Regional brain stiffness changes across the Alzheimer's disease spectrum☆

Magnetic resonance elastography (MRE) is an MRI-based technique to noninvasively measure tissue stiffness. Currently well established for clinical use in the liver, MRE is increasingly being investigated to measure brain stiffness as a novel biomarker of a variety of neurological diseases. The purpose of this work was to apply a recently developed MRE pipeline to measure regional brain stiffness changes in human subjects across the Alzheimer's disease (AD) spectrum, and to gain insights into the biological processes underlying those stiffness changes by correlating stiffness with existing biomarkers of AD. The results indicate that stiffness changes occur mostly in the frontal, parietal and temporal lobes, in accordance with the known topography of AD pathology. Furthermore, stiffness in those areas correlates with existing imaging biomarkers of AD including hippocampal volumes and amyloid PET. Additional analysis revealed preliminary but significant evidence that the relationship between brain stiffness and AD severity is nonlinear and non-monotonic. Given that similar relationships have been observed in functional MRI experiments, we used task-free fMRI data to test the hypothesis that brain stiffness was sensitive to structural changes associated with altered functional connectivity. The analysis revealed that brain stiffness is significantly and positively correlated with default mode network connectivity. Therefore, brain stiffness as measured by MRE has potential to provide new and essential insights into the temporal dynamics of AD, as well as the relationship between functional and structural plasticity as it relates to AD pathophysiology.

• Publication year

  2012

• Venue

  NeuroImage: Clinical

• Publication date

  2012-07-01

• Fields of study

  Medicine, Psychology

• Identifiers
  DOI 10.1016/j.nicl.2015.12.007PMID 26900568PMCID 4724025
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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  2013influential reference
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  2013cited by this paper
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  2013cited by this paper
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• Age-related changes in the default mode network are more advanced in Alzheimer disease

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  2011influential reference
• The diagnosis of mild cognitive impairment due to Alzheimer's disease: Recommendations from the National Institute on Aging‐Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease

  2011influential reference
• Toward defining the preclinical stages of Alzheimer's disease: Recommendations from the National Institute on Aging‐Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease

  2011cited by this paper
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  2010cited by this paper
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  2010cited by this paper
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• The global signal and observed anticorrelated resting state brain networks.

  2009influential reference
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  2009influential reference
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• Probability and Statistics for Engineering and the Sciences

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  2004cited by this paper
• Alzheimer disease in the US population: prevalence estimates using the 2000 census.

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  1991cited by this paper
• Clinical diagnosis of Alzheimer's disease

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