Vascular cognitive impairments in chronic kidney disease

Objective: to study the specific features of development of cognitive impairments (CIs), the role of traditional cardiovascular risk factors and renal failure-induced factors in patients with Stages I–IV chronic kidney disease (CKD) and to assess an association of CIs with the signs of vascular wall remodeling in them.
Patients and methods. Fifty-one patients aged 53±10 years with CKD were examined. Among them, there were 20 patients with Stages I–II CKD: a glomerular filtration rate (GFR) of і60 ml/min/1.73 m2, signs of renal lesion; 20 with Stages III CKD: a GFR of <60–30 ml/min/1.73 m2, and 11 with Stages VI CKD: a GFR of <30–15 ml/min/1.73 m2. 
Results and discussion. CIs were more common in the patients with Stages III–IV than in those with Stages I–II, as shown by the scores of the mini-mental state examination (p<0.001), the frontal assessment battery (p=0.001), and the regulatory function test (p<0.001). These tests showed that the magnitude of CIs increased with the higher stage of CKD. Stages III–IV CKD is an independent predictor of CIs in persons with predialysis-stage kidney lesion. CIs were found to be related to hyperhomocysteinemia, anemia, abdominal obesity, left ventricular hypertrophy, and patient age. The signs of atherosclerotic lesion of the common carotid arteries and the indicators of arterial stiffness were also associated with the incidence and magnitude of CIs in CKD. 

The detection of CIs in patients with early CKD allows one to timely initiate adequate therapy aimed particularly at improving cerebral circulation, eliminating the impact of risk factors, and slowing down the vascular remodeling. The management tactics for patients with CKD must involve the identification and correction of cardiovascular risk factors, and duplex scanning of the wall of the common carotid arteries may be used as a noninvasive method to assess the risk of the development and progression of CIs in predialysis CKD. 

1. United States Renal Data System. Excerpts from the 2000 U.S. Renal Data System Annual Data Report: Atlas of End Stage Renal Disease in the United States. Am J Kidney Dis. 2000;36:1–279.

2. Tonelli M, Wiebe N, Culleton B, et al. Chronic kidney disease and mortality risk: a systematic review. J Am Soc Nephrol. 2006 Jul;17(7):2034–47. Epub 2006 May 31.

3. Кутырина ИА. Ремоделирование сосудов при хронической почечной недостаточности. В кн.: Нефрология. Национальное руководство. Под ред. Н.А. Мухина. Москва: ГЭОТАР-Медиа; 2009. С. 608–16. [Kutyrina IA. Vascular remodeling in chronic renal failure. In: Nefrologiya. Natsional'noe rukovodstvo [Nephrology. National Guide]. Mukhin NA, editor. Moscow: GEOTAR-Media; 2009. P. 608–16.]

4. National Kidney Foundation. KDOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and Stratification. Am J Kidney Dis. 2002 Feb;39 (2 Suppl 1):S1–266.

5. Кутырина ИМ, Руденко ТЕ, Швецов МЮ. Почечная недостаточность как фактор «старения» сосудов. Терапевтический архив. 2007;(6):49–52. [Kutyrina IM, Rudenko TE, Shvetsov MYu. Renal failure as a factor in the aging of blood vessels. Terapevticheskii arkhiv. 2007;(6):49–52. (In Russ.)].

6. Bots ML, Dijk JM, Oren A, Grobbee DE. Carotid intima-media thickness, arterial stiffness and risk of cardiovascular disease: current evidence. J Hypertens. 2002 Dec;20(12):2317–25.

7. Karras A, Haymann JP, Bozec E, et al. On behalf of the Nephro Test Study Group. Large artery stiffening and remodeling are independently associated with all-cause mortality and cardiovascular events in chronic kidney disease. Hypertension. 2012 Dec;60(6):1451–7. doi: 10.1161/HYPERTENSIONAHA.112.197210. Epub 2012 Oct 22.

8. Sato M, Ogawa T, Sugimoto H, et al. Relation of carotid intima-media thickness and silent cerebral infarction to cardiovascular events and all-cause mortality in chronic hemodialysis patients. Intern Med. 2012;51(16):2111–7. Epub 2012 Aug 15.

9. Bots ML, Hoes AW, Koudstaal PJ, et al. Common carotid intima-media thickness and risk of stroke and myocardial infarction: the Rotterdam Study. Circulation. 1997 Sep 2;96(5):1432–7.

10. Simons PC, Algra A, Bots ML, et al. Common carotid intima-media thickness and arterial stiffness: indicators of cardiovascular risk in high-risk patients. The SMART Study (Second Manifestations of ARTerial disease). Circulation. 1999 Aug 31;100(9):951–7.

11. Miwa K, Hoshi T, Hougaku H, et al. Silent cerebral infarction is associated with incident stroke and TIA independent of carotid intimamedia thickness. Intern Med. 2010;49(9):817–22. Epub 2010 Apr 30.

12. Милованова ЛЮ, Николаев АЮ, Милованов ЮС. Гиперфосфатемия как фактор риска сердечно-сосудистых заболеваний при ХПН. Нефрология и диализ. 2002;(2):113–7. [Milovanova LYu, Nikolaev AYu, Milovanov YuS. Hyperphosphatemia as a risk factor for cardiovascular disease in chronic renal failure. Nefrologiya i dializ. 2002;(2):113–7. (In Russ.)].

13. Blacher J, Guerin AP, Pannier B, et al. Impact of aortic stiffness on survival in endstage renal disease. Circulation. 1999 May 11;99(18):2434–9.

14. Laurent S, Katsahian S, Fassot C, et al. Aortic stiffness is an independent predictor of fatal stroke in essential hypertension. Stroke. 2003 May;34(5):1203–6. Epub 2003 Apr 3.

15. Laurent S, Cockcroft J, Van Bortel L, et al. for the European Network for Non-invasive Investigation of Large Arteries. Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J. 2006 Nov;27(21):2588–605. Epub 2006 Sep 25.

16. Clozel M, Kuhn H, Hefti F, Baumgartner HR. Endothelial dysfunction and subendothelial monocyte macrophages in hypertension. Effect of angiotensin converting enzyme inhibition. Hypertension. 1991 Aug;18(2):132–41.

17. Murray AM. Cognitive impairment in the aging dialysis and chronic kidney disease populations: an occult burden. Adv Chronic Kidney Dis. 2008 Apr;15(2):123–32. doi: 10.1053/j.ackd.2008.01.010.

18. Fazekas G, Fazekas F, Schmidt R, et al. Brain MRI findings and cognitive impairment in patients undergoing chronic hemodialysis treatment. J Neurol Sci. 1995 Dec;134(1–2):83–8.

19. Kurella M, Chertow GM, Fried LF, et al. Chronic kidney disease and cognitive impairment in the elderly: the health, aging, and body composition study. J Am Soc Nephrol. 2005 Jul;16(7):2127–33. Epub 2005 May 11.

20. Seliger SL, Siscovick DS, Stehman-Breen CO, et al. Moderate renal impairment and risk of dementia among older adults: The Cardiovascular Health Cognition study. J Am Soc Nephrol. 2004 Jul;15(7):1904–11.

21. Slinin Y, Paudel ML, Ishani A, et al. Kidney function and cognitive performance and decline in older men. J Am Geriatr Soc. 2008 Nov;56(11):2082–8. doi: 10.1111/j.15325415.2008.01936.x. Epub 2008 Sep 15.

22. Stein JH, Korcarz CE, Hurst RT, et al. Use of carotid ultrasound to identify subclinical vascular disease and evaluate cardiovascular disease risk: a consensus statement from the American Society of Echocardiography Carotid Intima-Media Thickness Task Force. J Am Soc Echocardiogr. 2008 Feb;21(2):93–111; quiz 189–90. doi: 10.1016/j.echo.2007.11.011.

23. Kurella Tamura M, Yaffe K, Shlipak MG, et al. Chronic kidney disease and cognitive impairment in menopausal women. Am J Kidney Dis. 2005 Jan;45(1):66–76.

24. Kurella Tamura M, Wadley V, Yaffe K, et al. Kidney function and cognitive impairment in US adults: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) study. Am J Kidney Dis. 2008 Aug;52(2):227–34. doi: 10.1053/j.ajkd.2008. 05.004. Epub 2008 Jun 30.

25. Seliger SL, Siscovick DS, Stehman-Breen CO, et al. Moderate renal impairment and risk of dementia among older adults: The Cardiovascular Health Cognition study. J Am Soc Nephrol. 2004 Jul;15(7):1904–11.

26. Murray AM. Cognitive impairment in the aging dialysis and chronic kidney disease populations: an occult burden. Adv Chronic Kidney Dis. 2008 Apr;15(2):123–32. doi: 10.1053/j.ackd.2008.01.010.

27. Khatri M, Nickolas T, Moon YP, et al. CKD associates with cognitive decline. J Am Soc Nephrol. 2009 Nov;20(11):2427–32. doi: 10.1681/ASN.2008101090. Epub 2009 Sep 3.

28. Elias MF, Elias PK, Seliger SL, et al. Chronic kidney disease, creatinine and cognitive functioning. Nephrol Dial Transplant. 2009 Aug;24(8):2446–52. doi: 10.1093/ndt/gfp107. Epub 2009 Mar 18.

29. Sander K, Bickel H, Fö rstl H, et al. Carotid intima-media thickness is independently associated with cognitive decline. The INVADE study. Int J Geriatr Psychiatry. 2010 Apr;25(4):389–94. doi: 10.1002/gps.2351.

30. Komulainen P, Kivipelto M, Lakka TA, et al. Carotid intima-media thickness and cognitive function in elderly women: a populationbased study. Neuroepidemiology. 2007;28(4):207–13. Epub 2007 Sep 11.

31. Wendell CR, Zonderman AB, Metter EJ, et al. Carotid intimal medial thickness predicts cognitive decline among adults without clinical vascular disease. Stroke. 2009 Oct;40(10): 3180–5. doi: 10.1161/STROKEHA.109.557280. Epub 2009 Jul 30.

32. Auperin A, Berr C, Bonithon-Kopp C, et al. Ultrasonographic assessment of carotid wall characteristics and cognitive functions in a community sample of 59to 71-year-olds. The EVA Study Group. Stroke. 1996 Aug;27(8):1290–5.

33. Zhong W, Cruickshanks KJ, Huang GH, et al. Carotid atherosclerosis and cognitive function in midlife: the Beaver Dam Offspring Study. Atherosclerosis. 2011 Nov;219(1):330–3. doi: 10.1016/j.atherosclerosis.2011.07.013. Epub 2011 Jul 20.

34. Rabkin SW. Arterial stiffness: detection and consequences in cognitive impairment and dementia of the elderly. J Alzheimers Dis. 2012;32(3):541–9. doi: 10.3233/JAD-2012-120757.

35. Hanon O, Haulon S, Lenoir H, et al. Relationship between arterial stiffness and cognitive function in elderly subjects with complaints of memory loss. Stroke. 2005 Oct;36(10):2193–7. Epub 2005 Sep 8.

36. Fujiwara Y, Chaves PH, Takahashi R, et al. Arterial pulse wave velocity as a marker of poor cognitive function in an elderly communitydwelling population. J Gerontol A Biol Sci Med Sci. 2005 May;60(5):607–12.

37. Scuteri A, Brancati AM, Gianni W, et al. Arterial stiffness is an independent risk factor for cognitive impairment in the elderly: a pilot study. J Hypertens. 2005 Jun;23(6):1211–6.

38. Mizushima Y, Oobasawa H, Yoshida S, et al. Pulse wave velocity in persons with vascular dementia. J Am Geriatr Soc. 2003 Sep;51(9):1329–30.

39. Garcia A, Zanibbi K. Homocysteine and cognitive function in elderly people. CMAJ. 2004 Oct 12;171(8):897–904.

40. Дамулин ИВ. Патогенетические, диагностические и терапевтические аспекты сосудистых когнитивных нарушений. Consilium Medicum. 2006;(8):80–5. [Damulin IV. Pathogenetic, diagnostic and therapeutic aspects of vascular cognitive impairment. Consilium Medicum. 2006;(8):80–5. (In Russ.)].

41. Stein G, Mü ller A, Busch M, et al. Homocysteine, its metabolites, and B-group vitamins in renal transplant patients. Kidney Int Suppl. 2001 Feb;78:S262–5.

42. Prins ND, Den Heijer T, Hofman A, et al.; Rotterdam Scan Study. Homocysteine and cognitive function in the elderly: the Rotterdam Scan Study. Neurology. 2002 Nov 12;59(9):1375–80.

43. Sachdev P. Homocysteine, cerebrovascular disease and brain atrophy. J Neurol Sci. 2004 Nov 15;226(1–2):25–9.

44. Гусев ЕИ, Скворцова ВИ. Ишемия головного мозга. Москва: Медицина; 2001. 328 с. [Gusev EI, Skvortsova VI. Ishemiya golovnogo mozga [Cerebral ischemia]. Moscow: Meditsina; 2001. 328 p.]