Demyelination in Mild Cognitive Impairment Suggests Progression Path to Alzheimer’s Disease

نویسندگان

  • Cristian Carmeli
  • Alessia Donati
  • Valérie Antille
  • Dragana Viceic
  • Joseph Ghika
  • Armin von Gunten
  • Stephanie Clarke
  • Reto Meuli
  • Richard S. Frackowiak
  • Maria G. Knyazeva
چکیده

The preclinical Alzheimer's disease (AD) - amnestic mild cognitive impairment (MCI) - is manifested by phenotypes classified into exclusively memory (single-domain) MCI (sMCI) and multiple-domain MCI (mMCI). We suggest that typical MCI-to-AD progression occurs through the sMCI-to-mMCI sequence as a result of the extension of initial pathological processes. To support this hypothesis, we assess myelin content with a Magnetization Transfer Ratio (MTR) in 21 sMCI and 21 mMCI patients and in 42 age-, sex-, and education-matched controls. A conjunction analysis revealed MTR reduction shared by sMCI and mMCI groups in the medial temporal lobe and posterior structures including white matter (WM: splenium, posterior corona radiata) and gray matter (GM: hippocampus; parahippocampal and lingual gyri). A disjunction analysis showed the spread of demyelination to prefrontal WM and insula GM in executive mMCI. Our findings suggest that demyelination starts in the structures affected by neurofibrillary pathology; its presence correlates with the clinical picture and indicates the method of MCI-to-AD progression. In vivo staging of preclinical AD can be developed in terms of WM/GM demyelination.

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عنوان ژورنال:

دوره 8  شماره 

صفحات  -

تاریخ انتشار 2013