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Table of Contents
Vol. 34, No. 6, 2011
Issue release date: November 2011
Section title: Original Paper
Kidney Blood Press Res 2011;34:430–438
(DOI:10.1159/000328722)

Decreased Kidney Function Is a Significant Factor Associated with Silent Cerebral Infarction and Periventricular Hyperintensities

Shima H.a · Ishimura E.a · Naganuma T.b · Ichii M.a · Yamasaki T.b · Mori K.a · Nakatani T.b · Inaba M.a
aDepartments of Endocrinology, Metabolism, Molecular Medicine and Nephrology, and bDepartment of Urology, Osaka City University Graduate School of Medicine, Osaka, Japan
email Corresponding Author

Abstract

Background/Aims: Silent cerebral lacunar infarction (SCI) and periventricular hyperintensities (PVH) have been reported to be markers of ischemic cerebral small-vessel disease and risk factors for future cerebrovascular events in the general population. The relationship between CKD and SCI/PVH is examined. Methods: In this cross-sectional study, brain magnetic resonance imaging was performed with a 1.5-T system in 324 predialysis CKD patients and in 60 normal subjects. Results: SCI was found in 103 CKD patients (31.8%), and PVH was found in 174 CKD patients (53.7%). SCI/PVH were more prevalent in patients with higher blood pressure, advanced age and decreased kidney function. There was a significant association between the prevalence of SCI/PVH and the CKD stage, with greater prevalence of SCI/PVH as the CKD stage advanced (p < 0.0001). PVH grade also advanced as the CKD stage advanced. The estimated glomerular filtration rate was a significant factor associated with the presence of SCI/PVH, independent of any other factors. There was a strong association between the prevalence of SCI/PVH (p < 0.0001). Conclusion: In CKD patients, decreased kidney function is a significant factor associated with SCI/PVH, both of which are significantly associated with each other. These results suggest that CKD patients with SCI/PVH are at greater risk of future cerebrovascular events.

© 2011 S. Karger AG, Basel


  

Key Words

  • Magnetic resonance imaging
  • Chronic kidney disease
  • Silent cerebral lacunar infarction
  • Periventricular hyperintensities

References

  1. Shlipak MG, Sarnak MJ, Katz R, Fried LF, Seliger SL, Newman AB, Siscovick DS, Stehman-Breen C: Cystatin C and the risk of death and cardiovascular events among elderly persons. N Engl J Med 2005;352:2049–2060.
  2. Descamps-Latscha B, Witko-Sarsat V, Nguyen-Khoa T, Nguyen AT, Gausson V, Mothu N, London GM, Jungers P: Advanced oxidation protein products as risk factors for atherosclerotic cardiovascular events in nondiabetic predialysis patients. Am J Kidney Dis 2005;45:39–47.
  3. Ninomiya T, Kiyohara Y, Kubo M, Tanizaki Y, Doi Y, Okubo K, Wakugawa Y, Hata J, Oishi Y, Shikata K, Yonemoto K, Hirakata H, Iida M: Chronic kidney disease and cardiovascular disease in a general Japanese population: the Hisayama Study. Kidney Int 2005;68:228–236.
  4. Yerkey MW, Kernis SJ, Franklin BA, Sandberg KR, McCullough PA: Renal dysfunction and acceleration of coronary disease. Heart 2004;90:961–966.
  5. Ikram MA, Vernooij MW, Hofman A, Niessen WJ, van der Lugt A, Breteler MM: Kidney function is related to cerebral small vessel disease. Stroke 2008;39:55–61.
  6. Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY: Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med 2004;351:1296–1305.
  7. Manjunath G, Tighiouart H, Ibrahim H, MacLeod B, Salem DN, Griffith JL, Coresh J, Levey AS, Sarnak MJ: Level of kidney function as a risk factor for atherosclerotic cardiovascular outcomes in the community. J Am Coll Cardiol 2003;41:47–55.
  8. Muntner P, He J, Hamm L, Loria C, Whelton PK: Renal insufficiency and subsequent death resulting from cardiovascular disease in the United States. J Am Soc Nephrol 2002;13:745–753.
  9. Tsushima Y, Tanizaki Y, Aoki J, Endo K: MR detection of microhemorrhages in neurologically healthy adults. Neuroradiology 2002;44:31–36.
  10. Viswanathan A, Chabriat H: Cerebral microhemorrhage. Stroke 2006;37:550–555.
  11. Roob G, Lechner A, Schmidt R, Flooh E, Hartung HP, Fazekas F: Frequency and location of microbleeds in patients with primary intracerebral hemorrhage. Stroke 2000;31:2665–2669.
  12. Movahed MR, Hashemzadeh M, Jamal MM: Diabetes mellitus is a strong, independent risk for atrial fibrillation and flutter in addition to other cardiovascular disease. Int J Cardiol 2005;105:315–318.
  13. Uehara T, Tabuchi M, Mori E: Risk factors for silent cerebral infarcts in subcortical white matter and basal ganglia. Stroke 1999;30:378–382.
  14. Bokura H, Kobayashi S, Yamaguchi S, Iijima K, Nagai A, Toyoda G, Oguro H, Takahashi K: Silent brain infarction and subcortical white matter lesions increase the risk of stroke and mortality: a prospective cohort study. J Stroke Cerebrovasc Dis 2006;15:57–63.
  15. Vermeer SE, Den Heijer T, Koudstaal PJ, Oudkerk M, Hofman A, Breteler MM: Incidence and risk factors of silent brain infarcts in the population-based Rotterdam Scan Study. Stroke 2003;34:392–396.
  16. Eguchi K, Kario K, Hoshide S, Hoshide Y, Ishikawa J, Morinari M, Hashimoto T, Shimada K: Smoking is associated with silent cerebrovascular disease in a high-risk Japanese community-dwelling population. Hypertens Res 2004;27:747–754.
  17. Longstreth WT Jr, Bernick C, Manolio TA, Bryan N, Jungreis CA, Price TR: Lacunar infarcts defined by magnetic resonance imaging of 3,660 elderly people: The Cardiovascular Health Study. Arch Neurol 1998;55:1217–1225.
  18. Longstreth WT Jr, Dulberg C, Manolio TA, Lewis MR, Beauchamp NJ Jr, O’Leary D, Carr J, Furberg CD: Incidence, manifestations, and predictors of brain infarcts defined by serial cranial magnetic resonance imaging in the elderly: The Cardiovascular Health Study. Stroke 2002;33:2376–2382.
  19. Seliger SL, Longstreth WT Jr, Katz R, Manolio T, Fried LF, Shlipak M, Stehman-Breen CO, Newman A, Sarnak M, Gillen DL, Bleyer A, Siscovick DS: Cystatin C and subclinical brain infarction. J Am Soc Nephrol 2005;16:3721–3727.
  20. Anan F, Takahashi N, Shimomura T, Imagawa M, Yufu K, Nawata T, Nakagawa M, Yonemochi H, Eshima N, Saikawa T, Yoshimatsu H: Hyperhomocysteinemia is a significant risk factor for silent cerebral infarction in patients with chronic renal failure undergoing hemodialysis. Metabolism 2006;55:656–661.
  21. Nakatani T, Naganuma T, Uchida J, Masuda C, Wada S, Sugimura T, Sugimura K: Silent cerebral infarction in hemodialysis patients. Am J Nephrol 2003;23:86–90.
  22. Kobayashi M, Hirawa N, Yatsu K, Kobayashi Y, Yamamoto Y, Saka S, Andoh D, Toya Y, Yasuda G, Umemura S: Relationship between silent brain infarction and chronic kidney disease. Nephrol Dial Transplant 2009;24:201–207.
  23. Naganuma T, Uchida J, Tsuchida K, Takemoto Y, Tatsumi S, Sugimura K, Nakatani T: Silent cerebral infarction predicts vascular events in hemodialysis patients. Kidney Int 2005;67:2434–2439.
  24. Kobayashi M, Hirawa N, Morita S, Yatsu K, Kobayashi Y, Yamamoto Y, Saka S, Toya Y, Yasuda G, Umemura S: Silent brain infarction and rapid decline of kidney function in patients with CKD: a prospective cohort study. Am J Kidney Dis 2010;56:468–476.
  25. Cook IA, Leuchter AF, Morgan ML, Dunkin JJ, Witte E, David S, Mickes L, O’Hara R, Simon S, Lufkin R, Abrams M, Rosenberg S: Longitudinal progression of subclinical structural brain disease in normal aging. Am J Geriatr Psychiatry 2004;12:190–200.
  26. Shintani S, Shiigai T, Arinami T: Silent lacunar infarction on magnetic resonance imaging: risk factors. J Neurol Sci 1998;160:82–86.
  27. Van Straaten EC, Harvey D, Scheltens P, Barkhof F, Petersen RC, Thal LJ, Jack CR Jr, DeCarli C: Periventricular white matter hyperintensities increase the likelihood of progression from amnestic mild cognitive impairment to dementia. J Neurol 2008;255:1302–1308.
  28. Sonohara K, Kozaki K, Akishita M, Nagai K, Hasegawa H, Kuzuya M, Yokote K, Toba K: White matter lesions as a feature of cognitive impairment, low vitality and other symptoms of geriatric syndrome in the elderly. Geriatr Gerontol Int 2008;8:93–100.
  29. Grangeon MC, Seixas C, Quarantinio LC, Miranda-Scippa A, Pompili M, Steffens DC, Wenzel A, Lacerda AL, de Oliveira IR: White matter hyperintensities and their association with suicidality in major affective disorders: a meta-analysis of magnetic resonance imaging studies. CNS Spectr 2010;15:375–381.

    External Resources

  30. Shinohara Y, Tohgi H, Hirai S, Terashi A, Fukuuchi Y, Yamaguchi T, Okudera T: Effect of the Ca antagonist nilvadipine on stroke occurrence or recurrence and extension of asymptomatic cerebral infarction in hypertensive patients with or without history of stroke (PICA Study). 1. Design and results at enrollment. Cerebrovasc Dis 2007;24:202–209.
  31. Shrestha I, Takahashi T, Nomura E, Ohtsuki T, Ohshita T, Ueno H, Kohriyama T, Matsumoto M: Association between central systolic blood pressure, white matter lesions in cerebral MRI and carotid atherosclerosis. Hypertens Res 2009;32:869–874.
  32. Bernick C, Kuller L, Dulberg C, Longstreth WT Jr, Manolio T, Beauchamp N, Price T: Silent MRI infarcts and the risk of future stroke: The Cardiovascular Health Study. Neurology 2001;57:1222–1229.
  33. Kuo HK, Lipsitz LA: Cerebral white matter changes and geriatric syndromes: is there a link? J Gerontol A Biol Sci Med Sci 2004;59:818–826.
  34. Lechner H, Schmidt R, Bertha G, Justich E, Offenbacher H, Schneider G: Nuclear magnetic resonance image white matter lesions and risk factors for stroke in normal individuals. Stroke 1988;19:263–265.
  35. Thomas AJ, Perry R, Barber R, Kalaria RN, O’Brien JT: Pathologies and pathological mechanisms for white matter hyperintensities in depression. Ann NY Acad Sci 2002;977:333–339.
  36. Zimmerman RD, Fleming CA, Lee BC, Saint-Louis LA, Deck MD: Periventricular hyperintensity as seen by magnetic resonance: prevalence and significance. AJR Am J Roentgenol 1986;146:443–450.
  37. Van Dijk EJ, Prins ND, Vermeer SE, Koudstaal PJ, Breteler MM: Frequency of white matter lesions and silent lacunar infarcts. J Neural Transm Suppl 2002,62:25–39.

    External Resources

  38. Khatri M, Wright CB, Nickolas TL, Yoshita M, Paik MC, Kranwinkel G, Sacco RL, DeCarli C: Chronic kidney disease is associated with white matter hyperintensity volume: The Northern Manhattan Study (NOMAS). Stroke 2007;38:3121–3126.
  39. Fazekas G, Fazekas F, Schmidt R, Kapeller P, Offenbacher H, Krejs GJ: Brain MRI findings and cognitive impairment in patients undergoing chronic hemodialysis treatment. J Neurol Sci 1995;134:83–88.
  40. Martinez-Vea A, Salvado E, Bardaji A, Gutierrez C, Ramos A, Garcia C, Compte T, Peralta C, Broch M, Pastor R, Angelet P, Marcas L, Sauri A, Oliver JA: Silent cerebral white matter lesions and their relationship with vascular risk factors in middle-aged predialysis patients with CKD. Am J Kidney Dis 2006;47:241–250.
  41. Levey AS, Eckardt KU, Tsukamoto Y, Levin A, Coresh J, Rossert J, De Zeeuw D, Hostetter TH, Lameire N, Eknoyan G: Definition and classification of chronic kidney disease: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 2005;67:2089–2100.
  42. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 1997;20:1183–1197.
  43. Imai E, Horio M, Nitta K, Yamagata K, Iseki K, Tsukamoto Y, Ito S, Makino H, Hishida A, Matsuo S: Modification of the Modification of Diet in Renal Disease (MDRD) study equation for Japan. Am J Kidney Dis 2007;50:927–937.
  44. Fazekas F, Kleinert R, Offenbacher H, Schmidt R, Kleinert G, Payer F, Radner H, Lechner H: Pathologic correlates of incidental MRI white matter signal hyperintensities. Neurology 1993;43:1683–1689.
  45. Davis PH, Clarke WR, Bendixen BH, Adams HP Jr, Woolson RF, Culebras A: Silent cerebral infarction in patients enrolled in the toast study. Neurology 1996;46:942–948.
  46. Kobayashi S, Okada K, Koide H, Bokura H, Yamaguchi S: Subcortical silent brain infarction as a risk factor for clinical stroke. Stroke 1997;28:1932–1939.
  47. Howard G, Wagenknecht LE, Cai J, Cooper L, Kraut MA, Toole JF: Cigarette smoking and other risk factors for silent cerebral infarction in the general population. Stroke 1998;29:913–917.
  48. Lee SC, Park SJ, Ki HK, Gwon HC, Chung CS, Byun HS, Shin KJ, Shin MH, Lee WR: Prevalence and risk factors of silent cerebral infarction in apparently normal adults. Hypertension 2000;36:73–77.
  49. Shima H, Ishimura E, Naganuma T, Yamazaki T, Kobayashi I, Shidara K, Mori K, Takemoto Y, Shoji T, Inaba M, Okamura M, Nakatani T, Nishizawa Y: Cerebral microbleeds in predialysis patients with chronic kidney disease. Nephrol Dial Transplant 2010;25:1554–1559.
  50. Kato H, Izumiyama M, Izumiyama K, Takahashi A, Itoyama Y: Silent cerebral microbleeds on T2*-weighted MRI: correlation with stroke subtype, stroke recurrence, and leukoaraiosis. Stroke 2002;33:1536–1540.
  51. Kinoshita T, Okudera T, Tamura H, Ogawa T, Hatazawa J: Assessment of lacunar hemorrhage associated with hypertensive stroke by echo-planar gradient-echo T2*-weighted MRI. Stroke 2000;31:1646–1650.
  52. Offenbacher H, Fazekas F, Schmidt R, Koch M, Fazekas G, Kapeller P: MR of cerebral abnormalities concomitant with primary intracerebral hematomas. AJNR Am J Neuroradiol 1996;17:573–578.
  53. Roob G, Schmidt R, Kapeller P, Lechner A, Hartung HP, Fazekas F: MRI evidence of past cerebral microbleeds in a healthy elderly population. Neurology 1999;52:991–994.
  54. Jeerakathil T, Wolf PA, Beiser A, Hald JK, Au R, Kase CS, Massaro JM, DeCarli C: Cerebral microbleeds: prevalence and associations with cardiovascular risk factors in the Framingham Study. Stroke 2004;35:1831–1835.
  55. Kwan BC, Kronenberg F, Beddhu S, Cheung AK: Lipoprotein metabolism and lipid management in chronic kidney disease. J Am Soc Nephrol 2007;18:1246–1261.
  56. Roman GC: From UBOs to Binswanger’s disease. Impact of magnetic resonance imaging on vascular dementia research. Stroke 1996;27:1269–1273.
  57. Furuta A, Ishii N, Nishihara Y, Horie A: Medullary arteries in aging and dementia. Stroke 1991;22:442–446.
  58. Isaka Y, Okamoto M, Ashida K, Imaizumi M: Decreased cerebrovascular dilatory capacity in subjects with asymptomatic periventricular hyperintensities. Stroke 1994;25:375–381.

  

Author Contacts

Eiji Ishimura, MD
Department of Nephrology
Osaka City University Graduate School of Medicine
1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585 (Japan)
Tel. +81 6 6645 3806, E-Mail ish@med.osaka-cu.ac.jp

  

Article Information

Received: January 6, 2011
Accepted: April 13, 2011
Published online: June 28, 2011
Number of Print Pages : 9
Number of Figures : 1, Number of Tables : 5, Number of References : 58

  

Publication Details

Kidney and Blood Pressure Research

Vol. 34, No. 6, Year 2011 (Cover Date: November 2011)

Journal Editor: Tesar V. (Prague)
ISSN: 1420-4096 (Print), eISSN: 1423-0143 (Online)

For additional information: http://www.karger.com/KBR


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References

  1. Shlipak MG, Sarnak MJ, Katz R, Fried LF, Seliger SL, Newman AB, Siscovick DS, Stehman-Breen C: Cystatin C and the risk of death and cardiovascular events among elderly persons. N Engl J Med 2005;352:2049–2060.
  2. Descamps-Latscha B, Witko-Sarsat V, Nguyen-Khoa T, Nguyen AT, Gausson V, Mothu N, London GM, Jungers P: Advanced oxidation protein products as risk factors for atherosclerotic cardiovascular events in nondiabetic predialysis patients. Am J Kidney Dis 2005;45:39–47.
  3. Ninomiya T, Kiyohara Y, Kubo M, Tanizaki Y, Doi Y, Okubo K, Wakugawa Y, Hata J, Oishi Y, Shikata K, Yonemoto K, Hirakata H, Iida M: Chronic kidney disease and cardiovascular disease in a general Japanese population: the Hisayama Study. Kidney Int 2005;68:228–236.
  4. Yerkey MW, Kernis SJ, Franklin BA, Sandberg KR, McCullough PA: Renal dysfunction and acceleration of coronary disease. Heart 2004;90:961–966.
  5. Ikram MA, Vernooij MW, Hofman A, Niessen WJ, van der Lugt A, Breteler MM: Kidney function is related to cerebral small vessel disease. Stroke 2008;39:55–61.
  6. Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY: Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med 2004;351:1296–1305.
  7. Manjunath G, Tighiouart H, Ibrahim H, MacLeod B, Salem DN, Griffith JL, Coresh J, Levey AS, Sarnak MJ: Level of kidney function as a risk factor for atherosclerotic cardiovascular outcomes in the community. J Am Coll Cardiol 2003;41:47–55.
  8. Muntner P, He J, Hamm L, Loria C, Whelton PK: Renal insufficiency and subsequent death resulting from cardiovascular disease in the United States. J Am Soc Nephrol 2002;13:745–753.
  9. Tsushima Y, Tanizaki Y, Aoki J, Endo K: MR detection of microhemorrhages in neurologically healthy adults. Neuroradiology 2002;44:31–36.
  10. Viswanathan A, Chabriat H: Cerebral microhemorrhage. Stroke 2006;37:550–555.
  11. Roob G, Lechner A, Schmidt R, Flooh E, Hartung HP, Fazekas F: Frequency and location of microbleeds in patients with primary intracerebral hemorrhage. Stroke 2000;31:2665–2669.
  12. Movahed MR, Hashemzadeh M, Jamal MM: Diabetes mellitus is a strong, independent risk for atrial fibrillation and flutter in addition to other cardiovascular disease. Int J Cardiol 2005;105:315–318.
  13. Uehara T, Tabuchi M, Mori E: Risk factors for silent cerebral infarcts in subcortical white matter and basal ganglia. Stroke 1999;30:378–382.
  14. Bokura H, Kobayashi S, Yamaguchi S, Iijima K, Nagai A, Toyoda G, Oguro H, Takahashi K: Silent brain infarction and subcortical white matter lesions increase the risk of stroke and mortality: a prospective cohort study. J Stroke Cerebrovasc Dis 2006;15:57–63.
  15. Vermeer SE, Den Heijer T, Koudstaal PJ, Oudkerk M, Hofman A, Breteler MM: Incidence and risk factors of silent brain infarcts in the population-based Rotterdam Scan Study. Stroke 2003;34:392–396.
  16. Eguchi K, Kario K, Hoshide S, Hoshide Y, Ishikawa J, Morinari M, Hashimoto T, Shimada K: Smoking is associated with silent cerebrovascular disease in a high-risk Japanese community-dwelling population. Hypertens Res 2004;27:747–754.
  17. Longstreth WT Jr, Bernick C, Manolio TA, Bryan N, Jungreis CA, Price TR: Lacunar infarcts defined by magnetic resonance imaging of 3,660 elderly people: The Cardiovascular Health Study. Arch Neurol 1998;55:1217–1225.
  18. Longstreth WT Jr, Dulberg C, Manolio TA, Lewis MR, Beauchamp NJ Jr, O’Leary D, Carr J, Furberg CD: Incidence, manifestations, and predictors of brain infarcts defined by serial cranial magnetic resonance imaging in the elderly: The Cardiovascular Health Study. Stroke 2002;33:2376–2382.
  19. Seliger SL, Longstreth WT Jr, Katz R, Manolio T, Fried LF, Shlipak M, Stehman-Breen CO, Newman A, Sarnak M, Gillen DL, Bleyer A, Siscovick DS: Cystatin C and subclinical brain infarction. J Am Soc Nephrol 2005;16:3721–3727.
  20. Anan F, Takahashi N, Shimomura T, Imagawa M, Yufu K, Nawata T, Nakagawa M, Yonemochi H, Eshima N, Saikawa T, Yoshimatsu H: Hyperhomocysteinemia is a significant risk factor for silent cerebral infarction in patients with chronic renal failure undergoing hemodialysis. Metabolism 2006;55:656–661.
  21. Nakatani T, Naganuma T, Uchida J, Masuda C, Wada S, Sugimura T, Sugimura K: Silent cerebral infarction in hemodialysis patients. Am J Nephrol 2003;23:86–90.
  22. Kobayashi M, Hirawa N, Yatsu K, Kobayashi Y, Yamamoto Y, Saka S, Andoh D, Toya Y, Yasuda G, Umemura S: Relationship between silent brain infarction and chronic kidney disease. Nephrol Dial Transplant 2009;24:201–207.
  23. Naganuma T, Uchida J, Tsuchida K, Takemoto Y, Tatsumi S, Sugimura K, Nakatani T: Silent cerebral infarction predicts vascular events in hemodialysis patients. Kidney Int 2005;67:2434–2439.
  24. Kobayashi M, Hirawa N, Morita S, Yatsu K, Kobayashi Y, Yamamoto Y, Saka S, Toya Y, Yasuda G, Umemura S: Silent brain infarction and rapid decline of kidney function in patients with CKD: a prospective cohort study. Am J Kidney Dis 2010;56:468–476.
  25. Cook IA, Leuchter AF, Morgan ML, Dunkin JJ, Witte E, David S, Mickes L, O’Hara R, Simon S, Lufkin R, Abrams M, Rosenberg S: Longitudinal progression of subclinical structural brain disease in normal aging. Am J Geriatr Psychiatry 2004;12:190–200.
  26. Shintani S, Shiigai T, Arinami T: Silent lacunar infarction on magnetic resonance imaging: risk factors. J Neurol Sci 1998;160:82–86.
  27. Van Straaten EC, Harvey D, Scheltens P, Barkhof F, Petersen RC, Thal LJ, Jack CR Jr, DeCarli C: Periventricular white matter hyperintensities increase the likelihood of progression from amnestic mild cognitive impairment to dementia. J Neurol 2008;255:1302–1308.
  28. Sonohara K, Kozaki K, Akishita M, Nagai K, Hasegawa H, Kuzuya M, Yokote K, Toba K: White matter lesions as a feature of cognitive impairment, low vitality and other symptoms of geriatric syndrome in the elderly. Geriatr Gerontol Int 2008;8:93–100.
  29. Grangeon MC, Seixas C, Quarantinio LC, Miranda-Scippa A, Pompili M, Steffens DC, Wenzel A, Lacerda AL, de Oliveira IR: White matter hyperintensities and their association with suicidality in major affective disorders: a meta-analysis of magnetic resonance imaging studies. CNS Spectr 2010;15:375–381.

    External Resources

  30. Shinohara Y, Tohgi H, Hirai S, Terashi A, Fukuuchi Y, Yamaguchi T, Okudera T: Effect of the Ca antagonist nilvadipine on stroke occurrence or recurrence and extension of asymptomatic cerebral infarction in hypertensive patients with or without history of stroke (PICA Study). 1. Design and results at enrollment. Cerebrovasc Dis 2007;24:202–209.
  31. Shrestha I, Takahashi T, Nomura E, Ohtsuki T, Ohshita T, Ueno H, Kohriyama T, Matsumoto M: Association between central systolic blood pressure, white matter lesions in cerebral MRI and carotid atherosclerosis. Hypertens Res 2009;32:869–874.
  32. Bernick C, Kuller L, Dulberg C, Longstreth WT Jr, Manolio T, Beauchamp N, Price T: Silent MRI infarcts and the risk of future stroke: The Cardiovascular Health Study. Neurology 2001;57:1222–1229.
  33. Kuo HK, Lipsitz LA: Cerebral white matter changes and geriatric syndromes: is there a link? J Gerontol A Biol Sci Med Sci 2004;59:818–826.
  34. Lechner H, Schmidt R, Bertha G, Justich E, Offenbacher H, Schneider G: Nuclear magnetic resonance image white matter lesions and risk factors for stroke in normal individuals. Stroke 1988;19:263–265.
  35. Thomas AJ, Perry R, Barber R, Kalaria RN, O’Brien JT: Pathologies and pathological mechanisms for white matter hyperintensities in depression. Ann NY Acad Sci 2002;977:333–339.
  36. Zimmerman RD, Fleming CA, Lee BC, Saint-Louis LA, Deck MD: Periventricular hyperintensity as seen by magnetic resonance: prevalence and significance. AJR Am J Roentgenol 1986;146:443–450.
  37. Van Dijk EJ, Prins ND, Vermeer SE, Koudstaal PJ, Breteler MM: Frequency of white matter lesions and silent lacunar infarcts. J Neural Transm Suppl 2002,62:25–39.

    External Resources

  38. Khatri M, Wright CB, Nickolas TL, Yoshita M, Paik MC, Kranwinkel G, Sacco RL, DeCarli C: Chronic kidney disease is associated with white matter hyperintensity volume: The Northern Manhattan Study (NOMAS). Stroke 2007;38:3121–3126.
  39. Fazekas G, Fazekas F, Schmidt R, Kapeller P, Offenbacher H, Krejs GJ: Brain MRI findings and cognitive impairment in patients undergoing chronic hemodialysis treatment. J Neurol Sci 1995;134:83–88.
  40. Martinez-Vea A, Salvado E, Bardaji A, Gutierrez C, Ramos A, Garcia C, Compte T, Peralta C, Broch M, Pastor R, Angelet P, Marcas L, Sauri A, Oliver JA: Silent cerebral white matter lesions and their relationship with vascular risk factors in middle-aged predialysis patients with CKD. Am J Kidney Dis 2006;47:241–250.
  41. Levey AS, Eckardt KU, Tsukamoto Y, Levin A, Coresh J, Rossert J, De Zeeuw D, Hostetter TH, Lameire N, Eknoyan G: Definition and classification of chronic kidney disease: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 2005;67:2089–2100.
  42. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 1997;20:1183–1197.
  43. Imai E, Horio M, Nitta K, Yamagata K, Iseki K, Tsukamoto Y, Ito S, Makino H, Hishida A, Matsuo S: Modification of the Modification of Diet in Renal Disease (MDRD) study equation for Japan. Am J Kidney Dis 2007;50:927–937.
  44. Fazekas F, Kleinert R, Offenbacher H, Schmidt R, Kleinert G, Payer F, Radner H, Lechner H: Pathologic correlates of incidental MRI white matter signal hyperintensities. Neurology 1993;43:1683–1689.
  45. Davis PH, Clarke WR, Bendixen BH, Adams HP Jr, Woolson RF, Culebras A: Silent cerebral infarction in patients enrolled in the toast study. Neurology 1996;46:942–948.
  46. Kobayashi S, Okada K, Koide H, Bokura H, Yamaguchi S: Subcortical silent brain infarction as a risk factor for clinical stroke. Stroke 1997;28:1932–1939.
  47. Howard G, Wagenknecht LE, Cai J, Cooper L, Kraut MA, Toole JF: Cigarette smoking and other risk factors for silent cerebral infarction in the general population. Stroke 1998;29:913–917.
  48. Lee SC, Park SJ, Ki HK, Gwon HC, Chung CS, Byun HS, Shin KJ, Shin MH, Lee WR: Prevalence and risk factors of silent cerebral infarction in apparently normal adults. Hypertension 2000;36:73–77.
  49. Shima H, Ishimura E, Naganuma T, Yamazaki T, Kobayashi I, Shidara K, Mori K, Takemoto Y, Shoji T, Inaba M, Okamura M, Nakatani T, Nishizawa Y: Cerebral microbleeds in predialysis patients with chronic kidney disease. Nephrol Dial Transplant 2010;25:1554–1559.
  50. Kato H, Izumiyama M, Izumiyama K, Takahashi A, Itoyama Y: Silent cerebral microbleeds on T2*-weighted MRI: correlation with stroke subtype, stroke recurrence, and leukoaraiosis. Stroke 2002;33:1536–1540.
  51. Kinoshita T, Okudera T, Tamura H, Ogawa T, Hatazawa J: Assessment of lacunar hemorrhage associated with hypertensive stroke by echo-planar gradient-echo T2*-weighted MRI. Stroke 2000;31:1646–1650.
  52. Offenbacher H, Fazekas F, Schmidt R, Koch M, Fazekas G, Kapeller P: MR of cerebral abnormalities concomitant with primary intracerebral hematomas. AJNR Am J Neuroradiol 1996;17:573–578.
  53. Roob G, Schmidt R, Kapeller P, Lechner A, Hartung HP, Fazekas F: MRI evidence of past cerebral microbleeds in a healthy elderly population. Neurology 1999;52:991–994.
  54. Jeerakathil T, Wolf PA, Beiser A, Hald JK, Au R, Kase CS, Massaro JM, DeCarli C: Cerebral microbleeds: prevalence and associations with cardiovascular risk factors in the Framingham Study. Stroke 2004;35:1831–1835.
  55. Kwan BC, Kronenberg F, Beddhu S, Cheung AK: Lipoprotein metabolism and lipid management in chronic kidney disease. J Am Soc Nephrol 2007;18:1246–1261.
  56. Roman GC: From UBOs to Binswanger’s disease. Impact of magnetic resonance imaging on vascular dementia research. Stroke 1996;27:1269–1273.
  57. Furuta A, Ishii N, Nishihara Y, Horie A: Medullary arteries in aging and dementia. Stroke 1991;22:442–446.
  58. Isaka Y, Okamoto M, Ashida K, Imaizumi M: Decreased cerebrovascular dilatory capacity in subjects with asymptomatic periventricular hyperintensities. Stroke 1994;25:375–381.