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Brain atrophy in Alzheimer's disease (AD) and frontotemporal dementia (FTD) correlates with altered brain connectivity, impacting cognitive function across dementia subtypes and stages.

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Area of Science:

  • Neuroscience
  • Neurology
  • Medical Imaging

Background:

  • Cognitive and behavioral deficits in Alzheimer's disease (AD) and frontotemporal dementia (FTD) are linked to brain atrophy and altered functional connectivity.
  • The precise relationship between atrophy and functional connectivity disruptions across diverse dementia subtypes and stages remains unclear.

Purpose of the Study:

  • To investigate the relationship between structural brain atrophy and functional connectivity disruptions in various dementia subtypes.
  • To determine how these structure-function relationships relate to cognitive deficits and brain activity gradients.

Main Methods:

  • Utilized structural and functional MRI data from 221 patients with AD, behavioral variant FTD, corticobasal syndrome, primary progressive aphasia variants, and 100 healthy controls.
  • Employed partial least squares regression to identify principal structure-function components and eigenmode analysis to explain connectivity changes.

Main Results:

  • Identified three components linking overall atrophy to cortical hypo-connectivity and subcortical/association cortical hyper-connectivity.
  • Demonstrated that syndrome-specific atrophy correlates with peri-lesional hypo-connectivity and distal hyper-connectivity.
  • Found that structural and functional component scores predict cognitive deficits, with connectivity changes reflecting brain activity gradients.

Conclusions:

  • Brain atrophy is a significant driver of functional connectivity changes in dementia, manifesting as both hypo- and hyper-connectivity patterns.
  • These structure-function relationships provide insights into the neurobiological underpinnings of cognitive and behavioral deficits in AD and FTD.
  • Eigenmode analysis suggests temporal phase and amplitude collapse as a mechanism for atrophy-induced connectivity alterations.