2013;7.54)</td>
<td align="left">(7.18&#x2013;8.03)</td>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
</tr>
<tr>
<td colspan="8" align="left">10-m Walk Test - 10MWT (seconds)</td>
</tr>
<tr>
<td align="left">
<italic>Baseline (pre)</italic>
</td>
<td align="left">5.17 &#xb1; 0.64</td>
<td align="left">5.21 &#xb1; 0.62</td>
<td align="left">5.32 &#xb1; 0.64</td>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
</tr>
<tr>
<td align="left">
<italic>Post_16_week</italic>
</td>
<td align="left">4.85 &#xb1; 0.50&#x2a;</td>
<td align="left">4.85 &#xb1; 0.44&#x2a;</td>
<td align="left">5.23 &#xb1; 0.54</td>
<td align="center">0.093</td>
<td align="center">0.079</td>
<td align="center">0.232</td>
<td align="center">1.00</td>
</tr>
<tr>
<td align="left">
<italic>&#x394;% - ES</italic>
</td>
<td align="left">&#x2b;6.19&#x2013;0.56<sup>M</sup>
</td>
<td align="left">&#x2b;6.91&#x2013;0.67<sup>M</sup>
</td>
<td align="left">&#x2b;1.69&#x2013;0.15<sup>T</sup>
</td>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
</tr>
<tr>
<td align="left">
<italic>CI (95%)</italic>
</td>
<td align="left">(4.78&#x2013;5.22)</td>
<td align="left">(4.80&#x2013;5.27)</td>
<td align="left">(5.01&#x2013;5.54)</td>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
</tr>
<tr>
<td colspan="8" align="left">Gallon Jug Shelf Transfer &#x2013; GJST (seconds)</td>
</tr>
<tr>
<td align="left">
<italic>Baseline (pre)</italic>
</td>
<td align="left">10.34 &#xb1; 1.06</td>
<td align="left">10.56 &#xb1; 0.97</td>
<td align="left">10.87 &#xb1; 1.29</td>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
</tr>
<tr>
<td align="left">
<italic>Post_16_week</italic>
</td>
<td align="left">9.74 &#xb1; 1.00&#x2a;</td>
<td align="left">10.06 &#xb1; 1.01</td>
<td align="left">10.97 &#xb1; 1.34</td>
<td align="center">0.018</td>
<td align="center">0.007</td>
<td align="center">0.176</td>
<td align="center">1.00</td>
</tr>
<tr>
<td align="left">
<italic>&#x394;% - ES</italic>
</td>
<td align="left">&#x2b;5.80&#x2013;0.58<sup>M</sup>
</td>
<td align="left">&#x2b;4.73&#x2013;0.51<sup>M</sup>
</td>
<td align="left">&#x2212;0.91 &#x2013; 0.04<sup>T</sup>
</td>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
</tr>
<tr>
<td align="left">
<italic>CI (95%)</italic>
</td>
<td align="left">(9.60&#x2013;10.50)</td>
<td align="left">(9.81&#x2013;10.80)</td>
<td align="left">(10.36&#x2013;11.50)</td>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
</tr>
<tr>
<td colspan="8" align="left">Dressing on and taking off a t-shirt &#x2013; DTTS (seconds)</td>
</tr>
<tr>
<td align="left">
<italic>Baseline (pre)</italic>
</td>
<td align="left">13.65 &#xb1; 2.72</td>
<td align="left">13.21 &#xb1; 2.39</td>
<td align="left">13.31 &#xb1; 1.99</td>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
</tr>
<tr>
<td align="left">
<italic>Post_16_week</italic>
</td>
<td align="left">12.00 &#xb1; 2.03&#x2a;</td>
<td align="left">12.64 &#xb1; 2.59</td>
<td align="left">13.19 &#xb1; 1.97</td>
<td align="center">0.003</td>
<td align="center">1.00</td>
<td align="center">1.00</td>
<td align="center">1.00</td>
</tr>
<tr>
<td align="left">
<italic>&#x394;% - ES</italic>
</td>
<td align="left">&#x2b;12.09&#x2013;0.69 <sup>M</sup>
</td>
<td align="left">&#x2b;4.31&#x2013;0.23 <sup>S</sup>
</td>
<td align="left">&#x2b;0.90&#x2013;0.06 <sup>T</sup>
</td>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
</tr>
<tr>
<td align="left">
<italic>CI (95%)</italic>
</td>
<td align="left">(11.95&#x2013;13.70)</td>
<td align="left">(11.95&#x2013;13.95)</td>
<td align="left">(12.20&#x2013;14.35)</td>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
</tr>
<tr>
<td colspan="8" align="left">Handgrip Strength &#x2013; HGS (kilogram)</td>
</tr>
<tr>
<td align="left">
<italic>Baseline (pre)</italic>
</td>
<td align="left">22.20 &#xb1; 3.93</td>
<td align="left">21.79 &#xb1; 4.67</td>
<td align="left">22.76 &#xb1; 4.41</td>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
</tr>
<tr>
<td align="left">
<italic>Post_16_week</italic>
</td>
<td align="left">24.81 &#xb1; 4.21&#x2a;</td>
<td align="left">22.66 &#xb1; 3.98</td>
<td align="left">22.52 &#xb1; 4.21</td>
<td align="center">0.001</td>
<td align="center">1.00</td>
<td align="center">1.00</td>
<td align="center">1.00</td>
</tr>
<tr>
<td align="left">
<italic>&#x394;% - ES</italic>
</td>
<td align="left">&#x2b;11.75&#x2013;0.64<sup>M</sup>
</td>
<td align="left">&#x2b;3.99&#x2013;0.20<sup>S</sup>
</td>
<td align="left">&#x2212;1.05 &#x2013; 0.05<sup>T</sup>
</td>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
</tr>
<tr>
<td align="left">
<italic>CI (95%)</italic>
</td>
<td align="left">(22.05&#x2013;25.20)</td>
<td align="left">(20.45&#x2013;24.00)</td>
<td align="left">(20.65&#x2013;24.65)</td>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn>
<p>Note: Values are presented as mean and standard deviation (M &#xb1; SD); p &#x2264; 0.05 (pre/post). &#x394;%: Percentage change between Baseline (pre) and Post_16 (% change &#x3d; 100&#xd7;final&#x2212;initial&#x2223;initial&#x2223;% change &#x3d; 100&#xd7;&#x2223;initial&#x2223;final&#x2212;initial). wks: Weeks. &#x2b;: performance improvement. -: performance reduction. ES: Effect Size (<sup>T</sup>Trivial: 0.0-0.19; <sup>S</sup>Small: 0.2-0.49; <sup>M</sup>Moderate: 0.5-0.79; <sup>L</sup>Large: 0.8-1.32; <sup>VL</sup>Very, Large: &#x3e;1.33). CI &#x2013; Confidence Interval.</p>
</fn>
<fn>
<p>The &#x2a; indicates the statistical difference when the p-value &#x2264; 0.05 in the pre- and post-values. The # indicates the statistical difference between the post-time points.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<p>For the tests assessing functional fitness involving the stand up ability to rise from a chair (FTSST) and gait speed (GS), we observed a difference between the groups only for GS (FT/CG: <italic>d</italic> &#x3d; 1.25; p &#x3d; 0.003). When compared to baseline values, both intervention groups improved the time to complete the task in the FTSST (FT: <italic>d</italic> &#x3d; 0.61; p &#x2264; 0.001/AT: <italic>d</italic> &#x3d; 0.41; p &#x3d; 0.021) and GS (FT: <italic>d</italic> &#x3d; 0.97; p &#x2264; 0.001/AT: <italic>d</italic> &#x3d; 0.59; p &#x2264; 0.001), with effect sizes ranging from small to large. The CG showed no adaptations following the intervention (<xref ref-type="table" rid="T5">Table 5</xref>).</p>
<p>Consistently, regarding walking ability, TUG and 10MWT, we observed no significant differences between the groups. When compared to baseline values, both intervention groups reduced the time to complete the task in the TUG (FT: <italic>d</italic> &#x3d; 0.69; p &#x2264; 0.001/AT: <italic>d</italic> &#x3d; 0.54; p &#x3d; 0.022) and similarly for the 10MWT (FT: <italic>d</italic> &#x3d; 0.56; p &#x2264; 0.001/AT: <italic>d</italic> &#x3d; 0.67; p &#x3d; 0.011), with moderate effect sizes. The CG showed no adaptations following the intervention (<xref ref-type="table" rid="T5">Table 5</xref>).</p>
<p>Finally, regarding the tests related to dexterity, GJST and DTTS, we observed differences between the groups only for GJST (FT/CG: <italic>d</italic> &#x3d; 1.04; p &#x3d; 0.007) with a large effect size. When compared to baseline values, only the FT group reduced the time for task completion in the GJST (<italic>d</italic> &#x3d; 0.58; p &#x3d; 0.004) and similarly for the DTTS (<italic>d</italic> &#x3d; 0.69; p &#x2264; 0.001), both with a moderate effect size. The AT and CG showed no adaptations following the intervention (<xref ref-type="table" rid="T5">Table 5</xref>).</p>
</sec>
<sec id="s2-6">
<title>2.6 Discussion</title>
<p>The present study aimed to evaluate the effects of 16 weeks of FT and AT on cognitive function, functional fitness, and serum BDNF levels in older women with mild cognitive impairment. Our main finding was that both training protocols promoted consistent improvements in cognitive state and semantic memory. However, only FT improved executive function and increased peripheral BDNF concentration. Regarding functional fitness, we observed larger effect sizes in the ability to stand up and in tasks involving manual dexterity, as well as specifically in handgrip strength, thus confirming our initial hypothesis.</p>
<p>The multisystem adaptations resulting from the combination of multicomponent stimuli with movement specificity for daily activities, together with the individualization and progression of the training load, have been previously evidenced by our group (<xref ref-type="bibr" rid="B67">Pantoja-Cardoso et al., 2023</xref>; <xref ref-type="bibr" rid="B95">Vasconcelos et al., 2022</xref>; <xref ref-type="bibr" rid="B17">Carrasco-Poyatos et al., 2019</xref>). The present study provides a consistent investigation into the effects of physical training on cognitive function and quantification of the training load, which suggests the absence of adaptive stagnation throughout the intervention.</p>
<p>Regarding cognitive status, significant effects with a large effect size (FT: d &#x3d; 0.99; AT: d &#x3d; 0.97) were observed for both training protocols. These findings likely stem from the positive adaptation of cardiorespiratory capacity, which is directly linked to enhanced cerebral vascularization (<xref ref-type="bibr" rid="B29">Ferrer-Uris et al., 2022</xref>; <xref ref-type="bibr" rid="B25">Dupuy et al., 2015</xref>; <xref ref-type="bibr" rid="B92">Tsai et al., 2014</xref>). This adaptation promotes increased connectivity between brain regions (<xref ref-type="bibr" rid="B40">Holzschneider et al., 2012</xref>), enhancing learning (<xref ref-type="bibr" rid="B29">Ferrer-Uris et al., 2022</xref>) and attenuate cognitive decline (<xref ref-type="bibr" rid="B39">Hoffmann et al., 2016</xref>). Our results are consistent with previous studies in older adults with MCI (<xref ref-type="bibr" rid="B97">Vega-&#xc1;vila et al., 2022</xref>; <xref ref-type="bibr" rid="B108">Yong et al., 2021</xref>). Furthermore, improvements caused by the FT protocol may be related to visuospatial stimuli (<xref ref-type="bibr" rid="B51">Lee et al., 2024</xref>) and the motor complexity of the exercises (<xref ref-type="bibr" rid="B30">Fontes et al., 2020</xref>). These stimuli may positively favor the availability of oxygen and nutrients to neural cells (<xref ref-type="bibr" rid="B19">Crichton et al., 2014</xref>), with continuous activation of areas related to movement planning and execution (<xref ref-type="bibr" rid="B51">Lee et al., 2024</xref>).</p>
<p>Executive function is crucial for problem-solving and the planning of cognitive or motor tasks. It comprises working memory, cognitive flexibility, and inhibitory control, all of which independently contribute to executive function (<xref ref-type="bibr" rid="B23">Diamond, 2013</xref>). Only the FT protocol showed significant effects on executive function with a moderate effect size (FT: d &#x3d; 0.63), which can be attributed to the motor demands of the neuromuscular-dominant block, combined with the high volume of multi-joint and multi-planar exercises. This requires more planning when compared to the rhythmic movements used in the AT protocol with a small effect size (AT: d &#x3d; 0.46) (<xref ref-type="bibr" rid="B77">La Scala Teixeira et al., 2019</xref>). Consequently, greater activation of areas responsible for motor planning, such as the supplementary motor area, premotor cortex, cerebellum, and basal ganglia, is expected (<xref ref-type="bibr" rid="B99">Vints et al., 2024</xref>; <xref ref-type="bibr" rid="B47">Ku&#x161;leikien et al., 2025</xref>; <xref ref-type="bibr" rid="B12">Barha et al., 2022</xref>).</p>
<p>Specifically, regarding short-term memory (DSF) (FT: d &#x3d; 0.05; AT: d &#x3d; 0.43) and working memory (DSB) (FT: d &#x3d; 0.43; AT: d &#x3d; 0.39), no significant adaptations were observed for any of the groups, with effect sizes ranging from trivial to small. The ineffectiveness of both FT and AT may stem from the absence of specific short-term memory stimuli (2&#x2013;10 min) for subsequent recall and manipulation. Possibly, the addition of motor-cognitive dual tasks could provide effective adaptations for working memory (<xref ref-type="bibr" rid="B64">Norouzi et al., 2019</xref>). This is because the inclusion of dual tasks will generate greater activation of the prefrontal cortex, which is related to improved short-term and working memory performance (<xref ref-type="bibr" rid="B57">Marvel et al., 2019</xref>). Still, some studies that did not use dual tasks found effects with longer intervention durations, as well as the short duration of the current intervention, given that these effects have been observed in studies lasting 24 weeks (<xref ref-type="bibr" rid="B86">Spruill, 2010</xref>; <xref ref-type="bibr" rid="B114">Zhidong et al., 2021</xref>).</p>
<p>In terms of semantic memory, both groups showed substantial improvement. These adaptations may be attributed to the moderate to high intensity of the sessions, which suggests an increase in cortical vascularization (<xref ref-type="bibr" rid="B66">O&#x2019;Callaghan et al., 2020</xref>), followed by greater excitability of prefrontal and temporal regions (<xref ref-type="bibr" rid="B62">Nocera et al., 2017</xref>) particularly the hippocampus (<xref ref-type="bibr" rid="B72">Rivas-Campo et al., 2023</xref>), contributing to the reorganization of neural circuits (<xref ref-type="bibr" rid="B85">Smith et al., 2013</xref>). Both findings are consistent with the existing literature, demonstrating that multicomponent and aerobic stimuli can promote adaptations in semantic memory (<xref ref-type="bibr" rid="B72">Rivas-Campo et al., 2023</xref>).</p>
<p>Pertaining to peripheral BDNF concentration, only the FT protocol showed significant increases compared to both baseline values, with a large effect size (d &#x3d; 0.95) and the CG (d &#x3d; 0.96). BDNF is essential for neural plasticity and is highly expressed in brain areas involved in cognitive processing. BDNF improves memory storage and dendritic spine plasticity. The action of BDNF is primarily mediated by the tyrosine kinase receptor B (TrkB) and initiates signaling pathways that promote neuroprotection (<xref ref-type="bibr" rid="B102">Wang et al., 2020</xref>; <xref ref-type="bibr" rid="B113">Zhao et al., 2022</xref>). Cognitive function and BDNF are modulated by the combination of cardiorespiratory, neuromuscular, and motor stimuli (<xref ref-type="bibr" rid="B98">Venegas-Sanabria et al., 2022</xref>; <xref ref-type="bibr" rid="B105">Yan et al., 2023</xref>).</p>
<p>Furthermore, at the peripheral level, maintaining the motor complexity in multi-joint and multi-planar exercises likely exerts greater neuromuscular activation, improving stability between the neuromuscular junction and the motor endplate (<xref ref-type="bibr" rid="B79">Sepulveda-Loyola et al., 2025</xref>). These alterations may favor an increase in BDNF synthesis within skeletal muscle and its subsequent release into the bloodstream (<xref ref-type="bibr" rid="B43">Imaizumi et al., 2025</xref>).</p>
<p>It has been demonstrated that aerobic exercise significantly increases serum BDNF levels, and a significant relationship between BDNF levels and physical activity levels has been reported (<xref ref-type="bibr" rid="B18">Coelho et al., 2014</xref>). The lack of response in AT may be related to the maintenance of the training load throughout the intervention period, as progressively applied intensity in aerobic exercise influences the modulation of BDNF concentration (<xref ref-type="bibr" rid="B42">Huang et al., 2024</xref>; <xref ref-type="bibr" rid="B11">Babaei et al., 2013</xref>). Additionally, genetic factors that can negatively impact BDNF synthesis, such as the Val66Met gene polymorphism and APOE&#x3b5;4 (&#x3b5;4), were not identified in the groups (<xref ref-type="bibr" rid="B27">Enette et al., 2020</xref>; <xref ref-type="bibr" rid="B52">Lemos et al., 2016</xref>; <xref ref-type="bibr" rid="B2">Allard et al., 2017</xref>). This may have affected the synthesis and increased peripheral BDNF concentration in AT.</p>
<p>For cardiorespiratory fitness, both groups showed moderate improvement (FT: d &#x3d; 0.66; AT: d &#x3d; 0.56). In fact, it is widely known that AT applied at moderate to high intensity promotes cardiovascular and respiratory adaptations that favor the enhancement of this physical capacity (<xref ref-type="bibr" rid="B1">Alemayehu and Teferi, 2023</xref>). While in FT, the use of sprints, changes of direction, and other movements performed at high intensity (<xref ref-type="bibr" rid="B71">de Resende-Neto et al., 2021</xref>; <xref ref-type="bibr" rid="B72">Rivas-Campo et al., 2023</xref>), combined with the circuit exercise structure (<xref ref-type="bibr" rid="B31">Gbiri and Amusa, 2020</xref>), may lead to positive changes in central and peripheral mechanisms that favor oxygen transport and utilization.</p>
<p>Concerning the ability to stand up, assessed by the FRT (FT: d &#x3d; 0.97; AT: d &#x3d; 0.59) and FTSST tests (FT: d &#x3d; 0.61; AT: d &#x3d; 0.41), both the AT and FT protocols showed significant improvements with effect sizes ranging from small to large. The rhythmic and high-intensity interval part applied in AT may stimulate muscle power and motor coordination, thus leading to improvements in this ability (<xref ref-type="bibr" rid="B54">Li et al., 2024</xref>). In addition, FT is predominantly neuromuscular, with training session parts focused on stimulating power and muscle strength of the lower limbs, in addition to including movements with a motor pattern similar to the functional tests analyzed (<xref ref-type="bibr" rid="B94">Vasconcelos et al., 2020</xref>; <xref ref-type="bibr" rid="B17">Carrasco-Poyatos et al., 2019</xref>).</p>
<p>As for walking ability, mimicked by the TUG (FT: d &#x3d; 0.69; AT: d &#x3d; 0.54) and 10MWT (FT: d &#x3d; 0.56; AT: d &#x3d; 0.67) tests, both the AT and FT protocols showed significant improvements with moderate effect sizes. The stimuli targeting velocity and dynamic balance during acceleration and deceleration actions, present in both protocols, stimulate muscle power (<xref ref-type="bibr" rid="B54">Li et al., 2024</xref>; <xref ref-type="bibr" rid="B17">Carrasco-Poyatos et al., 2019</xref>). It is already known that there is a strong correlation between lower limb power and dynamic balance, as well as usual gait speed (<xref ref-type="bibr" rid="B106">Yee et al., 2021</xref>). These stimuli constantly perturb the postural control system and activate stabilizing muscles, promoting adaptations in dynamic balance (<xref ref-type="bibr" rid="B80">Shahtahmassebi et al., 2019</xref>).</p>
<p>With respect dexterity, which was analyzed using the GJST (FT: d &#x3d; 0.58; AT: d &#x3d; 0.51) and DTTS (FT: d &#x3d; 0.69; AT: d &#x3d; 0.23) tests, only the FT protocol showed a significant improvement with moderate effect sizes for both tests. The absence of significant adaptation in the AT group may be due to the lack of task-specific exercises involving the upper limbs. FT presents a result similar to other studies, in which the quantity of exercises targeting the upper limbs, applied with pushing and pulling patterns, may favor dexterity (<xref ref-type="bibr" rid="B9">Arag&#xe3;o-Santos et al., 2024</xref>). Other studies involving strength training have highlighted that performing movements with large amplitudes favors gains in joint mobility (<xref ref-type="bibr" rid="B17">Carrasco-Poyatos et al., 2019</xref>; <xref ref-type="bibr" rid="B20">DE Matos et al., 2017</xref>).</p>
<p>Finally, regarding Handgrip Strength, which is considered a strong predictor of mortality and disability, a significant improvement was observed only for FT (d &#x3d; 0.64) with moderate effect sizes (<xref ref-type="bibr" rid="B88">Taekema et al., 2010</xref>). These adaptations in FT may be attributed to the manipulation of equipment (kettlebell, Bulgarian Bag, Weight Plates) during the strength exercises. This result is consistent with the current literature (<xref ref-type="bibr" rid="B7">Arag&#xe3;o-Santos et al., 2019</xref>).</p>
<p>Our findings provide important contributions regarding the effects of different interventions on functional fitness, with particularities not yet evidenced in the scientific community. One limitation of this study is the lack of intensity progression in AT, which may have influenced the absence of significant changes in BDNF and could potentially yield greater effects on functional fitness. However, the percentage of HRR was monitored to maintain moderate to high intensity during the sessions, as suggested in other studies to promote cardiorespiratory adaptations that are associated with improved cognitive function. Another limitation is that the ICC was not calculated; however, according to similar studies of our research group, the tests used exhibit sensitivity above 75% and an ICC greater than 0.80. Finally, the absence of intention-to-treat (ITT) analysis is considered a limitation of this study.</p>
<p>Based on our findings, future research should consider other cognitive subdomains, utilizing more sensitive and specific tests, and also verify the activation of different brain areas during interventions or assessments. We recommend comparisons between men and women, with and without mild cognitive impairment, regarding cognitive and physical performance, verifying the impact of the interventions on quality of life. Furthermore, it is essential to investigate the integration of cognitive and motor stimuli over time, analyzing the residual effect of physical exercise on cognition.</p>
</sec>
<sec id="s2-7">
<title>2.7 Conclusion</title>
<p>Sixteen weeks of FT and AT promoted improvements in cognitive status and semantic memory, but only FT enhanced overall executive function and BDNF serum levels. Regarding functional fitness, both training modalities improved cardiorespiratory fitness, as well as the ability to rise and walking ability. However, only FT positively altered dexterity and handgrip strength in older women with mild cognitive impairment. These results highlight the importance of structured, targeted training programs that are low-cost and offer several benefits for this specific population, making both protocols feasible for implementation in community or clinical settings that require physical training programs to enhance the autonomy and quality of life of the aging population. Thus, this study contributes evidence supporting non-pharmacological interventions aimed at mitigating cognitive and functional decline in older adults, specifically in women, who are disproportionately affected by MCI.</p>
<sec id="s2-7-1">
<title>2.7.1 Permission to reuse and copyright</title>
<p>Upon acceptance for publication, the Frontiers in Physiology requires a Copyright Transfer from all authors. Thus, we, the authors, will confirm through the authorship email sent by the journal that we are aware of the manuscript entitled &#x201c;Functional Training Improves Cognitive Function, Functional Fitness, And Bdnf Levels In Older Women With Mild Cognitive Impairment: A Randomized Controlled Trial&#x201d; and we hereby transfer to the Frontiers in Physiology the rights to publication, reproduction, transmission, and distribution of the manuscript, as well as the information contained therein, in its entirety or in part, in printed or electronic versions of the Frontiers in Physiology or in new media developed in the future. Furthermore, the authors permit the creation of versions in other languages of the aforementioned manuscript. The authors are prohibited from publishing the Manuscript without prior approval from the Frontiers in Physiology, in any printed or digital media, with the exception of personal websites. However, the content published herein may be freely used by the authors in the preparation of presentations such as classes, lectures, courses, or conferences.</p>
</sec>
</sec>
</sec>
</body>
<back>
<sec sec-type="data-availability" id="s3">
<title>Data availability statement</title>
<p>The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.</p>
</sec>
<sec sec-type="ethics-statement" id="s4">
<title>Ethics statement</title>
<p>The studies involving humans were approved by the Comit&#xea; de &#xc9;tica em Pesquisa da Universidade Federal de Sergipe. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study.</p>
</sec>
<sec sec-type="author-contributions" id="s5">
<title>Author contributions</title>
<p>SR-S: Conceptualization, Data curation, Formal Analysis, Investigation, Methodology, Project administration, Software, Validation, Writing &#x2013; original draft, Writing &#x2013; review and editing. AGR&#x2013;N: Data curation, Formal Analysis, Investigation, Methodology, Writing &#x2013; original draft, Writing &#x2013; review and editing. AV: Data curation, Formal Analysis, Writing &#x2013; review and editing. MP-M: Data curation, Formal Analysis, Writing &#x2013; review and editing. AP-C: Data curation, Methodology, Writing &#x2013; review and editing. LS: Data curation, Writing &#x2013; review and editing. NC: Data curation, Project administration, Writing &#x2013; review and editing. JJ: Methodology, Writing &#x2013; review and editing. JA-S: Data curation, Formal Analysis, Methodology, Software, Writing &#x2013; review and editing. DS: Methodology, Resources, Writing &#x2013; review and editing. JS: Data curation, Formal Analysis, Investigation, Methodology, Resources, Writing &#x2013; review and editing. EDS-G: Data curation, Formal Analysis, Methodology, Project administration, Resources, Supervision, Validation, Writing &#x2013; review and editing.</p>
</sec>
<sec sec-type="funding-information" id="s6">
<title>Funding</title>
<p>The author(s) declare that financial support was received for the research and/or publication of this article. Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior &#x2013; Brazil (CAPES).</p>
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<sec sec-type="COI-statement" id="s7">
<title>Conflict of interest</title>
<p>The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p>
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