Home About us Editorial board Ahead of print Current issue Search Archives Submit article Instructions Subscribe Contacts Login 
  • Users Online: 568
  • Home
  • Print this page
  • Email this page
Cover page of the Journal of Health Sciences

 Table of Contents  
Year : 2015  |  Volume : 8  |  Issue : 1  |  Page : 6-10

Exercise and neuro-cognitive functions in patients with diabetes mellitus: A Review

1 Department of Medicine, JNMC, KLE University, Belagavi, Karnataka, India
2 Department of Physiology, JNMC, KLE University, Belagavi, Karnataka, India

Date of Web Publication5-Jun-2015

Correspondence Address:
Dr. Harpreet kour
Department of Physiology, JNMC, KLE University, Belagavi - 590 010, Karnataka
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2349-5006.158213

Rights and Permissions

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 2021 Jan 16];8:6-10. Available from: https://www.ijournalhs.org/text.asp?2015/8/1/6/158213

  Introduction Top

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. [1] 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. [2] 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. [3] 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. [4]

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. [5],[6] 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 Top

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. [7],[8],[9]

Bruce [10] 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. [10] These findings are supported by previous reviews of the available longitudinal studies. [7],[8] 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. [11]

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. [12],[13] 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. [14] Few studies have suggested an increased incidence of Alzheimer's disease and increased the incidence of vascular dementia. [15],[16]

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. [14] 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. [17],[18] 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. [19],[20]

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. [21],[22],[23],[24],[25] 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. [26]

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. [27],[28]

  Physical Activity and Cognition in Diabetic Patients Top

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. [29],[30],[31] 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. [35] 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. [32],[33],[34],[35] 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. [36] 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. [33],[34],[35],[36]

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. [37] 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. [38] 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. [39]

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. [40]

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. [41],[42],[43] 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. [42] 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. [44] 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. [45] Animals with decreased IGF-1 levels have impaired learning and memory. [45] In humans, IGF-1 levels decrease with age, and in older adults, serum IGF-1 levels are positively correlated with cognitive performance. [46] Neurotrophins and growth factors can promote a cellular environment that supports cognition by increasing synaptic plasticity, neurogenesis, and vascular function. [42]

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. [43] 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. [47]

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. [48]

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. [49] 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. [50],[51] 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 Top

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.

  References Top

Huizinga MM, Rothman RL. Addressing the diabetes pandemic: A comprehensive approach. Indian J Med Res 2006;124:481-4.  Back to cited text no. 1
[PUBMED]  Medknow Journal  
Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: Estimates for the year 2000 and projections for 2030. Diabetes Care 2004;27:1047-53.  Back to cited text no. 2
Whiting DR, Guariguata L, Weil C, Shaw J. IDF diabetes atlas: Global estimates of the prevalence of diabetes for 2011 and 2030. Diabetes Res Clin Pract 2011;94:311-21.  Back to cited text no. 3
International Diabetes Federation. IDF Diabetes Atlas. 5 th ed. Brussels, Belgium: International Diabetes Federation; 2011. Available from: http://www.idf.org/diabetesatlas. [Last accessed on 25 Feb 2015].  Back to cited text no. 4
Biessels GJ, Kappelle LJ. Increased risk of Alzheimer′s disease in type II diabetes: Insulin induced pathology. Biochem Soc Trans 2005;33:1041-4.  Back to cited text no. 5
Kappelle JL, Heine RH, Dekker JM, Nijpels G, Kessels RP, Biesselset RJ. Cognitive functioning in elderly persons with type 2 diabetes and metabolic syndrome: The Hoorn Study. Dement Geriatr Cogn Dis 2008;26:261-9.  Back to cited text no. 6
Areosa Sastre A, Grimley Evans J. Effect of the treatment of type II diabetes mellitus on the development of cognitive impairment and dementia. Cochrane Libr 2005. Available from: http://www.cochrane.org/cochrane/revabstr/AB003804.htm. [Last accessed on 25 Feb 2015].  Back to cited text no. 7
Stewart R, Liolitsa D. Type 2 diabetes mellitus, cognitive impairment and dementia. Diabet Med 1999;16:93-112.  Back to cited text no. 8
Munshi M, Grande L, Hayes M, Ayres D, Suhl E, Capelson R. Cognitive dysfunction is associated with poor diabetes control in older adults. Diabetes Care 2006;29:1794-9.  Back to cited text no. 9
Bruce DG, Casey GP, Grange V, Clarnette RC, Almeida OP, Foster JK. Cognitive impairment, physical disability and depressive symptoms in older diabetic patients: The Fremantle Cognition in Diabetes Study. Diabetes Res Clin Pract 2003;61:59-67.  Back to cited text no. 10
Elias PK, Elias MF, D′Agostino RB, Cupples LA, Wilson PW, Silbershatz H. NIDDM and blood pressure as risk factors for poor cognitive performance. The Framingham Study. Diabetes Care 1997;20:1388-95.  Back to cited text no. 11
Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study Research Group, Jacobson AM, Musen G, Ryan CM, Silvers N, Cleary P. Long-term effect of diabetes and its treatment on cognitive function. N Engl J Med 2007;356:1842-52.  Back to cited text no. 12
Jacobson AM, Ryan CM, Cleary PA, Waberski BH, Weinger K, Musen G. Biomedical risk factors for decreased cognitive functioning in type 1 diabetes: An 18 year follow-up of the Diabetes Control and Complications Trial (DCCT) cohort. Diabetologia 2011;54:245-55.  Back to cited text no. 13
Cukierman-Yaffe T, Gerstein HC, Williamson JD, Lazar RM, Lovato L, Miller ME. Relationship between baseline glycemic control and cognitive function in individuals with type 2 diabetes and other cardiovascular risk factors: The action to control cardiovascular risk in diabetes-memory in diabetes (ACCORD-MIND) trial. Diabetes Care 2009;32:221-6.  Back to cited text no. 14
Imamine R, Kawamura T, Umemura T, Umegaki H, Kawano N, Hotta M. Does cerebral small vessel disease predict future decline of cognitive function in elderly people with type 2 diabetes? Diabetes Res Clin Pract 2011;94:91-9.  Back to cited text no. 15
Perantie DC, Koller JM, Weaver PM, Lugar HM, Black KJ, White NH. Prospectively determined impact of type 1 diabetes on brain volume during development. Diabetes 2011;60:3006-14.  Back to cited text no. 16
Logroscino G, Kang JH, Grodstein F. Prospective study of type 2 diabetes and cognitive decline in women aged 70-81 years. BMJ 2004;328:548.  Back to cited text no. 17
Kumari M, Marmot M. Diabetes and cognitive function in a middle-aged cohort: Findings from the Whitehall II study. Neurology 2005;65:1597-603.  Back to cited text no. 18
Sinclair AJ, Girling AJ, Bayer AJ. Cognitive dysfunction in older subjects with diabetes mellitus: Impact on diabetes self-management and use of care services. All Wales Research into Elderly (AWARE) Study. Diabetes Res Clin Pract 2000;50:203-12.  Back to cited text no. 19
Gregg EW, Brown AM. Cognitive and physical disabilities and aging-related complications of diabetes. Clin Diabetes 2003;21:113-8.  Back to cited text no. 20
Biessels GJ, Staekenborg S, Brunner E, Brayne C, Scheltens P. Risk of dementia in diabetes mellitus: A systematic review. Lancet Neurol 2006;5:64-74.  Back to cited text no. 21
Kodl CT, Seaquist ER. Cognitive dysfunction and diabetes mellitus. Endocr Rev 2008;29:494-511.  Back to cited text no. 22
Strachan MW. R D Lawrence Lecture 2010. The brain as a target organ in type 2 diabetes: Exploring the links with cognitive impairment and dementia. Diabet Med 2011;28:141-7.  Back to cited text no. 23
Heikkilä O, Lundbom N, Timonen M, Groop PH, Heikkinen S, Mäkimattila S. Hyperglycaemia is associated with changes in the regional concentrations of glucose and myo-inositol within the brain. Diabetologia 2009;52:534-40.  Back to cited text no. 24
Lyoo IK, Yoon SJ, Musen G, Simonson DC, Weinger K, Bolo N. Altered prefrontal glutamate-glutamine-gamma-aminobutyric acid levels and relation to low cognitive performance and depressive symptoms in type 1 diabetes mellitus. Arch Gen Psychiatry 2009;66:878-87.  Back to cited text no. 25
Yoshitake T, Kiyohara Y, Kato I, Ohmura T, Iwamoto H, Nakayama K. Incidence and risk factors of vascular dementia and Alzheimer′s disease in a defined elderly Japanese population: The Hisayama Study. Neurology 1995;45:1161-8.  Back to cited text no. 26
Feil DG, Rajan M, Soroka O, Tseng CL, Miller DR, Pogach LM. Risk of hypoglycemia in older veterans with dementia and cognitive impairment: Implications for practice and policy. J Am Geriatr Soc 2011;59:2263-72.  Back to cited text no. 27
Strachan MW, Dreary IJ, Ewing FM, Frier BM. Recovery of cognitive function and mood after severe hypoglycemia in adults with insulin-treated diabetes. Diabetes Care 2000;23:305-12.  Back to cited text no. 28
Sibley BA, Etnier JL, Le Masurier GC. Effects of an acute bout of exercise on cognitive aspects of Stroop performance. J Sport Exerc Psychol 2006;28:285-99.  Back to cited text no. 29
Hamilton MT, Hamilton DG, Zderic TW. Role of low energy expenditure and sitting in obesity, metabolic syndrome, type 2 diabetes, and cardiovascular disease. Diabetes 2007;56:2655-67.  Back to cited text no. 30
Etnier JL, Chang YK. The effect of physical activity on executive function: A brief commentary on definitions, measurement issues, and the current state of the literature. J Sport Exerc Psychol 2009;31:469-83.  Back to cited text no. 31
Polich J, Lardon MT. P300 and long-term physical exercise. Electroencephalogr Clin Neurophysiol 1997;103:493-8.  Back to cited text no. 32
Polich J. Updating P300: An integrative theory of P3a and P3b. Clin Neurophysiol 2007;118:2128-48.  Back to cited text no. 33
Pontifex MB, Hillman CH, Fernhall B, Thompson KM, Valentini TA. The effect of acute aerobic and resistance exercise on working memory. Med Sci Sports Exerc 2009;41:927-34.  Back to cited text no. 34
Kramer AF, Erickson KI, Colcombe SJ. Exercise, cognition, and the aging brain. J Appl Physiol 2006;101:1237-42.  Back to cited text no. 35
Hillman CH, Snook EM, Jerome GJ. Acute cardiovascular exercise and executive control function. Int J Psychophysiol 2003;48:307-14.  Back to cited text no. 36
Colcombe SJ, Erickson KI, Raz N, Webb AG, Cohen NJ, McAuley E. Aerobic fitness reduces brain tissue loss in aging humans. J Gerontol A Biol Sci Med Sci 2003;58:176-80.  Back to cited text no. 37
Gordon BA, Rykhlevskaia EI, Brumback CR, Lee Y, Elavsky S, Konopack JF. Neuroanatomical correlates of aging, cardiopulmonary fitness level, and education. Psychophysiology 2008;45:825-38.  Back to cited text no. 38
Erickson KI, Prakash RS, Voss MW, Chaddock L, Hu L, Morris KS. Aerobic fitness is associated with hippocampal volume in elderly humans. Hippocampus 2009;19:1030-9.  Back to cited text no. 39
Pereira AC, Huddleston DE, Brickman AM, Sosunov AA, Hen R, McKhann GM. An in vivo correlate of exercise-induced neurogenesis in the adult dentate gyrus. Proc Natl Acad Sci U S A 2007;104:5638-43.  Back to cited text no. 40
Cotman CW, Berchtold NC, Christie LA. Exercise builds brain health: Key roles of growth factor cascades and inflammation. Trends Neurosci 2007;30:464-72.  Back to cited text no. 41
Vaynman S, Gomez-Pinilla F. Revenge of the "sit": How lifestyle impacts neuronal and cognitive health through molecular systems that interface energy metabolism with neuronal plasticity. J Neurosci Res 2006;84:699-715.  Back to cited text no. 42
Trejo JL, Llorens-Martín MV, Torres-Alemán I. The effects of exercise on spatial learning and anxiety-like behavior are mediated by an IGF-I-dependent mechanism related to hippocampal neurogenesis. Mol Cell Neurosci 2008;37:402-11.  Back to cited text no. 43
Trejo JL, Carro E, Torres-Aleman I. Circulating insulin-like growth factor I mediates exercise-induced increases in the number of new neurons in the adult hippocampus. J Neurosci 2001;21:1628-34.  Back to cited text no. 44
Arwert LI, Deijen JB, Drent ML. The relation between insulin-like growth factor I levels and cognition in healthy elderly: A meta-analysis. Growth Horm IGF Res 2005;15:416-22.  Back to cited text no. 45
Holloszy JO, Hansen PA. Regulation of glucose transport into skeletal muscle. Rev Physiol Biochem Pharmacol 1996;128:99-193.  Back to cited text no. 46
Gligoroska JP, Manchevska S. The effect of physical activity on cognition - Physiological mechanisms. Mater Sociomed 2012;24:198-202.  Back to cited text no. 47
Poehlman ET, Dvorak RV, DeNino WF, Brochu M, Ades PA. Effects of resistance training and endurance training on insulin sensitivity in nonobese, young women: A controlled randomized trial. J Clin Endocrinol Metab 2000;85:2463-8.  Back to cited text no. 48
Garvey WT, Maianu L, Zhu JH, Brechtel-Hook G, Wallace P, Baron AD. Evidence for defects in the trafficking and translocation of GLUT4 glucose transporters in skeletal muscle as a cause of human insulin resistance. J Clin Invest 1998;101:2377-86.  Back to cited text no. 49
Hurley BF, Roth SM. Strength training in the elderly: Effects on risk factors for age-related diseases. Sports Med 2000;30:249-68.  Back to cited text no. 50
Boulé NG, Kenny GP, Haddad E, Wells GA, Sigal RJ. Meta-analysis of the effect of structured exercise training on cardiorespiratory fitness in type 2 diabetes mellitus. Diabetologia 2003;46:1071-81.  Back to cited text no. 51


  [Figure 1]

This article has been cited by
1 Association Between Physical Activity and Cognitive Function Among a National Sample of Adults With Diabetes
Emily Frith,Paul D. Loprinzi
Cardiopulmonary Physical Therapy Journal. 2018; 29(2): 81
[Pubmed] | [DOI]


Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

  In this article
Diabetes and Cog...
Physical Activit...
Article Figures

 Article Access Statistics
    PDF Downloaded319    
    Comments [Add]    
    Cited by others 1    

Recommend this journal