The Relationship of Dementia and Diabetes
Synopsis
Hypoglycemia, a common side effect of diabetes treatment, is associated with high morbidity and death, and it has become a significant barrier to the delivery of antidiabetic medication. Severe hypoglycemia, or abnormally low blood sugar, is linked to seizures and comas, but even mild hypoglycemia can induce uncomfortable symptoms including anxiety, palpitations, and confusion.Dementia frequently results in the loss of memory, language, problem solving, and other cognitive abilities that might interfere with daily activities. There is growing evidence that diabetes is linked to an increased risk of both vascular and non-vascular dementia. Neuroglycopenia caused by a hypoglycemia period in diabetic patients can result in brain cell destruction and cognitive impairment, ultimately leading to dementia. In light of new evidence, a better understanding of the relationship between hypoglycemia and dementia may help inform and guide preventive strategies. This review aims to discuss the epidemiology of dementia in patients with diabetes and the emerging mechanisms thought to underlie the relationship between hypoglycemia and dementia.
References
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Amiel SA. The consequences of hypoglycaemia. Diabetologia; 2021;64(5):963-970. doi: 10.1007/s00125-020-05366-3
Yanai H, Adachi H, Katsuyama H, Moriyama S, Hamasaki H, Sako A. Causative anti-diabetic drugs and the underlying clinical factors for hypoglycemia in patients with diabetes. World Journal of Diabetes; 2015;6(1):30-36. doi: 10.4239/wjd.v6.i1.30
Nakhleh A, Shehadeh N. Hypoglycemia in diabetes: An update on pathophysiology, treatment, and prevention. World Journal of Diabetes; 2021;12(12):2036-2049. doi: 10.4239/wjd.v12.i12.2036
Gangji AS, Cukierman T, Gerstein HC, Goldsmith CH, Clase CM. A systematic review and meta-analysis of hypoglycemia and cardiovascular events: a comparison of glyburide with other secretagogues and with insulin. Diabetes Care; 2007;30(2):389-394. doi: 10.2337/dc06-1789
Meneilly GS, Cheung E, Tuokko H. Counterregulatory hormone responses to hypoglycemia in the elderly patient with diabetes. Diabetes; 1994;43(3):403-410. doi: 10.2337/diab.43.3.403
Bremer JP, Jauch-Chara K, Hallschmid M, Schmid S, Schultes B. Hypoglycemia unawareness in older compared with middle-aged patients with type 2 diabetes. Diabetes Care; 2009;32(8):1513-1517. doi: 10.2337/dc09-0114
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Kane JPM, Surendranathan A, Bentley A, et al. Clinical prevalence of Lewy body dementia. Alzheimer's Research and Therapy; 2018;10(1):19. doi: 10.1186/s13195-018-0350-6
Gudala K, Bansal D, Schifano F, et al. Diabetes mellitus and risk of dementia: A meta-analysis of prospective observational studies. Journal of Diabetes Investigation; 2013;4(6):640-650. doi: 10.1111/jdi.12087
Epidemiology of severe hypoglycemia in the diabetes control and complications trial. The DCCT Research Group. The American Journal of Medicine; 1991;90(4):450-459.
Cryer PE. Mechanisms of hypoglycemia-associated autonomic failure and its component syndromes in diabetes. Diabetes; 2005;54(12):3592-3601. doi: 10.2337/diabetes.54.12.3592
Donnelly LA, Morris AD, Frier BM, et al. Frequency and predictors of hypoglycaemia in Type 1 and insulin-treated Type 2 diabetes: a population-based study. Diabetic medicine : a journal of the British Diabetic Association; 2005;22(6):749-755. doi: 10.1111/j.1464-5491.2005.01501.x
Miech RA, Breitner JC, Zandi PP, et al. Incidence of AD may decline in the early 90s for men, later for women: The Cache County study. Neurology; 2002;58(2):209-218. doi: 10.1212/wnl.58.2.209
McAulay V, Deary IJ, Frier BM. Symptoms of hypoglycaemia in people with diabetes. Diabetic medicine : a journal of the British Diabetic Association; 2001;18(9):690-705. doi: 10.1046/j.1464-5491.2001.00620.x
Kawamura T, Umemura T, Hotta N. Cognitive impairment in diabetic patients: Can diabetic control prevent cognitive decline? Journal of Diabetes Investigation; 2012;3(5):413-423. doi: 10.1111/j.2040-1124.2012.00234.x
Coucha M, Abdelsaid M, Ward R, Abdul Y, Ergul A. Impact of metabolic diseases on cerebral circulation: Structural and functional consequences. Comprehensive Physiology; 2018;8(2):773-799. doi: 10.1002/cphy.c170019
Salim S. Oxidative stress and the central nervous system. The Journal of Pharmacology and Experimental Therapeutics; 2017;360(1):201-205. doi: 10.1124/jpet.116.237503
Singh VP, Bali A, Singh N, et al. Advanced glycation end products and diabetic complications. The Korean Journal of Physiology and Pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology; 2014;18(1):1-14. doi: 10.4196/kjpp.2014.18.1.1
Nowotny K, Jung T, Hohn A, Weber D, Grune T. Advanced glycation end products and oxidative stress in type 2 diabetes mellitus. Biomolecules; 2015;5(1):194-222. doi: 10.3390/biom5010194
Ravona-Springer R, Schnaider-Beeri M. The association of diabetes and dementia and possible implications for nondiabetic populations. Expert Review of Neurotherapeutics; 2011;11(11):1609-1617. doi: 10.1586/ern.11.152
Dos Santos Matioli MNP, Suemoto CK, Rodriguez RD, et al. Diabetes is Not Associated with Alzheimer's Disease Neuropathology. Journal of Alzheimer's Disease; 2017;60(3):1035-1043. doi: 10.3233/JAD-170179
Kwa VI, van der Sande JJ, Stam J, et al. Amsterdam Vascular Medicine G. Retinal arterial changes correlate with cerebral small-vessel disease. Neurology; 2002;59(10):1536-1540. doi: 10.1212/01.wnl.0000033093.16450.5c
Matsuda M, Shimomura I. Increased oxidative stress in obesity: implications for metabolic syndrome, diabetes, hypertension, dyslipidemia, atherosclerosis, and cancer. Obesity Research and Clinical Practice; 2013;7(5):e330-341. doi: 10.1016/j.orcp.2013.05.004
American Geriatrics Society Expert Panel on the Care of Older Adults with M. Patient-centered care for older adults with multiple chronic conditions: a stepwise approach from the American Geriatrics Society: American Geriatrics Society Expert Panel on the Care of Older Adults with Multimorbidity. Journal of the American Geriatrics Society; 2012;60(10):1957-1968. doi: 10.1111/j.1532-5415.2012.04187.x
Kalyani RR, Egan JM. Diabetes and altered glucose metabolism with aging. Endocrinology and Metabolism Clinics of North America; 2013;42(2):333-347. doi: 10.1016/j.ecl.2013.02.010
American Diabetes A. 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2019. Diabetes Care; 2019;42(Suppl 1):S13-S28. doi: 10.2337/dc19-S002
Longo M, Bellastella G, Maiorino MI, et al. Diabetes and aging: From treatment goals to pharmacologic therapy. Frontiers in Endocrinology; 2019;10:45. doi: 10.3389/fendo.2019.00045
Correia SC, Santos RX, Carvalho C, et al. Insulin signaling, glucose metabolism and mitochondria: major players in Alzheimer's disease and diabetes interrelation. Brain Research; 2012;1441:64-78. doi: 10.1016/j.brainres.2011.12.063
Rojas M, Chavez-Castillo M, Bautista J, et al. Alzheimer's disease and type 2 diabetes mellitus: Pathophysiologic and pharmacotherapeutics links. World Journal of Diabetes; 2021;12(6):745-766. doi: 10.4239/wjd.v12.i6.745
Zhang L, Chopp M, Jiang Q, et al. Role of the glymphatic system in ageing and diabetes mellitus impaired cognitive function. Stroke and Vascular Neurology; 2019;4(2):90-92. doi: 10.1136/svn-2018-000203
Jiang Q, Zhang L, Ding G, et al. Impairment of the glymphatic system after diabetes. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism; 2017;37(4):1326-1337. doi: 10.1177/0271678X16654702
Reddy OC, van der Werf YD. The Sleeping Brain: Harnessing the power of the glymphatic system through lifestyle choices. Brain Sciences; 2020;10(11). doi: 10.3390/brainsci10110868
Pugazhenthi S, Qin L, Reddy PH. Common neurodegenerative pathways in obesity, diabetes, and Alzheimer's disease. Biochimica et Biophysica Acta. Molecular Basis of Disease; 2017;1863(5):1037-1045. doi: 10.1016/j.bbadis.2016.04.017
Chen L, Chen R, Wang H, et al. Mechanisms linking inflammation to insulin resistance. International Journal of Endocrinology; 2015;2015:508409. doi: 10.1155/2015/508409
Xu WL, Atti AR, Gatz M, et al. Midlife overweight and obesity increase late-life dementia risk: a population-based twin study. Neurology; 2011;76(18):1568-1574. doi: 10.1212/WNL.0b013e3182190d09
Alwafi H, Alsharif AA, Wei L, et al. Incidence and prevalence of hypoglycaemia in type 1 and type 2 diabetes individuals: A systematic review and meta-analysis. Diabetes Research and Clinical Practice; 2020;170:108522. doi: 10.1016/j.diabres.2020.108522
Karan NS. Assessment of the cognitive status in diabetes mellitus. Journal of Clinical and Diagnostic Research:JCDR; 2012;6(10):1658-1662. doi: 10.7860/JCDR/2012/4837.2649
Gomez-Guijarro MD, Alvarez-Bueno C, Saz-Lara A, et al. Association between severe hypoglycaemia and risk of dementia in patients with type 2 diabetes mellitus: A systematic review and meta-analysis. Diabetes/metabolism Research and Reviews; 2023;39(3):e3610. doi: 10.1002/dmrr.3610
Kim YG, Park DG, Moon SY, et al. Hypoglycemia and dementia risk in older patients with Type 2 diabetes mellitus: A Propensity-score matched analysis of a population-based cohort study. Diabetes and Metabolism Journal; 2020;44(1):125-133. doi: 10.4093/dmj.2018.0260
Whitmer RA, Karter AJ, Yaffe K, et al. Hypoglycemic episodes and risk of dementia in older patients with type 2 diabetes mellitus. Jama; 2009;301(15):1565-1572. doi: 10.1001/jama.2009.460
Saik OV, Klimontov VV. Hypoglycemia, vascular disease and cognitive dysfunction in diabetes: Insights from text mining-based reconstruction and bioinformatics analysis of the gene networks. International Journal of Molecular Sciences; 2021;22(22). doi: 10.3390/ijms222212419
Lin L, Wu Y, Chen Z, et al. Severe hypoglycemia contributing to cognitive dysfunction in diabetic mice is associated with pericyte and blood-brain barrier dysfunction. Frontiers in Aging Neuroscience; 2021;13:775244. doi: 10.3389/fnagi.2021.775244
Yaffe K, Falvey CM, Hamilton N, et al. Association between hypoglycemia and dementia in a biracial cohort of older adults with diabetes mellitus. JAMA Internal Medicine; 2013;173(14):1300-1306. doi: 10.1001/jamainternmed.2013.6176
Mattishent K, Loke YK. Meta-Analysis: Association between hypoglycemia and serious adverse events in older patients treated with glucose-lowering agents. Frontiers in Endocrinology; 2021;12:571568. doi: 10.3389/fendo.2021.571568
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Pages
53-70
Published
April 16, 2024
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1.
Tugrak Sakarya M. The Relationship of Dementia and Diabetes. In: Yamalı C, editor. Current Research in Pharmacy and Pharmaceutical Sciences II-2024 [Internet]. Türkiye: Academician Publishing Book DOI Portal; 2024 [cited 2026 Jul. 13]. pp. 53-70. Available from: https://www.omp35.books.akademisyen.net/index.php/akya/catalog/book/3054/chapter/13719
