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Alzheimer's Imaging Consortium.

Quentin Devignes1, Patrick J Pruitt1, Kenneth Petscavage1,2

  • 1University of Michigan, Ann Arbor, MI, USA.

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Summary
This summary is machine-generated.

Neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) are linked to microstructural gray matter changes in the salience network, not amyloid or tau burden. These findings suggest NPS severity correlates more with brain structure alterations than AD pathology.

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Area of Science:

  • Neuroscience
  • Neurology
  • Medical Imaging

Background:

  • Neuropsychiatric symptoms (NPS) are core features of Alzheimer's disease (AD).
  • Functional connectivity disruptions in the salience network are associated with NPS severity.
  • The structural and pathological underpinnings of NPS in AD require further investigation.

Purpose of the Study:

  • To investigate the relationship between NPS severity and gray matter (GM) microstructural integrity.
  • To examine the association of NPS severity with amyloid and tau burden in individuals with mild cognitive impairment (MCI) and mild AD dementia (DAT).

Main Methods:

  • 178 participants with MCI or DAT underwent PET scans for amyloid ([11C]-Pittsburgh compound B) and tau ([18F]AV-1451) deposition.
  • Diffusion tensor imaging (DTI) using neurite orientation dispersion and density imaging (NODDI) assessed GM microstructural integrity (NDI, ODI).
  • Voxel-wise regression analyses correlated NPS severity (NPIQ scores) with PET and DTI measures, controlling for age, sex, and education.

Main Results:

  • Higher NPS severity correlated with reduced orientation dispersion index (ODI) in the right insula and inferior frontal gyrus, indicating altered microstructural integrity.
  • No significant associations were found between NPS severity and amyloid or tau burden.
  • A lenient threshold revealed a potential association between NPS severity and increased tau deposition in the left striatum.

Conclusions:

  • NPS severity in AD is associated with altered white matter diffusivity in salience network regions, potentially reflecting reduced dendritic complexity.
  • Microstructural gray matter changes, rather than amyloid or tau burden, may be more closely linked to NPS severity in AD.
  • These findings support the salience network's role in NPS within the context of AD.