A Review of Accelerated Long-Term Forgetting in Alzheimer's Disease: Current Situation and Prospects

Objective: Advances in our understanding of the Alzheimer's disease (AD) continuum through in vivo biomarkers have highlighted the need to develop neuropsychological tests that are more sensitive to subtle cognitive changes in the preclinical stages of the disease. Recent data suggest that the assessment of memory retention over extended delays, to detect so-called accelerated long-term forgetting (ALF), may be a reliable way to discriminate between presymptomatic AD and healthy aging. This review aims to present the scientific evidence published to date on this particular aspect of memory. Method: A comprehensive review of all published articles on ALF in AD to the present day. Results: We present findings relating to ALF in neurological disease, discuss theoretical aspects related to the integration of the concept of ALF in the framework of memory models, explain mechanisms that may be involved in its genesis and present supportive work from research in animal models. We focus particularly on aspects relevant to the assessment of ALF in clinical practice. Conclusions: Despite many advances, further research will be needed to define more precisely what ALF is, what neural structures and mechanisms are involved in its occurrence, whether there are distinct patterns of forgetting according to etiology, and when and how to detect ALF most reliably.