Markers of cognitive impairment in patients with type 2 diabetes

Open access


Background. The study aimed to evaluate the correlations of cognitive function with metabolic, nutritional, hormonal and immunologic parameters in patients with type 2 diabetes (T2D), in order to identify markers of cognitive impairment.

Material and methods. This cross-sectional study included 216 T2D patients and 23 healthy individuals (HC). The cognitive status was evaluated by the MoCA test. From HC and 145 T2D patients several parameters were also determined: C-peptide, vitamin B12, high-sensitivity CRP (by chemiluminescent immunometric assay), HbA1c, lipids, cortisol, TSH, Mg (by a Cobas 6000 analyzer), glucose (by glucose-oxidase method) and leptin and adiponectin (by ELISA method). Statistical significance was set at p < 0.05.

Results. There was a significant difference in the MoCA scores between HC and T2D groups (26.0(17.0-29.0) vs. 23.0(13.0- 31.0) points; p: 0.004). T2D patients with cognitive dysfunction were significantly older and less formally educated (p < 0.0001). Age negatively correlated with MoCA scores (-0.31; 95%CI:-0.42,-0.18; p < 0.0001). T2D patients had significantly lower visuospatial/executive (4.0(0.0-5.0) vs. 5.0(2.0-5.0) points; p: 0.04) and delayed recall scores (2.0(0.0- 5.0) vs. 3.0(1.0-5.0) points; p: 0.03) and lower serum Mg concentrations (0.81(0.12-0.99) vs. 0.92(0.41-1.35) mmol/l, p < 0.0001). Serum Mg levels positively correlated with MoCA scores (0.24, 95%CI: 0.07, 0.39; p: 0.003) and with visuospatial/ executive (0.30; 95%CI: 0.14, 0.45; p: 0.0002) and naming functions (0.18; 95%CI: 0.01, 0.34; p: 0.02).

Conclusions. Patients with T2D had significant cognitive impairment, with decrements in the visuospatial/executive and delayed recall domains. Younger age and higher education correlated with better cognitive function. Serum Mg levels correlated positively with overall cognitive function and with visuospatial/executive and naming domains.

1. Reijmer YD, van den Berg E, Ruis C, Kappelle LJ, Biessels GJ. Co+gnitive dysfunction in patients with type 2 diabetes. Diabetes Metab Res Rev. 2010;26(7):507-19. DOI: 10.1002/dmrr.1112.

2. Feinkohl I, Price JF, Strachan MW, Frier BM. The impact of diabetes on cognitive decline: potential vascular, metabolic, and psychosocial risk factors. Alzheimers Res Ther. 2015;7(1):46. DOI: 10.1186/s13195-015-0130-5.

3. Bordier L, Doucet J, Boudet J, Bauduceau B. Update on cognitive decline and dementia in elderly patients with diabetes. Diabetes Metab. 2014;40(5):331-7. DOI: 10.1016/j.diabet.2014.02.002.

4. American Diabetes Association. Standards of Medical Care in Diabetes. Diabetes Care 2015;38(Suppl. 1):S41-S48.

5. Nasreddine ZS, Phillips NA, Bédirian V, Charbonneau S, Whitehead V, Collin I, et al. The Montreal Cognitive Assessment, MoCA:A Brief Screening Tool For Mild Cognitive Impairment. J Am Geriatr Soc 53:695-699, 2005. DOI: 10.1111/j.1532-5415.2005.53221.x.

6. HOMA software downloaded from site

7. Cernea S, Zoltai C, Berbecilă D, Şular FL. Prevalence of depression, anxiety and cognitive impairment in patients with type 2 diabetes from the Central part of Romania. Acta Medica Marisiensis. 2016 Apr 27; [Epub ahead of print]. DOI: 10.1515/amma-2016-0014.

8. Mayeda ER, Whitmer RA, Yaffe K. Diabetes and cognition. Clin Geriatr Med. 2015;31(1):101-15. DOI: 10.1016/j.cger.2014.08.021.

9. Biessels GJ, Reijmer YD. Brain changes underlying cognitive dysfunction in diabetes: what can we learn from MRI? Diabetes. 2014;63(7):2244-52. DOI: 10.2337/db14-0348.

10. Jongen C, van der Grond J, Kappelle LJ, Biessels GJ, Viergever MA, Pluim JP. Utrecht Diabetic Encephalopathy Study Group. Automated measurement of brain and white matter lesion volume in type 2 diabetes mellitus. Diabetologia. 2007;50(7):1509-16. DOI: 10.1007/s00125-007-0688-y.

11. Reijmer YD, van den Berg E, de Bresser J, Kessels RP, Kappelle LJ, Algra A, et al. Utrecht Diabetic Encephalopathy Study Group. Accelerated cognitive decline in patients with type 2 diabetes:MRI correlates and risk factors. Diabetes Metab Res Rev. 2011;27(2):195-202. DOI: 10.1002/dmrr.1163.

12. Guerrero-Berroa E, Ravona-Springer R, Schmeidler J, Silverman JM, Sano M, Koifmann K, et al. Age, gender, and education are associated with cognitive performance in an older Israeli sample with type 2 diabetes. Int J Geriatr Psychiatry. 2014;29(3):299-309. DOI: 10.1002/gps.4008.

13. Hayashi K, Kurioka S, Yamaguchi T, Morita M, Kanazawa I, Takase H, et al. Association of cognitive dysfunction with hippocampal atrophy in elderly Japanese people with type 2 diabetes. Diabetes Res Clin Pract. 2011;94(2):180-5. DOI: 10.1016/j.diabres.2011.07.002.

14. Ruis C, Biessels GJ, Gorter KJ, van den Donk M, Kappelle LJ, Rutten GE. Cognition in the early stage of type 2 diabetes. Diabetes Care. 2009;32(7):1261-5. DOI: 10.2337/dc08-2143.

15. Fischer AL, de Frias CM, Yeung SE, Dixon RA. Short-term longitudinal trends in cognitive per formance in older adults with type 2 diabetes. J Clin Exp Neuropsychol. 2009;31(7):809-22. DOI: 10.1080/13803390802537636.

16. van den Berg E, Reijmer YD, de Bresser J, Kessels RP, Kappelle LJ, Biessels GJ. Utrecht Diabetic Encephalopathy Study Group. A 4 year follow-up study of cognitive functioning in patients with type 2 diabetes mellitus. Diabetologia. 2010;53(1):58-65. DOI: 10.1007/s00125-009-1571-9.

17. Mori Y, Futamura A, Murakami H, Kohashi K, Hirano T, Kawamura M. Increased detection of mild cognitive impairment with type 2 diabetes mellitus using the Japanese version of the Montreal Cognitive Assessment: A pilot study. Neurology and Clinical Neuroscience. 2015, 3(3):89-93. DOI: 10.1111/ncn3.153.

18. Sadanand S, Balachandar R, Bharath S. Memory and executive functions in persons with type 2 diabetes:a meta- analysis. Diabetes Metab Res Rev. 2016;32(2):132-42. DOI: 10.1002/dmrr.2664.

19. Spauwen PJ, Köhler S, Verhey FR, Stehouwer CD, van Boxtel MP. Effects of type 2 diabetes on 12-year cognitive change:results from the Maastricht Aging Study. Diabetes Care. 2013;36(6):1554-61. DOI: 10.2337/dc12-0746.

20. Samaras K, Lutgers HL, Kochan NA, Crawford JD, Campbell LV, Wen W, et al. The impact of glucose disorders on cognition and brain volumes in the elderly: the Sydney Memory and Ageing Study. Age (Dordr). 2014;36(2):977-93. DOI: 10.1007/s11357-013-9613-0.

21. Julayanont P, Phillips N, Chertkow H, Nasreddine ZS. Montreal Cognitive Assessment (MoCA): Concept and Clinical Review. In Larner A. J. (ed). Cognitive Screening Instruments: A Practical Approach. 2013, Springer-Verlag, pp:111-51. DOI: 10.1007/978-1-4471-2452-8_6.

22. Cherbuin N, Sachdev P, Anstey KJ. Higher normal fasting plasma glucose is associated with hippocampal atrophy: The PATH Study. Neurology. 2012;79(10):1019-26. DOI: 10.1212/WNL.0b013e31826846de.

23. Jones N, Riby LM, Mitchell RL, Smith MA. Type 2 diabetes and memory: using neuroimaging to understand the mechanisms. Curr Diabetes Rev. 2014;10(2):118-23. DOI: 10.2174/1573399810666140425160811.

24. Li R, Singh M. Sex differences in cognitive impairment and Alzheimer’s disease. Front Neuroendocrinol. 2014;35(3):385-403. DOI: 10.1016/j. yfrne.2014.01.002.

25. Corsonello A, Pedone C, Pahor M, Malara A, Carosella L, Mazzei B, et al. Gruppo Italiano di Farmacovigilanza nell’Anziano (GIFA). Serum magnesium levels and cognitive impairment in hospitalized hypertensive patients. Magnes Res. 2001;14(4):273-82.

26. Barbagallo M, Belvedere M, Di Bella G, Dominguez LJ. Altered ionized magnesium levels in mild-to-moderate Alzheimer’s disease. Magnes Res. 2011;24(3):S115-21.

27. Andrási E, Páli N, Molnár Z, Kösel S. Brain aluminum, magnesium and phosphorus contents of control and Alzheimer-diseased patients. J Alzheimers Dis. 2005;7(4):273-84.

28. Gerhardsson L, Lundh T, Minthon L, Londos E. Metal concentrations in plasma and cerebrospinal fluid in patients with Alzheimer’s disease. Dement Geriatr Cogn Disord. 2008;25(6):508-15. DOI: 10.1159/000129365.

29. Cherbuin N, Kumar R, Sachdev PS, Anstey KJ. Dietary Mineral Intake and Risk of Mild Cognitive Impairment: The PATH through Life Project. Front Aging Neurosci. 2014;6:4. DOI: 10.3389/fnagi.2014.00004.

30. Gómez-Ramos A, Domínguez J, Zafra D, Corominola H, Gomis R, Guinovart JJ, et al. Inhibition of GSK3 dependent tau phosphorylation by metals. Curr Alzheimer Res. 2006;3(2):123-7. DOI: 10.2174/156720506776383059.

31. Yu J, Sun M, Chen Z, Lu J, Liu Y, Zhou L, et al. Magnesium modulates amyloid-beta protein precursor trafficking and processing. J Alzheimers Dis. 2010;20(4):1091-106.

32. Wang P, Yu X, Guan PP, Guo JW, Wang Y, Zhang Y, et al. Magnesium ion influx reduces neuroinflammation in Aβ precursor protein/Presenilin 1 transgenic mice by suppressing the expression of interleukin-1β. Cell Mol Immunol. 2015 Nov 9. [Epub ahead of print]. DOI: 10.1038/cmi.2015.93.

33. Xu ZP, Li L, Bao J, Wang ZH, Zeng J, Liu EJ, et al. Magnesium protects cognitive functions and synaptic plasticity in streptozotocin-induced sporadic Alzheimer’s model. PLoS One. 2014;9(9):e108645. DOI: 10.1371/journal.pone.0108645.

34. Barbagallo M, Dominguez LJ. Magnesium and type 2 diabetes. World J Diabetes. 2015;6(10):1152-7. DOI: 10.4239/wjd.v6.i10.1152.

35. Liu G, Weinger JG, Lu ZL, Xue F, Sadeghpour S. Efficacy and Safety of MMFS-01, a Synapse Density Enhancer, for Treating Cognitive Impairment in Older Adults: A Randomized, Double-Blind, Placebo- Controlled Trial. J Alzheimers Dis. 2015;49(4):971-90. DOI: 10.3233/JAD-150538.

36. West R, Beeri MS, Schmeidler J, Hannigan CM, Angelo G, Grossman HT, et al. Better memory functioning associated with higher total and LDL cholesterol levels in very elderly subjects without the APOE4 allele. Am J Geriatr Psychiatry. 2008;16(9):781-5. DOI: 10.1097/ JGP.0b013e3181812790.

37. Leritz EC, McGlinchey RE, Salat DH, Milberg WP. Elevated levels of serum cholesterol are associated with better performance on tasks of episodic memory. Metab Brain Dis. 2016;31(2):465-73. DOI: 10.1007/ s11011-016-9797-y.

38. Wang SH, Huang Y, Yuan Y, Xia WQ, Wang P, Huang R. LDL receptor knock-out mice show impaired spatial cognition with hippocampal vulnerability to apoptosis and deficits in synapses. Lipids Health Dis. 2014;13:175. DOI: 10.1186/1476-511X-13-175.

39. Gunstad J, Spitznagel MB, Keary TA, Glickman E, Alexander T, Karrer J, et al. Serum leptin levels are associated with cognitive function in older adults. Brain Res. 2008;1230:233-6. DOI: 10.1016/j.brainres.2008.07.045.

40. Labad J, Price JF, Strachan MW, Deary IJ, Seckl JR, Sattar N, et al. Edinburgh Type 2 Diabetes Study Investigators. Serum leptin and cognitive function in people with type 2 diabetes. Neurobiol Aging. 2012;33(12):2938-41. DOI: 10.1016/j.neurobiolaging.2012.02.026.

Revista Romana de Medicina de Laborator

Romanian Journal of Laboratory Medicine

Journal Information

IMPACT FACTOR 2017: 0.400
5-year IMPACT FACTOR: 0.320

CiteScore 2017: 0.31

SCImago Journal Rank (SJR) 2017: 0.144
Source Normalized Impact per Paper (SNIP) 2017: 0.195


All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 252 252 21
PDF Downloads 88 88 5