Alzheimer's dementia (AD) is a worsening of cognitive function characterized by memory loss and executive function impairment as a result of neurodegeneration. AD is the primary cause of disability and dependency among the elderly, and it is growing in tandem with the worldwide aged population. In 2019, there were approximately 55 million people living with dementia globally, and this number is expected to triple by 2050. Although aging is a risk factor for cognitive decline, AD is not a natural part of the aging process (WHO, 2021). Because there is now no effective medication for Alzheimer's disease, it is critical to create preventative efforts by altering risk factors to slow down the pathological process (Tivadar, 2017).

Lack of physical exercise is a modifiable risk factor for dementia (Tivadar, 2017). Nowadays, most people do not engage in regular physical exercise, partly due to time constraints and various difficulties to keep doing physical exercises (Rauf et al., 2018). As a type of endurance exercise, moderate intensity intermittent exercise (MIIE) is considered to be as more enjoyable and has been shown to be as effective as continuous exercise (Afzalpour et al., 2015, Delwing-de Lima et al., 2018, Zoladz et al., 2014). It is also considered safer, more suitable, and easier to tolerate for the elderly population compared to high intensity intermittent exercise (HIIE) due to its lower intensity. Previous studies have reported that MIIE increased serum brain-derived neurotrophic factor (BDNF) levels of patients with Parkinson disease (Zoladz et al., 2014), reduced ovariectomy induced-oxidative stress in the hippocampus, prefrontal cortex, and cerebellum, and also improves spatial learning, memory retention, working memory, and locomotor activity of ovariectomized rats (Kaidah et al., 2018, Rauf et al., 2018). However, currently, there have been no studies that examine the effects of MIIE on the structure and function of the rat hippocampus and its effects on preventing dementia in animal models of hippocampal degeneration.

Because of the necessity of invasive examinations, the forensic autopsy is infrequently performed. Thus, the studies on tissue pathology and molecular biomarkers of the brain of the Alzheimer's disease patient are limited. As a result, animal models will continue to be used to better understand AD pathophysiology and develop treatment and prevention options. Trimethyltin (TMT) can be utilized as an AD induction due to its simplicity of administration and relatively short time from induction to development of AD features (Nurmasitoh et al., 2021). Memory impairment (Yuliani et al., 2018), hippocampal degeneration (Yuliani et al., 2018), neuroinflammation (Lee et al., 2016), and changes in neurotrophic factors (Lee et al., 2016) have all been linked to TMT administration. Furthermore, differential expressions of AD-associated genes such as PSEN-1 and p-tau have been reported in a transcriptome high-throughput analytical analysis of TMT (Little et al., 2012). This study aimed at investigating the possible beneficial effects of MIIE in preventing the impairment of spatial memory function as well as decreasing the hippocampal pyramidal neurons, elevated markers of AD markers, and expression of tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), and BDNF in the hippocampus of TMT-exposed rats.