Glycemic Control is Related to Cognitive Dysfunction in Elderly People with Type 2 Diabetes Mellitus in a Rural Chinese Population

Author(s): Shuling Liu, Yanhui Lu, Xue Cai, Rizhao Cong, Jun Li, Hua Jiang, Mingzi Li*.

Journal Name: Current Alzheimer Research

Volume 16 , Issue 10 , 2019

  Journal Home
Translate in Chinese
Become EABM
Become Reviewer

Abstract:

Background: There is an increasing interest on Cognitive Impairment (CI) in patients with type 2 diabetes mellitus (T2DM), but evidence is conflicting regarding the association between CI and glycemic control.

Objective: The present study aimed to estimate the prevalence of CI in patients with T2DM from northern rural China in order to determine whether cognitive dysfunction is related to glycemic control.

Methods: First, we conducted a study with a cross-sectional design. We performed cluster random sampling of 1848 residents who were aged 60 years or older and lived in the countryside in China. All eligible participants with and without T2DM were interviewed and screened for cognitive function status. Diagnoses for dementia and Cognitive Impairment No Dementia (CIND) were based on the standard criteria. Second, on the basis of the results of the cross-sectional survey, we conducted a case-control study. In the T2DM group, we identified cases of T2DM with Cognitive Impairment (T2DM-CI), as well as cases of T2DM with normal cognition (T2DM-NC) to be used as controls. The effects of specific diabetes-related variables were examined. After matching for sex, age, and education level in the T2DM-CI and T2DM-NC groups, multivariate logistic regression analyses were performed to evaluate risk factors for T2DM-CI.

Results: In the cross-sectional study, the prevalence of T2DM with CIND and dementia were 28.3% (95% CI: 23.5-33.2) and 9.5% (95% CI: 6.3-12.6), respectively. Compared with subjects without DM, the prevalence of CI in T2DM patients was more frequent than the prevalence of CI in the general population in almost every age group. In the case-control study, the multivariate logistic regression analyses showed that variables, including duration from diabetes onset, glycosylated hemoglobin A1c level (HbA1c), and severe hypoglycemia history, were significantly associated with an increased risk of CI in patients with T2DM (odds ratios [ORs] [95%CIs]: 1.67 [1.03-2.70], 1.40 [1.15-1.72], and 2.72 [1.02- 7.21], respectively [P <0.05]).

Conclusion: The present study demonstrates a high prevalence of CI in patients with T2DM among the elderly population of rural China. Glycemic control, including HbA1c and exposure to severe hypoglycemia, affected cognitive function in patients with T2DM.

Keywords: Cognitive impairment, dementia, HbA1c, hypoglycemia, type 2 diabetes mellitus (T2DM), rural China.

[1]
Jia J, Wang F, Wei C, Zhou A, Jia X, Li F, et al. The prevalence of dementia in urban and rural areas of China. Alzheimers Dement 10(1): 1-9. (2014).
[http://dx.doi.org/10.1016/j.jalz.2013.01.012] [PMID: 23871765]
[2]
Jia J, Zhou A, Wei C, Jia X, Wang F, Li F, et al. The prevalence of mild cognitive impairment and its etiological subtypes in elderly Chinese. Alzheimers Dement 10(4): 439-47. (2014).
[http://dx.doi.org/10.1016/j.jalz.2013.09.008] [PMID: 24418053]
[3]
Leibson CL, Rocca WA, Hanson VA, Cha R, Kokmen E, O’Brien PC, et al. The risk of dementia among persons with diabetes mellitus: a population-based cohort study. Ann N Y Acad Sci 826: 422-7. (1997).
[http://dx.doi.org/10.1111/j.1749-6632.1997.tb48496.x] [PMID: 9329716]
[4]
Brayne C, Gill C, Huppert FA, Barkley C, Gehlhaar E, Girling DM, et al. Vascular risks and incident dementia: results from a cohort study of the very old. Dement Geriatr Cogn Disord 9(3): 175-80. (1998).
[http://dx.doi.org/10.1159/000017043] [PMID: 9622006]
[5]
Irie F, Fitzpatrick AL, Lopez OL, Kuller LH, Peila R, Newman AB, et al. Enhanced risk for Alzheimer disease in persons with type 2 diabetes and APOE epsilon4: the Cardiovascular Health Study Cognition Study. Arch Neurol 65(1): 89-93. (2008).
[http://dx.doi.org/10.1001/archneurol.2007.29] [PMID: 18195144]
[6]
Cukierman T, Gerstein HC, Williamson JD. Cognitive decline and dementia in diabetes-systematic overview of prospective observational studies. Diabetologia 48(12): 2460-9. (2005).
[http://dx.doi.org/10.1007/s00125-005-0023-4] [PMID: 16283246]
[7]
Profenno LA, Porsteinsson AP, Faraone SV. Meta-analysis of Alzheimer’s disease risk with obesity, diabetes, and related disorders. Biol Psychiatry 67(6): 505-12. (2010).
[http://dx.doi.org/10.1016/j.biopsych.2009.02.013] [PMID: 19358976]
[8]
Cheng PY, Sy HN, Wu SL, Wang WF, Chen YY. Newly diagnosed type 2 diabetes and risk of dementia: a population-based 7-year follow-up study in Taiwan. J Diabetes Complications 26(5): 382-7. (2012).
[http://dx.doi.org/10.1016/j.jdiacomp.2012.06.003] [PMID: 22785052]
[9]
Strachan MW, Reynolds RM, Marioni RE, Price JF. Cognitive function, dementia and type 2 diabetes mellitus in the elderly. Nat Rev Endocrinol 7(2): 108-14. (2011).
[http://dx.doi.org/10.1038/nrendo.2010.228] [PMID: 21263438]
[10]
Biessels GJ, Staekenborg S, Brunner E, Brayne C, Scheltens P. Risk of dementia in diabetes mellitus: a systematic review. Lancet Neurol 5(1): 64-74. (2006).
[http://dx.doi.org/10.1016/S1474-4422(05)70284-2] [PMID: 16361024]
[11]
Winkler A, Dlugaj M, Weimar C, Jöckel KH, Erbel R, Dragano N, et al. Association of diabetes mellitus and mild cognitive impairment in middle-aged men and women. J Alzheimers Dis 42(4): 1269-77. (2014).
[http://dx.doi.org/10.3233/JAD-140696] [PMID: 25024326]
[12]
de la Monte SM, Wands JR. Alzheimer’s disease is type 3 diabetes-evidence reviewed. J Diabetes Sci Technol 2(6): 1101-13. (2008).
[http://dx.doi.org/10.1177/193229680800200619] [PMID: 19885299]
[13]
American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 33(1): S62-9. (2010).
[http://dx.doi.org/10.2337/dc10-S062] [PMID: 20042775]
[14]
Selvin E, Steffes MW, Zhu H, Matsushita K, Wagenknecht L, Pankow J, et al. Glycated hemoglobin, diabetes, and cardiovascular risk in nondiabetic adults. N Engl J Med 362(9): 800-11. (2010).
[http://dx.doi.org/10.1056/NEJMoa0908359] [PMID: 20200384]
[15]
Rawlings AM, Sharrett AR, Schneider AL, Coresh J, Albert M, Couper D, et al. Diabetes in midlife and cognitive change over 20 years: a cohort study. Ann Intern Med 161(11): 785-93. (2014).
[http://dx.doi.org/10.7326/M14-0737] [PMID: 25437406]
[16]
Tuligenga RH, Dugravot A, Tabák AG, Elbaz A, Brunner EJ, Kivimäki M, et al. Midlife type 2 diabetes and poor glycaemic control as risk factors for cognitive decline in early old age: a post-hoc analysis of the Whitehall II cohort study. Lancet Diabetes Endocrinol 2(3): 228-35. (2014).
[http://dx.doi.org/10.1016/S2213-8587(13)70192-X] [PMID: 24622753]
[17]
Honig LS, Vellas B, Woodward M, Boada M, Bullock R, Borrie M, et al. Trial of Solanezumab for Mild Dementia Due to Alzheimer’s Disease. N Engl J Med 378(4): 321-30. (2018).
[http://dx.doi.org/10.1056/NEJMoa1705971] [PMID: 29365294]
[18]
Ostrowitzki S, Lasser RA, Dorflinger E, Scheltens P, Barkhof F, Nikolcheva T, et al. SCarlet RoAD Investigators. A phase III randomized trial of gantenerumab in prodromal Alzheimer’s disease. Alzheimers Res Ther 9(1): 95. (2017).
[http://dx.doi.org/10.1186/s13195-017-0318-y] [PMID: 29221491]
[19]
Sperling RA, Jack CR Jr, Aisen PS. Testing the right target and right drug at the right stage. Sci Transl Med 3(111)111cm33 (2011).
[http://dx.doi.org/10.1126/scitranslmed.3002609] [PMID: 22133718]
[20]
Chinese Hypertesion Society. Clinical guideline for prevention and treatment of hypertesion in China. Chinese J Hypertesion 19: 701-43. (2011).
[21]
Piccinin AM, Muniz-Terrera G, Clouston S, Reynolds CA, Thorvaldsson V, Deary IJ, et al. Coordinated analysis of age, sex, and education effects on change in MMSE scores. J Gerontol B Psychol Sci Soc Sci 68(3): 374-90. (2013).
[http://dx.doi.org/10.1093/geronb/gbs077] [PMID: 23033357]
[22]
Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12(3): 189-98. (1975).
[http://dx.doi.org/10.1016/0022-3956(75)90026-6] [PMID: 1202204]
[23]
Lu J, Li D, Li F, Zhou A, Wang F, Zuo X, et al. Montreal cognitive assessment in detecting cognitive impairment in Chinese elderly individuals: a population-based study. J Geriatr Psychiatry Neurol 24(4): 184-90. (2011).
[http://dx.doi.org/10.1177/0891988711422528] [PMID: 22228824]
[24]
Chen KL, Xu Y, Chu AQ, Ding D, Liang XN, Nasreddine ZS, et al. Validation of the Chinese version of montreal cognitive assessment basic for screening mild cognitive impairment. J Am Geriatr Soc 64(12): e285-90. (2016).
[http://dx.doi.org/10.1111/jgs.14530] [PMID: 27996103]
[25]
Zhang M, Zhu Z, Chen P. Community investigation of the activities of daily living (ADL) and medical conditions of the elderly in Shanghai. Zhonghua Yi Xue Za Zhi 78(2): 124-7. (1998).
[PMID: 10923424]
[26]
Chinese Diabetes Society. Clinical guideline for prevention and treatment of type 2 diabetes in China. Chinese J Diabetes 22(8): 2-42. (2014).
[27]
Whitmer RA, Karter AJ, Yaffe K, Quesenberry CP Jr, Selby JV. Hypoglycemic episodes and risk of dementia in older patients with type 2 diabetes mellitus. JAMA 301(15): 1565-72. (2009).
[http://dx.doi.org/10.1001/jama.2009.460] [PMID: 19366776]
[28]
Shi Z, Zhang Y, Yue W, Liu M, Huo YR, Liu S, et al. Prevalence and clinical predictors of cognitive impairment in individuals aged 80 years and older in rural China. Dement Geriatr Cogn Disord 36(3-4): 171-8. (2013).
[http://dx.doi.org/10.1159/000350811] [PMID: 23900137]
[29]
Zhang Y, Shi Z, Liu M, Liu S, Yue W, Liu S, et al. Prevalence of cognitive impairment no dementia in a rural area of Northern China. Neuroepidemiology 42(4): 197-203. (2014).
[http://dx.doi.org/10.1159/000360138] [PMID: 24751796]
[30]
American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders 4th ed Washington, DC: American Psychiatric Association 1994.
[31]
Espeland MA, Luchsinger JA, Baker LD, Neiberg R, Kahn SE, Arnold SE, et al. Look AHEAD Study Group. Effect of a long-term intensive lifestyle intervention on prevalence of cognitive impairment. Neurology 88(21): 2026-35. (2017).
[http://dx.doi.org/10.1212/WNL.0000000000003955] [PMID: 28446656]
[32]
Bello-Chavolla OY, Aguilar-Salinas CA, Avila-Funes JA. Geriatric syndromes and not cardiovascular risk factors are associated with cognitive impairment among mexican community-dwelling elderly with type 2 diabetes revista de investigacion clinica; organo del hospital de enfermedades de la nutricion 69(3): 166-72 (2017).
[33]
Bai J, Wei P, Zhao N, Xiao Y, Yang C, Zhong J, et al. A study of mild cognitive impairment in veterans: role of hypertension and other confounding factors. Neuropsychol Dev Cogn B Aging Neuropsychol Cogn 23(6): 703-15. (2016).
[http://dx.doi.org/10.1080/13825585.2016.1161000] [PMID: 26999624]
[34]
Ciudin A, Espinosa A, Simó-Servat O, Ruiz A, Alegret M, Hernández C, et al. Type 2 diabetes is an independent risk factor for dementia conversion in patients with mild cognitive impairment. J Diabetes Complications 31(8): 1272-4. (2017).
[http://dx.doi.org/10.1016/j.jdiacomp.2017.04.018] [PMID: 28545893]
[35]
Ma F, Wu T, Miao R, Xiao YY, Zhang W, Huang G. Conversion of mild cognitive impairment to dementia among subjects with diabetes: a population-based study of incidence and risk factors with five years of follow-up. J Alzheimers Dis 43(4): 1441-9. (2015).
[http://dx.doi.org/10.3233/JAD-141566] [PMID: 25159674]
[36]
Zheng F, Yan L, Yang Z, Zhong B, Xie W. HbA1c, diabetes and cognitive decline: the English Longitudinal Study of Ageing. Diabetologia 61(4): 839-48. (2018).
[http://dx.doi.org/10.1007/s00125-017-4541-7] [PMID: 29368156]
[37]
Luchsinger JA, Reitz C, Patel B, Tang MX, Manly JJ, Mayeux R. Relation of diabetes to mild cognitive impairment. Arch Neurol 64(4): 570-5. (2007).
[http://dx.doi.org/10.1001/archneur.64.4.570] [PMID: 17420320]
[38]
Longstreth WT Jr, Bernick C, Manolio TA, Bryan N, Jungreis CA, Price TR. Lacunar infarcts defined by magnetic resonance imaging of 3660 elderly people: the Cardiovascular Health Study. Arch Neurol 55(9): 1217-25. (1998).
[http://dx.doi.org/10.1001/archneur.55.9.1217] [PMID: 9740116]
[39]
Vermeer SE, Den Heijer T, Koudstaal PJ, Oudkerk M, Hofman A, Breteler MM. Rotterdam Scan Study. Incidence and risk factors of silent brain infarcts in the population-based Rotterdam Scan Study. Stroke 34(2): 392-6. (2003).
[http://dx.doi.org/10.1161/01.STR.0000052631.98405.15] [PMID: 12574548]
[40]
Munshi MN. Cognitive dysfunction in older adults with diabetes: what a clinician needs to know. Diabetes Care 40(4): 461-7. (2017).
[http://dx.doi.org/10.2337/dc16-1229] [PMID: 28325796]
[41]
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 29(8): 1794-9. (2006).
[http://dx.doi.org/10.2337/dc06-0506] [PMID: 16873782]
[42]
Launer LJ, Miller ME, Williamson JD, Lazar RM, Gerstein HC, Murray AM, et al. ACCORD MIND investigators. Effects of intensive glucose lowering on brain structure and function in people with type 2 diabetes (ACCORD MIND): a randomised open-label substudy. Lancet Neurol 10(11): 969-77. (2011).
[http://dx.doi.org/10.1016/S1474-4422(11)70188-0] [PMID: 21958949]
[43]
Mattishent K, Loke YK. Bi-directional interaction between hypoglycaemia and cognitive impairment in elderly patients treated with glucose-lowering agents: a systematic review and meta-analysis. Diabetes Obes Metab 18(2): 135-41. (2016).
[http://dx.doi.org/10.1111/dom.12587] [PMID: 26446922]
[44]
Yaffe K, Falvey CM, Hamilton N, Harris TB, Simonsick EM, Strotmeyer ES, et al. Health ABC Study. Association between hypoglycemia and dementia in a biracial cohort of older adults with diabetes mellitus. JAMA Intern Med 173(14): 1300-6. (2013).
[http://dx.doi.org/10.1001/jamainternmed.2013.6176] [PMID: 23753199]
[45]
Wright RJ, Frier BM. Vascular disease and diabetes: is hypoglycaemia an aggravating factor? Diabetes Metab Res Rev 24(5): 353-63. (2008).
[http://dx.doi.org/10.1002/dmrr.865] [PMID: 18461635]
[46]
Kristensen PL, Høi-Hansen T, Boomsma F, Pedersen-Bjergaard U, Thorsteinsson B. Vascular endothelial growth factor during hypoglycemia in patients with type 1 diabetes mellitus: relation to cognitive function and renin-angiotensin system activity. Metabolism 58(10): 1430-8. (2009).
[http://dx.doi.org/10.1016/j.metabol.2009.04.026] [PMID: 19573885]
[47]
Jacobson AM, Musen G, Ryan CM, Silvers N, Cleary P, Waberski B, et al. Diabetes control and complications trial/epidemiology of diabetes interventions and complications study research group. Long-term effect of diabetes and its treatment on cognitive function. N Engl J Med 356(18): 1842-5. (2007).
[http://dx.doi.org/10.1056/NEJMoa066397] [PMID: 17476010]
[48]
Bruce DG, Davis WA, Casey GP, Clarnette RM, Brown SG, Jacobs IG, et al. Severe hypoglycaemia and cognitive impairment in older patients with diabetes: the Fremantle Diabetes Study. Diabetologia 52(9): 1808-15. (2009).
[http://dx.doi.org/10.1007/s00125-009-1437-1] [PMID: 19575177]
[49]
Monnier L, Mas E, Ginet C, Michel F, Villon L, Cristol JP, et al. Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes. JAMA 295(14): 1681-7. (2006).
[http://dx.doi.org/10.1001/jama.295.14.1681] [PMID: 16609090]
[50]
Ceriello A, Esposito K, Piconi L, Ihnat MA, Thorpe JE, Testa R, et al. Oscillating glucose is more deleterious to endothelial function and oxidative stress than mean glucose in normal and type 2 diabetic patients. Diabetes 57(5): 1349-54. (2008).
[http://dx.doi.org/10.2337/db08-0063] [PMID: 18299315]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 16
ISSUE: 10
Year: 2019
Page: [950 - 962]
Pages: 13
DOI: 10.2174/1567205016666191023110712
Price: $65

Article Metrics

PDF: 37
HTML: 3