White-matter integrity on DTI and the pathologic staging of Alzheimer's disease

Kejal Kantarci, Melissa E. Murray, Christopher G. Schwarz, Robert I. Reid, Scott A. Przybelski, Timothy Lesnick, Samantha M. Zuk, Mekala R. Raman, Matthew L. Senjem, Jeffrey L. Gunter, Bradley F. Boeve, David S. Knopman, Joseph E. Parisi, Ronald C. Petersen, Clifford R. Jack, Dennis W. Dickson

Research output: Contribution to journalArticlepeer-review

69 Scopus citations


Pattern of diffusion tensor MRI (DTI) alterations were investigated in pathologically-staged Alzheimer's disease (AD) patients (n = 46). Patients with antemortem DTI studies and a range of AD pathology at autopsy were included. Patients with a high neurofibrillary tangle (NFT) stage (Braak IV–VI) had significantly elevated mean diffusivity (MD) in the crus of fornix and ventral cingulum tracts, precuneus, and entorhinal white matter on voxel-based analysis after adjusting for age and time from MRI to death (p < 0.001). Higher MD and lower fractional anisotropy in the ventral cingulum tract, entorhinal, and precuneus white matter was associated with higher Braak NFT stage and clinical disease severity. There were no MD and fractional anisotropy differences among the low (none and sparse) and high (moderate and frequent) β-amyloid neuritic plaque groups. The NFT pathology of AD is associated with DTI alterations involving the medial temporal limbic connections and medial parietal white matter. This pattern of diffusion abnormalities is also associated with clinical disease severity.

Original languageEnglish (US)
Pages (from-to)172-179
Number of pages8
JournalNeurobiology of aging
StatePublished - Aug 2017


  • Alzheimer's disease
  • DTI
  • Diffusion tensor imaging
  • Limbic tracts
  • Pathology
  • White matter

ASJC Scopus subject areas

  • General Neuroscience
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology


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