Objective The AGUEDA trial examined the effects of a 24-week resistance exercise (RE) intervention on executive function (EF) and other cognitive domains in cognitively normal older adults.

Method Ninety participants (71.75 ± 3.96 years, 57.8% female) were randomized to an RE group (n = 46) or a control group (n = 44). The RE group performed 180 minutes/week of supervised training, while the control group maintained usual activities. EF and other cognitive domains (e.g., attentional/inhibitory control, episodic memory, processing speed, visuospatial processing, and working memory) were assessed at baseline, and 24 weeks. Intervention effects were analyzed using intention-to-treat (ITT) and per-protocol (PP) approaches, with exploratory subgroup analyses based on sociodemographic and AD-related characteristics.

Results EF composite score improved in both groups, with no significant between-group differences (standardized mean difference (SMD) = 0.13, p = 0.37). In addition, the RE group showed significant improvements in attentional/inhibitory control compared to the control group (SMD = 0.43, p < 0.001), while the rest of cognitive domains showed no significant differences (p > 0.05). Subgroup analyses revealed greater EF benefits for the oldest adults, those with lower educational levels, and individuals with higher subjective cognitive decline (SCD) at baseline. RE had an effect on knee extension strength (SMD = 0.25, p = 0.02), which was positively correlated with better EF (r = 0.38, p = 0.0005) and improved episodic memory (r = 0.31, p = 0.008).

Conclusion The 24-week AGUEDA intervention revealed no significant differences in EF or other cognitive domains after 24 weeks. However, participants in the RE group demonstrated significantly greater improvements in attentional/inhibitory control compared to the control group. Moreover, our findings support the notion that RE can yield greater benefits in the more vulnerable subgroups, such as the oldest participants, those with SCD or fewer years of education. Although the mediation analysis did not find significant indirect effects, lower body muscular strength improvements were positively correlated with better EF and episodic memory, highlighting the potential role of strength in cognitive health.

The authors have declared no competing interest.

NCT05186090

https://pmc.ncbi.nlm.nih.gov/articles/PMC10239947/

https://pubmed.ncbi.nlm.nih.gov/37960912/

This work was supported by grant RTI2018/095284/J/100 funded by MCIN/AEI/10.13039/501100011033/ and ERDF Away of making Europe, and RYC2019/027287/I funded by MCIN/AEI/10.13039/501100011033/ and ESF Investing in your future. P.S.U, M.O.R, A.C.P, I.M.F, J.F.O and L.S.A were supported by the Spanish Ministry of Science, Innovation and Universities (Margarita Salas, FPU 22/02476, FPU21/02594, JDC2022/049642/I, FPU22/03052 and FPU21/06192, respectively). AT was supported by the Junta de Andalucia, Spain, under the Postdoctoral Research Fellows (Ref. POSTDOC/21/00745).J.S.M is supported by the National Agency for Research and Development (ANID)/Scholarship Program/DOCTORADO BECAS CHILE/2022(Grant N72220164). EAB has received funding from the European Unions Horizon 2020 research and innovation programme under the Marie Skłodowska Curie grant agreement No [101064851]. This work is part of Ph.D. Thesis conducted in the Biomedicine Doctoral Studies of the University of Granada. B.F.G is supported by MCIN/AEI/10.13039/501100011033 and FSE+ (PID2022/137399OB/I00).

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The trial protocol followed the principles of the Declaration of Helsinki and was approved by the Research Ethics Board of the Andalusian Health Service (CEIM/CEI Provincial de Granada; #2317-N-19) on May 25th, 2020

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