Journal of Yeungnam Medical Science

영남대 의대 학술지 편집위원회 (Yeungnam University College of Medicine, Yeungnam University Institute Medical Science)
권호 표지
DOI QR코드

DOI QR Code

Cognitive dysfunctions in individuals with diabetes mellitus

  • Kim, Hye-Geum (Department of Psychiatry, Yeungnam University College of Medicine)
  • 투고 : 2019.06.10
  • 심사 : 2019.07.10
  • 발행 : 2019.09.30
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Some patients with type 1 and type 2 diabetes mellitus (DM) present with cognitive dysfunctions. The pathophysiology underlying this complication is not well understood. Type 1 DM has been associated with a decrease in the speed of information processing, psychomotor efficiency, attention, mental flexibility, and visual perception. Longitudinal epidemiological studies of type 1 DM have indicated that chronic hyperglycemia and microvascular disease, rather than repeated severe hypoglycemia, are associated with the pathogenesis of DM-related cognitive dysfunction. However, severe hypoglycemic episodes may contribute to cognitive dysfunction in high-risk patients with DM. Type 2 DM has been associated with memory deficits, decreased psychomotor speed, and reduced frontal lobe/executive function. In type 2 DM, chronic hyperglycemia, long duration of DM, presence of vascular risk factors (e.g., hypertension and obesity), and microvascular and macrovascular complications are associated with the increased risk of developing cognitive dysfunction. The pathophysiology of cognitive dysfunction in individuals with DM include the following: (1) role of hyperglycemia, (2) role of vascular disease, (3) role of hypoglycemia, and (4) role of insulin resistance and amyloid. Recently, some investigators have proposed that type 3 DM is correlated to sporadic Alzheimer's disease. The molecular and biochemical consequences of insulin and insulin-like growth factor resistance in the brain compromise neuronal survival, energy production, gene expression, plasticity, and white matter integrity. If patients claim that their performance is worsening or if they ask about the effects of DM on functioning, screening and assessment are recommended.

키워드

참고문헌

  1. McCrimmon RJ, Ryan CM, Frier BM. Diabetes and cognitive dysfunction. Lancet 2012;379:2291-9. https://doi.org/10.1016/S0140-6736(12)60360-2
  2. Kodl CT, Seaquist ER. Cognitive dysfunction and diabetes mellitus. Endocr Rev 2008;29:494-511. https://doi.org/10.1210/er.2007-0034
  3. Brands AM, Biessels GJ, de Haan EH, Kappelle LJ, Kessels RP. The effects of type 1 diabetes on cognitive performance: a meta-analysis. Diabetes Care 2005;28:726-35. https://doi.org/10.2337/diacare.28.3.726
  4. Feinkohl I, Aung PP, Keller M, Robertson CM, Morling JR, McLachlan S, et al. Severe hypoglycemia and cognitive decline in older people with type 2 diabetes: the Edinburgh type 2 diabetes study. Diabetes Care 2014;37:507-15. https://doi.org/10.2337/dc13-1384
  5. Gold AE, Deary IJ, Frier BM. Recurrent severe hypoglycaemia and cognitive function in type 1 diabetes. Diabet Med 1993;10:503-8. https://doi.org/10.1111/j.1464-5491.1993.tb00110.x
  6. Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study Research Group; Jacobson AM, Musen G, Ryan CM, Silvers N, Cleary P, et al. Long-term effect of diabetes and its treatment on cognitive function. N Engl J Med 2007;356:1842-52. https://doi.org/10.1056/NEJMoa066397
  7. Jacobson AM, Ryan CM, Cleary PA, Waberski BH, Weinger K, Musen G, et al. 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. https://doi.org/10.1007/s00125-010-1883-9
  8. Wessels AM, Scheltens P, Barkhof F, Heine RJ. Hyperglycaemia as a determinant of cognitive decline in patients with type 1 diabetes. Eur J Pharmacol 2008;585:88-96. https://doi.org/10.1016/j.ejphar.2007.11.080
  9. Asvold BO, Sand T, Hestad K, Bjorgaas MR. Cognitive function in type 1 diabetic adults with early exposure to severe hypoglycemia: a 16-year follow-up study. Diabetes Care 2010;33:1945-7. https://doi.org/10.2337/dc10-0621
  10. Aye T, Reiss AL, Kesler S, Hoang S, Drobny J, Park Y, et al. The feasibility of detecting neuropsychologic and neuroanatomic effects of type 1 diabetes in young children. Diabetes Care 2011;34:1458-62. https://doi.org/10.2337/dc10-2164
  11. Northam EA, Anderson PJ, Jacobs R, Hughes M, Warne GL, Werther GA. Neuropsychological profiles of children with type 1 diabetes 6 years after disease onset. Diabetes Care 2001;24:1541-6. https://doi.org/10.2337/diacare.24.9.1541
  12. Ferguson SC, Blane A, Perros P, McCrimmon RJ, Best JJ, Wardlaw J, et al. Cognitive ability and brain structure in type 1 diabetes: relation to microangiopathy and preceding severe hypoglycemia. Diabetes 2003;52:149-56. https://doi.org/10.2337/diabetes.52.1.149
  13. Ryan CM, Geckle MO, Orchard TJ. Cognitive efficiency declines over time in adults with Type 1 diabetes: effects of micro- and macrovascular complications. Diabetologia 2003;46:940-8. https://doi.org/10.1007/s00125-003-1128-2
  14. Ryan CM, Williams TM, Finegold DN, Orchard TJ. Cognitive dysfunction in adults with type 1 (insulin-dependent) diabetes mellitus of long duration: effects of recurrent hypoglycaemia and other chronic complications. Diabetologia 1993;36:329-34. https://doi.org/10.1007/BF00400236
  15. Wessels AM, Rombouts SA, Remijnse PL, Boom Y, Scheltens P, Barkhof F, et al. Cognitive performance in type 1 diabetes patients is associated with cerebral white matter volume. Diabetologia 2007;50:1763-9. https://doi.org/10.1007/s00125-007-0714-0
  16. Skenazy JA, Bigler ED. Neuropsychological findings in diabetes mellitus. J Clin Psychol 1984;40:246-58. https://doi.org/10.1002/1097-4679(198401)40:1<246::AID-JCLP2270400148>3.0.CO;2-P
  17. Schoenle EJ, Schoenle D, Molinari L, Largo RH. Impaired intellectual development in children with Type I diabetes: association with HbA(1c), age at diagnosis and sex. Diabetologia 2002;45:108-14. https://doi.org/10.1007/s125-002-8250-6
  18. Cukierman T, Gerstein HC, Williamson JD. Cognitive decline and dementia in diabetes--systematic overview of prospective observational studies. Diabetologia 2005;48:2460-9. https://doi.org/10.1007/s00125-005-0023-4
  19. Curb JD, Rodriguez BL, Abbott RD, Petrovitch H, Ross GW, Masaki KH, et al. Longitudinal association of vascular and Alzheimer's dementias, diabetes, and glucose tolerance. Neurology 1999;52:971-5. https://doi.org/10.1212/WNL.52.5.971
  20. Kuusisto J, Koivisto K, Mykkanen L, Helkala EL, Vanhanen M, Hanninen T, et al. Association between features of the insulin resistance syndrome and Alzheimer's disease independently of apolipoprotein E4 phenotype: cross sectional population based study. BMJ 1997;315:1045-9. https://doi.org/10.1136/bmj.315.7115.1045
  21. Leibson CL, Rocca WA, Hanson VA, Cha R, Kokmen E, O'Brien PC, et al. Risk of dementia among persons with diabetes mellitus: a population-based cohort study. Am J Epidemiol 1997;145:301-8. https://doi.org/10.1093/oxfordjournals.aje.a009106
  22. Luchsinger JA, Tang MX, Stern Y, Shea S, Mayeux R. Diabetes mellitus and risk of Alzheimer's disease and dementia with stroke in a multiethnic cohort. Am J Epidemiol 2001;154:635-41. https://doi.org/10.1093/aje/154.7.635
  23. Bruce DG, Casey GP, Grange V, Clarnette RC, Almeida OP, Foster JK, et al. 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. https://doi.org/10.1016/S0168-8227(03)00084-6
  24. Gregg EW, Brown A. Cognitive and physical disabilities and aging-related complications of diabetes. Clin Diabetes 2003;21:113-8. https://doi.org/10.2337/diaclin.21.3.113
  25. Yaffe K, Blackwell T, Whitmer RA, Krueger K, Barrett Connor E. Glycosylated hemoglobin level and development of mild cognitive impairment or dementia in older women. J Nutr Health Aging 2006;10:293-5.
  26. Grodstein F, Chen J, Wilson RS, Manson JE; Nurses' Health Study. Type 2 diabetes and cognitive function in community-dwelling elderly women. Diabetes Care 2001;24:1060-5. https://doi.org/10.2337/diacare.24.6.1060
  27. Munshi M, Grande L, Hayes M, Ayres D, Suhl E, Capelson R, et al. Cognitive dysfunction is associated with poor diabetes control in older adults. Diabetes Care 2006;29:1794-9. https://doi.org/10.2337/dc06-0506
  28. Perlmuter LC, Hakami MK, Hodgson-Harrington C, Ginsberg J, Katz J, Singer DE, et al. Decreased cognitive function in aging non-insulin-dependent diabetic patients. Am J Med 1984;77:1043-8. https://doi.org/10.1016/0002-9343(84)90186-4
  29. Reaven GM, Thompson LW, Nahum D, Haskins E. Relationship between hyperglycemia and cognitive function in older NIDDM patients. Diabetes Care 1990;13:16-21.
  30. Ryan CM, Geckle MO. Circumscribed cognitive dysfunction in middle-aged adults with type 2 diabetes. Diabetes Care 2000;23:1486-93. https://doi.org/10.2337/diacare.23.10.1486
  31. Effects of intensive diabetes therapy on neuropsychological function in adults in the Diabetes Control and Complications Trial. Ann Intern Med 1996;124:379-88. https://doi.org/10.7326/0003-4819-124-4-199602150-00001
  32. Duckworth W, Abraira C, Moritz T, Reda D, Emanuele N, Reaven PD, et al. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med 2009;360:129-39. https://doi.org/10.1056/NEJMoa0808431
  33. Action to Control Cardiovascular Risk in Diabetes Study Group; Gerstein HC, Miller ME, Byington RP, Goff DC Jr, Bigger JT, et al. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med 2008;358:2545-59. https://doi.org/10.1056/NEJMoa0802743
  34. Williamson JD, Miller ME, Bryan RN, Lazar RM, Coker LH, Johnson J, et al. The Action to Control Cardiovascular Risk in Diabetes Memory in Diabetes Study (ACCORD-MIND): rationale, design, and methods. Am J Cardiol 2007;99:112i-22i. https://doi.org/10.1016/j.amjcard.2007.03.029
  35. Ding J, Strachan MW, Reynolds RM, Frier BM, Deary IJ, Fowkes FG, et al. Diabetic retinopathy and cognitive decline in older people with type 2 diabetes: the Edinburgh Type 2 Diabetes Study. Diabetes 2010;59:2883-9. https://doi.org/10.2337/db10-0752
  36. Reijmer YD, van den Berg E, Ruis C, Kappelle LJ, Biessels GJ. Cognitive dysfunction in patients with type 2 diabetes. Diabetes Metab Res Rev 2010;26:507-19. https://doi.org/10.1002/dmrr.1112
  37. Vanhanen M, Koivisto K, Kuusisto J, Mykkanen L, Helkala EL, Hanninen T, et al. Cognitive function in an elderly population with persistent impaired glucose tolerance. Diabetes Care 1998;21:398-402. https://doi.org/10.2337/diacare.21.3.398
  38. Kanaya AM, Barrett-Connor E, Gildengorin G, Yaffe K. Change in cognitive function by glucose tolerance status in older adults: a 4-year prospective study of the Rancho Bernardo study cohort. Arch Intern Med 2004;164:1327-33. https://doi.org/10.1001/archinte.164.12.1327
  39. Biessels GJ, van der Heide LP, Kamal A, Bleys RL, Gispen WH. Ageing and diabetes: implications for brain function. Eur J Pharmacol 2002;441:1-14. https://doi.org/10.1016/S0014-2999(02)01486-3
  40. Brownlee M. The pathobiology of diabetic complications: a unifying mechanism. Diabetes 2005;54:1615-25. https://doi.org/10.2337/diabetes.54.6.1615
  41. Klein JP, Waxman SG. The brain in diabetes: molecular changes in neurons and their implications for end-organ damage. Lancet Neurol 2003;2:548-54. https://doi.org/10.1016/S1474-4422(03)00503-9
  42. Toth C, Schmidt AM, Tuor UI, Francis G, Foniok T, Brussee V, et al. Diabetes, leukoencephalopathy and rage. Neurobiol Dis 2006;23:445-61. https://doi.org/10.1016/j.nbd.2006.03.015
  43. Reske-Nielsen E, Lundbaek K. Pathological changes in the central and peripheral nervous system of young long-term diabetics. II. The spinal cord and peripheral nerves. Diabetologia 1968;4:34-43. https://doi.org/10.1007/BF01241031
  44. Reske-Nielsen E, Lundbaek K, Rafaelsen OJ. Pathological changes in the central and peripheral nervous system of young long-term diabetics: i. diabetic encephalopathy. Diabetologia 1966;1:233-41. https://doi.org/10.1007/BF01257917
  45. McCall AL. The impact of diabetes on the CNS. Diabetes 1992;41:557-70. https://doi.org/10.2337/diab.41.5.557
  46. Johnson PC, Brendel K, Meezan E. Thickened cerebral cortical capillary basement membranes in diabetics. Arch Pathol Lab Med 1982;106:214-7.
  47. Biessels GJ, Kappelle AC, Bravenboer B, Erkelens DW, Gispen WH. Cerebral function in diabetes mellitus. Diabetologia 1994;37:643-50. https://doi.org/10.1007/BF00417687
  48. Kushner M, Nencini P, Reivich M, Rango M, Jamieson D, Fazekas F, et al. Relation of hyperglycemia early in ischemic brain infarction to cerebral anatomy, metabolism, and clinical outcome. Ann Neurol 1990;28:129-35. https://doi.org/10.1002/ana.410280204
  49. Coyle JT, Puttfarcken P. Oxidative stress, glutamate, and neurodegenerative disorders. Science 1993;262:689-95. https://doi.org/10.1126/science.7901908
  50. Li PA, Shuaib A, Miyashita H, He QP, Siesjo BK, Warner DS. Hyperglycemia enhances extracellular glutamate accumulation in rats subjected to forebrain ischemia. Stroke 2000;31:183-92. https://doi.org/10.1161/01.STR.31.1.183
  51. Auer RN. Hypoglycemic brain damage. Forensic Sci Int 2004;146:105-10. https://doi.org/10.1016/j.forsciint.2004.08.001
  52. Patrick AW, Campbell IW. Fatal hypoglycaemia in insulin-treated diabetes mellitus: clinical features and neuropathological changes. Diabet Med 1990;7:349-54. https://doi.org/10.1111/j.1464-5491.1990.tb01403.x
  53. Comi G. Evoked potentials in diabetes mellitus. Clin Neurosci 1997;4:374-9.
  54. Siesjo BK, Bengtsson F. Calcium fluxes, calcium antagonists, and calcium-related pathology in brain ischemia, hypoglycemia, and spreading depression: a unifying hypothesis. J Cereb Blood Flow Metab 1989;9:127-40. https://doi.org/10.1038/jcbfm.1989.20
  55. Wieloch T. Hypoglycemia-induced neuronal damage prevented by an N-methyl-D-aspartate antagonist. Science 1985;230:681-3. https://doi.org/10.1126/science.2996146
  56. de la Monte SM, Wands JR. Review of insulin and insulin-like growth factor expression, signaling, and malfunction in the central nervous system: relevance to Alzheimer's disease. J Alzheimers Dis 2005;7:45-61. https://doi.org/10.3233/JAD-2005-7106
  57. de la Monte SM, Longato L, Tong M, Wands JR. Insulin resistance and neurodegeneration: roles of obesity, type 2 diabetes mellitus and non-alcoholic steatohepatitis. Curr Opin Investig Drugs 2009;10:1049-60.
  58. Broughton SK, Chen H, Riddle A, Kuhn SE, Nagalla S, Roberts CT Jr, et al. Large-scale generation of highly enriched neural stem-cell-derived oligodendroglial cultures: maturation-dependent differences in insulin-like growth factor-mediated signal transduction. J Neurochem 2007;100:628-38. https://doi.org/10.1111/j.1471-4159.2006.04171.x
  59. de la Monte SM. Contributions of brain insulin resistance and deficiency in amyloid-related neurodegeneration in Alzheimer's disease. Drugs 2012;72:49-66. https://doi.org/10.2165/11597760-000000000-00000
  60. Steen E, Terry BM, Rivera EJ, Cannon JL, Neely TR, Tavares R, et al. Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer's disease--is this type 3 diabetes? J Alzheimers Dis 2005;7:63-80. https://doi.org/10.3233/JAD-2005-7107
  61. Rivera EJ, Goldin A, Fulmer N, Tavares R, Wands JR, de la Monte SM. Insulin and insulin-like growth factor expression and function deteriorate with progression of Alzheimer's disease: link to brain reductions in acetylcholine. J Alzheimers Dis 2005;8:247-68. https://doi.org/10.3233/JAD-2005-8304
  62. Watson GS, Peskind ER, Asthana S, Purganan K, Wait C, Chapman D, et al. Insulin increases CSF Abeta42 levels in normal older adults. Neurology 2003;60:1899-903. https://doi.org/10.1212/01.WNL.0000065916.25128.25
  63. Gasparini L, Gouras GK, Wang R, Gross RS, Beal MF, Greengard P, et al. Stimulation of beta-amyloid precursor protein trafficking by insulin reduces intraneuronal beta-amyloid and requires mitogen-activated protein kinase signaling. J Neurosci 2001;21:2561-70. https://doi.org/10.1523/JNEUROSCI.21-08-02561.2001
  64. Gasparini L, Netzer WJ, Greengard P, Xu H. Does insulin dysfunction play a role in Alzheimer's disease? Trends Pharmacol Sci 2002;23:288-93. https://doi.org/10.1016/S0165-6147(02)02037-0
  65. Messier C, Teutenberg K. The role of insulin, insulin growth factor, and insulin-degrading enzyme in brain aging and Alzheimer's disease. Neural Plast 2005;12:311-28. https://doi.org/10.1155/NP.2005.311
  66. Schubert M, Brazil DP, Burks DJ, Kushner JA, Ye J, Flint CL, et al. Insulin receptor substrate-2 deficiency impairs brain growth and promotes tau phosphorylation. J Neurosci 2003;23:7084-92. https://doi.org/10.1523/JNEUROSCI.23-18-07084.2003
  67. Schubert M, Gautam D, Surjo D, Ueki K, Baudler S, Schubert D, et al. Role for neuronal insulin resistance in neurodegenerative diseases. Proc Natl Acad Sci U S A 2004;101:3100-5. https://doi.org/10.1073/pnas.0308724101
  68. Lester-Coll N, Rivera EJ, Soscia SJ, Doiron K, Wands JR, de la Monte SM. Intracerebral streptozotocin model of type 3 diabetes: relevance to sporadic Alzheimer's disease. J Alzheimers Dis 2006;9:13-33. https://doi.org/10.3233/JAD-2006-9102
  69. Weinstock M, Shoham S. Rat models of dementia based on reductions in regional glucose metabolism, cerebral blood flow and cytochrome oxidase activity. J Neural Transm (Vienna) 2004;111:347-66. https://doi.org/10.1007/s00702-003-0058-y
  70. Welsh B, Wecker L. Effects of streptozotocin-induced diabetes on acetylcholine metabolism in rat brain. Neurochem Res 1991;16:453-60. https://doi.org/10.1007/BF00965566
  71. Stone WS, Cottrill KL, Walker DL, Gold PE. Blood glucose and brain function: interactions with CNS cholinergic systems. Behav Neural Biol 1988;50:325-34. https://doi.org/10.1016/S0163-1047(88)91018-7
  72. Craft S, Newcomer J, Kanne S, Dagogo-Jack S, Cryer P, Sheline Y, et al. Memory improvement following induced hyperinsulinemia in Alzheimer's disease. Neurobiol Aging 1996;17:123-30. https://doi.org/10.1016/0197-4580(95)02002-0
  73. Kamal A, Biessels GJ, Urban IJ, Gispen WH. Hippocampal synaptic plasticity in streptozotocin-diabetic rats: impairment of long-term potentiation and facilitation of long-term depression. Neuroscience 1999;90:737-45. https://doi.org/10.1016/S0306-4522(98)00485-0
  74. Palovcik RA, Phillips MI, Kappy MS, Raizada MK. Insulin inhibits pyramidal neurons in hippocampal slices. Brain Res 1984;309:187-91. https://doi.org/10.1016/0006-8993(84)91028-X
  75. Craft S, Asthana S, Cook DG, Baker LD, Cherrier M, Purganan K, et al. Insulin dose-response effects on memory and plasma amyloid precursor protein in Alzheimer's disease: interactions with apolipoprotein E genotype. Psychoneuroendocrinology 2003;28:809-22. https://doi.org/10.1016/S0306-4530(02)00087-2
  76. Kalman J, Palotas A, Bodi N, Kincses TZ, Benedek G, Janka Z, et al. Lactate infusion fails to improve semantic categorization in Alzheimer's disease. Brain Res Bull 2005;65:533-9. https://doi.org/10.1016/j.brainresbull.2005.03.009
  77. Craft S, Asthana S, Schellenberg G, Cherrier M, Baker LD, Newcomer J, et al. Insulin metabolism in Alzheimer's disease differs according to apolipoprotein E genotype and gender. Neuroendocrinology 1999;70:146-52. https://doi.org/10.1159/000054469
  78. de la Monte SM, Tong M, Lester-Coll N, Plater M Jr, Wands JR. Therapeutic rescue of neurodegeneration in experimental type 3 diabetes: relevance to Alzheimer's disease. J Alzheimers Dis 2006;10:89-109. https://doi.org/10.3233/JAD-2006-10113
  79. Watson GS, Cholerton BA, Reger MA, Baker LD, Plymate SR, Asthana S, et al. Preserved cognition in patients with early Alzheimer disease and amnestic mild cognitive impairment during treatment with rosiglitazone: a preliminary study. Am J Geriatr Psychiatry 2005;13:950-8. https://doi.org/10.1097/00019442-200511000-00005
  80. Risner ME, Saunders AM, Altman JF, Ormandy GC, Craft S, Foley IM, et al. Efficacy of rosiglitazone in a genetically defined population with mild-to-moderate Alzheimer's disease. Pharmacogenomics J 2006;6:246-54. https://doi.org/10.1038/sj.tpj.6500369
  81. Cao B, Rosenblat JD, Brietzke E, Park C, Lee Y, Musial N, et al. Comparative efficacy and acceptability of antidiabetic agents for Alzheimer's disease and mild cognitive impairment: a systematic review and network meta-analysis. Diabetes Obes Metab 2018;20:2467-71. https://doi.org/10.1111/dom.13373

피인용 문헌

  1. Melatonin: new insights on its therapeutic properties in diabetic complications vol.12, 2019, https://doi.org/10.1186/s13098-020-00537-z
  2. Relationship between peripheral neuropathy and cognitive performance in the elderly population vol.100, pp.20, 2019, https://doi.org/10.1097/md.0000000000026071
  3. The effect of cordycepin on brain oxidative stress and protein expression in streptozotocin-induced diabetic mice vol.83, pp.9, 2021, https://doi.org/10.1292/jvms.21-0268
  4. Impact of diabetes on the accuracy and speed of accessing information from episodic and working memory vol.8, pp.1, 2019, https://doi.org/10.1080/23311908.2021.1982470
  5. Peripheral Polyneuropathy and Cognitive Impairment in Type II Diabetes Mellitus vol.17, 2019, https://doi.org/10.2147/ndt.s284308
  6. No Effects of Acute Psychosocial Stress on Working Memory in Older People With Type 2 Diabetes vol.11, 2021, https://doi.org/10.3389/fpsyg.2020.596584
  7. The Candidate Schizophrenia Risk Gene Tmem108 Regulates Glucose Metabolism Homeostasis vol.12, 2019, https://doi.org/10.3389/fendo.2021.770145
  8. Repurposing of Anti-Diabetic Agents as a New Opportunity to Alleviate Cognitive Impairment in Neurodegenerative and Neuropsychiatric Disorders vol.12, 2019, https://doi.org/10.3389/fphar.2021.667874
  9. The link between nutrition and Alzheimer’s disease: from prevention to treatment vol.11, pp.2, 2019, https://doi.org/10.2217/nmt-2020-0023
  10. The Association between the Binding Processes of Working Memory and Vascular Risk Profile in Adults vol.11, pp.9, 2021, https://doi.org/10.3390/brainsci11091140