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Hypersynchronization in mild cognitive impairment: the 'X' model.

Sandra Pusil1,2, María Eugenia López2,3,4, Pablo Cuesta2,5

  • 1Laboratory of Neuropsychology, University of the Balearic Islands, Spain.

Brain : a Journal of Neurology
|October 22, 2019
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Summary

Hypersynchronization in mild cognitive impairment (MCI) predicts Alzheimer's disease conversion. Progressive MCI shows network breakdown, while stable MCI exhibits a potential compensatory mechanism, offering a predictive biomarker for dementia risk.

Keywords:
classificationfunctional connectivitylongitudinal studymagnetoencephalographystable and progressive mild cognitive impairment

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Area of Science:

  • Neuroscience
  • Biomarkers
  • Neurodegenerative Diseases

Background:

  • Alzheimer's disease (AD) continuum research seeks biomarkers for early detection.
  • Hypersynchronization is a proposed synaptic dysfunction biomarker in AD, linked to altered excitation/inhibition balance.
  • Evidence for hypersynchronization in human AD progression is limited.

Purpose of the Study:

  • To investigate hypersynchronization as a predictor of conversion from mild cognitive impairment (MCI) to Alzheimer's disease.
  • To evaluate functional brain network alterations in patients with progressive versus stable MCI.

Main Methods:

  • Longitudinal study of 54 MCI patients, followed for 6 months.
  • Eyes-closed resting-state magnetoencephalography (MEG) to assess functional connectivity networks.
  • Network-based statistics with ANCOVA to analyze functional connectivity ratios (post-/pre-condition) in theta and beta bands, controlling for age.

Main Results:

  • Progressive MCI patients showed a diminished functional connectivity ratio in fronto-temporal and fronto-occipital networks in theta and beta bands.
  • At baseline, progressive MCI patients exhibited higher synchronization than stable MCI patients.
  • Post-condition, this pattern reversed, with stable MCI showing increased synchrony and progressive MCI showing network failure.

Conclusions:

  • Hypersynchronization may predict conversion to AD, followed by network breakdown in progressive MCI.
  • Stable MCI patients may show a compensatory hypersynchronization, suggesting they are further along the AD continuum.
  • This hypersynchronization model could predict dementia risk in MCI patients.