Alzheimer’s disease (AD) is characterized by deficits in learning and memory. A pathological feature of AD is the alterations in the number and size of synapses, axon length, dendritic complexity, and dendritic spine numbers in the hippocampus and prefrontal cortex. Treadmill exercise can enhance synaptic plasticity in mouse or rat models of stroke, ischemia, and dementia. The aim of this study was to examine the effects of treadmill exercise on learning and memory, and structural synaptic plasticity in 3×Tg-AD mice, a mouse model of AD. Here, we show that 12 weeks treadmill exercise beginning in three-month-old mice improves spatial working memory in six-month-old 3×Tg-AD mice, while non-exercise six-month-old 3×Tg-AD mice exhibited impaired spatial working memory. To investigate potential mechanisms for the treadmill exercise-induced improvement of spatial learning and memory, we examined structural synaptic plasticity in the hippocampus and prefrontal cortex of six-month-old 3×Tg-AD mice that had undergone 12 weeks of treadmill exercise. We found that treadmill exercise led to increases in synapse numbers, synaptic structural parameters, the expression of synaptophysin (Syn, a presynaptic marker), the axon length, dendritic complexity, and the number of dendritic spines in 3×Tg-AD mice and restored these parameters to similar levels of non-Tg control mice without treadmill exercise. In addition, treadmill exercise also improved these parameters in non-Tg control mice. Strengthening structural synaptic plasticity may represent a potential mechanism by which treadmill exercise prevents decline in spatial learning and memory and synapse loss in 3×Tg-AD mice.

This study aimed to evaluate the effects of exercise on vascular flow-mediated dilation (FMD) in patients with heart failure (HF) and to identify the optimal exercise model for this population. A comprehensive search was conducted in the Web of Science, Scopus, PubMed, Embase, and Cochrane databases, including data published up to 18 August 2025. A meta-analysis was conducted to calculate standardized mean difference (SMD) and 95% confidence interval. Eleven studies met the inclusion criteria, comprising 224 participants in the intervention groups and 185 participants in the control groups. The results demonstrated that exercise significantly improved FMD (SMD = 1.14, p < 0.0001). Subgroup analysis showed that aerobic exercise (SMD = 1.25, p < 0.0001), intervention period ≤ 8 weeks (SMD = 2.19, p < 0.00001) Intervention frequency > 3 times per week (SMD = 2.82, p < 0.00001) and each intervention duration < 60 min (SMD = 1.22, p = 0.01) were the most effective in improving FMD in patients with HF. This meta-analysis indicates that aerobic exercise performed more than three times per week, for sessions under 60 min and over an intervention period of up to 8 weeks, is associated with meaningful improvements in FMD in HF patients. These findings offer clear and actionable guidance for clinicians when prescribing exercise to support vascular health in this population.