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September 13, 2016; 87 (11) Article

Late-onset depressive symptoms increase the risk of dementia in small vessel disease

Ingeborg W.M. van Uden, Helena M. van der Holst, Esther M.C. van Leijsen, Anil M. Tuladhar, Anouk G.W. van Norden, Karlijn F. de Laat, Jurgen A.H.R. Claassen, Ewoud J. van Dijk, Roy P.C. Kessels, Edo Richard, Indira Tendolkar, Frank-Erik de Leeuw
First published August 12, 2016, DOI: https://doi.org/10.1212/WNL.0000000000003089
Ingeborg W.M. van Uden
From the Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Departments of Neurology (I.W.M.v.U., H.M.v.d.H., E.M.C.v.L., A.M.T., E.J.v.D., E.R., F.-E.d.L.), Geriatrics (J.A.H.R.C.), Medical Psychology (R.P.C.K.), and Psychiatry (I.T.), Nijmegen; Department of Neurology (A.G.W.v.N.), Amphia Ziekenhuis Breda; and Department of Neurology (K.F.d.L.), HagaZiekenhuis The Hague, the Netherlands.
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Helena M. van der Holst
From the Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Departments of Neurology (I.W.M.v.U., H.M.v.d.H., E.M.C.v.L., A.M.T., E.J.v.D., E.R., F.-E.d.L.), Geriatrics (J.A.H.R.C.), Medical Psychology (R.P.C.K.), and Psychiatry (I.T.), Nijmegen; Department of Neurology (A.G.W.v.N.), Amphia Ziekenhuis Breda; and Department of Neurology (K.F.d.L.), HagaZiekenhuis The Hague, the Netherlands.
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Esther M.C. van Leijsen
From the Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Departments of Neurology (I.W.M.v.U., H.M.v.d.H., E.M.C.v.L., A.M.T., E.J.v.D., E.R., F.-E.d.L.), Geriatrics (J.A.H.R.C.), Medical Psychology (R.P.C.K.), and Psychiatry (I.T.), Nijmegen; Department of Neurology (A.G.W.v.N.), Amphia Ziekenhuis Breda; and Department of Neurology (K.F.d.L.), HagaZiekenhuis The Hague, the Netherlands.
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Anil M. Tuladhar
From the Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Departments of Neurology (I.W.M.v.U., H.M.v.d.H., E.M.C.v.L., A.M.T., E.J.v.D., E.R., F.-E.d.L.), Geriatrics (J.A.H.R.C.), Medical Psychology (R.P.C.K.), and Psychiatry (I.T.), Nijmegen; Department of Neurology (A.G.W.v.N.), Amphia Ziekenhuis Breda; and Department of Neurology (K.F.d.L.), HagaZiekenhuis The Hague, the Netherlands.
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Anouk G.W. van Norden
From the Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Departments of Neurology (I.W.M.v.U., H.M.v.d.H., E.M.C.v.L., A.M.T., E.J.v.D., E.R., F.-E.d.L.), Geriatrics (J.A.H.R.C.), Medical Psychology (R.P.C.K.), and Psychiatry (I.T.), Nijmegen; Department of Neurology (A.G.W.v.N.), Amphia Ziekenhuis Breda; and Department of Neurology (K.F.d.L.), HagaZiekenhuis The Hague, the Netherlands.
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Karlijn F. de Laat
From the Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Departments of Neurology (I.W.M.v.U., H.M.v.d.H., E.M.C.v.L., A.M.T., E.J.v.D., E.R., F.-E.d.L.), Geriatrics (J.A.H.R.C.), Medical Psychology (R.P.C.K.), and Psychiatry (I.T.), Nijmegen; Department of Neurology (A.G.W.v.N.), Amphia Ziekenhuis Breda; and Department of Neurology (K.F.d.L.), HagaZiekenhuis The Hague, the Netherlands.
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Jurgen A.H.R. Claassen
From the Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Departments of Neurology (I.W.M.v.U., H.M.v.d.H., E.M.C.v.L., A.M.T., E.J.v.D., E.R., F.-E.d.L.), Geriatrics (J.A.H.R.C.), Medical Psychology (R.P.C.K.), and Psychiatry (I.T.), Nijmegen; Department of Neurology (A.G.W.v.N.), Amphia Ziekenhuis Breda; and Department of Neurology (K.F.d.L.), HagaZiekenhuis The Hague, the Netherlands.
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Ewoud J. van Dijk
From the Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Departments of Neurology (I.W.M.v.U., H.M.v.d.H., E.M.C.v.L., A.M.T., E.J.v.D., E.R., F.-E.d.L.), Geriatrics (J.A.H.R.C.), Medical Psychology (R.P.C.K.), and Psychiatry (I.T.), Nijmegen; Department of Neurology (A.G.W.v.N.), Amphia Ziekenhuis Breda; and Department of Neurology (K.F.d.L.), HagaZiekenhuis The Hague, the Netherlands.
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Roy P.C. Kessels
From the Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Departments of Neurology (I.W.M.v.U., H.M.v.d.H., E.M.C.v.L., A.M.T., E.J.v.D., E.R., F.-E.d.L.), Geriatrics (J.A.H.R.C.), Medical Psychology (R.P.C.K.), and Psychiatry (I.T.), Nijmegen; Department of Neurology (A.G.W.v.N.), Amphia Ziekenhuis Breda; and Department of Neurology (K.F.d.L.), HagaZiekenhuis The Hague, the Netherlands.
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Edo Richard
From the Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Departments of Neurology (I.W.M.v.U., H.M.v.d.H., E.M.C.v.L., A.M.T., E.J.v.D., E.R., F.-E.d.L.), Geriatrics (J.A.H.R.C.), Medical Psychology (R.P.C.K.), and Psychiatry (I.T.), Nijmegen; Department of Neurology (A.G.W.v.N.), Amphia Ziekenhuis Breda; and Department of Neurology (K.F.d.L.), HagaZiekenhuis The Hague, the Netherlands.
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Indira Tendolkar
From the Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Departments of Neurology (I.W.M.v.U., H.M.v.d.H., E.M.C.v.L., A.M.T., E.J.v.D., E.R., F.-E.d.L.), Geriatrics (J.A.H.R.C.), Medical Psychology (R.P.C.K.), and Psychiatry (I.T.), Nijmegen; Department of Neurology (A.G.W.v.N.), Amphia Ziekenhuis Breda; and Department of Neurology (K.F.d.L.), HagaZiekenhuis The Hague, the Netherlands.
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Frank-Erik de Leeuw
From the Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Departments of Neurology (I.W.M.v.U., H.M.v.d.H., E.M.C.v.L., A.M.T., E.J.v.D., E.R., F.-E.d.L.), Geriatrics (J.A.H.R.C.), Medical Psychology (R.P.C.K.), and Psychiatry (I.T.), Nijmegen; Department of Neurology (A.G.W.v.N.), Amphia Ziekenhuis Breda; and Department of Neurology (K.F.d.L.), HagaZiekenhuis The Hague, the Netherlands.
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Full PDF
Citation
Late-onset depressive symptoms increase the risk of dementia in small vessel disease
Ingeborg W.M. van Uden, Helena M. van der Holst, Esther M.C. van Leijsen, Anil M. Tuladhar, Anouk G.W. van Norden, Karlijn F. de Laat, Jurgen A.H.R. Claassen, Ewoud J. van Dijk, Roy P.C. Kessels, Edo Richard, Indira Tendolkar, Frank-Erik de Leeuw
Neurology Sep 2016, 87 (11) 1102-1109; DOI: 10.1212/WNL.0000000000003089

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Abstract

Objective: We prospectively investigated the role of depressive symptoms (DS) on all-cause dementia in a population with small vessel disease (SVD), considering onset age of DS and cognitive performance.

Methods: The RUN DMC study (Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Cohort) is a prospective cohort study among 503 older adults with SVD on MRI without dementia at baseline (2006), with a follow-up of 5 years (2012). Kaplan-Meier curves stratified for DS and dementia risk were compared using log-rank test. We calculated hazard ratios using Cox regression analyses.

Results: Follow-up was available for 496 participants (mean baseline age 65.6 years [SD 8.8]; mean follow-up time 5.2 years). All-cause dementia developed in 41 participants. The 5.5-year dementia risk was higher in those with DS (hazard ratio 2.7, 95% confidence interval 1.4–5.2), independent of confounders. This was driven by those with late-onset DS. Five-year cumulative risk difference for dementia was higher in participants with depressive symptoms who had high baseline cognitive performance (no DS 0.0% vs DS 6.9%, log-rank p < 0.001) compared with those who had low cognitive performance at baseline.

Conclusions: Late-onset DS increases dementia risk, independent of SVD. Especially in those with relatively high cognitive performance, DS indicate a higher risk. In contrast to current practice, clinicians should monitor those with DS who also show relatively good cognitive test scores.

GLOSSARY

CES-D=
Center for Epidemiologic Studies Depression Scale;
CI=
confidence interval;
DS=
depressive symptoms;
DSM-IV=
Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition);
EODS=
early-onset depressive symptoms;
GM=
gray matter;
HR=
hazard ratio;
LODS=
late-onset depressive symptoms;
MMSE=
Mini-Mental State Examination;
MPRAGE=
magnetization-prepared rapid-acquisition gradient echo;
RUN DMC=
Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Cohort;
SAT=
speed–accuracy trade-off;
SVD=
small vessel disease;
TBV=
total brain volume;
WM=
white matter;
WMH=
white matter hyperintensity

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 December 10, 2015.
  • Accepted in final form May 30, 2016.
  • © 2016 American Academy of Neurology
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