Moderate aerobic training modulates cytokines and cortisol profiles in older adults with cognitive abilities
Introduction
Both optimal brain function and optimal cognitive ability result from a status of complete harmony between the functions of the various biological, neural, and hormonal systems. Any disturbance or irregularity in the classical work of these systems caused by age-related factors such as chronic inflammation, abnormal hormone levels, insulin resistance, and oxidative stress results in physical retrogradation of the brain and subsequent cognitive decline [1], [2], [3], [4], [5].
In all aging humans, some degree of decline in cognitive capacity has been shown to be associated with progress in human life. In one’s mid-twenties, significant distortion and changes in the biological framework that controls both thinking and reason occur, as previously reported [6], [7], [8].
Many biological changes, such as a drop in regional brain volume [8], [9], loss of myelin integrity [10], [11], cortical thinning [12], [13], accumulation of neurofibrillary tangles [8], and impairment in levels of hormones such as serotonin, acetylcholine, dopamine receptor binding, and signaling [14], [15], [16], [17], [18], have been reported in many cases of cognitive disabilities. In addition, alterations in the levels of various brain metabolites have been reported in many cases of cognitive disabilities [13]. The unequal occurrence of cognitive decline was investigated among people of older ages [19], [20], [21], [22], [23], [24], [25]. In these studies, it was shown that the rate and severity of cognitive decline is significantly correlated with changes in lifestyle, including adiposity, diet, social network, and medical conditions, along with alterations in biological, physiological, and biochemical systems related to brain function [19], [20], [21], [22], [23], [24], [25]. Previous research reports tried to explain the correlation between experimentally and naturally occurring cortisol levels and cognitive function (CF) [26], [27]. More cortisol (glucocorticoid) is secreted from the adrenal gland under stress conditions. The secretion of cortisol is suggested to be regulated by the release of ACTH from the pituitary gland [26], [27]. Physiologically, cortisol, in combination with the functions of both epinephrine and norepinephrine, activates large skeletal muscles via rapid shifting of blood flow and permits an individual to be ready for threatening situations [28]. Diurnal cortisol levels have gained much more interest not only as an indicator of human stress but also as a measure of neuroendocrine function which potentially links with physical, emotional, and cognitive health [29]. More studies have reported that prolonged exposure to cortisol may have proximal effects on CF by linking with neural transmission and subsequent behavioral performance [30], [31] and more durable and distal effects via neuronal death [32]. Also, it was reported that cortisol and glucocorticoid-related hormones play a pivotal role in association with memory parts in the brain, such as the hippocampus, prefrontal cortex, and amygdala, to improve memory processes via expressing higher levels of GC receptors [33], [34]. These receptors play a role in controlling many cellular changes in brain tissues, such as the reduction of neurogenesis, suppression of LTP in excitatory synapses, cell death through apoptosis, and extensive dendritic re-organization in the prefrontal cortex [34], [35], [36], [37]. The diurnal changes in cortisol levels from higher in the morning to lower in both the afternoon and evening periods show a significant association with higher [38] and lower cognitive function [39].
In older adults, many brain pathological complications, including lower hippocampal volumes, vascular changes in the brain, and neurotransmitter deficits, have been reported to be significantly associated with cognitive impairment [40]. These changes are proposed to occur via chronic inflammation processes, whereas inflammation was shown to play a significant role in the progression and the development of moderate cognitive impairment (MCI) [40]. Previously, the levels of inflammatory mediators C-reactive protein (CRP), tumor necrosis factor (TNF)-α, and interleukin-6 (IL-6) were estimated in the sera of patients with MCI [41], [42], [43]. A significant increase in the risk of cognitive decline in attention/executive function domain scores and MCI was diagnosed in older patients with higher IL-6, CRP, and TNF-α concentrations [41], [42], [43].
Recently, lifestyle variables have been shown to be associated with differential cognitive aging. Generally, active lifestyles are associated with better outcomes, and aerobic exercise in particular has been shown to produce substantial benefits in terms of cognitive function, particularly those tasks requiring executive control [44]. Good physical activity was shown to be correlated with normal hippocampal size and normal cognitive measures, whereas an increase in the levels of physical activity led to an increase in hippocampal volume and subsequent improvement in cognition among older adults following exercise [45]. In addition to that, a direct association with increased hippocampal volume, enhanced spatial memory, increased cerebral blood, and a reduction in brain tissue loss in both healthy individuals and patients with schizophrenia was reported following participation in higher levels of physical exercise [46], [47]. Also, positive effects of increased physical activity have been demonstrated in most studies via significantly improved longevity, easing of multiple chronic disorders, and suppression of age-related degeneration of brain tissues [47], [48], [49].
Various types of physical exercise appear to produce noticeable effects on the brain and cognition [50]. Cross-sectional studies have shown a significant positive association between regular physical exercise or physical fitness and cognitive function, especially executive function in older adults [51]. With inflammation and hormonal stress potentially contributing to the severity and progression of cognitive decline, new exercise-based prevention strategies have been elucidated to reduce or minimize the risk of cognitive decline or dementia [52].
Regular exercise improves human health via enhancing cardiovascular fitness, strengthening the immune system, and improving functional performance in older adults [52], [53], [54], [55], [56]. Also, exercise is suggested to improve and preserve cognitive performance with age in older adults with pre-existing cognitive impairments [54], [57], [58]. Etiologically, regular exercise is considered both neuro-protective and anti-inflammatory and may improve cognition independent of the specific disease state [54], [59], [60]. However, in this type of study, the causal relationship between physical activity and cognitive functions has not been fully elucidated. Thus, the objective of this study was to evaluate both the neuro-protective and anti-inflammatory activities of moderate aerobic exercise in improving cognitive performance among healthy older adults. To this end, serum levels of CRP, TNF-α, IL-6, and cortisol and their correlation with cognitive performance were estimated in all participants.
Section snippets
Subjects
A total of 60 healthy older adults aged 50–85 years were invited to participate in this study via random selection criteria. Participants included in this study were without physical disability; having no endocrine, immune, psychiatric, or eating disorders; and not taking medications such as glucocorticoids or anti-inflammatory drugs that may interfere with cytokine and cortisol blood profiling or cognitive ability measurements. According to the Loewenstein Occupational Therapy Cognitive
Results
A total of 60 healthy older adults participated in this study. Seventy-five percent of the sample were male (n = 45), and 80% of the subjects were highly educated (n = 48). The participants’ cognitive abilities were measured using LOTCA 7-subset scores. Exactly 50% of the participants (n = 30) showed moderate cognitive impairment (LOTCA scores: 84.8 ± 8.2), and the remaining 50% of the participants (n = 30) were diagnosed as normal healthy subjects (LOTCA scores: 98.7 ± 8.1). There were
Discussion
More clinical and sociodemographic studies have reported higher prevalence rates of cognitive disorders at all ages. The occurrence of cognitive impairment, along with its progression rates to AD or dementia, depends mainly on multiple varying factors, including age, gender, and other causal parameters. The prevalence and progression rates of MCI to AD vary according to the type of study, such as clinic-based studies (12–17%), community-based studies (4–15%), and clinical cohorts (14–40%) [72],
Conclusions
Moderate aerobic exercise for 12 weeks showed beneficial effects on cognitive performance in older adults. Our results suggest that 12 weeks of aerobic exercise improves cognitive disorders in older adults via modulating stress and pro-inflammatory cytokines. This may have been due to significant changes in the levels of cortisol, IL-6, TNF-α, and CRP, and physical activity may thus be used as a non-drug strategy for treating cognitive disorders.
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgement
The authors are grateful to the Deanship of Scientific Research, King Saud University for funding through Vice Deanship of Scientific Research Chairs.
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