|Year : 2015 | Volume
| Issue : 1 | Page : 6-10
Exercise and neuro-cognitive functions in patients with diabetes mellitus: A Review
Harpreet kour1, VA Kothivale2, Shivaprasad S Goudar2
1 Department of Medicine, JNMC, KLE University, Belagavi, Karnataka, India
2 Department of Physiology, JNMC, KLE University, Belagavi, Karnataka, India
|Date of Web Publication||5-Jun-2015|
Dr. Harpreet kour
Department of Physiology, JNMC, KLE University, Belagavi - 590 010, Karnataka
Source of Support: None, Conflict of Interest: None
The current review integrates findings of published data which provides a comprehensive summary of the neuropsychological assessments conducted and have assessed the patients with type 2 diabetes mellitus (T2DM) for cognitive function. There is a convincing evidence of increased prevalence of T2DM in inactive individuals and cognitive deficits due to poorer control and inappropriate management of the T2DM. Exercise therapy has beneficial effects on improving glycemic control, cardiovascular risk profile, body composition, cardiorespiratory fitness, physical functioning, cognitive functions, and the well-being of patients with T2DM.
Keywords: Cognition, Exercise, Neuropsychology, Type 2 diabetes mellitus
|How to cite this article:|
kour H, Kothivale V A, Goudar SS. Exercise and neuro-cognitive functions in patients with diabetes mellitus: A Review. Indian J Health Sci Biomed Res 2015;8:6-10
|How to cite this URL:|
kour H, Kothivale V A, Goudar SS. Exercise and neuro-cognitive functions in patients with diabetes mellitus: A Review. Indian J Health Sci Biomed Res [serial online] 2015 [cited 2020 Jun 4];8:6-10. Available from: http://www.ijournalhs.org/text.asp?2015/8/1/6/158213
| Introduction|| |
The prevalence of diabetes is rapidly rising all over the globe at an alarming rate due to population growth, aging, urbanization, and an increase of obesity and physical inactivity.  Over the past 30 years, the status of diabetes has changed from being considered as a mild disorder of the elderly to one of the major causes of morbidity and mortality affecting the youth and middle aged people.  The International Diabetes Federation estimates the total number of diabetic subjects to be around 61.3 million in 2011 in India and this is further set to rise to 101.2 million by the year 2030.  In virtually all populations, higher fat diets and decreased physical activity and sedentary occupational habits have accompanied the process of modernization, which has resulted in the doubling of the prevalence of obesity and type 2 diabetes mellitus (T2DM) in less than a generation. 
A less addressed not as well recognized complication of diabetes is cognitive dysfunction. Patients with diabetes mellitus have been found to have cognitive deficits that can be attributed to their disease. Both hypoglycemia and hyperglycemia have been implicated as causes of cognitive dysfunction. Mild to moderate impairments of cognitive functioning has been reported both in patients with T1DM and T2DM. , Exercise has been considered a cornerstone of diabetes management, along with diet and medication. However, high-quality evidence on the importance of exercise and fitness in diabetes was lacking until recent years. This paper tried to review the possible mechanism of cognitive dysfunction and impact of exercise therapy on cognitive functions in patients with T2DM.
| Diabetes and Cognition|| |
There have been a number of studies suggesting an association of diabetes and for cognitive dysfunction and revealed that diabetes is an independent risk factor for neurological disorders. However, many of these studies were cross-sectional and were thus unable to provide estimates of diabetes as a risk factor for cognitive dysfunction. ,,
Bruce  found that 17.5% of elderly patients with T2DM had moderate to severe deficits in activities of daily living, 11.3% had cognitive impairment, and 14.2% had depression.  These findings are supported by previous reviews of the available longitudinal studies. , Framingham study also supported the above statements. In his study 2,123 subjects aged 55-88 completed a neuropsychological test battery and reported people with diabetes status were more likely to achieve scores below the 25 th percentile on most tests than non-diabetic individuals. 
The diabetes control and complications trail was a long-term study, which followed up diabetic patients for about 18 years reported the association between glycemic control and cognitive dysfunction such as a decrease in motor speed and psychomotor efficiency. , The action to control cardiovascular risk in diabetes-memory in diabetes trail also observed the decline in cognitive functions and reported a 0.14 point drop in mini-mental state examination score for each 1% increase in hemoglobin A1c.  Few studies have suggested an increased incidence of Alzheimer's disease and increased the incidence of vascular dementia. ,
Cukierman, concluded that people with diabetes had a 1.2-1.5-fold greater change over time in measures of cognitive functioning and that the odds of future dementia were increased 1.6-fold.  In addition, the risk of cognitive decline was greater for those who had a longer duration of diabetes and for those who were not on treatment. , Sinclair, observed that subjects with mini-mental status exam scores <23 fared worse on measures of self-care and ability to perform activities of daily living. Patients with diabetes have been found to have slower walking speed, lack of balance, and increased falls but whether the cerebral effects of diabetes contributed to these abnormalities is debatable. ,
Few studies have explained number of possibilities showing the association between diabetes and cognitive decline. Hyperglycemia results in neuronal changes to the formation of the advanced glycosylated end product. It is postulated that hyperglycemia leads to neuronal and vascular damage as it caused high osmotic stress, enhanced oxidative phosphorylation and increased the level of glutamate, altogether causes neuronal damage. The relation between hyperglycemia and insulin causing cognitive dysfunction is reported by various cohort studies. ,,,, The study by Hisayama reported the findings of the autopsy as enhanced neurotic plaque formation due to hyperglycemia and hyperinsulinemia. There are many receptors of insulin in the hippocampus and cerebral cortex, which are playing a role in the process of memory. Due to the insufficient action of insulin and down-regulation, the Beta -amyloid peptide will be accumulated and causes cognitive dysfunction. 
Both prospective and longitudinal studies of cognitive function have been so plagued by methodological problems that it is difficult to unequivocally determine whether patients who experience repeated episodes of severe hypoglycemia are at risk for permanent brain injury or intellectual impairment. The relationship between hypoglycemia and cognitive impairment remains unclear. ,
| Physical Activity and Cognition in Diabetic Patients|| |
A growing quantity of the literature reveals that physical activity influences brain function mainly frontal lobe mediated cognitive process such as planning, scheduling, and working memory. ,, Electro cortical activity measured by event-related brain potentials have also shown the effects of exercise on cognition by recording P300. Event-related brain potentials are well studies by P300 and provides an indication of attentional resources allocated to the stimulus. This attention-driven neural activity signal is thought to be generated by multiple brain regions involved in information processing and memory encoding, including the frontal lobes, anterior cingulated cortex, temporal lobe, and parietal cortex.The frontal lobes mediate tasks that require executive cognitive function such as planning, scheduling, inhibition, and working memory.  The anterior cingulate cortex is thought to monitor response conflict. Temporo-parietal activity is thought to be associated with attention and subsequent memory processing, particularly by the hippocampal formation in the medial temporal lobe. ,,, Hillman, in an electrophysiological study of 20 young adults, recorded P300 amplitude and latency during an executive cognitive task performed at baseline and after a single bout of treadmill exercise and shown that exercise increased allocation of attention and memory resources at the neuro-electric level.  Other studies have reported that adults with better physical fitness have larger P300 amplitudes and shorter P300 latencies. These studies show the improvement in cognitive function after exercise. ,,,
The neuro-imaging studies have also provided insights into the effects of physical activity on brain activity and cognition. Structural magnetic resonance imaging studies in older adults have revealed that physical fitness is related to preservation of brain volume.  Adults with better fitness have significantly greater brain volume in frontal, temporal, and parietal cortices in older adults with a 6 month regimen of aerobic training.  The study by Erickson, stated that aerobic fitness not only had increased hippocampal volume compared but also had better performance on a task of spatial memory, a cognitive process sub-served by the hippocampus. 
Pereira, performed a study on adults aged 21-45 years participated in a 3-month aerobic exercise regimen revealed performance on a word recall memory task, the Rey auditory verbal learning test, along with changes in regional cerebral blood volume in the hippocampus, was assessed before and after the exercise training period. 
There are two well-studied molecular mediators that is, brain-derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF-1), which helps in understanding the effect of exercise on cognition.Studies in rats and mice have shown that exercise on running wheel increases hippocampal levels of BDNF, which is very important for synaptic plasticity, learning, and memory. Animal studies have shown that exercise improves performance on the Morris water maze, a task that involves spatial learning and memory, and that injection of a drug that blocks BDNF activity in the hippocampus also blocked the benefit of exercise on the water maze task. ,, In exercising mice, hippocampal BDNF levels increased immediately after exercise and remained elevated for several weeks before returning to baseline levels. Thus, the effects of BDNF on hippocampal function, learning, and plasticity make it a potentially important factor in the mediation of the effects of exercise on cognition.  The IGF-1 provides trophic support to the brain, both through serum IGF-1 that crosses the blood-brain barrier and through IGF-1 produced locally in the brain.  Animal studies have shown that exercise stimulates uptake of IGF-1 from the bloodstream into specific brain areas, including the hippocampus and that blocking IGF-1 uptake in the brain also blocks exercise-mediated increases in adult neurogenesis.  Animals with decreased IGF-1 levels have impaired learning and memory.  In humans, IGF-1 levels decrease with age, and in older adults, serum IGF-1 levels are positively correlated with cognitive performance.  Neurotrophins and growth factors can promote a cellular environment that supports cognition by increasing synaptic plasticity, neurogenesis, and vascular function. 
Exercise increases long-term potentiation in the hippocampus and lowers the threshold for synaptic plasticity. Exercise also increases BDNF signaling and glutamate-mediated synaptic transmission and contributed to the exercise-induced enhancement of synaptic plasticity. Additional research has shown that exercise affects synaptic plasticity through BDNF-and IGF-1-activated kinase signaling cascades (e.g., mitogen-activated protein kinase, calcium/calmodulin protein kinase II), which in turn promote transmission at the synapse through upregulation of synaptic proteins, like synapsin I.  The effect of exercise on BDNF is exerted through the functions of intracellular signaling system, including calcium-calmodulin kinase II and mitogen-activated protein kinase which further helps in functioning of CAMP response element binding protein. It is been documented that infusion of BDNF enhances learning. 
Aerobic exercise improves the physiological parameters including glycemic control, fasting blood-glucose level, and lipid profile. Moreover, it can restore the endothelial function and reduces the arterial stiffness, which is the positive denominator for developing cardiovascular complications in T2DM. Both insulin and exercise increase glucose uptake into skeletal muscle via the glucose transporter from an intracellular to the cell-surface. 
Resistance exercise leads to the development of proper glucose control and less insulin resistance among T2DM Number of studies have documented the potential effects of resistance training.  Various studies have reported to enhance insulin sensitivity, daily energy expenditure, and quality of life with resistance exercises. Furthermore, resistance training has the potential for increasing muscle strength, lean muscle mass, and bone mineral density, which could enhance the functional status and glycemic control. Aerobic exercises have gained attention to improve neurocognitive functioning. Cross-sectional studies have shown that physically active individuals tend to exhibit better neurocognitive function relative to inactive individuals. Prospective observational studies have reported similar findings, demonstrating that individuals who maintain greater levels of physical activity show improvements in neurocognitive function compared to their sedentary counterparts. , However, randomized trials have provided inconsistent results, with some reporting cognitive gains and others equivocal findings [Figure 1].
|Figure 1: Conceptual model: Showing the possible mechanism of cognitive dysfunction and effect of exercise therapy to improve cognitive functions in diabetic population|
Click here to view
| Conclusion|| |
Evidence from both animal and human studies supports the role of physical exercise in modifying metabolic, structural, and functional dimensions of the brain and preserving cognitive performance.
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