1. Introduction
The global average life expectancy has been increasing, leading to a rapid progression of aging worldwide and the prevalence of dementia is rapidly increasing worldwide [
1]
Dementia is the loss of cognitive functioning and ability to lead one’s daily life. It is the most prevalent neurodegenerative disease among the elderly, and such cognitive dysfunction is a primary cause of poor quality of life [
2].
The types of dementia include Alzheimer’s Disease (AD), vascular dementia, Parkinson’s Disease, and other types of dementia caused by various underlying factors. AD, which accounts for approximately 70% of dementia cases [
3], causes dysfunction of the synapses as nerve cells die [
4] due to deposition of β-amyloid (Aβ) [
5] and reduction of brain-derived neurotrophic factor (BDNF) [
6]. It negatively affects cognitive and neurodegenerative processes and causes a state of cognitive dysfunction in perception, logic, reasoning, and awareness [
7].
According to a report by Seoul National University Hospital [
8], the neuropathology of AD begins 15 to 20 years prior to the appearance of such symptoms as problems with memory and spatiotemporal abilities, loss of linguistic abilities, and loss of identity, and the decline in cognitive function begins in the 50s and accelerates after the age of 65 [
9]. In addition, the prevalence of dementia is higher among females than males [
3], and females aged 60 to 74 are at a higher risk of cognitive decline than females aged 50 to 59 [
10]. Therefore, to prevent AD, it is important to manage the pathological factors that cause dementia, and the pathological risk factors include Aβ and BDNF [
11].
Aβ is generated in the brain when the amyloid precursor protein (APP) is metabolized by β-secretase and γ-secretase, which are enzymes located in the hippocampus, the most crucial area of the brain for memory and cognitive function. Aβ then aggregates to form amyloid plaques in the brain [
12]. The accumulated Aβ induces neuronal cell death through the formation of amyloid plaques [
13], leading to oxidative damage, blood-brain barrier (BBB) dysfunction, and the development of neurofibrillary tangles in nerve fibers [
14]. This, in turn, causes AD by impairing learning and memory formation abilities, disturbing the processing of new information, and causing behavioral dysfunctions [
15].
In this respect, reducing or inhibiting Aβ has been proposed as a primary treatment method for AD, but most treatments depend on existing medications. However, it is possible to lower plasma Aβ concentrations through exercise [
16], and the greater the amount of physical activity, the lower the Aβ concentration that has been observed [
17].
BDNF concentration in the body, on the other hand, becomes lower with increasing age. Because its concentration in elderly females is lower than in elderly males, it serves as an indicator of memory and cognitive impairment in older females [
18]. Thus, a decrease in plasma BDNF levels increases the probability of AD onset [
6], but it is possible to delay the progression of dementia by increasing BDNF levels through exercise (Nagahara et al., 2009).
Cognitive function is critical in determining quality of life in old age, so managing cognitive decline is necessary to maintain and improve quality of life [
19]. Regular exercise in old age can reduce the occurrence of dementia by up to 60%, while low levels of physical activity increase the prevalence of AD by 25% [
20].
Regular exercise can promote cognitive function and act as a major factor in the prevention of AD by increasing the expression of proteins involved in neuroregeneration in the brain, such as BDNF, and decreasing the expression of Aβ, a key component of AD [
21].
While exercise can maintain and improve cognitive function, social distancing, as well as limited operations and closures of exercise facilities due to COVID-19, has changed existing patterns of daily life. This has led to decreased time spent on physical activities [
22] and lower rates of participation in regular exercise compared to the pre-pandemic period [
23]. This decline in physical activities has reduced energy consumption, leading to an increase in the probability of sarcopenic obesity [
24].
Furthermore, obesity causes functional and structural changes in the brain by reducing the expression of neurotrophic factors such as BDNF, which plays a vital role in neuroplasticity and neurogenesis, and by damaging cerebral vessels and BBB, leading to reduced cognitive functions and cognitive impairments [
25]. Obese elderly individuals are less cognitively capable than elderly persons with normal body weight [
26].
Those newly participating in or continuing physical exercises require easy accessibility in terms of time and location and generation of internal motivation. Exercising with others is more effective than exercising alone, and combinations of two or more safe exercises are more effective in improving motor functions in the elderly than performing a single type of exercise [
27].
Among physical exercises, circuit training using weight load alternates between aerobic and resistance exercises and allows for engaging in various exercises within a short period of time and continued participation with interest. Additionally, circuit training is an enjoyable exercise method for anyone because of its low risk of injury, limited spatial restrictions, and flexibility to be performed with a group rather than alone.
Therefore, the present study aims to investigate the effect of circuit training on β-amyloid, BDNF, and cognitive function in untrained obese elderly Korean women aged 65 to 70, who are at a higher risk of developing dementia and accelerated cognitive decline than elderly males. It also aims to provide baseline data to be used in programs for preventing AD and improving physical functions and quality of life in the future.
4. Discussion
Because hippocampal neurons are produced even after a person has reached adulthood [
30], long-term exercises of appropriate intensity have a positive effect on preventing AD [
31] and improving cognitive functions through enhancing cognitive performance, short-term memory, and long-term memory [
32].
Therefore, exercise in the elderly at the onset of aging can improve cognitive function by affecting the reduction of Aβ and increase of BDNF, which are risk factors for AD [
21].
Aβ decreased in elderly females after the intervention of 60-minute sessions of aerobic and anaerobic exercises three times a week for 12 weeks [
21]. A decrease in Aβ was also observed in elderly females who engaged in 8quarobics exercises for 50 minutes per session three times a week for 24 weeks [
33], as well as in elderly females who performed a combination of elastic band and 8quarobics exercises for 90 minutes per session three times a week for 16 weeks [
16].
Prior studies on Aβ and exercise intensity in elderly females reported a significant decrease in Aβ after participants performed Taekwondo Poomsae at 50–75% HRR for 60 minutes per session three times a week for 12 weeks [
34], a decrease in the Aβ index after participants performed a combination of physical stimulation and walking exercises at 60–70% of maximum heart rate for 45–60 minutes per session for 24 weeks [
35], and a decrease in Aβ after participants performed combined aerobic and anaerobic exercises at 50–70% intensity of target heart rate for 60 minutes per session three times a week for 12 weeks [
21].
The mechanism of Aβ decrease can generally be explained as follows: α-secretase metabolizes APP when blood flow to the brain is increased during exercise and inhibits the formation of plaques in the brain [
36].
Therefore, the reason for the decrease in Aβ in the present study appears to be the choice of 40–70% HRR as an appropriate exercise intensity for elderly females whose overall strength has been reduced due to aging. Regular circuit training increased the blood flow to and stable oxygenation of the brain, causing a rise in BDNF concentration, which is essential for the survival of nerve cells. The increased BDNF concentration activated non-amyloidogenic pathways with α-secretase and γ-secretase, leading to enhanced amyloid metabolism and a decrease in Aβ.
Serum and plasma BDNF in circulation can be indicators of BDNF in the central nervous system because BDNF is a myokine that is released by skeletal muscle cells and can cross the BBB in both directions [
37], and the elevated plasma BDNF concentration is influenced by the type and intensity of exercise [
38].
Prior studies on BDNF expression according to types of exercises showed that, for myokinetic BDNF, muscular resistance exercises that directly stimulate muscles could increase plasma BDNF concentration [
39]. However, aerobic exercises were more effective than resistance exercises [
40], and concurrent exercises were more effective than single resistance exercises in increasing plasma BDNF concentration [
41].
As BDNF is affected by the exercise intensity, the increase of BDNF concentration was higher for mid- and high-intensity exercises (70% oxygen uptake reserve; %VO2R) than for low-intensity exercises (40% VO2R) [
42], and only exercising with an intensity of 60% HRR or higher makes that increase possible [
43]. Choi and Yoon [
44] reported a significant increase in BDNF as a result of performing concurrent exercises of RPE 11–15.
Therefore, the increase in BDNF in the current study is most likely due to the application of aerobic-type circuit exercises with 65–70% intensity, which could provide more nutrition and oxygen to the brain cells by increasing the flow of blood and its speed to the brain. In addition, resistance exercises involving repeated contractions of skeletal muscles are likely more effective than than a single movement.
The general characteristics of BDNF changes are the decrease of plasma BDNF levels with increased age [
45], lower levels for ill or diseased persons [
46], and lower levels in females than in males [
18]. However, adults without existing medical conditions who have stable BDNF concentrations can no longer significantly increase BDNF concentrations due to the ceiling effect [
47]. Additionally, reduced body fat through exercise increases the rate of BDNF expression in obese persons [
48], and the sensitivity of BDNF change is higher in obese females than in obese males [
49].
Therefore, the higher sensitivity to BDNF of the participants, who were obese elderly females, and the improvement in body fat percentage from positive changes in body composition through exercise are suspected to be additional factors explaining a significant increase in BDNF concentration in the current study.
Cognitive functions are enhanced by regenerating damaged neurons and peripheral nerves and generating cerebral neurons through the expression of neurotropic factors [
50,
51].
The MMSE-K index improved in elderly females after they performed 60 minutes of circuit exercises three times a week for 12 weeks [
28], and the MMSE-K score increased from 25.14 to 26.86 after 12 weeks of concurrent exercise among women with a mean age of 65 [
52]. In addition, an improvement in physical and psychological abilities was observed after participation in exercises; as a result of performing combination exercises including 15-to-30-minute walks, strength exercises, and aquarobic exercises three or more times per week, elderly persons aged 65 and above showed enhanced memory, problem-solving abilities, linguistic abilities, attention, concentration, and mind and body stability [
53].
Exercise must be of appropriate duration, intensity, and frequency to improve cognitive function [
54], and cognitive decline cannot be prevented when the duration and intensity of exercises are reduced [
55].
Analysis of cognitive function and the duration of exercise intervention showed that the effect was prominent in the order of 16 weeks or more, 12 weeks, 8 weeks, and 4 weeks, with the most significant effect of exercise observed for 16 weeks, followed by 12 weeks [
56,
57]. Mid- and high-intensity physical activities correlated highly with cognitive function [
58]. The group that participated the least in mid- and high-intensity exercises was 0.65 times more likely to be at risk of cognitive dysfunction than the group that participated the most [
59]. Those who were more active, especially those who exercised more than three times a week, were at a lower risk of developing dementia [
60].
The results of these prior studies collectively show that exercises are effective in maintaining cognitive functions or slowing cognitive decline only when mid- and high-intensity exercises are performed more than three times a week for 16 weeks.
Therefore, the improvement in cognitive function in the current study seems to have resulted from continuous and regular exercise participation three times a week for 16 weeks, while increasing HRR and RPE every four weeks to mid- to high-intensity exercise with 65–70% HRR during the final weeks. The expression of BDNF, a myokine released during the contraction of skeletal muscles, is increased due to repeated muscle contraction in the upper and lower extremities, and cognitive functions are enhanced by the mechanism of inhibiting the α-secretase activity in the non-amyloidogenic pathway that results in the production of Aβ, which causes toxicity.
People who have been physically active or participated in regular exercise programs before becoming elderly delay cognitive decline, have lower Aβ expression, are at less risk of cognitive impairment when elderly [
61], and have increased BDNF [
62] compared to those who have not. A 10-year follow-up study of 295 males revealed that the cognitive function of the group of elderly persons with reduced physical activity decreased 2.6 times more than the group that maintained physical activity, and the delay of cognitive decline was only possible when engaging in exercises of moderate intensity or higher [
63]. An analysis of the relationship between walking and cognitive function among women aged 65 years or older showed that the group that walked effectively prevented the decline of cognitive functions after six to eight years [
64].
Therefore, when elderly females begin to age, they must exercise regularly and continuously to avoid an increase in Aβ and decrease in BDNF, risk factors of AD, thereby preventing cognitive decline and maintaining and improving their quality of life.