Skip to main content
Log in

Dementia in Patients Undergoing Long-Term Dialysis

Aetiology, Differential Diagnoses, Epidemiology and Management

  • Therapy in Practice
  • Published:
CNS Drugs Aims and scope Submit manuscript

Abstract

Dementia in patients undergoing long-term dialysis has not been clearly defined; however, four different entities have been described.

Uraemic encephalopathy is a complication of uraemia and responds well to dialysis.

Dialysis encephalopathy syndrome, the result of acute intoxication of aluminium caused by the use of an aluminium-containing dialysate, was a common occurrence prior to 1980. However, using modern techniques of water purification, such acute intoxication can now be avoided.

Dialysis-associated encephalopathy/dementia (DAE) is always associated with elevated serum aluminium levels. Pathognomonic morphological changes in the brain have been described, but the mechanism for the entry of aluminium into the CNS is incompletely understood. The mechanisms involved in the pathogenesis of the neurotoxicity associated with aluminium are numerous. Although only a very small fraction of ingested aluminium is absorbed, the continuous oral aluminium intake from aluminium-based phosphate binders, and also of dietary or environmental origin, is responsible for aluminium overload in dialysis patients.

Age-related dementia, especially vascular dementia, occurs in patients undergoing long-term dialysis as frequently as it does in the general population.

The differential diagnoses of dialysis-associated dementias should include investigation for metabolic encephalopathies, heavy metal or trace element intoxications, and distinct structural neurological lesions such as subdural haematoma, normal pressure hydrocephalus, stroke and, particularly, hypertensive encephalopathy and multi-infarct dementia.

To prevent DAE, dietary training programmes should aim to achieve the lowest phosphate intake and pharmacological tools should be used to keep serum phosphate levels below 2 mmol/L. To prevent vascular dementia, lifestyle modification should be undertaken, including optimal physical activity and fat intake, nicotine abstinence, and targeting optimal blood glucose, cholesterol and triglyceride levels, and blood pressure, to those outlined in current recommendations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Table I

Similar content being viewed by others

References

  1. Fratiglioni L, De Ronchi D, Aguero-Torres H. Worldwide prevalence and incidence of dementia. Drugs Aging 1999 Nov; 15(5): 365–75

    Article  PubMed  CAS  Google Scholar 

  2. Lobo A, Launer LJ, Fratiglioni L, et al. Prevalence of dementia and major subtypes in Europe: a collaborative study of population-based cohorts. Neurology 2000; 54(5 Suppl.): S4–9

    PubMed  CAS  Google Scholar 

  3. Teschan PE, Ginn HE, Bourne JR, et al. Quantitative indices of clinical uremia. Kidney Int 1983 Apr; (13): 676–82

  4. Alfrey AC, LeGendre GR, Kaehny WD. The dialysis encephalopathy syndrome: possible aluminium intoxication. N Engl J Med 1976 Jan; 294(4): 184–8

    Article  PubMed  CAS  Google Scholar 

  5. Fuchs C, Armstrong VW, Quellhorst E, et al. Prophylaxis an methods for early recognition of aluminium intoxication. Contrib Nephrol 1984; 38: 81–91

    PubMed  CAS  Google Scholar 

  6. Campbell IR, Cass JS, Cholak J. Aluminium in the environment of man. Arch Indust Health 1957; 15: 359–68

    CAS  Google Scholar 

  7. Kaehny WD, Hegg AP, Alfrey AC. Gastrointestinal absorption of aluminium from aluminium-containing antacids. N Engl J Med 1977 Jun; 296(24): 1389–90

    Article  PubMed  CAS  Google Scholar 

  8. Pogglitsch H, Wawschinek O, Holzer H, et al. The natural history of dialysis encephalopathy. Acta Med Austriaca 1980; 7:71–6

    PubMed  CAS  Google Scholar 

  9. Chazan JA, Blonsky SL, Abuelo JG, et al. Increased body aluminium: an independent risk factor in patients undergoing long-term hemodialysis? Arch Intern Med 1988 Aug; 148(8): 1817–20

    Article  PubMed  CAS  Google Scholar 

  10. von Herrath D, Asmus G, Pauls A, et al. Renal osteodystrophy in asymptomatic hemodialysis patients: evidence of a sex-dependent distribution and predictive value of serum aluminium measurement. Am J Kidney Dis 1986 Dec; 8(6): 430–5

    Google Scholar 

  11. Reusche E, Koch V, Friedrich HJ, et al. Correlation of drug-related aluminum intake and dialysis treatment with the deposition of argyrophilic aluminum-containing inclusions in CNS and organ systems of patients with dialysis-associated encephalopathy. Clin Neuropathol 1996 Nov–Dec; 15(6): 342–7

    PubMed  CAS  Google Scholar 

  12. Winkelman MD, Ricanati ES. Dialysis encephalopathy: neuropathological aspects. Hum Pathol 1986 Aug; 17(8): 823–33

    Article  PubMed  CAS  Google Scholar 

  13. Reusche E. Silver staining of senile plaques and neurofibrillary tangles in paraffin sections — a simple and effective method. Pathol Res Pract 1991 Dec; 187(8): 1045–9

    Article  PubMed  CAS  Google Scholar 

  14. Reusche E, Ogomori K, Diebold J, et al. Electron microscopic study of paired helical filaments and cerebral amyloid using a novel en bloc silver staining method. Virchows Arch 1992; 420(6): 519–25

    Article  CAS  Google Scholar 

  15. Reusche E, Seydel U. Dialysis-associated encephalopathy: light and electron microscopic morphology and topography with evidence of aluminum by laser microprobe mass analysis. Acta Neuropathol 1993; 86(3): 249–58

    Article  PubMed  CAS  Google Scholar 

  16. Greger JL. Dietary and other sources of aluminium intake. In: Williams RJP, editor. Aluminium in biology and medicine. Ciba Foundation symposium 169; 1991 Nov 19–21; Basel, Switzerland. Chichester: John Wiley & Sons Ltd., 1992: 26–49

    Google Scholar 

  17. Mayor GH, Sprague SM, Hounrani MR, et al. Parathyroid hormone mediated aluminium deposition and egress in the rat. Kidney Int 1980 Jan; 17(1): 40–4

    Article  PubMed  CAS  Google Scholar 

  18. Mocan MZ, Mocan H, Fell GS, et al. Autonomous hyperparathyroidism not associated with increased aluminium absorbtion. Isr J Med Sci 1992; 28: 24–6

    PubMed  CAS  Google Scholar 

  19. Demontis R, Leflon A, Fournier A, et al. 1 alpha(OH) vitamin D3 increases plasma aluminium in hemodialized patients taking Al(OH) 3. Clin Nephrol 1986; 26: 146–9

    PubMed  CAS  Google Scholar 

  20. Farrar G, Morton AP, Blair JA. Possible models to describe the bioavailability of aluminium. In: Bratter P, Schramel P, editors. Trace element analytical chemistry in medicine and biology. Berlin: Walter de Gruyter, 1988: 343–51

    Google Scholar 

  21. Van Landeghem GF, D’Haese PC, Lamberts LV, et al. Aluminium speciation in cerebrospinal fluid of acutely aluminium-intoxicated dialysis patient before and after desferrioxamine treatment: a step in the understanding of the element’s neurotoxicity. Nephrol Dial Transplant 1997; 1692–8

  22. Roskams JA, Connor JR. Aluminium access to the brain: a role for the transferrin and its receptor. Proc Natl Acad Sci U S A 1990; 87: 9024–7

    Article  PubMed  CAS  Google Scholar 

  23. Prill A. The value of the blood brain barrier in the pathogenesis of neurologic diseases in extraneural metabolism disorders — example of kidney insufficiency. Nervenarzt 1970 Oct; 41(19): 487–94

    PubMed  CAS  Google Scholar 

  24. Smithers JL, Nicholls PJ, Maddocks JL. Studies of experimental chronic renal failure: increased permeability of the rats blood-brain barrier to phenglutarimide hydrochloride. J Pharm Pharmacol 1975; 27(2 Suppl.): 36S–40S

    Google Scholar 

  25. Lin TH, Suygiyama Y, Sawada Y, et al. Effect of serum from renal failure and cirrhotic patients on the blood-brain barrier permeability to DL-propranolol in rats. Drug Metab Dispos 1988 Mar–Apr; 16(2): 290–5

    PubMed  CAS  Google Scholar 

  26. Wisniewski HM, Wen GY. Aluminium and Alzheimer’s disease. In: Williams RJP, editor. Aluminium in biology and medicine. CIBA Foundation symposium 169; 1991 Nov 19–21; Basel, Switzerland. Chichester: John Wiley & Sons Ltd., 1992: 142–54

    Google Scholar 

  27. Forbes WF, Hill GB. Is exposure to aluminium a risk factor for the development of Alzheimer’s disease? — yes. Arch Neurol 1998 May; 55(5): 740–1

    Article  PubMed  CAS  Google Scholar 

  28. Munoz DG. Is exposure to aluminium a risk factor for the development of Alzheimers disease? — no. Arch Neurol 1998 May; 55(5): 737–9

    Article  PubMed  CAS  Google Scholar 

  29. Kaehny WD, Alfrey AC, Holman RE, et al. Aluminium transfer during hemodialysis. Kidney Int 1977; 12: 361–5

    Article  PubMed  CAS  Google Scholar 

  30. Flaten TP. Components of drinking water and risk of cognitive impairment in the elderly. Am J Epidemiol 1995 Jan; 141(2): 173–4

    PubMed  CAS  Google Scholar 

  31. McLachlan DR, Bergeron C, Smith JE, et al. Risk for neuropathologically confirmed Alzheimer’s disease and residual aluminium in municipal drinking water employing weighted residential histories. Neurology 1996 Feb; 46(2): 401–5

    Article  PubMed  CAS  Google Scholar 

  32. Neri LC, Hewitt D. Aluminium, Alzheimer’s disease and drinking water. Lancet 1991 Aug; 338(8763): 390

    Article  PubMed  CAS  Google Scholar 

  33. Broe GA, Henderson AS, Creasey H, et al. A case-control study of Alzheimer’s disease in Australia. Neurology 1990 Nov; 40(11): 1698–707

    Article  PubMed  CAS  Google Scholar 

  34. Forster DP, Newens M, Kay DW, et al. Risk factors in clinically diagnosed presenile dementia of the Alzheimer type: a case-control study in northern England. J Epidemiol Community Health 1995 Jun; 49(3): 253–8

    Article  PubMed  CAS  Google Scholar 

  35. Martyn CN, Osmond C, Edwardson JA, et al. Geographical relation between Alzheimer’s disease and aluminium in drinking water. Lancet 1989; I(8629): 59–62

    Google Scholar 

  36. Martyn CN, Coggon DN, Inskip H, et al. Aluminium concentrations in drinking water and risk of Alzheimer’s disease. Epidemiology 1997 May; 8(3): 281–6

    Article  PubMed  CAS  Google Scholar 

  37. Reusche E. Argyrophilic inclusions distinct from Alzheimer neurofibrillary changes in one case of dialysis-associated encephalopathy. Acta Neuropathol (Berl) 1997 Dec; 94(6): 612–6

    Article  CAS  Google Scholar 

  38. Reusche E, Gerke P, Krüger S, et al. Long-term organic brain syndrome and stroke-like brain stem symptoms in undiagnosed dialysis-associated encephalopathy. Dtsch Med Wochenschr 1999 Feb; 124(7): 176–81

    Article  PubMed  CAS  Google Scholar 

  39. Banks WA, Kastin AJ. Aluminium-induced neurotoxicity: alterations in membrane function at the blood-brain barrier. Neurosci Biobehav Rev 1989; 13(1): 47–53

    Article  PubMed  CAS  Google Scholar 

  40. Levi R, Wolf T, Fleminger G, et al. Immuno-detection of aluminium induced conformation changes in calmodulin — implications in Alzheimer’s disease. Mol Cell Biochem 1998 Dec; 189(1–2): 41–6

    Article  PubMed  CAS  Google Scholar 

  41. Altmann P, Al-Salihi F, Butter K, et al. Serum aluminium levels and erythrocyte dihydrobiopterine reductase activity in patients on hemodialysis. N Engl J Med 1987 Jul; 317(2): 80–4

    Article  PubMed  CAS  Google Scholar 

  42. Zheng YX, Liang YX. The antagonistic effect of L-dopa and eserine on Al-induced neurobehavior deficits in rats. Biomed Environ Sci 1998 Dec; 11(4): 321–30

    PubMed  CAS  Google Scholar 

  43. Manthys PW, Ghilardi JR, Rogers S, et al. Aluminium, iron, and zinc ions promote aggregation of physiological concentrations of beta-amyloid peptide. J Neurochem 1993 Sep; 61(3): 1171–4

    Article  Google Scholar 

  44. Xie CX, Mattson MP, Lovell MA, et al. Intraneuronal aluminium potentiates iron-mediated oxidative stress in cultured hippocampal neurons. Brain Res 1996 Dec; 743(1–2): 271–7

    Article  PubMed  CAS  Google Scholar 

  45. Exley CA. Molecular mechanism of aluminium-induced Alzheimer’s disease? J Inorg Biochem 1999 Aug; 76(2): 133–40

    Article  PubMed  CAS  Google Scholar 

  46. Hümpfner A, Hummel S, Schulz W. Diagnostic and therapeutic approaches to aluminium overload in dialysed patients — representative study in West German dialysis units in 1989–1990. Nephrol Dial Transplant 1993; 8(1 Suppl.): S51–4

    Article  Google Scholar 

  47. Wetterling T, Kanitz RD, Borgis KJ. The ICD-10 criteria for vascular dementia. Dementia 1994 May–Aug; 5(3–4): 185–8

    PubMed  CAS  Google Scholar 

  48. Ott A, Stolk RP, van Harskamp F, et al. Diabetes mellitus and the risk of dementia. The Rotterdama Study. Neurology 1999 Dec; 53(9): 1937–42

    CAS  Google Scholar 

  49. Aguero-Torres H, Winblad B. Alzheimer’s disease and vascular dementia: some points of confluence. Ann N Y Acad Sci 2000 Apr; 903: 547–52

    Article  PubMed  CAS  Google Scholar 

  50. Sachdev P, Brodaty H. Vascular dementia: an Australian perspective. Alzheimer Dis Assoc Disord 1999 Oct–Dec; 13(3 Suppl.): S206–12

    PubMed  Google Scholar 

  51. Rockwood K, Machnight C, Wentzel C, et al. The diagnosis of mixed dementia in the Consortium for the Investigation of Vascular Impairment and Cognition (CIVIC). Ann N Y Acad Sci 2000 Apr; 903: 522–8

    Article  PubMed  CAS  Google Scholar 

  52. Dialysis dementia in Europe. Report from the Registration Committee of the European Dialysis and Transplant Association. Lancet 1980 Jul; II(8187): 190–2

    Google Scholar 

  53. Alter MJ, Favero MS, Moyer LA, et al. National surveillance of dialysis-associated diseases in the United States, 1989. ASAIO Trans 1991 Apr–Jun; 37(2): 97–109

    PubMed  CAS  Google Scholar 

  54. Harris S, Brown E. Patients surviving more than 10 years on hemodialysis: the natural history of the complications of treatment. Nephrol Dial Transplant 1998; 13: 1226–33

    Article  PubMed  CAS  Google Scholar 

  55. Johnson JG, Gore SM, Firth J. The effect of age, diabetes, and other comorbidity on the survival of patients on dialysis: a systematic quantitative overview of the literature. Nephrol Dial Transplant 1999; 14: 2156–64

    Article  PubMed  CAS  Google Scholar 

  56. Altmann P, Hamon C, Blair J, et al. Disturbance of cerebral function by aluminium in haemodialysis patients without overt aluminium toxicity. Lancet 1989 Jul; II(8653): 7–12

    Article  Google Scholar 

  57. Slatopolsky EA, Burke SK, Dillon MA. RenaGel, a non-absorbed calcium- and aluminium free phosphate binder and parathyroid hormone. The RenaGel Study Group. Kidney Int 1999 Jan; 55(1): 299–307

    Article  PubMed  CAS  Google Scholar 

  58. Bleyer AJ, Burke SK, Dillon M, et al. A comparison of calcium-free phosphate binder sevelamer hydrochloride with calcium acetate in the treatment of hyperphosphatemia in hemodialysis patients. Am J Kidney Dis 1999; 33: 694–701

    Article  PubMed  CAS  Google Scholar 

  59. Zimmermann E, Wassmer S, Steudle V. Long-term treatment with calcium-alpha-ketoglutarate corrects secondary hyperparathyroidism. Miner Electrolyte Metab 1996; 22(1–3): 196–9

    PubMed  CAS  Google Scholar 

  60. Raine AE, Oliver DO. Management of hyperphosphataemia in renal dialysis patients. Lancet 1987 Mar 14; I(8533): 633–4

    Article  Google Scholar 

  61. D’Haese PC, Couttenye MM, Goodman WG, et al. Use of the low-dose desferrioxamine test to diagnose and differentiate between patients with aluminium-related bone disease, increased risk for aluminium toxicity, or aluminium overload. Nephrol Dial Transplant 1995; 10: 1874–84

    PubMed  Google Scholar 

  62. D’Haese PC, Couttenye MM, De Broe ME. Diagnosis and treatment of aluminium bone disease. Nephrol Dial Transplant 1996, Suppl. 3: 74–9

    Article  Google Scholar 

  63. Barata JD, D’Haese PC, Pires C, et al. Low-dose (5 mg/kg) desferrioxamine treatment in acutely aluminium-intoxicated haemodialysis patients using two drug administration schedules. Nephrol Dial Transplant 1996; 11: 125–32

    Article  PubMed  CAS  Google Scholar 

  64. De Broe ME, Drüeke TB, Ritz E. Diagnosis and treatment of aluminium overload in end-stage renal failure patients. Nephrol Dial Transplant 1993; Suppl. 1: 1–4

    Google Scholar 

  65. Meema HE, Oreopulos DG, Rapoport A. Serum magnesium levels and arterial calcifications in end stage renal disease. Kidney Int 1987; 32: 388–94

    Article  PubMed  CAS  Google Scholar 

  66. Brayne C. Smoking and the brain. BMJ 2000 Apr; 320(7242): 1087–8

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Peter Maria Rob.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Maria Rob, P., Niederstadt, C. & Reusche, E. Dementia in Patients Undergoing Long-Term Dialysis. Mol Diag Ther 15, 691–699 (2001). https://doi.org/10.2165/00023210-200115090-00003

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00023210-200115090-00003

Keywords

Navigation