Alzheimer’s disease is a pathology characterized by the progressive loss of neuronal connections, which leads to gray matter atrophy in the brain. Alzheimer’s disease is the most prevalent type of dementia and has been classified into two types, early onset, which has been associated with genetic factors, and late onset, which has been associated with environmental factors. One of the greatest challenges regarding Alzheimer’s disease is the high economic cost involved, which is why the number of studies aimed at prevention and treatment have increased. One possible approach is the use of resistance exercise training, given that it has been shown to have neuroprotective effects associated with Alzheimer’s disease, such as increasing cortical and hippocampal volume, improving neuroplasticity, and promoting cognitive function throughout the life cycle. However, how resistance exercise training specifically prevents or ameliorates Alzheimer’s disease has not been fully characterized. Therefore, the aim of this review was to identify the molecular basis by which resistance exercise training could prevent or treat Alzheimer’s disease.

Mild cognitive impairment (MCI) and sarcopenia are prevalent age-related conditions that often coexist and share common mechanisms such as chronic inflammation, reduced neuroplasticity, and impaired muscle function. Resistance exercise training (RET) has emerged as a promising non-pharmacological strategy capable of addressing both physical and cognitive decline. The aim of this narrative review is to synthesize preclinical and clinical evidence on the effects of RET in older adults with MCI and sarcopenia, with a specific focus on its impact on neuroinflammation, cognitive performance and structural brain changes. At the molecular level, RET activates anabolic pathways, including PI3K/Akt/mTOR, enhances neurotrophic support via BDNF, NT-3, and IGF-1, and promotes hippocampal neurogenesis through exercise-induced myokines such as irisin and cathepsin B. RET also exerts immunomodulatory actions by shifting microglia toward anti-inflammatory M2 phenotypes, attenuating reactive astrogliosis, and supporting oligodendrocyte precursor cell differentiation, thereby improving myelin integrity. Neuroimaging studies consistently report preservation of hippocampal and precuneus gray matter, as well as improved white matter connectivity following RET. Clinically, RET has demonstrated significant and sustained improvements in executive function, memory, and global cognition, with effects persisting for up to 18 months. Collectively, RET represents a multifaceted intervention with the potential to delay progression from MCI to Alzheimer’s disease by integrating neuroprotective, anti-inflammatory, and anabolic effects. Standardization of RET protocols and identification of biomarkers of responsiveness are needed to optimize its role within multimodal dementia-prevention strategies.

Enhancing our understanding of the specific characteristics that disuse-induced models should possess, based on the immobilized joint, could significantly enhance the effectiveness of research in this field. Objective: Our objective was to quantify the decrease in skeletal muscle mass and strength in humans subjected to upper limb disuse-induced models. Methods: PubMed, Scopus, Web of Science, Embase, LILACS, SPORTDiscus, CINAHL, and Epistemonikos databases were searched from inception to November 2025. Randomized controlled trials, cross-over clinical trials, or quasi-experimental studies performed in healthy adults ≥18 years old, subjected to an induced-disuse model to investigate the effects on skeletal muscle mass or strength were included. Results: Forty-five studies were included. Significant differences in skeletal muscle mass, equivalent to a small effect size (SMD = −0.453; 95% CI = −0.698 to −0.208; p < 0.001) and a total loss of 3.44% (estimated average daily decline = 0.16%) were observed after 21 days of immobilization. Skeletal muscle mass loss was heterogeneous between the arm (5.03%), forearm (1.56%), and hand (4.67%) muscles. Significant differences in strength, equivalent to a large effect size (SMD = −1.36; 95% CI = −1.69 to −1.02; p < 0.001) and a total loss of 18.06% (estimated average daily decline = 1.55%), were observed after 18 days of immobilization. Strength decreases were heterogeneous between the arm (16.67%), forearm (21.42%), and hand (10.46%) muscles. Conclusion: Based on evidence of very low certainty, upper limb disuse-induced models appear to induce a nonlinear loss of skeletal muscle mass and a suggested substantially more severe and rapid loss of strength in healthy young adults, with effects varying heterogeneously across different muscle groups. Despite data limitations, these estimates provide a basis for designing experimental countermeasures, though caution is warranted due to the heterogeneity of the findings.

Ageing and obesity represent major public health challenges and are associated with metabolic dysfunction, chronic inflammation, and loss of skeletal muscle mass. Resistance training (RT) is an effective strategy to increase muscle mass; however, its effects on metabolic and immune parameters in older women with obesity remain unclear. The study aimed to compare the effects of 12-week progressive overload RT programme on metabolic and immune responses in women aged 60–79 years with obesity and normal-weight women. Thirty older women were allocated into two groups according to body composition: women with obesity (OB: 68 ± 4.21 years; body mass index [BMI] = 33.01 ± 2.62 kg/m²; body fat percentage = 42.23% ± 2.98%; n = 16) and normal-weight women (NW: 66 ± 4.31 years; BMI = 22.60 ± 1.36 kg/m²; body fat percentage = 33.11% ± 3.61%; n = 14). At baseline, the OB group showed higher serum concentrations of leptin, insulin, triglycerides, and HOMA-IR and lower HDL cholesterol concentrations compared with the NW group, while no differences were observed in circulating cytokines or NETosis. After 12 weeks of RT, fasting glucose decreased only in the OB group (p = 0.030). Both groups exhibited reductions in total cholesterol and adiponectin, along with an increase in NETosis. Leptin, insulin, and pro-inflammatory cytokines were associated with lower muscle quality, whereas higher baseline adiponectin concentrations were associated with greater muscle mass gains in the NW group (p < 0.05). In conclusion, baseline metabolic differences were observed between normal-weight older women and those with obesity; however, both groups showed changes after 12 weeks of RT in metabolic and immune parameters. Furthermore, higher baseline adiponectin concentrations were associated with greater muscle mass gains in the NW group.