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Demyelination in mild cognitive impairment suggests progression path to Alzheimer's disease

Cristian Carmeli1, Alessia Donati, Valérie Antille

  • 1LREN, Department of Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois (CHUV), and University of Lausanne, Lausanne, Switzerland.

Plos One
|September 12, 2013
PubMed

Insights

Preclinical Alzheimer's disease progression involves memory loss, potentially tracked by myelin content reduction. This study shows demyelination spreads from initial memory areas to broader brain regions in mild cognitive impairment.

Area of Science:

  • Neuroscience
  • Radiology
  • Neurology

Background:

  • Preclinical Alzheimer's disease (AD) presents as amnestic mild cognitive impairment (MCI), with subtypes including single-domain MCI (sMCI) and multiple-domain MCI (mMCI).
  • The progression from MCI to AD is hypothesized to follow a sequence from sMCI to mMCI, driven by expanding pathological processes.

Purpose of the Study:

  • To investigate myelin content changes using Magnetization Transfer Ratio (MTR) in sMCI and mMCI patients.
  • To explore the relationship between demyelination patterns and the progression of cognitive decline in preclinical AD.

Main Methods:

  • Magnetization Transfer Ratio (MTR) imaging was performed on 21 sMCI patients, 21 mMCI patients, and 42 healthy controls.
  • Conjunction and disjunction analyses were used to identify shared and distinct regions of MTR reduction between MCI subtypes.

Main Results:

  • Both sMCI and mMCI groups showed MTR reduction in medial temporal lobe and posterior brain structures (white and gray matter).
  • Executive mMCI patients exhibited additional demyelination in prefrontal white matter and insula gray matter.
  • Demyelination was observed in brain areas affected by neurofibrillary pathology, correlating with clinical presentation.

Conclusions:

  • Demyelination is an early indicator in MCI, potentially marking the progression pathway from sMCI to mMCI and towards AD.
  • In vivo imaging of white matter (WM) and gray matter (GM) demyelination could enable staging of preclinical AD.

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