White matter fiber density abnormalities in cognitively normal adults at risk for late-onset Alzheimer's disease

Stella M. Sánchez, Bárbara Duarte-Abritta, Carolina Abulafia, Gabriela De Pino, Hernan Bocaccio, Mariana N. Castro, Gustavo E. Sevlever, Greg A. Fonzo, Charles B. Nemeroff, Deborah R. Gustafson, Salvador M. Guinjoan, Mirta F. Villarreal

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Tau accumulation affecting white matter tracts is an early neuropathological feature of late-onset Alzheimer's disease (LOAD). There is a need to ascertain methods for the detection of early LOAD features to help with disease prevention efforts. The microstructure of these tracts and anatomical brain connectivity can be assessed by analyzing diffusion MRI (dMRI) data. Considering that family history increases the risk of developing LOAD, we explored the microstructure of white matter through dMRI in 23 cognitively normal adults who are offspring of patients with Late-Onset Alzheimer's Disease (O-LOAD) and 22 control subjects (CS) without family history of AD. We also evaluated the relation of white matter microstructure metrics with cortical thickness, volumetry, in vivo amyloid deposition (with the help of PiB positron emission tomography -PiB-PET) and regional brain metabolism (as FDG-PET) measures. Finally we studied the association between cognitive performance and white matter microstructure metrics. O-LOAD exhibited lower fiber density and fractional anisotropy in the posterior portion of the corpus callosum and right fornix when compared to CS. Among O-LOAD, reduced fiber density was associated with lower amyloid deposition in the right hippocampus, and greater cortical thickness in the left precuneus, while higher mean diffusivity was related with greater cortical thickness of the right superior temporal gyrus. Additionally, compromised white matter microstructure was associated with poorer semantic fluency. In conclusion, white matter microstructure metrics may reveal early differences in O-LOAD by virtue of parental history of the disorder, when compared to CS without a family history of LOAD. We demonstrate that these differences are associated with lower fiber density in the posterior portion of the corpus callosum and the right fornix.

Original languageEnglish (US)
Pages (from-to)79-87
Number of pages9
JournalJournal of Psychiatric Research
StatePublished - Mar 2020


  • Amyloid deposition
  • Cognitive tests
  • Corpus callosum
  • Diffusion MRI
  • Preclinical late-onset Alzheimer's disease
  • White matter microstructure

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry


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