A continuous increase in life expectancy, especially in the older age groups, has become a prevailing trend in many countries. Consequently, population aging is now a global phenomenon that demands a deeper understanding of effective solutions to the challenges associated with the care and well-being of older individuals.⁽¹⁾ According to a United Nations report,⁽²⁾ the number of individuals aged 65 and over is expected to grow significantly from 0.7 billion (9% of the global population) in 2019 to 1.5 billion (16%) in 2050. Furthermore, recent studies⁽³⁾ have indicated that population aging will be accompanied by a 55% increase in disability-adjusted life years in people aged over 60 years between 2004 and 2030.

Notably, changes in body composition due to aging do not follow a linear trajectory and do not affect men or women in the same manner. After menopause, hormonal fluctuations, including decreased estrogen and testosterone levels, result in the loss of muscle quality and reduced strength in women, especially in the lower limbs.^(4,5) However, regardless of sex, researchers⁽⁶⁾ suggest that the loss of muscle quality with aging may be the result of several factors and adaptations related to the nervous system, including decreased efficiency of the cerebral cortex, spinal cord, and neuromuscular connections. Therefore, exploring the role of these factors is crucial to better understand the reasons for muscle function deterioration in older adults.

Aging-related supraspinal adaptations have been observed in the motor cortical regions of the frontal lobe, which houses a variety of excitatory and inhibitory neurons, including glutaminergic neurons which are involved in neural development, synaptic plasticity, learning, and memory, and play a fundamental role in the mechanism of some neurodegenerative diseases.⁽⁷⁾ Several studies^(8,9) have highlighted cortical atrophy in these regions, with a decrease in the total volume of these regions, ranging from 4%-16%, throughout the aging process. These adaptations observed in the primary motor cortex appear to be associated with a reduction in the size of motor and premotor neurons, as well as a reduction in synaptic transmission. This phenomenon is known as neural atrophy.⁽⁸⁾ A study using dissections in cadavers revealed that older adults present, on average, a 43% reduction in the size of motor cortex cells compared with that in young adults.⁽¹⁰⁾ Moreover, another study⁽¹¹⁾ of cadavers carried out at the University of São Paulo revealed that brain weight and volume decreased during aging by approximately 45 g and 43 mL per decade, respectively, and these reductions were more pronounced in women. These findings have now been corroborated by recent studies employing high-resolution magnetic resonance imaging in living subjects. In a 15-year cohort study, Fujita et al.⁽¹¹⁾ reported an annual decrease of -0.5% of the cerebral cortex; the frontal lobe showed a great dependence on age (annual decrease in volume -0.5%) and was related with morphological changes in neural cells. Other motor functions, such as a decline in the motor performance of the lower limbs⁽¹³⁾ and gait, also appear to be affected by neural atrophy.⁽¹⁴⁾ A meta-analysis of brain imaging studies addressed the effects of aging on motor control and described a behavioral decline in older participants, suggesting a general deterioration in motor functions associated with the physiological process of aging; older adults showed increased reaction times (five studies), reduced precision (12 studies), or both (four studies) during the execution of different motor tasks.⁽¹⁵⁾

However, neural atrophy is not the only factor associated with aging as significant changes also occur in the cortical white matter of individuals aged >65 years.^(16,17) This region, which is composed mainly of glial cells and myelinated axons, is crucial for the connectivity between different cortical areas and the spinal cord. A previous study⁽¹²⁾ reported considerable deterioration in the integrity of white matter with an age-related decrease in volume and an accelerated rate of atrophy. Additionally, experimental research^(18,19) has revealed a reduction in the length of myelinated nerve fibers in the white matter of older individuals compared to that in younger individuals. These age-related morphological changes may contribute to a state of disconnection between cortical areas, which is associated with declines in executive function in both fine and gross motor skills and in information processing speed.^(18,20) Furthermore, evidence indicates that changes in white matter may lead to reduced stability, manifested by greater oscillation in the trajectory and impairment of static balance.⁽¹⁹⁾

Dysfunction of the glutamatergic system is one of the neurochemical mechanisms underlying this increase in neural noise, because glutamate plays a central role in modulating excitatory signals in the central nervous system. Accordingly, the significant reduction in glutamate absorption caused by aging, which leads to an increase in the glutamate concentration around cortical neurons, has been associated with increased neural noise.⁽²¹⁾ Additionally, neuromuscular decline, which involves several physiological processes that affect the nervous and muscular systems, such as loss of motor neurons, is associated with aging. Aging decreases the number of motor neurons in the spinal cord that are responsible for sending nerve signals to the muscles. This can lead to a reduction in the ability to recruit motor units, which are groups of muscle fibers controlled by motor neurons.⁽²²⁾ The speed at which these signals are transmitted by peripheral nerves also tends to decrease because of structural changes in the motor endplate, where the connection between the motor neuron and the muscle fiber occurs.⁽²³⁾ Furthermore, muscle fibers tend to change, resulting in a transition from fast- to slower-twitch fibers, which affects muscle speed and strength.⁽²⁴⁾ Several studies have reported that the ability of muscles to regenerate after injury or exercise can also reduce with age, owing to changes in the cellular and molecular environment.⁽²⁵⁾ This reduction may be related to failures in the denervation and reinnervation processes, which normally help compensate for neuronal loss and consequent problems with muscle strength and control. Fiber denervation rates far exceed reinnervation rates, and a decrease in fiber size is directly linked to increased oxidative stress and cellular apoptosis, resulting in a significant reduction in the number of satellite cells responsible for muscle regeneration.⁽²⁶⁾

Despite these neuromuscular changes, conditions such as sarcopenia, another major challenge faced by many older adults, can exacerbate neural and muscular decline. According to the European Working Group on Sarcopenia in Older People (EWGSOP 2),⁽²⁶⁾ sarcopenia is characterized by dynapenia, muscle atrophy, and poor physical performance. This phenomenon not only compromises the physical strength and mobility of this population, but is also closely linked to changes in the central nervous system (CNS) and a high risk of adverse health outcomes, including low survival rates, postoperative complications, and longer hospital stays in patients, as well as falls and fractures, metabolic disorders, cognitive impairment, and loss of autonomy.^(27-32) Given the increasing population of older adults, the prevalence of sarcopenia is expected to increase in the future. A recent study⁽³³⁾ showed that according to the definition of prevalence estimates, the number of people affected by sarcopenia in Europe is likely to increase from 10,869,527 in 2016 to 18,735,173 in 2045, representing a 72.4% increase in the global prevalence of sarcopenia in older individuals, rising from 11.1% in 2016 to 12.9% in 2045. This growth may have considerable implications for society in terms of the demand for healthcare and associated costs.⁽³⁴⁾ Despite advances in the understanding of sarcopenia, the neurophysiological mechanisms underlying motor performance across different stages of the condition remain insufficiently explored. In particular, cortical activity during motor tasks, especially in relation to motor reaction time, has not been adequately investigated in this context.

Consequently, interventions aimed at minimizing impairments associated with sarcopenia in this population are essential. However, no previous study has evaluated cortical activity patterns in relation to motor reaction time across different stages of sarcopenia in older women or explored how these responses may inform targeted rehabilitation strategies.

In this context, electroencephalography represents a promising tool for assessing brain activity, as it allows the analysis of electrical signals across different brain regions with high temporal resolution. This approach may provide important insights into activation patterns, including compensatory mechanisms in pre-sarcopenia and reduced responsiveness in sarcopenia.

Therefore, investigating these mechanisms may contribute to a better understanding of the muscle-brain interaction in aging and support the development of more effective neuromuscular rehabilitation strategies.^(34,35)

This study aimed to analyze cortical activity using an electroencephalogram during the motor reaction time in older women with sarcopenia and pre-sarcopenia.

The findings of this study indicate a depression of cortical excitation assessed with EEG in older women with sarcopenia and a statistically significant difference (p<0.001) in the level of cortical excitation in older women with pre-sarcopenia compared to that in the Control Group. Although cortical excitation changes might also reflect attentional or sensory processing, our analyses focused on motor-related cortical areas (F3, FC5, FC6, F4) and on alpha and beta rhythms classically associated with voluntary motor preparation and execution. The temporal alignment of EEG epochs to response onset, together with the predominance of contralateral activation, supports the interpretation of motor-related rather than purely sensory cortical activity.

Studies on aging in the human brain have shown that the regulation of dopamine action is significantly reduced in old age and, according to the literature,⁽⁵¹⁾ the increased reaction time in older adults is related to the loss of dopamine receptors. This change occurs because of structural degradation, including neuronal loss, reduction in neuroreceptor sites, and a decline in transporter molecules.⁽⁵²⁾ Older people have higher rates of cortical hypoexcitability⁽⁵³⁾ and progressive degeneration of dopaminergic neurons in the midbrain is associated with deficits in the initiation, speed, and flow of voluntary movement.⁽⁵⁴⁾

Older women with pre-sarcopenia had a significantly higher level of cortical excitation as the body was undergoing adaptations and adjustments due to the loss of muscle percentage, which makes the motor conduction time and cortical activation faster. The Scaffolding Theory of Aging and Cognition (STAC) postulates that increased brain activity with age, especially in the prefrontal cortex, is a compensatory mechanism caused by brain reorganization in response to age-related declines in neural structures and functioning.⁽⁵⁵⁾ For high-demand tasks that require processing beyond the level of available neural resources, older brains may use compensatory mechanisms to improve age-related declines in the temporal processing of sensory stimuli when producing movements.⁽⁵⁶⁾

Significant differences were found between the control and pre-sarcopenic groups in the correlation between the MRT and muscle percentage, fat percentage, HGS, leg strength, and resistance assessed using the 30-second sit-to-stand test.

In the pre-sarcopenia group, strength showed a favorable correlation with MRTS and MRTF reduction. There was a strong correlation with the 30-second sit- to-stand test and a moderate correlation with HGS. This difference may have occurred because the 30-second sit-to-stand test requires not only isometric strength (as in HGS) but also concentric and eccentric strength.

The difference in HGS was significant between the groups because muscular hypotrophy is a characteristic of aging and associated with significantly impaired function (such as slowness of movement and muscle weakness), consequently impairing the exchange of sensorimotor information.⁽⁵⁷⁾

In the healthy aging process, muscle regeneration pathways are activated in healthy older people without sarcopenia but can be dysregulated or simply overloaded in sarcopenic older adults.⁽⁵⁸⁾ Muscles may be damaged, and because of their inability to regenerate when injured, they become slower in performing tasks, thus affecting older people's functioning.

These data corroborate the present research, which found a positive correlation between muscle percentage and MRT, showing that the lower this percentage, the slower the MRT, as well as muscle strength and the 30-second sit-to-stand test; that is, the lower the strength and the fewer the repetitions in the test, the slower the response to the stimulus.

Our findings suggest that older women with sarcopenia need a long motor processing time to achieve a good balance score; that is, they slow down as a strategy to make functional balance adjustments. The correlations of MRT with fear of falling (assessed with FES-I) and static balance (assessed with the 4-stage balance test) were significantly different between the groups. This can be explained by the aging process, which leads to the loss of muscle mass, muscle strength, and reduced mobility, which are factors directly related to the risk of falling. In addition, according to a systematic review, older people with sarcopenia have a 34-91% significantly greater risk of falling.⁽³⁰⁾

This study did not find significant correlations between MRT, body structure and function, or personal factors in older women with sarcopenia. A possible explanation is that such women supposedly have an impaired pyramidal system and worsened brain-muscle communication. In other words, a neuromuscular system that does not function well in sarcopenia may be due to impaired corticospinal interactions, which, in turn, can cause the muscle microenvironment to lose muscle mass, strength, and functionality.⁽⁵⁸⁾

The correlations between gait speed, step length, and MRT were significantly different between the groups, which can be explained by the different changes in gait associated with aging, such as slowness and greater gait variability.⁽⁵⁹⁾

Older people have greater metabolic costs in terms of gait, mainly owing to the loss of strength and muscle mass. Furthermore, a slower gait speed in older adults is a form of adaptation that occurs in response to various muscle-related physiological changes.⁽⁶⁰⁾ This is in line with the findings of this study, in which slowed down sarcopenic older people had decreased gait speed and step length, leading to a longer MRT.

The data in this study show that the higher the gait speed, the lower the MRTF. Hence, as older women can remain attentive to the task, their "sixth functional vital sign" (i.e., the gait speed) improves – as described in the literature that an association was also found between gait speed and the attention level.⁽⁶¹⁾

According to these data, pre-sarcopenia seems to be the ideal time to carry out interventions, as the brain is attentive to dysfunction and is receptive to stimuli. These results suggest that resistance exercise is a promising strategy to ensure brain health and prevent neurological diseases. They may also shape the frontal lobe, which is accompanied by an improvement in executive function. Thus, exercise is a promising approach for ensuring brain health.⁽⁶²⁾

Future clinical research should focus on the application of these findings to the design of new therapeutic interventions. What is emphasized here is that in the future, further external relationships may be included in studies correlating brain activation patterns (EEG) in sarcopenic older women and MRT. An intervention protocol may also be developed for older women with pre-sarcopenia, thus helping prevent and treat sarcopenia, further understanding its complexity and relationship with brain health, and better interpreting it for clinical practice.

Notably, the use of scalp EEG inherently limits spatial precision. Source reconstruction analyses were not performed in this study; therefore, anatomical interpretations should be regarded as topographical rather than region specific. Nevertheless, the Emotiv EPOC+ system used here follows the international 10-20 electrode placement standard, ensuring consistent anatomical correspondence across participants. Previous validation studies confirmed the reliability of this montage for cortical mapping and alpha- and beta-band analyses of motor processing.^(63-65) These characteristics support the reproducibility and physiological plausibility of topographical findings.

This study has some limitations that should be considered. The inclusion of only older women may limit the generalizability of the results to other populations. Future studies should include more diverse samples and incorporate advanced neuroimaging techniques to provide a more comprehensive understanding of the neural mechanisms underlying sarcopenia.

Sarcopenia is not only a result of natural aging processes but is also directly related to central changes in neurodegenerative processes. EEG has proven effective in assessing these changes, as observed in the cortical activity of older women.

According to the results of this study, the pre-sarcopenia phase is the ideal time to initiate neurotherapeutic interventions aimed at mitigating the adverse consequences of sarcopenia, as the brain is most sensitive to dysfunction and most receptive to stimuli at this stage.

Variables related to body structure, body function, and personal factors did not appear to affect motor reaction time to activity in older women with sarcopenia, thus highlighting the complexity of this condition and the need for a holistic approach.

Based on these findings, this study may contribute to targeting strategic points for interventions and more in-depth investigations into brain behavior and neurodegenerative processes in this specific population, highlighting the importance of integrated approaches that consider a variety of physical, emotional, and social factors.