Hippocampal disconnection contributes to memory dysfunction in individuals at risk for Alzheimer's disease

Proc Natl Acad Sci U S A. 2006 Jun 27;103(26):10041-5. doi: 10.1073/pnas.0603414103. Epub 2006 Jun 19.


The concept of amnestic mild cognitive impairment (MCI) describes older people who show a decline predominantly in memory function, but who do not meet criteria for dementia. Because such individuals are at high risk for developing Alzheimer's disease, they are of great interest for understanding the prodromal stages of the disease process. The mechanism underlying memory dysfunction in people with MCI is not fully understood. The present study uses quantitative, high-resolution structural MRI techniques to investigate, in vivo, the anatomical substrate of memory dysfunction associated with MCI. Changes in brain structures were assessed with two imaging techniques: (i) whole-brain, voxel-based morphometry to determine regions of reduced white matter volume and (ii) sensitive volumetric segmentation of the entorhinal cortex and hippocampus, gray matter regions that are critically important for memory function. In participants with amnestic MCI, compared with age-matched controls, results showed a significant decrease in white matter volume in the region of the parahippocampal gyrus that includes the perforant path. There was also significant atrophy in both the entorhinal cortex and the hippocampus. Regression models demonstrated that both hippocampal volume and parahippocampal white matter volume were significant predictors of declarative memory performance. These results suggest that, in addition to hippocampal atrophy, disruption of parahippocampal white matter fibers contributes to memory decline in elderly individuals with MCI by partially disconnecting the hippocampus from incoming sensory information.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / pathology*
  • Alzheimer Disease / physiopathology
  • Amnesia / pathology*
  • Amnesia / physiopathology
  • Atrophy / pathology
  • Brain Mapping
  • Female
  • Hippocampus / pathology*
  • Hippocampus / physiopathology
  • Humans
  • Magnetic Resonance Imaging / methods
  • Male
  • Memory
  • Nerve Fibers / pathology*