Mechanisms of Cognitive Decline in Newly Diagnosed Diabetics: A Review of Pathophysiological Contributions and Intervention Strategies

Kun Ma; Yang Xiao

doi:10.23977/medbm.2024.020203

Mechanisms of Cognitive Decline in Newly Diagnosed Diabetics: A Review of Pathophysiological Contributions and Intervention Strategies

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DOI: 10.23977/medbm.2024.020203 | Downloads: 2 | Views: 30

Author(s)

Kun Ma ¹, Yang Xiao ²

Affiliation(s)

¹ Department of First Clinical Medicine, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, 712046, China
² Shaanxi Provincial Hospital of Chinese Medicine, Xi'an, Shaanxi, 710003, China

Corresponding Author

Kun Ma

ABSTRACT

The correlation between diabetes mellitus and cognitive decline is well-documented, with numerous studies highlighting the significant impact of diabetic pathophysiology on cognitive functions. This review synthesizes current research on the mechanisms underlying cognitive decline in individuals newly diagnosed with diabetes, focusing on hyperglycemia, insulin resistance, cerebrovascular damage, neuroinflammation, and protein deposition. Hyperglycemia contributes to cognitive impairment through disruption of neuronal glucose metabolism and increased oxidative stress, while insulin resistance interferes with insulin signaling in the brain, affecting neuronal growth and synaptic plasticity. Cerebrovascular damage, exacerbated by diabetes, leads to reduced cerebral blood flow and oxygen supply, further impairing cognitive functions. Neuroinflammation, a consequence of chronic systemic inflammation in diabetes, results in synaptic dysfunction and neuronal loss. Additionally, the accumulation of amyloid-beta and tau proteins, facilitated by diabetic conditions, links diabetes with neurodegenerative pathways similar to those seen in Alzheimer's disease. This review emphasizes the complexity of these mechanisms and suggests that comprehensive management of diabetes, addressing both glycemic control and these pathophysiological factors, is crucial for mitigating cognitive decline. Future research should focus on detailed pathways and interactions to develop targeted interventions that can effectively delay or prevent cognitive deterioration in diabetic patients.

KEYWORDS

Diabetes mellitus, cognitive decline, pathophysiological mechanisms

CITE THIS PAPER

Kun Ma, Yang Xiao, Mechanisms of Cognitive Decline in Newly Diagnosed Diabetics: A Review of Pathophysiological Contributions and Intervention Strategies. MEDS Basic Medicine (2024) Vol. 2: 13-19. DOI: http://dx.doi.org/10.23977/medbm.2024.020203.

REFERENCES

[1] Biessels G J, Despa F. Cognitive decline and dementia in diabetes mellitus: mechanisms and clinical implications[J]. Nature Reviews Endocrinology, 2018, 14(10): 591-604.
[2] Roberts R O, Knopman D S, Przybelski S A, et al. Association of type 2 diabetes with brain atrophy and cognitive impairment [J]. Neurology, 2014, 82(13): 1132-1141.
[3] Kodl C T, Seaquist E R. Cognitive dysfunction and diabetes mellitus[J]. Endocrine reviews, 2008, 29(4): 494-511.
[4] Cukierman T, Gerstein H C, Williamson J D. Cognitive decline and dementia in diabetes—systematic overview of prospective observational studies[J]. Diabetologia, 2005, 48: 2460-2469.
[5] Rad S K, Arya A, Karimian H, et al. Mechanism involved in insulin resistance via accumulation of β-amyloid and neurofibrillary tangles: Link between type 2 diabetes and Alzheimer’s disease[J]. Drug design, development and therapy, 2018: 3999-4021.
[6] Blázquez E, Velázquez E, Hurtado-Carneiro V, et al. Insulin in the brain: its pathophysiological implications for States related with central insulin resistance, type 2 diabetes and Alzheimer’s disease[J]. Frontiers in endocrinology, 2014, 5: 161.
[7] Michailidis M, Moraitou D, Tata D A, et al. Alzheimer’s disease as type 3 diabetes: common pathophysiological mechanisms between Alzheimer’s disease and type 2 diabetes[J]. International journal of molecular sciences, 2022, 23(5): 2687.
[8] Dutta B J, Singh S, Seksaria S, et al. Inside the diabetic brain: Insulin resistance and molecular mechanism associated with cognitive impairment and its possible therapeutic strategies[J]. Pharmacological Research, 2022, 182: 106358.
[9] Bellia C, Lombardo M, Meloni M, et al. Diabetes and cognitive decline[J]. Advances in clinical chemistry, 2022, 108: 37-71.
[10] Ehtewish H, Arredouani A, El-Agnaf O. Diagnostic, prognostic, and mechanistic biomarkers of diabetes mellitus-associated cognitive decline[J]. International journal of molecular sciences, 2022, 23(11): 6144.
[11] Zhang S, Zhang Y, Wen Z, et al. Cognitive dysfunction in diabetes: Abnormal glucose metabolic regulation in the brain [J]. Frontiers in Endocrinology, 2023, 14: 1192602.
[12] Ly H, Despa F. Hyperamylinemia as a risk factor for accelerated cognitive decline in diabetes[J]. Expert review of proteomics, 2015, 12(6): 575-577.
[13] Patching S G. Glucose transporters at the blood-brain barrier: function, regulation and gateways for drug delivery [J]. Molecular neurobiology, 2017, 54(2): 1046-1077.
[14] Rom S, Heldt N A, Gajghate S, et al. Hyperglycemia and advanced glycation end products disrupt BBB and promote occludin and claudin-5 protein secretion on extracellular microvesicles[J]. Scientific reports, 2020, 10(1): 7274.
[15] Venkat P, Chopp M, Chen J. Blood–brain barrier disruption, vascular impairment, and ischemia/reperfusion damage in diabetic stroke[J]. Journal of the American Heart Association, 2017, 6(6): e005819.
[16] Rom S, Zuluaga-Ramirez V, Gajghate S, et al. Hyperglycemia-driven neuroinflammation compromises BBB leading to memory loss in both diabetes mellitus (DM) type 1 and type 2 mouse models[J]. Molecular neurobiology, 2019, 56: 1883-1896.
[17] Coucha M, Abdelsaid M, Ward R, et al. Impact of metabolic diseases on cerebral circulation: structural and functional consequences[J]. Comprehensive Physiology, 2018, 8(2): 773.
[18] Østergaard L, Engedal T S, Moreton F, et al. Cerebral small vessel disease: capillary pathways to stroke and cognitive decline[J]. Journal of Cerebral Blood Flow & Metabolism, 2016, 36(2): 302-325.
[19] De Silva T M, Miller A A. Cerebral small vessel disease: targeting oxidative stress as a novel therapeutic strategy? [J]. Frontiers in pharmacology, 2016, 7: 185462.
[20] Arnold S E, Arvanitakis Z, Macauley-Rambach S L, et al. Brain insulin resistance in type 2 diabetes and Alzheimer disease: concepts and conundrums[J]. Nature Reviews Neurology, 2018, 14(3): 168-181.
[21] Tumminia A, Vinciguerra F, Parisi M, et al. Type 2 diabetes mellitus and Alzheimer’s disease: role of insulin signalling and therapeutic implications[J]. International journal of molecular sciences, 2018, 19(11): 3306.
[22] Blázquez E, Velázquez E, Hurtado-Carneiro V, et al. Insulin in the brain: its pathophysiological implications for States related with central insulin resistance, type 2 diabetes and Alzheimer’s disease[J]. Frontiers in endocrinology, 2014, 5: 161.
[23] Verdile G, Fuller S J, Martins R N. The role of type 2 diabetes in neurodegeneration[J]. Neurobiology of disease, 2015, 84: 22-38.
[24] van der Heide L P, Ramakers G M J, Smidt M P. Insulin signaling in the central nervous system: learning to survive [J]. Progress in neurobiology, 2006, 79(4): 205-221.
[25] Schulingkamp R J, Pagano T C, Hung D, et al. Insulin receptors and insulin action in the brain: review and clinical implications[J]. Neuroscience & Biobehavioral Reviews, 2000, 24(8): 855-872.
[26] Ghasemi R, Haeri A, Dargahi L, et al. Insulin in the brain: sources, localization and functions[J]. Molecular neurobiology, 2013, 47: 145-171.
[27] Ahmad R M A H, Ababneh N A, Al-Domi H A. Brain insulin resistance as a mechanistic mediator links peripheral metabolic disorders with declining cognition[J]. Diabetes & Metabolic Syndrome: Clinical Research & Reviews, 2022, 16(4): 102468.
[28] Mullins R J, Diehl T C, Chia C W, et al. Insulin resistance as a link between amyloid-beta and tau pathologies in Alzheimer’s disease[J]. Frontiers in aging neuroscience, 2017, 9: 118.
[29] Sharma VK, Singh TG. Insulin resistance and bioenergetic manifestations: Targets and approaches in Alzheimer's disease. Life Sci. 2020;262:118401. doi:10.1016/j.lfs.2020.118401
[30] Bramen JE, Siddarth P, Popa ES, et al. Impact of Eating a Carbohydrate-Restricted Diet on Cortical Atrophy in a Cross-Section of Amyloid Positive Patients with Alzheimer's Disease: A Small Sample Study. J Alzheimers Dis. 2023; 96(1):329-342. doi:10.3233/JAD-230458
[31] Kopp KO, Glotfelty EJ, Li Y, Greig NH. Glucagon-like peptide-1 (GLP-1) receptor agonists and neuroinflammation: Implications for neurodegenerative disease treatment. Pharmacol Res. 2022;186:106550. doi:10.1016/j.phrs. 2022. 106550
[32] Leung A, Amaram V, Natarajan R. Linking diabetic vascular complications with LncRNAs. Vascul Pharmacol. 2019; 114:139-144. doi:10.1016/j.vph.2018.01.007
[33] Maida CD, Daidone M, Pacinella G, Norrito RL, Pinto A, Tuttolomondo A. Diabetes and Ischemic Stroke: An Old and New Relationship an Overview of the Close Interaction between These Diseases. Int J Mol Sci. 2022;23(4):2397. Published 2022 Feb 21. doi:10.3390/ijms23042397
[34] Bai B, Yang Y, Wang Q, et al. NLRP3 inflammasome in endothelial dysfunction. Cell Death Dis. 2020;11(9):776. Published 2020 Sep 18. doi:10.1038/s41419-020-02985-x
[35] Emerging Risk Factors Collaboration, Sarwar N, Gao P, et al. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies [published correction appears in Lancet. 2010 Sep 18;376(9745):958. Hillage, H L [corrected to Hillege, H L]]. Lancet. 2010; 375(9733):2215-2222. doi:10.1016/S0140-6736(10)60484-9
[36] Constantin-Teodosiu D. Regulation of muscle pyruvate dehydrogenase complex in insulin resistance: effects of exercise and dichloroacetate. Diabetes Metab J. 2013;37(5):301-314. doi:10.4093/dmj.2013.37.5.301
[37] Wellen KE, Fucho R, Gregor MF, et al. Coordinated regulation of nutrient and inflammatory responses by STAMP2 is essential for metabolic homeostasis. Cell. 2007;129(3):537-548. doi:10.1016/j.cell.2007.02.049
[38] Kandimalla R, Thirumala V, Reddy PH. Is Alzheimer's disease a Type 3 Diabetes? A critical appraisal. Biochim Biophys Acta Mol Basis Dis. 2017;1863(5):1078-1089. doi:10.1016/j.bbadis.2016.08.018
[39] Pereira PR, Carrageta DF, Oliveira PF, Rodrigues A, Alves MG, Monteiro MP. Metabolomics as a tool for the early diagnosis and prognosis of diabetic kidney disease. Med Res Rev. 2022; 42(4):1518-1544. doi:10.1002/med.21883
[40] Singh R,Devi S, Gollen R. Role of free radical in atherosclerosis, diabetes and dyslipidaemia: larger-than-life. Diabetes Metab Res Rev. 2015;31(2):113-126. doi:10.1002/dmrr.2558
[41] Pasquel FJ, Lansang MC, Dhatariya K, Umpierrez GE. Management of diabetes and hyperglycaemia in the hospital. Lancet Diabetes Endocrinol. 2021;9(3):174-188. doi:10.1016/S2213-8587(20)30381-8
[42] Davies MJ, Aroda VR, Collins BS, et al. Management of Hyperglycemia in Type 2 Diabetes, 2022. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2022;45(11):2753-2786. doi:10.2337/dci22-0034
[43] Lambrinou E, Hansen TB, Beulens JW. Lifestyle factors, self-management and patient empowerment in diabetes care. Eur J Prev Cardiol. 2019;26(2_suppl):55-63. doi:10.1177/2047487319885455
[44] Kuang ZM. Effect of Combined Antihypertensive and Lipid-Lowering Therapies on Cognitive Function: A New Treatment Strategy? Cardiol Res Pract. 2020;2020:1484357. Published 2020 Apr 14. doi:10.1155/2020/1484357
[45] Gelber RP, Ross GW, Petrovitch H, Masaki KH, Launer LJ, White LR. Antihypertensive medication use and risk of cognitive impairment:the Honolulu-Asia Aging Study. Neurology. 2013;81(10):888-895. doi:10.1212/WNL. 0b013e 3182a 351d4
[46] Le DC, Vu TB, Tran TN, et al. The Effectiveness of Lifestyle Changes in Glycemic Control among Pregnant Women withGestational Diabetes Mellitus. Medicina (Kaunas). 2023 ;59(9):1587. Published 2023 Sep 1. doi:10.3390/ medicina 59091587
[47] Fatima MT, Bhat AA, Nisar S, Fakhro KA, Al-Shabeeb Akil AS. The role of dietary antioxidants in type 2 diabetes and neurodegenerative disorders: An assessment of the benefit profile. Heliyon. 2022;9(1):e12698. Published 2022 Dec 30. doi:10.1016/j.heliyon.2022.e12698
[48] Mallah K, Couch C, Borucki DM, Toutonji A, Alshareef M, Tomlinson S. Anti-inflammatory and Neuroprotective Agents in Clinical Trials for CNS Disease and Injury: Where Do We Go From Here?. Front Immunol. 2020;11:2021. Published 2020 Sep 10. doi:10.3389/fimmu.2020.02021
[49] Charness N, Best R, Souders D. Memory function and supportive technology. Gerontechnology. 2012;11(1):10. 4017/gt.2012.11.01.006.00. doi:10.4017/gt.2012.11.01.006.00

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Mechanisms of Cognitive Decline in Newly Diagnosed Diabetics: A Review of Pathophysiological Contributions and Intervention Strategies

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