Clinical validity of delayed recall tests as a gateway biomarker for Alzheimer's disease in the context of a structured 5-phase development framework

Neurobiol Aging. 2017 Apr:52:153-166. doi: 10.1016/j.neurobiolaging.2016.03.034.


Although Alzheimer's disease criteria promote the use of biomarkers, their maturity in clinical routine still needs to be assessed. In the light of the oncology framework, we conducted a literature review on measures used to assess delayed recall impairment due to medial temporal lobe dysfunction (i.e., free and cued word list recall tests). Ample evidence is available for phases 1 (rationale for use), 2 (discriminative ability), and 3 (early detection ability) for many of the tests in routine use. Evidence about phase 4 (performance in real world) and phase 5 (quantify impact and costs) is yet to come. Administration procedures have been standardized and cutoff scores are well validated in large Alzheimer's disease and mild cognitive impaired series. Some aspects (e.g., different task formats), however, hamper the comparability of results among different populations and the reproducibility between laboratories. No definite guideline for their use can thus be proposed at the moment. Accordingly, the maturity of such markers is not yet sufficient and requires future investigation to promote the proper use of memory measures in clinical settings.

Keywords: 5-Phases; Alzheimer's disease; Biomarker development; Biomarker-based diagnosis; Cued recall tasks; Delayed recall; Early diagnosis; Episodic memory; Free word list tests; Mild cognitive impairment.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / diagnosis*
  • Alzheimer Disease / physiopathology
  • Alzheimer Disease / psychology*
  • Biomarkers / analysis
  • Cognitive Dysfunction / diagnosis
  • Cognitive Dysfunction / psychology
  • Cues
  • Early Diagnosis
  • Humans
  • Memory, Episodic*
  • Mental Recall*
  • Neuropsychological Tests*
  • Reproducibility of Results
  • Temporal Lobe / physiopathology


  • Biomarkers