The research drew on the Geriatric Assessment for Patients (GAP70+) study, a multicentre, cluster-randomized clinical trial conducted across 39 community oncology clinics affiliated with the University of Rochester Cancer Center NCI Community Oncology Research Program Research Base. Participants were aged 70 or older, had incurable stage III or IV solid tumours or lymphoma, and were scheduled to begin a new systemic treatment regimen known to carry a high risk of toxicity. From the trial’s usual care arm, the investigators collected abdominal and pelvic CT or PET/CT scans performed as part of routine care, applying strict time windows around enrollment and rigorous quality control. That process yielded 161 patients whose imaging and clinical data could be fully analysed, with a mean age of 76.6 years, nearly 61 percent male, and most carrying gastrointestinal or lung cancers.

What sets this analysis apart from the bulk of prior sarcopenia research in oncology is its adherence to a full clinical definition of the condition rather than a single imaging measurement. The European Working Group on Sarcopenia in Older People, known as EWGSOP2, defines sarcopenia using three criteria: reduced muscle strength, reduced muscle quantity and quality, and reduced physical performance. In this study, strength was assessed with a five-time chair-stand test, where a time exceeding 16.7 seconds signalled weakness. Muscle quantity was quantified from the mid-L3 lumbar vertebra slice of each CT scan using validated automatic segmentation software, producing a skeletal muscle index with sex- and BMI-specific thresholds. Muscle quality was captured through Hounsfield Unit measures of tissue density on the same scans, and physical performance was evaluated with the timed up-and-go test. Meeting the strength and quantity or quality criteria classified a patient as sarcopenic; meeting all three criteria indicated severe sarcopenia.

The prevalence figures were sobering. More than two-thirds of participants, 68.3 percent, had low muscle quantity by imaging criteria, and 56.5 percent met the full clinical definition of sarcopenia. Among those, 59 percent were classified as having severe sarcopenia. Patients with sarcopenia were on average about two years older than those without it and were significantly more likely to have diabetes. More tellingly, sarcopenia tracked closely with broader geriatric vulnerability: those with the severe form were significantly more likely to show impaired nutrition, dependence in activities of daily living and instrumental activities, recent falls and impaired cognition compared with patients whose muscles were preserved. In other words, the clinical sarcopenia label captured a constellation of ageing-related frailty that a simple muscle measurement did not.

When the researchers turned to treatment outcomes, documented through clinician-reported adverse events graded with the Common Terminology Criteria for Adverse Events, version 4.0, a nuanced picture emerged. Overall severe toxicity, defined as Grades 3 through 5, during the first three months of therapy did not differ significantly between patients with and without sarcopenia. But severe nonhematologic toxicities—a category that includes complications such as dehydration, electrolyte disturbances, infections, fatigue and pain, which frequently lead to hospitalization—were substantially more common in the sarcopenic group, affecting 64 percent versus 44 percent. In multivariable logistic regression adjusting for age, tumour site, sex, comorbidities and treatment type, sarcopenia more than doubled the odds of severe nonhematologic toxicity, with an odds ratio of 2.24. Notably, patients who suffered these severe nonhematologic events also had significantly slower chair-stand times, and each additional second on that strength test raised the odds of toxicity by roughly 15 percent.

The mortality findings were even more striking. At one year, only 46 percent of participants with sarcopenia were alive, compared with 60 percent of those without it. After statistical adjustment this difference fell just short of significance in the full cohort, but when the analysis focused on patients starting first-line chemotherapy, sarcopenia was clearly associated with poorer survival, with a hazard ratio of 2.12. For severe sarcopenia the signal was unmistakable: one-year survival was just 40 percent versus 60 percent among patients without sarcopenia, a difference that remained significant after adjustment with a hazard ratio of 2.08. The mortality gap opened early—within three months, nearly 21 percent of patients with severe sarcopenia had died, versus 7 percent of those without the condition. Crucially, when the investigators evaluated skeletal muscle index alone, stripped of the strength and performance components, no significant association with survival appeared at all.

That last result may be the study’s most important technical message. Much of the oncology literature has equated sarcopenia with low muscle quantity on imaging, treating the skeletal muscle index as a standalone prognostic marker. This analysis suggests that in older adults that approach is insufficient, because muscle mass declines physiologically with age and is not a linear proxy for what muscles can actually do. The consensus definitions that incorporate grip-equivalent strength measures and performance tests appear to identify a genuinely distinct population of patients whose functional reserve is depleted and who are therefore less able to withstand the catabolic assault of cytotoxic therapy. The authors note this contrasts with patterns seen in younger patients, in whom imaging-based muscle measures have shown stronger associations with outcomes.

The comparison with the limited prior work reinforces the point. Only one earlier study, in men with metastatic castrate-resistant prostate cancer, had evaluated treatment toxicity in older adults using a definition of sarcopenia encompassing strength, quantity and performance; it reported a prevalence of 27 percent, lower than the 57 percent seen here, likely reflecting stricter criteria that resemble the severe sarcopenia category. That study likewise linked sarcopenia to poorer survival and heightened toxicity risk. Two recent studies in gastrointestinal cancer patients that relied on muscle index alone produced inconsistent survival associations, underscoring the value of the multi-domain approach. The new analysis also benefits from real-world breadth: patients were treated in community clinics nationwide rather than tertiary referral centres, and toxicity data met the annotation standards of a randomized trial.

The limitations are worth noting. The cohort was predominantly non-Hispanic white, limiting generalizability to other populations. Scans were not mandated by the protocol, and the strict time windows that ensured data quality reduced the analysable sample. As an exploratory secondary analysis, p-values were not corrected for multiple testing, so the findings are hypothesis-generating and require confirmation in prospective cohorts. Treatment regimens and dosing were left to each patient’s oncologist rather than standardized. Even so, the clinical implications are hard to dismiss. Patients with severe sarcopenia received some of the most intensive treatments in the cohort yet had the worst survival, raising the possibility of overtreatment and suggesting that comprehensive geriatric evaluation should precede decisions about aggressive therapy.

The authors argue that sarcopenia screening should become routine in geriatric oncology, and they point to a practical path. Although CT scans are already available for nearly every cancer patient and software tools exist to quantify muscle from them, the expertise to interpret such measurements is not yet part of routine practice. The geriatric assessment, by contrast, is already recommended by ASCO guidelines and captures exactly the measures—chair-stand strength, timed up-and-go performance, falls, daily functioning—that this study linked to toxicity and death. Integrating those simple tests into treatment planning, and designing intervention trials that incorporate sarcopenia status into treatment selection and dosing, could spare the most vulnerable older adults the cruelest harms of therapy while preserving its benefits for those robust enough to tolerate it.

Subject of Research: Sarcopenia and treatment toxicity and mortality in older adults with advanced cancer

Article Title: Sarcopenia Is Associated With Severe Treatment Toxicity and Mortality in Older Adults With Advanced Cancer: A Secondary Analysis

Article References: Mattick, L. J., Mohammed, M., Li, C.-S., Tylock, R. G., Loh, K. P., Flannery, M. A., Peppone, L. J., Lin, P.-J., Goncalves, M. D., Caan, B. J., Cespedes Feliciano, E. M., Popuri, K., Beg, M. F., Bearden, J. D., Berenberg, J., Katato, K., Mustian, K. M., Mohile, S. G., & Dunne, R. F. (2026). Sarcopenia Is Associated With Severe Treatment Toxicity and Mortality in Older Adults With Advanced Cancer: A Secondary Analysis. Journal of Cachexia, Sarcopenia and Muscle, 17(5), Article e70388. https://doi.org/10.1002/jcsm.70388

Image Credits: AI Generated

DOI: 10.1002/jcsm.70388

Keywords: sarcopenia, geriatric oncology, advanced cancer, chemotherapy toxicity, muscle strength, mortality, CT body composition, EWGSOP2, geriatric assessment, cancer cachexia, older adults, clinical trial

The research, led by Xiangyu Zhai and Doris S. F. Yu at The University of Hong Kong, examined 4,477 community-dwelling older adults classified as prefrail or frail, with a mean age of 72.2 years and 72.5 percent of participants being women. Participants were drawn from two large healthy-aging programs spanning all 18 administrative districts of Hong Kong, and frailty was assessed using a modified version of the well-known Fried frailty phenotype, which counts criteria including unintentional weight loss or muscle shrinking, weakness, slowness, low physical activity, and exhaustion. Those meeting one or two criteria were classed as prefrail, while three or more indicated frailty. In total, 3,385 participants were prefrail and 1,092 were frail. The scale of the sample is notable, because most previous exercise studies in frail populations have been small trials with inconsistent findings, leaving clinicians without clear guidance on how to balance efficacy against tolerability.

The study’s central innovation lies in how it disentangled two distinct fitness components that reflect two distinct exercise modalities. Cardiorespiratory fitness, or CRF, is the physiological outcome of aerobic exercise and was measured here with a two-minute walk test, in which participants walked at their comfortable usual pace and the maximum distance covered was recorded. This field test is well suited to frail populations who cannot manage treadmill or cycle ergometry, and it correlates moderately with laboratory-measured peak oxygen uptake. Muscle strength, the outcome of resistance training, was assessed with a digital handgrip dynamometer, the most widely used clinical proxy for overall strength. Cognitive function was screened with the five-minute Montreal Cognitive Assessment protocol, using age- and education-adjusted cutoffs for the Hong Kong population to classify cognitive impairment. In total, 315 participants, or 7.0 percent, met criteria for cognitive impairment.

The results reveal a striking dose-response relationship for cardiorespiratory fitness. Compared with the least fit quartile, participants in the second, third, and fourth quartiles of walking performance had progressively lower odds of cognitive impairment, with fully adjusted odds ratios of 0.57, 0.32, and 0.15 respectively. In other words, the fittest quartile showed roughly 85 percent lower odds of impairment than the least fit, even after accounting for age, sex, education, marital status, living arrangement, body mass index, physical activity, frailty status, and muscle strength. Treated as a continuous variable, every additional 5 meters covered in the two-minute walk was associated with 7 percent lower odds of cognitive impairment. The association held consistently across prefrail and frail subgroups, and across nearly every demographic and clinical stratum the researchers examined, with the sole exception of a small underweight subgroup.

Muscle strength told a more complicated story. On its own, higher handgrip strength was associated with lower odds of cognitive impairment, with a significant linear trend across quartiles and roughly 3 percent lower odds per additional kilogram of grip strength. But when the researchers additionally adjusted for cardiorespiratory fitness, the strength association was substantially attenuated, and only the third and fourth quartiles retained statistical significance. The pattern suggests that much of the apparent protective effect of grip strength may be shared with, or mediated through, overall aerobic capacity. This matters because grip strength predominantly reflects upper-limb muscle function, whereas the two-minute walk test requires adequate lower-limb strength to complete, meaning the fitness measure already incorporates a component of leg strength. The two physiological markers are therefore not fully independent, and the overlap appears to favor CRF as the more comprehensive indicator of the physical fitness relevant to cognitive health.

The joint analysis drove the point home. Participants were divided into four groups: unfit and weak, unfit but strong, fit but weak, and fit and strong, with unfit and weak defined as the bottom quartile of each distribution. Compared with the unfit-and-weak reference group, the fit-but-weak group had an odds ratio of 0.47 for cognitive impairment, while the unfit-but-strong group had an odds ratio of 0.71. Being fit and strong conferred the lowest odds of all, at 0.38. Crucially, when the researchers used the unfit-but-strong group as the reference instead, the fit-but-weak group still fared better, with an odds ratio of 0.66. High cardiorespiratory fitness alone thus conferred about 56 percent lower odds of cognitive impairment than high muscle strength alone. For a population in which every bout of exertion carries a cost, that hierarchy is potentially practice-changing.

Why might aerobic capacity be so tightly linked to brain health in this vulnerable group? The authors point to several plausible biological pathways. Frailty is accompanied by accelerated physiological decline, elevated oxidative stress, and heightened neuroinflammation, processes that can precede and potentiate cognitive deterioration. Higher CRF may buffer these insults by enhancing cerebral blood flow, reducing oxidative damage, promoting synaptogenesis, and modulating neurotrophic factors and neurotransmitter systems. Aerobic exercise is also known to optimize metabolic regulation and support neurogenesis. Resistance training, by contrast, is thought to act mainly by reducing systemic inflammation and stimulating the release of neuroprotective myokines from contracting muscle. Both pathways are real, but the integrated performance of the cardiovascular, respiratory, and musculoskeletal systems captured by CRF may more fully reflect the bodily reserve on which the aging brain depends.

The clinical implications are considerable. Because frail older adults face fatigue, limited activity tolerance, and high dropout rates in demanding multicomponent programs, the findings suggest that aerobic exercise aimed at improving CRF may warrant evaluation as a first-line strategy in future intervention trials, with individualized resistance training added when feasible. The authors emphasize that low-impact or chair-based aerobic programs involving continuous movement and mild exertion could offer suitable entry points for those unable to manage conventional training. Just as important, the two-minute walk test itself could serve as a cheap, scalable screening tool: a simple measure of walking distance, requiring no specialized equipment, might identify prefrail and frail adults at elevated risk of cognitive decline and flag them for timely intervention. Whether raising CRF yields cognitive benefits before strength improves remains an open question that only randomized trials can answer.

The researchers are careful about the limits of their evidence. This was a cross-sectional study, so it cannot establish causation; early subclinical cognitive decline could plausibly reduce physical activity and thereby lower fitness, rather than low fitness causing impairment. The walk test was performed at a self-selected pace, making it a submaximal proxy rather than a direct measure of maximal aerobic capacity, and grip strength captures only upper-limb function. The cognitive screen assessed global performance without distinguishing specific domains, and all participants were recruited in Hong Kong, which may limit generalizability. Sensitivity analyses, including reclassifying participants excluded from the walk test as having the lowest fitness, nonetheless supported the robustness of the main findings. The study was funded by the Hong Kong Jockey Club Charities Trust and approved by the Hospital Authority Clinical Research Ethics Committee.

Even with those caveats, the study is the first to compare the independent and combined associations of CRF and muscle strength with cognitive impairment specifically in prefrail and frail older adults, and its message is unusually actionable. Notably, participants with cognitive impairment in the sample were older, less educated, more likely to live alone, less likely to meet physical activity guidelines, and had higher frailty prevalence and lower fitness and strength than their cognitively intact peers, underscoring how these risks cluster. For clinicians, caregivers, and older adults navigating the exhausting reality of frailty, the findings suggest a pragmatic hierarchy: if resources and energy are limited, prioritize the heart and lungs, and let the walk test tell you where you stand. The next step, the authors argue, is to test directly in prospective cohorts and randomized controlled trials whether aerobic exercise, potentially combined with tailored resistance training, can actually slow cognitive decline in this population rather than merely marking those at risk.

Subject of Research: Associations of cardiorespiratory fitness and muscle strength with cognitive impairment in prefrail and frail older adults

Article Title: Optimizing frailty care: an analysis of dual exercise targets and cognitive function among frail older adults

Article References: Zhai, X., Xi, J., Miao, M., & Yu, D. S. F. (2026). Optimizing frailty care: an analysis of dual exercise targets and cognitive function among frail older adults. GeroScience. https://doi.org/10.1007/s11357-026-02520-4

Image Credits: AI Generated

DOI: 10.1007/s11357-026-02520-4

Keywords: frailty, cardiorespiratory fitness, muscle strength, cognitive impairment, older adults, aerobic exercise, resistance training, handgrip strength, two-minute walk test, dementia prevention, geroscience, exercise prescription

The trial, published in the Journal of Cachexia, Sarcopenia and Muscle, was designed to test a hypothesis grounded in solid physiology. Human performance does not hold steady across the day. Strength and endurance typically peak in the afternoon and evening, and the underlying biology is real: skeletal muscle carries its own molecular clock, built around the CLOCK/BMAL1 transcription factors, which governs substrate use, mitochondrial function, metabolic gene expression, mTOR-mediated anabolic signalling and the secretion of myokines. Laboratory studies have shown that the same exercise session can trigger different molecular and metabolic responses depending on when it is performed, and even the anabolic signalling that follows a contraction appears to be time-of-day dependent. If the muscle’s internal clock shapes how it responds to training, then aligning workouts with the body’s daily high point seemed a plausible way to amplify adaptation.

What set the Basel study apart from earlier attempts was its individualized design. Most previous trials simply randomized volunteers to two fixed training times, most commonly 7:30 and 17:30, and compared the outcomes. That approach ignores a crucial fact: while average performance is higher later in the day, the timing of an individual’s personal peak varies enormously from person to person. In the new trial, every participant completed standardized strength tests at four times of day, 08:00, 12:00, 16:00 and 20:00, on four separate days with at least 24 hours between sessions. Researchers then randomized 108 participants in a 2:2:1 ratio to train at their personal peak time, at their personal trough time, or to maintain their habitual lifestyle as a control group. To the authors’ knowledge, this is the first randomized controlled trial to test such a peak-versus-trough design in resistance training.

The intervention itself was demanding and carefully supervised. Participants in the two training groups completed three supervised sessions per week for twelve weeks: two resistance sessions and one 30-minute endurance session on a cycle ergometer at 60 percent of their individual peak oxygen uptake. Each resistance session comprised three sets of five exercises, including leg press, chest press, deadlift, one-arm cable row and back squat, lasting 45 to 65 minutes. After a two-week familiarization period, participants trained to volitional failure, meaning they repeated each lift until they could not complete another repetition with proper technique. Loads were adjusted using a repetition-based progression algorithm, and training volume was tracked exercise by exercise. Adherence was impressively high in both groups, at roughly 91 to 93 percent for resistance sessions, and volume and load progressed in essentially identical patterns whether people trained at their peak or their trough.

The primary outcome was maximal isometric strength measured with the isometric midthigh pull, a safe and highly reproducible whole-body force test well suited to older adults. Secondary outcomes included handgrip strength and appendicular lean mass index, the gold-standard measure of limb muscle mass obtained by dual-energy X-ray absorptiometry. Crucially, the researchers assessed strength as a daily mean, averaging each participant’s maximum values across all four measurement times, so the results would not be biased by whether someone was simply tested at the hour they happened to train. Assessors were blinded to group allocation, participants and trainers were blinded to the trial hypotheses, and the analysis followed a modified intention-to-treat principle.

The baseline profiling confirmed the expected diurnal rhythm. Peak strength values occurred most often in the afternoon and evening, while troughs clustered around noon and in the morning. On average, participants were about 11 percent stronger at their peak time than at their trough, a difference of 2.6 newtons per kilogram in relative midthigh pull strength. But the individual spread was striking: some people’s daily amplitude was as little as 1 percent, while others swung by 34 percent. That variability is precisely why the investigators argued that fixed-time trials may have missed real effects, since two people assigned to the same clock time could be training at profoundly different relative physiological states.

Yet when the twelve weeks were over, the hypothesis collapsed. Everyone got stronger and leaner, including the control group to a lesser degree, but the differences between the peak and trough groups were trivial. Adjusted effect sizes hovered near zero for all three outcomes, with confidence intervals that largely overlapped zero: roughly 0.07 newtons per kilogram for midthigh pull strength, minus 0.20 kilograms per square metre for handgrip strength, and 0.04 kilograms per square metre for appendicular lean mass index. Comparisons among the fixed training times, morning, noon, afternoon and evening, told the same story, with wide, zero-overlapping confidence intervals and no consistent pattern. Even exploratory analyses of whether testing at the same time of day as training, a so-called congruent condition, conferred an advantage found nothing.

Why did aligning training with peak performance fail to pay off? The authors offer a compelling biological explanation rooted in the decentralized nature of human chronobiology. Although the suprachiasmatic nucleus in the brain acts as the master pacemaker, peripheral tissues such as skeletal muscle harbour semi-autonomous molecular clocks that do not necessarily run in synchrony with central rhythms or with each other. The systems driving acute performance, such as neuromuscular activation and thermoregulation, may peak at different hours than the cellular machinery governing muscle protein synthesis and tissue repair. Training when you are strongest, in other words, may not coincide with the window in which your muscle fibers are most responsive to growth signals. Moreover, because participants trained to volitional failure, the relative stimulus delivered to the muscle was probably comparable regardless of clock time, erasing any advantage that higher achievable loads at peak hours might have conferred.

The authors also acknowledge methodological caveats. Peak and trough times were estimated from a single four-day profiling period, so day-to-day variability in strength may have blurred the intended physiological contrast. Repeated training at a consistent hour may itself induce temporal acclimatization, flattening circadian differences over time. The cohort was relatively healthy and high-functioning, with grip strength above population averages, and early strength gains in older adults are predominantly neural rather than hypertrophic, leaving only about ten weeks of progressive overload after familiarization, which may have limited sensitivity to detect small differences in muscle mass. As a single-centre trial of healthy, independently living older adults, the findings may not extend to frail or sarcopenic populations.

The practical takeaway, however, is refreshingly liberating. For healthy older adults, resistance training appears to be equally effective whether performed in the morning, at noon, in the afternoon or in the evening, and there is no clinically meaningful benefit to scheduling workouts around a personal performance peak. Given that exercise guidelines for older adults already emphasize frequency, intensity, time and type without reference to circadian timing, this trial suggests that flexibility is the wisest policy: the best time to train is the time you can stick with. In an ageing world where more than a quarter of Europeans and North Americans will be over 65 by 2050, removing a perceived barrier to when exercise counts may do far more for muscle health than any chronobiological fine-tuning ever could.

Subject of Research: Time-of-day effects of rhythm-aligned resistance training on skeletal muscle adaptation in older adults

Article Title: Effects of Daily Rhythm‐Aligned Training on Skeletal Muscle Adaptation in Older Adults: A Randomized Controlled Trial

Article References: Bruggisser, F., Ritter, S., Roth, R., Ritter, E. T., Infanger, D., Ledergerber, R., Hinrichs, T., Scheer, F. A. J. L., Handschin, C., Hanssen, H., & Knaier, R. (2026). Effects of Daily Rhythm‐Aligned Training on Skeletal Muscle Adaptation in Older Adults: A Randomized Controlled Trial. Journal of Cachexia, Sarcopenia and Muscle, 17(5), Article e70390. https://doi.org/10.1002/jcsm.70390

Image Credits: AI Generated

DOI: 10.1002/jcsm.70390

Keywords: circadian rhythms, resistance training, sarcopenia, skeletal muscle, older adults, randomized controlled trial, exercise timing, muscle strength, lean mass, chronobiology, healthy ageing, molecular clock

The research team recruited twenty-two players from the Tunisian national U15 soccer program, all of whom qualified as Tier 3, or highly trained, athletes under the classification framework proposed by McKay and colleagues. The girls, aged 14.9 plus or minus 0.8 years and assessed at Tanner stage 3 of pubertal development, were randomly assigned to either a strength training group of eleven players or an active control group of eleven who continued their normal soccer schedule. Both groups trained five times per week for ninety minutes and played a competitive match each weekend, and statistical analysis confirmed that total training loads, calculated by multiplying session ratings of perceived exertion by session duration, were essentially identical between groups at roughly 1,160 arbitrary units. That equivalence matters, because any difference in outcomes could then be attributed to the strength intervention itself rather than to a simple mismatch in workload.

The strength program was deliberately periodized across three four-week cycles. In the first cycle, players performed full-body exercises such as leg press, hip thrust, squat, bench press, lat pull-down and calf raises at 40 to 60 percent of their one-repetition maximum, completing three sets of fifteen repetitions with deliberately slow movement. The second cycle escalated to three sets of twelve, ten and eight repetitions at 60 to 75 percent of one-repetition maximum, while the third cycle climbed to sets of ten, eight and six repetitions at intensities approaching 85 percent. One-repetition maximum tests were repeated before each cycle to recalibrate loads, ensuring progressive overload, and no strength work was performed during the fourth week of each cycle to allow recovery and consolidation of adaptations.

The physical results were unambiguous. After twelve weeks, the strength group posted large and statistically significant gains in maximal dynamic strength across all three tested lifts, with one-repetition maximum improvements on the bench press, lat pull-down and leg press reaching post hoc significance at p less than 0.001 and partial eta squared values of 0.41, 0.43 and 0.36 respectively, all well beyond the threshold for large effects. Body composition shifted in parallel: the strength group gained lean body mass while simultaneously reducing body fat percentage, a combination the authors attribute to stimulated muscle hypertrophy and increased energy expenditure. The control group showed no comparable changes. Because these athletes had never previously undergone systematic strength training, the researchers suggest the early gains were driven largely by neural adaptations, including improved motor unit recruitment and firing frequency, a phenomenon typically dominant during the first four to six weeks of a resistance program before hypertrophy becomes the primary mechanism.

The soccer-specific findings may be the most striking for coaches. Using the Loughborough Soccer Passing Test, a validated field assessment in which players complete sixteen timed passes against color-coded targets while penalties are added for misses, wrong targets and handling errors, the strength group improved its total score by roughly 22 percent. Crucially, the improvement came overwhelmingly from a reduction in penalties, which fell by more than 65 percent in the strength group compared with only about 11 percent in controls. The test demands simultaneous ball control, rapid decision-making and precise body positioning in a confined space, so the authors interpret the penalty reduction as evidence of better information processing and a strengthened connection between cognition and motor execution. Previous reviews have shown that various training modalities can improve passing test scores, but demonstrating this from a pure strength intervention in adolescent girls adds a genuinely novel data point.

Executive function, the suite of mental skills that governs inhibition, cognitive flexibility and attentional control, was assessed with the classic Stroop test, in which participants must name the ink color of a word when the word itself names a different color, thereby forcing the brain to suppress an automatic reading response. Across three subtasks covering word reading, color naming and the interfering word-color condition, the strength training group improved significantly, with the critical group-by-time interaction for the Stroop word-color test reaching p equal to 0.006 and a large effect size, while the control group did not improve beyond time-related practice effects. The authors caution that some portion of the gain may reflect measurement variability or learning effects, but the pattern aligns with a 2020 meta-analysis by Landrigan and colleagues showing that resistance exercise reliably lifts cognitive performance, and with neurophysiological work by Kidgell and by Hortobágyi linking strength training to enhanced corticospinal excitability and synaptic efficiency.

The study also probed the molecular machinery that is often assumed to underlie these cognitive benefits. Blood samples were drawn in a fasted state, twenty-four hours after the final training session and during the follicular phase to control for hormonal fluctuation, and analyzed for basal serum concentrations of brain-derived neurotrophic factor, or BDNF, and insulin-like growth factor 1, or IGF-1. In animal models, exercise-induced elevations of these molecules drive neurogenesis, long-term potentiation and synaptic plasticity, and several human studies have reported increased IGF-1 after resistance training. Yet here, despite clear behavioral improvements, neither marker changed significantly between or within groups. The authors suggest several explanations: athletes with already high fitness levels may maintain BDNF and IGF-1 at a physiological homeostasis that leaves little room for further elevation, participants had an average body mass index below 25, a range in which exercise typically produces no detectable BDNF change, and the effects of long-term training on circulating BDNF may be transient rather than cumulative, with acute spikes returning to baseline between sessions.

The findings carry practical weight for a sport in which cognition increasingly appears to separate elite from sub-elite performers. Soccer constantly presents players with multi-task demands, requiring them to dribble or pass while simultaneously tracking opponents, teammates and passing lanes under severe time pressure, and prior research has shown that Stroop performance can distinguish high-level from low-level players. If two supervised strength sessions per week, easily accommodated within an in-season schedule, can meaningfully sharpen inhibitory control and reduce passing errors, the cost-benefit calculation for youth academies changes considerably. The researchers explicitly recommend that coaches integrate strength training into regular programs to develop both physical fitness and cognitive function in young female athletes, noting that adherence in this trial exceeded 99 percent and that no training-related injuries occurred.

The study is not without limitations, which the authors transparently enumerate. Executive flexibility was measured with only a narrow test battery; additional neurotrophins such as NT-3 and NT-4 were not sampled; sleep, stress and fatigue were uncontrolled; and the power analysis was based on a single outcome despite multiple tested domains, leaving a residual risk of type I error. Pubertal development and menstrual cycle phase may also have introduced variability despite careful scheduling of blood draws. Still, as the first trial of its kind in young, highly trained female soccer players, the work opens a productive line of inquiry. The authors call for future studies measuring neurovascular and neuroendocrine responses during and after strength interventions, and for trials comparing strength training against dedicated cognitive training, to determine whether the mental gains observed here can be amplified, sustained and, ultimately, translated into match-day advantage on the pitch.

Subject of Research: Effects of strength training on cognitive function and neuroplasticity markers in highly trained young female soccer players.

Article Title: Effects of Strength Training on Cognitive Function, Brain-Derived Neurotrophic Factor and Insulin-Like Growth Factor 1 in Highly-Trained Young Female Soccer Players

Article References: Bousselmi, M., Zouhal, H., Darragi, M., Karamti, H. M., Ben Hmid, A., Zamali, I., Ben Ahmed, M., Krir, A., Zouita, S., Laher, I., Hackney, A. C., Granacher, U., & Ben Moussa Zouita, A. (2026). Effects of Strength Training on Cognitive Function, Brain-Derived Neurotrophic Factor and Insulin-Like Growth Factor 1 in Highly-Trained Young Female Soccer Players. Sports Medicine – Open, 12(1), Article 138. https://doi.org/10.1186/s40798-026-01103-z

Image Credits: AI Generated

DOI: 10.1186/s40798-026-01103-z

Keywords: strength training, cognitive function, female soccer, BDNF, IGF-1, Stroop test, LSPT, youth athletes, neuroplasticity, muscle strength, executive function, randomized controlled trial

The scientific rationale behind the study rests on two well-established but rarely merged lines of evidence. Malnutrition in older adults is a recognized prognostic factor for total mortality, and in geriatric medicine it is commonly assessed using the Geriatric Nutritional Risk Index, or GNRI. This index integrates serum albumin levels—a marker of protein status and systemic health—with the ratio of actual to ideal body weight derived from height. Separately, muscle weakness has repeatedly been linked to elevated mortality risk, whether measured through handgrip, quadriceps, or respiratory muscle strength. Yet most previous studies that combined nutrition and strength focused on hospitalized patients or people with cancer, and the few community-based analyses either followed participants for only four or five years or relied on body mass index, a contested proxy for nutritional status.

The new study distinguishes itself in a second, more technical way: it measured leg-press strength directly rather than estimating it. Leg-press strength captures the simultaneous explosive extension of the hip, knee, and ankle joints in both lower extremities, recruiting the gluteal muscles, femoral muscles, and calf muscles. Because it engages most of the major leg muscle groups at once, it evaluates a far larger muscle mass than handgrip or isolated quadriceps tests and reflects the functional capacity needed for complex movements such as rising from a chair or climbing stairs. Notably, it is the only conventional strength measure that incorporates the calf muscles, a point of growing relevance since the Asian Working Group for Sarcopenia’s 2025 consensus update designated calf circumference as the key primary tool for sarcopenia case-finding.

Participants were drawn from the Tsurugaya Project, which in 2002 invited 2,730 community-dwelling residents aged 70 or older; 1,198 enrolled and 1,175 consented. After excluding individuals lacking leg-press data, Mini-Mental State Examination data, or albumin values, 1,065 participants entered the final analysis. Each participant sat on a horizontal leg extension device with feet secured on the pedal at a 90-degree knee angle and exerted maximal power as rapidly as possible across five trials, with the highest value recorded in watts. To account for body size, strength was divided by body mass index. Nutritional status was calculated from the GNRI formula: serum albumin in grams per liter multiplied by 1.489, plus the ratio of measured to optimal body weight multiplied by 41.7, with optimal weight determined by sex-specific Lorentz equations.

Rather than importing cutoffs designed for short-term outcomes in hospitalized patients, the researchers derived study-specific thresholds optimized for 16-year all-cause mortality using maximally selected rank statistics. This yielded sex-specific leg-press cutoffs of 272.63 W/kg/m² for men and 129.78 W/kg/m² for women, and a sex-neutral GNRI threshold of 105.11. Critically, the two indices proved nearly independent: the correlation coefficient between leg-press strength and GNRI was just 0.096, and the variance inflation factor of 1.009 ruled out multicollinearity. That statistical independence is precisely what makes their combination informative—each index carries distinct prognostic information that the other cannot supply. Crossing the two binary classifications produced four groups: high-strength/good-GNRI (589 people), high-strength/poor-GNRI (196), low-strength/good-GNRI (157), and low-strength/poor-GNRI (123).

Over 16 years of follow-up, during which mortality data were collected from the Sendai Municipal Authority through July 2018, 415 participants died. Kaplan–Meier survival curves revealed a stark gradient across the four groups. Five-year mortality was 5.60 percent in the high-strength/good-GNRI group but 27.64 percent in the low-strength/poor-GNRI group—nearly five times higher. Intriguingly, the high-strength/poor-GNRI group initially showed better survival than the low-strength/good-GNRI group, hinting that preserved muscle power might partially buffer the dangers of suboptimal nutrition. In fully adjusted Cox proportional hazards models accounting for sex, age, smoking history, Timed Up and Go performance, cognitive scores, and histories of hypertension, diabetes, cardiovascular disease, liver disease, and kidney disease, hazard ratios for all-cause mortality were 1.55 for high-strength/poor-GNRI, 1.69 for low-strength/good-GNRI, and 2.47 for low-strength/poor-GNRI, compared with the reference group. A stepwise increase in risk across categories remained highly significant.

Analyses treating the measures as continuous variables reinforced the pattern: each unit increase in leg-press strength was associated with a small but significant reduction in mortality risk in both men and women, and each unit increase in GNRI was similarly protective. To guard against reverse causality—the possibility that pre-existing illness at baseline had already weakened both strength and nutrition—the researchers excluded the 30 participants who died within the first two years. The stepwise survival gradient persisted, with an adjusted hazard ratio of 2.39 for the low-strength/poor-GNRI group, suggesting the findings were not merely an artifact of pre-existing disease.

The most consequential results concern predictive performance. The concordance index, which quantifies how well a model discriminates between those who die and those who survive, was 0.54 for muscle strength alone and 0.59 for GNRI alone—but rose to 0.63 for the combined MS-GNRI index, a statistically significant improvement. Net reclassification improvement, which measures how many individuals are correctly shifted into appropriate risk categories, reached 0.62 over muscle strength alone and 0.41 over GNRI alone, implying gains in predictive accuracy of 62 percent and 41 percent respectively. Time-dependent area-under-the-curve analyses told the same story at both 8 years (0.70 for the combined index versus 0.65 and 0.61 for the individual measures) and 12 years (0.67 versus 0.64 and 0.59).

The authors place these findings in the context of Japan’s leading causes of death—malignancy, cardiovascular disease, and pneumonia. Prior cohort work suggests diminished leg-press strength raises cancer mortality risk, while studies of quadriceps weakness in the very old point to possible links with pneumonia death; malnutrition, by contrast, worsens mortality across all major causes. The study has limitations the authors acknowledge candidly: without head-to-head comparison, it cannot establish whether leg-press strength outperforms handgrip or quadriceps measures, the cohort was exclusively Japanese so generalizability to other ethnic groups remains untested, and the study-specific cutoffs require validation in independent cohorts. Still, the message is clear and clinically actionable. Adequate nutrition is essential for longevity, but preserved muscle strength appears to be a critical, partially independent determinant of survival. Whether deliberately training leg-press power can actually reduce mortality risk remains the field’s next great question—and one that could reshape how clinicians screen the world’s aging populations.

Subject of Research: Combining leg-press muscle strength and nutritional status to predict long-term all-cause mortality in community-dwelling older adults

Article Title: Integrating Leg‐Press Strength and Nutritional Status Improves 16‐Year Mortality Risk Stratification in General Older Adults

Article References: Du, Y., Okazaki, T., Li, X., Obata, K., Suzuki, N., Miura, T., Miyagi, M., Nagatomi, R., Kogure, M., Nakaya, N., Hozawa, A., & Ebihara, S. (2026). Integrating Leg‐Press Strength and Nutritional Status Improves 16‐Year Mortality Risk Stratification in General Older Adults. Journal of Cachexia, Sarcopenia and Muscle, 17(5), Article e70375. https://doi.org/10.1002/jcsm.70375

Image Credits: AI Generated

DOI: 10.1002/jcsm.70375

Keywords: leg-press strength, Geriatric Nutritional Risk Index, all-cause mortality, older adults, sarcopenia, malnutrition, Tsurugaya Project, risk stratification, muscle strength, aging, cohort study, serum albumin

Congenital myopathies are a heterogeneous family of disorders that typically announce themselves in early childhood with floppiness and generalised muscle weakness, most prominently in the muscles closest to the trunk. Severity spans an enormous range: the most affected infants are born with respiratory insufficiency and swallowing difficulties, while milder cases may only become apparent in adolescence or adulthood. Birth prevalence has been estimated at roughly 15 per 100,000 live births, and more than 40 different genes have been implicated, although about one in five patients still lack a confirmed genetic diagnosis. Despite this genetic diversity, the underlying cellular defects converge on a handful of mechanisms, including disturbed calcium handling in muscle fibres, abnormal sarcomeric proteins, and defects in membrane trafficking and cytoskeletal organisation.

It is precisely this convergence that made salbutamol an attractive candidate. As a β2-adrenergic agonist, the drug exerts anabolic effects on skeletal muscle, increasing protein synthesis, reducing protein degradation, and shifting myosin heavy chain expression from slow type I fibres towards fast type IIa fibres. Many congenital myopathies share type 1 fibre predominance and muscle fibre atrophy, so a drug that counteracts these features could plausibly help patients regardless of which faulty gene they carry. Earlier open-label studies in Duchenne muscular dystrophy and facioscapulohumeral muscular dystrophy hinted at short-term gains, but placebo-controlled trials failed to show sustained benefit, and a small pilot in core myopathies was too limited in design to be conclusive.

The new trial, known as COMPIS, was designed to settle the question with far greater rigour. Led by researchers at Queen Silvia’s Children’s Hospital in Gothenburg, with nationwide recruitment through paediatric neuromuscular centres in Stockholm, Lund/Malmö and Uppsala, the study enrolled 18 participants aged 6 to 30 with genetically verified congenital myopathies. Crucially, the cohort included both children who could walk and those who could not, and baseline functional severity ranged from severely impaired to mildly affected. Genetic causes included variants in RYR1, ACTA1, NEB, SELENON, TPM2, TPM3 and MYBPC1, reflecting the true diversity of clinical practice rather than a narrowly selected subgroup.

The crossover design meant every participant served as their own control. After a screening visit, participants were randomised to receive either 24 weeks of daily oral salbutamol added to standard of care, or standard of care alone, followed by a four-week washout and then the alternate treatment. Because participants and treating physicians inevitably knew which treatment was being given, the investigators masked the physiotherapists and occupational therapists who performed all functional assessments, ensuring that outcome measurement remained objective. The primary endpoint was the Motor Function Measure-32, a validated 32-task assessment of gross and fine motor function scored out of 96 points.

The results were unambiguous. During salbutamol treatment, the mean MFM-32 total score rose by 3.72 points, compared with an essentially flat 0.11 points during standard care alone, yielding an adjusted mean difference of 3.61 points in favour of the drug. That margin exceeds previously established thresholds for clinically meaningful change in congenital-onset neuromuscular disorders. Improvements were concentrated in the domains most affected by the disease, namely standing and transfers, and axial and proximal motor function. Dominant hand grip strength also increased significantly, and muscle strength measured by hand-held myometry trended upwards across all tested muscle groups.

Perhaps most striking were the gains in respiratory and ambulatory function. Seated forced vital capacity, a key indicator of breathing capacity, increased by 0.20 litres relative to control, a difference the authors consider particularly important because respiratory insufficiency is a common and morbid manifestation of congenital myopathies even when limb function appears stable. Among the 11 ambulatory participants, six-minute walking distance improved by an estimated 38 metres, and the time needed to rise from lying on the floor fell by 1.6 seconds, corresponding on log-scale analysis to a 9 percent increase in walking distance and a 23 percent reduction in rise time. For families, such gains translate into greater independence and delayed reliance on assistive devices and home adaptations.

Safety and tolerability were reassuring. Only two adverse events occurred during salbutamol treatment, neither clearly related to the drug, and there were no serious adverse events. Six participants experienced mild, expected pharmacological side effects, chiefly transient palpitations and one case of tremor, which resolved within one to two weeks in nearly all cases. No arrhythmias or clinically relevant electrocardiographic abnormalities emerged, blood pressure and heart rate stayed within normal ranges, and no participant discontinued treatment. Notably, every single participant chose to continue taking salbutamol after the study ended. Five participants gained a clinically significant amount of weight during treatment, reporting increased appetite, but statistical adjustment for weight change did not alter the findings.

The authors are careful to acknowledge limitations. The sample of 18 participants, while a triumph of recruitment in such a rare disease, was too small to detect differences in response by genotype, age or sex, and the open-label nature means patient-reported outcomes could be influenced by expectation. Longer-term studies will be needed to determine whether the benefits persist. Nevertheless, the trial stands as the first randomised, controlled, blinded-endpoint study of salbutamol in this population, and its implications reach beyond congenital myopathies. At a time when gene therapies for these disorders have stumbled, one trial was halted after treatment-related deaths, salbutamol offers a low-cost, globally marketed alternative that could be deployed now under multidisciplinary neuromuscular care, with baseline cardiac evaluation and monitoring. The researchers also emphasise a broader lesson: as repurposed medicines enter clinical practice, preserving the affordability and worldwide availability of generic drugs will be essential to ensuring equitable access for the patients who need them.

Subject of Research: A randomised crossover trial of oral salbutamol for motor function and muscle strength in congenital myopathies

Article Title: Effects of oral salbutamol treatment on motor function and muscle strength in congenital myopathies (COMPIS): a single-centre, randomised, open-label, blinded-endpoint, crossover trial in Sweden

Article References: Michael, E., Staaf, P., Gudmundsson, M., Klanac, B., Weichbrodt, J., Edofsson, U., Thuestad, I. J., Sejersen, T., Imberg, H., & Darin, N. (2026). Effects of oral salbutamol treatment on motor function and muscle strength in congenital myopathies (COMPIS): a single-centre, randomised, open-label, blinded-endpoint, crossover trial in Sweden. eClinicalMedicine, Article 104186. https://doi.org/10.1016/j.eclinm.2026.104186

Image Credits: AI Generated

DOI: 10.1016/j.eclinm.2026.104186

Keywords: congenital myopathies, salbutamol, drug repurposing, neuromuscular disorders, randomised crossover trial, muscle strength, motor function, respiratory function, RYR1, pediatric neurology, eClinicalMedicine, rare disease