Reduced structural connectivity of the medial temporal lobe including the perforant path is associated with aging and verbal memory impairment

Steven J. Granger, Luis Colon-Perez, Myra Saraí Larson, Ilana J. Bennett, Michael Phelan, David B. Keator, John T. Janecek, Mithra T. Sathishkumar, Anna P. Smith, Liv McMillan, Dana Greenia, Maria M. Corrada, Claudia H. Kawas, Michael A. Yassa

Research output: Contribution to journalArticlepeer-review

Abstract

The perforant path, the white matter bundle connecting the entorhinal cortex (ERC) with the hippocampal formation deteriorates with age-related cognitive decline. Previous investigations using diffusion-weighted MRI to quantify perforant path integrity in-vivo have been limited due to image resolution or have quantified the perforant path using methods susceptible to partial volume effects such as the tensor model and without consideration of its 3-dimensional morphology. In this investigation, we use quantitative-anisotropy informed tractography derived from ultra-high resolution diffusion imaging (ZOOMit) to investigate structural connectivity of the perforant path and other medial temporal lobe (MTL) pathways in older adults (63 to 98 years old, n = 51). We show that graph density within the MTL declines with age and is associated with lower delayed recall performance. We also show that older age and poorer delayed recall are associated with reduced streamlines connecting the ERC and dentate gyrus of the hippocampus (the putative perforant path). This work suggest that intra-MTL connectivity may new candidate biomarkers for age-related cognitive decline.

Original languageEnglish
Pages (from-to)119-128
Number of pages10
JournalNeurobiology of Aging
Volume121
DOIs
StatePublished - Jan 2023

Keywords

  • Aging
  • Diffusion weighted MRI
  • High resolution
  • Memory
  • Perforant path

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