Parahippocampal white matter volume predicts Alzheimer's disease risk in cognitively normal old adults

Neurobiol Aging. 2014 Aug;35(8):1855-61. doi: 10.1016/j.neurobiolaging.2014.01.153. Epub 2014 Feb 18.


An in vivo marker of the underlying pathology in Alzheimer's disease (AD) is atrophy in select brain regions detected with quantitative magnetic resonance imaging (MRI). Although gray matter changes have been documented to be predictive of cognitive decline culminating in AD among healthy older adults, very little attention has been given to alterations in white matter as a possible MRI biomarker predictive of AD. In this investigation, we examined parahippocampal white matter (PWM) volume derived from baseline MRI scans in 2 independent samples of 65 cognitively normal older adults, followed longitudinally, to determine if it was predictive of AD risk. The average follow-up period for the 2 samples was 8.5 years. Comparisons between the stable participants (N = 50) and those who declined to AD (N = 15) over time revealed a significant difference in baseline PWM volume (p < 0.001). Furthermore, baseline PWM volume was predictive not only of time to AD (hazard ratio = 3.1, p < 0.05), but also of baseline episodic memory performance (p = 0.041). These results demonstrate that PWM atrophy provides a sensitive MRI biomarker of AD dementia risk among those with normal cognitive function.

Keywords: Aging; Entorhinal cortex; Hippocampus; Imaging; Perforant pathway; Structural MRI.

Publication types

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

MeSH terms

  • Aged
  • Alzheimer Disease / diagnosis
  • Alzheimer Disease / pathology*
  • Alzheimer Disease / psychology
  • Atrophy
  • Biomarkers
  • Cognition
  • Female
  • Hippocampus / pathology*
  • Humans
  • Magnetic Resonance Imaging*
  • Male
  • Organ Size
  • Risk
  • White Matter / pathology*


  • Biomarkers