Abstract
According to existing scientific evidence, diabetes mellitus is associated with mild to modest decrements in cognitive function. Domains of psychomotor speed, mental flexibility, attention, and general intelligence are those most frequently affected. Hypoglycemia is not usually risk factor for cognitive decline; however, this may not be true for children with young age at onset of diabetes. Relevant risk factors for the development of cognitive decline are an early age of onset and the presence of microvascular complications. Since age and duration of diabetes are important contributors to the changes in cognitive function, we need longitudinal studies looking at cognitive function, especially in elderly subject with type 1 diabetes mellitus. In addition, more information is needed in order to better understand the clinical implications of these mild-moderate decrements in cognitive function, also in terms of impact on daily lives and habits. In addition, the underlying mechanism and the risk factors that may lead to the development of more severe cognitive dysfunction like dementia in some, but not all diabetic patients are not clear.
Diabetic autonomic neuropathy (DAN) represents a particular aspect of diabetic neuropathy, which may lead to impairment of several organs, including the heart, both in type 1 and type 2 diabetic patients. The pathogenesis of DAN is not entirely clear, but metabolic, genetic, and hormonal factors may be involved; however, the final pathway probably involves oxidative stress and inflammation caused by hyperglycemia. Since no therapy was demonstrated to effectively reverse DAN, prevention with close glycemic control, multifactorial intervention, and lifestyle modification remain crucial.
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References
Biessels GJ. Risk of dementia in diabetes mellitus: a systematic review. Lancet Neurol. 2006;5:64–74.
Miles WR, Root HF. Psychologic tests applied to diabetic patients. Arch Intern Med. 1922;30:767.
Dejong R. The nervous system complications of diabetes mellitus, with special reference to cerebrovascular changes. J Nerv Ment Dis. 1950;111:181–206.
Mijnhout GS, Scheltens P, Diamant M, Biessels GJ, Wessels AM, Simsek S, et al. Diabetic encephalopathy: a concept in need of a definition. Diabetologia. 2006;49:1447–8.
Moheet A, Mangia S, Seaquist ER. Impact of diabetes on cognitive function and brain structure. Ann N Y Acad Sci. 2015;1353:60–71.
Qureshi AI, Caplan LR. Intracranial atherosclerosis. Lancet. 2014;383(9921):984–98.
Ergul A, Kelly-Cobbs A, Abdalla M, Fagan SC. Cerebrovascular complications of diabetes: focus on stroke. Endocr Metab Immune Disord Drug Targets. 2012;12:148–58.
van Sloten TT, Sedaghat S, Carnethon MR, Launer LJ, Stehouwer CDA. Cerebral microvascular complications of type 2 diabetes: stroke, cognitive dysfunction, and depression. Lancet Diabetes Endocrinol. 2020;8:325–36.
Bell DSH, Goncalves E. Stroke in the patient with diabetes (Part 1)—epidemiology, etiology, therapy and prognosis. Diabetes Res Clin Pract. 2020;164:108193.
Kodl C, Franc D, Rao J, et al. Diffusion tensor imaging identifies deficits in white matter microstructure in subjects with type 1 diabetes that correlate with reduced neurocognitive function. Diabetes. 2008;57:3083–9.
Mangia S, Kumar AF, Moheet AA, Roberts RJ, Eberly LE, Seaquist ER, et al. Neurochemical profile of patients with type 1 diabetes measured by H-1-MRS at 4 T. J Cereb Blood Flow Metab. 2013;33:754–9.
Fang F, Zhan YF, Zhuo YY, Yin DZ, Li KA, Wang YF. Brain atrophy in middle-aged subjects with type 2 diabetes mellitus, with and without microvascular complications. J Diabetes. 2018;10:625–32.
Moran C, Phan TG, Chen J, Blizzard L, Beare R, Venn A, et al. Brain atrophy in type 2 diabetes regional distribution and influence on cognition. Diabetes Care. 2013;36:4036–42.
den Heijer T, Vermeer SE, van Dijk EJ, Prins ND, Koudstaal PJ, Hofman A, et al. Type 2 diabetes and atrophy of medial temporal lobe structures on brain MRI. Diabetologia. 2003;46:1604–10.
Mankovsky B, Zherdova N, van den Berg E, Biessels GJ, de Bresser J. Cognitive functioning and structural brain abnormalities in people with Type 2 diabetes mellitus. Diabet Med. 2018;35:1663–70.
Sanjari Moghaddam H, Ghazi Sherbaf F, Aarabi MH. Brain microstructural abnormalities in type 2 diabetes mellitus: A systematic review of diffusion tensor imaging studies. Front Neuroendocrinol. 2019;55:100782.
Horton WB, Barrett EJ. Microvascular dysfunction in diabetes mellitus and cardiometabolic disease. Endocr Rev. 2021;42:29–55.
Manolis AJ, Kallistratos MS, Vlahakos DS, Mitrakou A, Poulimenos LE. Comorbidities often associated with brain damage in hypertension: diabetes, coronary artery disease, chronic kidney disease and obstructive sleep apnea. In: Coca A, editor. Hypertension and brain damage. Springer Switzerland; 2016. p. 35–46.
Zhao X, Han Q, Gang X, Wang G. Altered brain metabolites in patients with diabetes mellitus and related complications—evidence from 1H MRS study. Biosci Rep. 2018;38(5):BSR20180660.
Brands AM, Biessels GJ, de Haan EH, Kappelle LJ, Kessels RPC. The effects of type 1 diabetes on cognitive performance: a meta-analysis. Diabetes Care. 2005;28:726–35.
Gaudieri PA. Cognitive function in children with type 1 diabetes: a meta-analysis. Diabetes Care. 2008;31:1892–7.
Jacobson A, Musen G, Ryan C, Silvers N, Cleary P, Waberski B, et al. Long-term effect of diabetes and its treatment on cognitive function. N Engl J Med. 2007;356:1842–52.
Reichard P, Pihl M, Rosenqvist U, Sule J. Complications in IDDM are caused by elevated blood glucose level: the Stockholm Diabetes Intervention Study (SDIS) at 10-year follow up. Diabetologia. 1996;39:1483–8.
Rawlings AM, Sharrett AR, Schneider ALC, Coresh J, Albert M, Couper D, et al. Diabetes in midlife and cognitive change over 20 years: a cohort study. Ann Intern Med. 2014;161:785–93.
Ott A, Stolk RP, van Harskamp F, Pols HA, Hofman A, Breteler MM. Diabetes mellitus and the risk of dementia—the Rotterdam study. Neurology. 1999;53:1937–42.
van den Berg E, Kloppenborg RP, Kessels RPC, Kappelle LJ, Biessels GJ. Type 2 diabetes mellitus, hypertension, dyslipidemia and obesity: a systematic comparison of their impact on cognition. Biochim Biophys Acta. 2009;1792:470–81.
Palta P, Schneider ALC, Biessels GJ, Touradji P, Hill-Briggs F. Magnitude of cognitive dysfunction in adults with type 2 diabetes: a meta-analysis of six cognitive domains and the most frequently reported neuropsychological tests within domains. J Int Neuropsychol Soc. 2014;20:278–91.
Hajek T, McIntyre R, Alda M. Bipolar disorders, type 2 diabetes mellitus, and the brain. Curr Opin Psychiatry. 2016;29:1–6.
Zilliox LA, Chadrasekaran K, Kwan JY, Russell JW. Diabetes and cognitive impairment. Curr Diab Rep. 2016;16:87.
Cameron FJ, Northam EA, Ryan CM. The effect of type 1 diabetes on the developing brain. Lancet Child Adolesc Health. 2019;3:427–36.
Agabiti-Rosei E, Rizzoni D, Cunha P. Pathophysiology of brain damage in hypertension. In: Coca A, editor. Hypertension and brain damage. Springer Switzerland; 2016. p. 47–60.
De Ciuceis C. Microvascular alterations in diabetes: focus on small resistance arteries. In: Agabiti-Rosei E, Heagerty AM, Rizzoni D, editors. Microcirculation in cardiovascular diseases. Springer Switzerland; 2020. p. 149–64.
Muriach M, Flores-Bellver M, Romero FJ, Barcia JM. Diabetes and the brain: oxidative stress, inflammation, and autophagy. Oxid Med Cell Longev. 2014;2014:102158.
Bogush M, Heldt NA, Persidsky. Blood brain barrier injury in diabetes: unrecognized effects on brain and cognition. J Neuroimmune Pharmacol. 2017;12:593–601.
Goldwaser EL, Acharya NK, Sarkar A, Godsey G, Nagele RG. Breakdown of the cerebrovasculature and blood-brain barrier: a mechanistic link between diabetes mellitus and Alzheimer's disease. J Alzheimers Dis. 2016;54:445–56.
Li W, Risacher SL, Huang E, Saykin AJ, Alzheimer's Disease Neuroimaging Initiative. Type 2 diabetes mellitus is associated with brain atrophy and hypometabolism in the ADNI cohort. Neurology. 2016;87:595–600.
Biessels GJ. Cerebral complications of diabetes: clinical findings and pathogenetic mechanism. Neth J Med. 1999;54:35–45.
Talbot F, Nouwen A. A review of the relationship between depression and diabetes in adults. Diabetes Care. 2000;23:1556–62.
Said G. Diabetic neuropathy. Handb Clin Neurol. 2013;115:579–89.
Verrotti A, Prezioso G, Scattoni R, Chiarelli F. Autonomic neuropathy in diabetes mellitus. Front Endocrinol (Lausanne). 2014;5:205.
Pasnoor M, Dimachkie MM, Kluding P, Barohn RJ. Diabetic neuropathy part1:overview and symmetric phenotypes. Neurol Clin. 2013;31:425–45.
Boulton AJ, Gries FA, Jervell JA. Guidelines for diagnosis and outpatient management of diabetic peripheral neuropathy. Diabetes Metab. 1998;15:508–14.
Tesfaye S, Boulton AJ, Dyck PJ, Freeman R, Horowitz M, Kempler P, et al. Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments. Diabetes Care. 2010;33:2285–93.
Ewing DJ, Martyn CN, Young RJ, Clarke BF. The value of cardiovascular autonomic function tests: 10 years’ experience in diabetes. Diabetes Care. 1985;8:491–8.
Pop-Busui R. Cardiac autonomic neuropathy in diabetes: a clinical perspective. Diabetes Care. 2010;33:434–41.
Pavy-LeTraon A, Fontaine S, Tap G, Guidolin B, Senard JM, Hanaire H. Cardiovascular autonomic neuropathy and other complications in type 1 diabetes. Clin Auton Res. 2010;20:153–60.
Tantucci C, Scionti L, Bottini P, Dottorini ML, Puxeddu E, Casucci G, et al. Influence of autonomic neuropathy of different severities on the hypercapnic drive to breathing in diabetic patients. Chest. 1997;112:145–53.
Fujihara K, Kodama S, Horikawa C, Yoshizawa S, Sugawara A, Hirasawa R, et al. The relationship between diabetic neuropathy and sleep apnea syndrome: a meta-analysis. Sleep Disord. 2013;2013:150371.
Chandrasekharan B, Srinivasan S. Diabetes and the enteric nervous system. Neurogastroenterol Motil. 2007;19:951–60.
Chang J, Rayner CK, Jones KL, Horowitz M. Diabetic gastroparesis—backwards and forwards. J Gastroenterol Hepatol. 2011;26(Suppl 1):46–57.
Tang M, Donaghue KC, Cho YH, Craig ME. Autonomic neuropathy in young people with type 1 diabetes: a systematic review. Pediatr Diabetes. 2013;14:239–48.
Tentolouris N, Marinou K, Kokotis P, Karanti A, Diakoumopoulou E, Katsilambros N. Sudomotor dysfunction is associated with foot ulceration in diabetes. Diabet Med. 2009;26:302–5.
Vinik AI, Erbas T. Diabetic autonomic neuropathy. Handb Clin Neurol. 2013;117:279–94.
Dimitropoulos G, Tahrani AA, Stevens MJ. Cardiac autonomic neuropathy in patients with diabetes mellitus. World J Diabetes. 2014;5:17–39.
Maser RE, Mitchell BD, Vinik AI, Freeman R. The association between cardiovascular autonomic neuropathy and mortality in individuals with diabetes: a meta-analysis. Diabetes Care. 2003;26:1895–901.
Ziegler D, Gries FA, Spüler M, Lessmann F. The epidemiology of diabetic neuropathy. J Diabetes Complications. 1992;6:49–57.
Frontoni S, Bracaglia D, Gigli F. Relationship between autonomic dysfunction, insulin resistance and hypertension, in diabetes. Nutr Metab Cardiovasc Dis. 2005;15:441–9.
Ejskjaer N, Arif S, Dodds W, Zanone MM, Vergani D, Watkins PJ, et al. Prevalence of autoantibodies to autonomic nervous tissue structures in type 1diabetes mellitus. Diabet Med. 1999;16:544–9.
Schmidt RE, Dorsey DA, Beaudet LN, Plurad SB, Parvin CA, Ohara S. Effect of IGF-I and neurotrophin-3 on gracile neuroaxonal dystrophy in diabetic and aging rats. Brain Res. 2000;876:88–94.
Callaghan BC, Little AA, Feldman EL, Hughes RA. Enhanced glucose control for preventing and treating diabetic neuropathy. Cochrane Database Syst Rev. 2012;6:CD007543.
Lee SS, Han HS, Kim H. A 5-yr follow-up nerve conduction study for the detection of subclinical diabetic neuropathy in children with newly diagnosed insulin-dependent diabetes mellitus. Pediatr Diabetes. 2010;11:521–8.
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Rizzoni, D., Desenzani, P. (2023). Cerebrovascular Structural Alterations/Dysautonomic Disorders in Diabetes Mellitus. In: Berbari, A.E., Mancia, G. (eds) Blood Pressure Disorders in Diabetes Mellitus. Updates in Hypertension and Cardiovascular Protection. Springer, Cham. https://doi.org/10.1007/978-3-031-13009-0_14
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