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January 10, 2017; 88 (2) Views and Reviews

Dementia risk in renal dysfunction

A systematic review and meta-analysis of prospective studies

Kay Deckers, Ileana Camerino, Martin P.J. van Boxtel, Frans R.J. Verhey, Kate Irving, Carol Brayne, Miia Kivipelto, John M. Starr, Kristine Yaffe, Peter W. de Leeuw, Sebastian Köhler
First published December 14, 2016, DOI: https://doi.org/10.1212/WNL.0000000000003482
Kay Deckers
From Alzheimer Centrum Limburg (K.D., I.C., M.P.J.v.B., F.R.J.V., S.K.), School for Mental Health and Neuroscience, Maastricht University; Alzheimer Centre and Department of Neurology (I.C.), VU University Medical Centre, Amsterdam, the Netherlands; School of Nursing and Human Sciences (K.I.), Dublin City University, Ireland; Department of Public Health and Primary Care (C.B.), University of Cambridge, UK; Alzheimer Disease Research Center (M.K.), Karolinska Institute, Stockholm, Sweden; Centre for Cognitive Ageing and Cognitive Epidemiology (J.M.S.), University of Edinburgh, UK; Departments of Psychiatry, Neurology, Epidemiology and Biostatistics (K.Y.), School of Medicine, University of California, San Francisco; Department of Medicine (P.W.d.L.), Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre; and Department of Medicine (P.W.d.L.), Zuyderland MC, Sittard-Geleen/Heerlen, the Netherlands.
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Ileana Camerino
From Alzheimer Centrum Limburg (K.D., I.C., M.P.J.v.B., F.R.J.V., S.K.), School for Mental Health and Neuroscience, Maastricht University; Alzheimer Centre and Department of Neurology (I.C.), VU University Medical Centre, Amsterdam, the Netherlands; School of Nursing and Human Sciences (K.I.), Dublin City University, Ireland; Department of Public Health and Primary Care (C.B.), University of Cambridge, UK; Alzheimer Disease Research Center (M.K.), Karolinska Institute, Stockholm, Sweden; Centre for Cognitive Ageing and Cognitive Epidemiology (J.M.S.), University of Edinburgh, UK; Departments of Psychiatry, Neurology, Epidemiology and Biostatistics (K.Y.), School of Medicine, University of California, San Francisco; Department of Medicine (P.W.d.L.), Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre; and Department of Medicine (P.W.d.L.), Zuyderland MC, Sittard-Geleen/Heerlen, the Netherlands.
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Martin P.J. van Boxtel
From Alzheimer Centrum Limburg (K.D., I.C., M.P.J.v.B., F.R.J.V., S.K.), School for Mental Health and Neuroscience, Maastricht University; Alzheimer Centre and Department of Neurology (I.C.), VU University Medical Centre, Amsterdam, the Netherlands; School of Nursing and Human Sciences (K.I.), Dublin City University, Ireland; Department of Public Health and Primary Care (C.B.), University of Cambridge, UK; Alzheimer Disease Research Center (M.K.), Karolinska Institute, Stockholm, Sweden; Centre for Cognitive Ageing and Cognitive Epidemiology (J.M.S.), University of Edinburgh, UK; Departments of Psychiatry, Neurology, Epidemiology and Biostatistics (K.Y.), School of Medicine, University of California, San Francisco; Department of Medicine (P.W.d.L.), Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre; and Department of Medicine (P.W.d.L.), Zuyderland MC, Sittard-Geleen/Heerlen, the Netherlands.
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Frans R.J. Verhey
From Alzheimer Centrum Limburg (K.D., I.C., M.P.J.v.B., F.R.J.V., S.K.), School for Mental Health and Neuroscience, Maastricht University; Alzheimer Centre and Department of Neurology (I.C.), VU University Medical Centre, Amsterdam, the Netherlands; School of Nursing and Human Sciences (K.I.), Dublin City University, Ireland; Department of Public Health and Primary Care (C.B.), University of Cambridge, UK; Alzheimer Disease Research Center (M.K.), Karolinska Institute, Stockholm, Sweden; Centre for Cognitive Ageing and Cognitive Epidemiology (J.M.S.), University of Edinburgh, UK; Departments of Psychiatry, Neurology, Epidemiology and Biostatistics (K.Y.), School of Medicine, University of California, San Francisco; Department of Medicine (P.W.d.L.), Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre; and Department of Medicine (P.W.d.L.), Zuyderland MC, Sittard-Geleen/Heerlen, the Netherlands.
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Kate Irving
From Alzheimer Centrum Limburg (K.D., I.C., M.P.J.v.B., F.R.J.V., S.K.), School for Mental Health and Neuroscience, Maastricht University; Alzheimer Centre and Department of Neurology (I.C.), VU University Medical Centre, Amsterdam, the Netherlands; School of Nursing and Human Sciences (K.I.), Dublin City University, Ireland; Department of Public Health and Primary Care (C.B.), University of Cambridge, UK; Alzheimer Disease Research Center (M.K.), Karolinska Institute, Stockholm, Sweden; Centre for Cognitive Ageing and Cognitive Epidemiology (J.M.S.), University of Edinburgh, UK; Departments of Psychiatry, Neurology, Epidemiology and Biostatistics (K.Y.), School of Medicine, University of California, San Francisco; Department of Medicine (P.W.d.L.), Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre; and Department of Medicine (P.W.d.L.), Zuyderland MC, Sittard-Geleen/Heerlen, the Netherlands.
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Carol Brayne
From Alzheimer Centrum Limburg (K.D., I.C., M.P.J.v.B., F.R.J.V., S.K.), School for Mental Health and Neuroscience, Maastricht University; Alzheimer Centre and Department of Neurology (I.C.), VU University Medical Centre, Amsterdam, the Netherlands; School of Nursing and Human Sciences (K.I.), Dublin City University, Ireland; Department of Public Health and Primary Care (C.B.), University of Cambridge, UK; Alzheimer Disease Research Center (M.K.), Karolinska Institute, Stockholm, Sweden; Centre for Cognitive Ageing and Cognitive Epidemiology (J.M.S.), University of Edinburgh, UK; Departments of Psychiatry, Neurology, Epidemiology and Biostatistics (K.Y.), School of Medicine, University of California, San Francisco; Department of Medicine (P.W.d.L.), Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre; and Department of Medicine (P.W.d.L.), Zuyderland MC, Sittard-Geleen/Heerlen, the Netherlands.
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Miia Kivipelto
From Alzheimer Centrum Limburg (K.D., I.C., M.P.J.v.B., F.R.J.V., S.K.), School for Mental Health and Neuroscience, Maastricht University; Alzheimer Centre and Department of Neurology (I.C.), VU University Medical Centre, Amsterdam, the Netherlands; School of Nursing and Human Sciences (K.I.), Dublin City University, Ireland; Department of Public Health and Primary Care (C.B.), University of Cambridge, UK; Alzheimer Disease Research Center (M.K.), Karolinska Institute, Stockholm, Sweden; Centre for Cognitive Ageing and Cognitive Epidemiology (J.M.S.), University of Edinburgh, UK; Departments of Psychiatry, Neurology, Epidemiology and Biostatistics (K.Y.), School of Medicine, University of California, San Francisco; Department of Medicine (P.W.d.L.), Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre; and Department of Medicine (P.W.d.L.), Zuyderland MC, Sittard-Geleen/Heerlen, the Netherlands.
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John M. Starr
From Alzheimer Centrum Limburg (K.D., I.C., M.P.J.v.B., F.R.J.V., S.K.), School for Mental Health and Neuroscience, Maastricht University; Alzheimer Centre and Department of Neurology (I.C.), VU University Medical Centre, Amsterdam, the Netherlands; School of Nursing and Human Sciences (K.I.), Dublin City University, Ireland; Department of Public Health and Primary Care (C.B.), University of Cambridge, UK; Alzheimer Disease Research Center (M.K.), Karolinska Institute, Stockholm, Sweden; Centre for Cognitive Ageing and Cognitive Epidemiology (J.M.S.), University of Edinburgh, UK; Departments of Psychiatry, Neurology, Epidemiology and Biostatistics (K.Y.), School of Medicine, University of California, San Francisco; Department of Medicine (P.W.d.L.), Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre; and Department of Medicine (P.W.d.L.), Zuyderland MC, Sittard-Geleen/Heerlen, the Netherlands.
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Kristine Yaffe
From Alzheimer Centrum Limburg (K.D., I.C., M.P.J.v.B., F.R.J.V., S.K.), School for Mental Health and Neuroscience, Maastricht University; Alzheimer Centre and Department of Neurology (I.C.), VU University Medical Centre, Amsterdam, the Netherlands; School of Nursing and Human Sciences (K.I.), Dublin City University, Ireland; Department of Public Health and Primary Care (C.B.), University of Cambridge, UK; Alzheimer Disease Research Center (M.K.), Karolinska Institute, Stockholm, Sweden; Centre for Cognitive Ageing and Cognitive Epidemiology (J.M.S.), University of Edinburgh, UK; Departments of Psychiatry, Neurology, Epidemiology and Biostatistics (K.Y.), School of Medicine, University of California, San Francisco; Department of Medicine (P.W.d.L.), Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre; and Department of Medicine (P.W.d.L.), Zuyderland MC, Sittard-Geleen/Heerlen, the Netherlands.
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Peter W. de Leeuw
From Alzheimer Centrum Limburg (K.D., I.C., M.P.J.v.B., F.R.J.V., S.K.), School for Mental Health and Neuroscience, Maastricht University; Alzheimer Centre and Department of Neurology (I.C.), VU University Medical Centre, Amsterdam, the Netherlands; School of Nursing and Human Sciences (K.I.), Dublin City University, Ireland; Department of Public Health and Primary Care (C.B.), University of Cambridge, UK; Alzheimer Disease Research Center (M.K.), Karolinska Institute, Stockholm, Sweden; Centre for Cognitive Ageing and Cognitive Epidemiology (J.M.S.), University of Edinburgh, UK; Departments of Psychiatry, Neurology, Epidemiology and Biostatistics (K.Y.), School of Medicine, University of California, San Francisco; Department of Medicine (P.W.d.L.), Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre; and Department of Medicine (P.W.d.L.), Zuyderland MC, Sittard-Geleen/Heerlen, the Netherlands.
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Sebastian Köhler
From Alzheimer Centrum Limburg (K.D., I.C., M.P.J.v.B., F.R.J.V., S.K.), School for Mental Health and Neuroscience, Maastricht University; Alzheimer Centre and Department of Neurology (I.C.), VU University Medical Centre, Amsterdam, the Netherlands; School of Nursing and Human Sciences (K.I.), Dublin City University, Ireland; Department of Public Health and Primary Care (C.B.), University of Cambridge, UK; Alzheimer Disease Research Center (M.K.), Karolinska Institute, Stockholm, Sweden; Centre for Cognitive Ageing and Cognitive Epidemiology (J.M.S.), University of Edinburgh, UK; Departments of Psychiatry, Neurology, Epidemiology and Biostatistics (K.Y.), School of Medicine, University of California, San Francisco; Department of Medicine (P.W.d.L.), Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre; and Department of Medicine (P.W.d.L.), Zuyderland MC, Sittard-Geleen/Heerlen, the Netherlands.
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Citation
Dementia risk in renal dysfunction
A systematic review and meta-analysis of prospective studies
Kay Deckers, Ileana Camerino, Martin P.J. van Boxtel, Frans R.J. Verhey, Kate Irving, Carol Brayne, Miia Kivipelto, John M. Starr, Kristine Yaffe, Peter W. de Leeuw, Sebastian Köhler
Neurology Jan 2017, 88 (2) 198-208; DOI: 10.1212/WNL.0000000000003482

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Abstract

Objective: Renal dysfunction has been linked with increased risk for cognitive impairment and dementia, but studies are conflicting. For that reason, the aim of the present systematic review and meta-analysis is to summarize the best available evidence on the prospective association between potential markers of renal dysfunction and development of cognitive impairment or dementia.

Methods: Medline, Embase, and Cochrane Database of Systematic Reviews were searched for potential publications until August 1, 2016. Studies were eligible if they fulfilled the following criteria: population-based study, prospective design, ≥100 participants, aged ≥45 years, ≥1 year follow-up, and cognition/dementia outcomes. Where appropriate, random effects meta-analyses were conducted yielding pooled odds ratios (OR) and 95% confidence intervals (CI).

Results: Twenty-two out of 8,494 abstracts fulfilled the eligibility criteria. Sufficient evidence was found for albuminuria, mixed results for estimated glomerular filtration rate (eGFR), insufficient support for cystatin C, and tentative evidence for serum creatinine and creatinine clearance. Meta-analyses of 5 studies representing 27,805 persons showed a 35% increased risk of cognitive impairment or dementia in those with albuminuria (OR 1.35, 95% CI 1.06–1.73, p = 0.015), whereas eGFR <60 mL/min/1.73 m2 showed no significant association (OR 1.28, 95% CI 0.99–1.65, p = 0.063). No meta-analyses could be done for serum creatinine, creatinine clearance, or cystatin C.

Conclusions: The overall evidence for an association between renal dysfunction and cognitive impairment or dementia is modest. Evidence suggests that albuminuria is associated with higher odds of developing cognitive impairment or dementia.

GLOSSARY

Aβ=
β-amyloid;
AD=
Alzheimer disease;
CCl=
creatinine clearance;
CI=
confidence interval;
CKD=
chronic kidney disease;
DSM-IV=
Diagnostic and Statistical Manual of Mental Disorders, 4th edition;
eGFR=
estimated glomerular filtration rate;
MMSE=
Mini-Mental State Examination;
NOS=
Newcastle-Ottawa Scale;
OR=
odds ratio;
SCr=
serum creatinine

Footnotes

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Supplemental data at Neurology.org

  • Received May 14, 2016.
  • Accepted in final form September 29, 2016.
  • © 2016 American Academy of Neurology
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Letters: Rapid online correspondence

  • Author response: Dementia risk in renal dysfunction
    • Kay Deckers, Postdoctoral Researcher, Maastricht University; Alzheimer Centre Limburgkay.deckers@maastrichtuniversity.nl
    • Ileana Camerino, Martin P.J. van Boxtel, Frans R.J. Verhey, Kate Irving, Carol Brayne, Miia Kivipelto, John M. Starr, Kristine Yaffe, Peter W. de Leeuw, Sebastian Kohler
    Submitted August 15, 2017
  • Dementia risk in renal dysfunction
    • Tomoyuki Kawada, Professor, Nippon Medical Schoolkawada@nms.ac.jp
    Submitted May 25, 2017
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