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Functional network collapse in neurodegenerative disease.

Jesse A Brown1,2, Alex J Lee3, Kristen Fernhoff3

  • 1University of California, San Francisco, Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, San Francisco, CA, USA. jbrown81@gmail.com.

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Brain atrophy in Alzheimer's disease (AD) and frontotemporal dementia (FTD) correlates with altered brain connectivity, impacting cognitive function. These changes offer insights into neurodegeneration mechanisms.

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Area of Science:

  • Neuroimaging
  • Neuroscience
  • Neurology

Background:

  • Alzheimer's disease (AD) and frontotemporal dementia (FTD) cause cognitive and behavioral deficits linked to brain atrophy and altered functional connectivity.
  • The precise relationship between brain structure and function across the dementia spectrum is not fully understood.

Purpose of the Study:

  • To investigate the structure-function relationship in the context of neurodegenerative diseases.
  • To explore how gray matter atrophy relates to functional connectivity alterations and cognitive deficits in AD and FTD.

Main Methods:

  • Combined structural and functional MRI data from 221 patients with AD, FTD, corticobasal syndrome, primary progressive aphasia, and 100 healthy controls.
  • Utilized partial least-squares regression to identify structure-function components.
  • Employed eigenmode analysis to examine the impact of atrophy on intrinsic activity gradients.

Main Results:

  • Identified three key structure-function components linking atrophy to altered sensorimotor and association cortical connectivity.
  • Focal atrophy was associated with peri-lesional hypo-connectivity and distal hyper-connectivity.
  • Structural and functional scores explained 34% of the variance in cognitive deficits, with atrophy affecting intrinsic activity gradients.

Conclusions:

  • Brain atrophy in dementia is mechanistically linked to altered functional connectivity and network collapse.
  • Changes in intrinsic activity gradients provide a framework for understanding neurodegeneration's impact on brain networks.
  • This study elucidates the structure-function interplay in dementia, offering insights into cognitive decline.