An Exploratory Study of the Short-Term Association of Resistance Training With Circulating Inflammatory Biomarkers, Plasma Brain-Derived Neurotrophic Factor, and Cognitive Function in Healthy Midlife Adults.
Ziyan Y, Deqin C, Fanyue C • Brain and behavior • 2026
A 4-week supervised resistance-training program was associated with lower circulating IL-6 and TNF-α, higher plasma BDNF, and modest improvement in working-memory and inhibitory-control performance in healthy midlife adults.
Key Findings
Results
Plasma IL-6 decreased significantly after 4 weeks of resistance training in the full analytic cohort.
IL-6 decreased from 2.83 ± 1.60 to 2.09 ± 1.34 pg/mL, a mean change of -0.74 pg/mL.
The paired comparison was statistically significant.
Assessments were completed at baseline and 72 hours after the final training session.
Full-cohort analysis included 500 healthy adults aged 50-65 years.
Results
Plasma TNF-α decreased significantly after 4 weeks of resistance training in the full analytic cohort.
TNF-α decreased from 3.61 ± 1.07 to 3.12 ± 0.96 pg/mL, a mean change of -0.49 pg/mL.
The paired comparison was statistically significant.
The study was a single-arm interventional pre-post design with no control group.
Training was conducted three times weekly for 4 weeks.
Results
Plasma BDNF increased significantly after 4 weeks of resistance training in the full analytic cohort.
BDNF increased from 23.4 ± 5.6 to 26.1 ± 6.2 ng/mL, a mean change of +2.7 ng/mL.
The paired comparison was statistically significant.
The study measured plasma rather than central (cerebrospinal fluid) BDNF, which is noted as a limitation.
Participants were healthy adults aged 50-65 years.
Results
Working memory performance as measured by the two-back task improved after 4 weeks of resistance training.
Two-back accuracy increased from 83.7 ± 8.9% to 87.6 ± 7.2%.
Two-back reaction time decreased from 690 ± 89 ms to 652 ± 82 ms.
These changes were part of the primary full-cohort outcomes.
Assessments were completed 72 hours after the final training session.
Results
Inhibitory control performance as measured by the Stroop task improved after 4 weeks of resistance training.
Stroop accuracy increased from 89.8 ± 7.4% to 91.9 ± 6.2%.
Stroop interference decreased from 238 ± 47 ms to 211 ± 41 ms.
These were primary full-cohort outcomes alongside the biomarker measures.
The Stroop task assessed inhibitory control, one component of executive function.
Results
Adherence-stratified analyses showed larger numerical biomarker and cognitive changes among participants completing 11 or more sessions.
The maximum possible sessions over 4 weeks at 3 sessions/week was 12.
These subgroup findings were interpreted descriptively because adherence groups were not randomized.
Secondary adherence-stratified analyses were pre-specified as secondary rather than primary analyses.
Methods
The study enrolled 500 healthy midlife adults after screening 647 individuals, with a single-arm pre-post design.
647 individuals were screened and 500 healthy adults aged 50-65 years entered the supervised resistance-training program.
Training was supervised and conducted three times weekly for 4 weeks.
The study had no control or comparator group, making it a single-arm interventional pre-post design.
Full-cohort analyses were treated as primary analyses, while per-protocol, adherence-stratified, and sensitivity analyses were reported as secondary analyses.
Discussion
The authors identified key limitations including the single-arm design, absence of central biomarkers, and short follow-up duration.
The single-arm design precludes causal inference or comparative efficacy conclusions.
Only plasma BDNF was measured; central biomarkers such as cerebrospinal fluid BDNF were not assessed.
Follow-up was limited to 72 hours after the final session at the end of 4 weeks.
The findings 'reflect within-cohort pre-post associations rather than comparative efficacy and should be interpreted cautiously.'
What This Means
This research suggests that a short, structured resistance exercise program lasting just four weeks may be associated with meaningful changes in both brain-related biology and mental performance in healthy adults aged 50 to 65. Specifically, after completing three supervised sessions per week for four weeks, 500 participants showed lower blood levels of two markers of inflammation (IL-6 and TNF-α) and higher levels of a protein called BDNF (brain-derived neurotrophic factor), which is associated with brain health. Participants also performed better on tests of working memory and the ability to focus and ignore distractions.
This research suggests that even a relatively brief resistance training program may influence inflammatory processes and cognitive function in middle-aged adults, a life stage when low-grade inflammation and subtle mental declines can begin to emerge. People who attended more sessions (11 or more out of a possible 12) tended to show larger improvements in these measures, though this pattern was observed descriptively and was not part of a controlled comparison.
However, it is important to understand the study's limitations: there was no control group of people who did not exercise, so it is not possible to confirm that the training itself caused these changes rather than other factors like seasonal variation, expectation effects, or natural fluctuation. The follow-up period was very short, and the brain-related protein was measured in blood rather than directly in the brain. These findings are best understood as preliminary and hypothesis-generating, pointing toward the need for larger randomized controlled trials to confirm whether resistance training truly causes these benefits.
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Ziyan Y, Deqin C, Fanyue C. (2026). An Exploratory Study of the Short-Term Association of Resistance Training With Circulating Inflammatory Biomarkers, Plasma Brain-Derived Neurotrophic Factor, and Cognitive Function in Healthy Midlife Adults.. Brain and behavior. https://doi.org/10.1002/brb3.71723