Regional multimodal relationships between tau, hypometabolism, atrophy, and fractional anisotropy in atypical Alzheimer's disease

Irene Sintini, Christopher G. Schwarz, Peter R. Martin, Jonathan Graff-Radford, Mary M. Machulda, Matthew L. Senjem, Robert I. Reid, Anthony J. Spychalla, Daniel A. Drubach, Val J. Lowe, Clifford R. Jack, Keith A. Josephs, Jennifer L. Whitwell

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


Alzheimer's disease (AD) can present with atypical clinical forms where the prominent domain of deficit is not memory, that is, atypical AD. Atypical AD patients show cortical atrophy on MRI, hypometabolism on [ 18 F]fluorodeoxyglucose (FDG) PET, tau uptake on [ 18 F]AV-1451 PET, and white matter tract degeneration on diffusion tensor imaging (DTI). How these disease processes relate to each other locally and distantly remains unclear. We aimed to examine multimodal neuroimaging relationships in individuals with atypical AD, using univariate and multivariate techniques at region- and voxel-level. Forty atypical AD patients underwent MRI, FDG-PET, tau-PET, beta-amyloid PET, and DTI. Patients were all beta-amyloid positive. Partial Pearson's correlations were performed between tau and FDG standardized uptake value ratios, gray matter MRI-volumes and white matter tract fractional anisotropy. Sparse canonical correlation analysis was applied to identify multivariate relationships between the same quantities. Voxel-level associations across modalities were also assessed. Tau showed strong local negative correlations with FDG metabolism in the occipital and frontal lobes. Tau in frontal and parietal regions was negatively associated with temporoparietal gray matter MRI-volume. Fractional anisotropy in a set of posterior white matter tracts, including the splenium of the corpus callosum, cingulum, and posterior thalamic radiation, was negatively correlated with parietal and occipital tau, atrophy and, predominantly, with hypometabolism. These results support the view that tau is the driving force behind neurodegeneration in atypical AD, and that a breakdown in structural connectivity is related to cortical neurodegeneration, particularly hypometabolism.

Original languageEnglish (US)
Pages (from-to)1618-1631
Number of pages14
JournalHuman Brain Mapping
Issue number5
StatePublished - Apr 1 2019


  • DTI
  • FDG
  • MRI
  • atypical Alzheimer's disease
  • multimodal imaging
  • multivariate analysis
  • tau

ASJC Scopus subject areas

  • Anatomy
  • Radiological and Ultrasound Technology
  • Radiology Nuclear Medicine and imaging
  • Neurology
  • Clinical Neurology


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