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April 09, 2013; 80 (15) Article

Disruption of cerebral networks and cognitive impairment in Alzheimer disease

Yael D. Reijmer, Alexander Leemans, Karen Caeyenberghs, Sophie M. Heringa, Huiberdina L. Koek, Geert Jan Biessels, On behalf of the Utrecht Vascular Cognitive Impairment Study Group
First published March 13, 2013, DOI: https://doi.org/10.1212/WNL.0b013e31828c2ee5
Yael D. Reijmer
From the Department of Neurology (Y.D.R., S.M.H., G.J.B.), Image Sciences Institute (A.L.), and Geriatric Department (H.L.K.), University Medical Center Utrecht, Utrecht, the Netherlands; and Motor Control Laboratory (K.C.), Research Center for Movement Control and Neuroplasticity, KU Leuven, Belgium.
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Alexander Leemans
From the Department of Neurology (Y.D.R., S.M.H., G.J.B.), Image Sciences Institute (A.L.), and Geriatric Department (H.L.K.), University Medical Center Utrecht, Utrecht, the Netherlands; and Motor Control Laboratory (K.C.), Research Center for Movement Control and Neuroplasticity, KU Leuven, Belgium.
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Karen Caeyenberghs
From the Department of Neurology (Y.D.R., S.M.H., G.J.B.), Image Sciences Institute (A.L.), and Geriatric Department (H.L.K.), University Medical Center Utrecht, Utrecht, the Netherlands; and Motor Control Laboratory (K.C.), Research Center for Movement Control and Neuroplasticity, KU Leuven, Belgium.
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Sophie M. Heringa
From the Department of Neurology (Y.D.R., S.M.H., G.J.B.), Image Sciences Institute (A.L.), and Geriatric Department (H.L.K.), University Medical Center Utrecht, Utrecht, the Netherlands; and Motor Control Laboratory (K.C.), Research Center for Movement Control and Neuroplasticity, KU Leuven, Belgium.
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Huiberdina L. Koek
From the Department of Neurology (Y.D.R., S.M.H., G.J.B.), Image Sciences Institute (A.L.), and Geriatric Department (H.L.K.), University Medical Center Utrecht, Utrecht, the Netherlands; and Motor Control Laboratory (K.C.), Research Center for Movement Control and Neuroplasticity, KU Leuven, Belgium.
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Geert Jan Biessels
From the Department of Neurology (Y.D.R., S.M.H., G.J.B.), Image Sciences Institute (A.L.), and Geriatric Department (H.L.K.), University Medical Center Utrecht, Utrecht, the Netherlands; and Motor Control Laboratory (K.C.), Research Center for Movement Control and Neuroplasticity, KU Leuven, Belgium.
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From the Department of Neurology (Y.D.R., S.M.H., G.J.B.), Image Sciences Institute (A.L.), and Geriatric Department (H.L.K.), University Medical Center Utrecht, Utrecht, the Netherlands; and Motor Control Laboratory (K.C.), Research Center for Movement Control and Neuroplasticity, KU Leuven, Belgium.
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Disruption of cerebral networks and cognitive impairment in Alzheimer disease
Yael D. Reijmer, Alexander Leemans, Karen Caeyenberghs, Sophie M. Heringa, Huiberdina L. Koek, Geert Jan Biessels, On behalf of the Utrecht Vascular Cognitive Impairment Study Group
Neurology Apr 2013, 80 (15) 1370-1377; DOI: 10.1212/WNL.0b013e31828c2ee5

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Abstract

Objective: To examine the relation between measures of whole-brain white matter connectivity and cognitive performance in patients with early Alzheimer disease (AD) using a network-based approach and to assess whether network parameters provide information that is complementary to conventional MRI markers of AD.

Methods: Fifty patients (mean age 78.8 ± 7.1 years) with early AD were recruited via a memory clinic. In addition, 15 age-, sex-, and education-matched control participants were used as a reference group. All participants underwent a 3-T MRI scan and cognitive assessment. Diffusion tensor imaging–based tractography was used to reconstruct the brain network of each individual, followed by graph theoretical analyses. Overall network efficiency was assessed by measures of local (clustering coefficient, local efficiency) and global (path length, global efficiency) connectivity. Age-, sex-, and education-adjusted cognitive scores were related to network measures and to conventional MRI parameters (i.e., degree of cerebral atrophy and small-vessel disease).

Results: The structural brain network of patients showed reduced local efficiency compared to controls. Within the patient group, worse performance in memory and executive functioning was related to decreased local efficiency (r = 0.434; p = 0.002), increased path length (r = −0.538; p < 0.001), and decreased global efficiency (r = 0.431; p = 0.005). Measures of network efficiency explained up to 27% of the variance in cognitive functioning on top of conventional MRI markers (p < 0.01).

Conclusion: This study shows that network-based analysis of brain white matter connections provides a novel way to reveal the structural basis of cognitive dysfunction in AD.

GLOSSARY

AAL=
automated anatomical labeling atlas;
AD=
Alzheimer disease;
aMCI=
amnesic mild cognitive impairment;
DTI=
diffusion tensor imaging;
FLAIR=
fluid-attenuated inversion recovery;
MCI=
mild cognitive impairment;
MMSE=
Mini-Mental State Examination;
RAVLT=
Rey Auditory Verbal Learning Task;
WMH=
white matter hyperintensity

Footnotes

  • Contributors are listed on the Neurology® Web site at www.neurology.org.

  • 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.

  • Editorial, page 1360

  • Supplemental data at www.neurology.org

  • Received June 20, 2012.
  • Accepted in final form November 16, 2012.
  • © 2013 American Academy of Neurology
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