Clinical validity of medial temporal atrophy as a biomarker for Alzheimer's disease in the context of a structured 5-phase development framework

Neurobiol Aging. 2017 Apr:52:167-182.e1. doi: 10.1016/j.neurobiolaging.2016.05.024.


Research criteria for Alzheimer's disease recommend the use of biomarkers for diagnosis, but whether biomarkers improve the diagnosis in clinical routine has not been systematically assessed. The aim is to evaluate the evidence for use of medial temporal lobe atrophy (MTA) as a biomarker for Alzheimer's disease at the mild cognitive impairment stage in routine clinical practice, with an adapted version of the 5-phase oncology framework for biomarker development. A literature review on visual assessment of MTA and hippocampal volumetry was conducted with other biomarkers addressed in parallel reviews. Ample evidence is available for phase 1 (rationale for use) and phase 2 (discriminative ability between diseased and control subjects). Phase 3 (early detection ability) is partly achieved: most evidence is derived from research cohorts or clinical populations with short follow-up, but validation in clinical mild cognitive impairment cohorts is required. In phase 4, only the practical feasibility has been addressed for visual rating of MTA. The rest of phase 4 and phase 5 have not yet been addressed.

Keywords: Alzheimer's disease; Dementia; Hippocampus; MRI; Medial temporal lobe atrophy; Mild cognitive impairment; Roadmap.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / diagnosis
  • Alzheimer Disease / diagnostic imaging*
  • Alzheimer Disease / pathology*
  • Atrophy
  • Biomarkers*
  • Cognitive Dysfunction / diagnosis
  • Cognitive Dysfunction / diagnostic imaging
  • Cognitive Dysfunction / pathology
  • Cohort Studies
  • Hippocampus / diagnostic imaging
  • Hippocampus / pathology
  • Humans
  • Magnetic Resonance Imaging
  • Reproducibility of Results
  • Temporal Lobe / diagnostic imaging*
  • Temporal Lobe / pathology*
  • Tomography, X-Ray Computed


  • Biomarkers