Accelerated long-term forgetting in Alzheimer's disease continuum: A systematic review and meta-analysis

Background Accelerated long-term forgetting (ALF), the disproportionate loss of information over days or weeks despite normal performance at standard delays, has been proposed as an early cognitive marker of Alzheimer's disease (AD). Objective Provide a qualitative and quantitative synthesis of current evidence on ALF across the AD continuum. Methods We performed a systematic review and meta-analysis following the PRISMA 2020 guidelines. Eligible studies evaluated episodic memory with delays of at least 1 h in participants across the AD continuum compared to healthy controls. Risk of bias was assessed using the Joanna Briggs Institute (JBI) tools, and pooled effect sizes (Hedges’ g) were calculated for delays of 1 day, 1 week, and 1 month or longer. Results Twenty-eight studies (n = 1399) were included; 16 entered quantitative analyses. The 1-day effect was nonsignificant (g = 0.55, 95% CI −0.03–1.12). At 1 week, ALF effect was robust (g = 0.63, 95% CI 0.40–0.87; I 2 = 0%) and evident in at-risk groups (g = 0.61, 95% CI 0.37–0.86) despite intact early retention. Both verbal (g = 0.74) and non-verbal (g = 0.53) tasks, as well as recall (g = 0.61) and recognition (g = 0.70), showed similar sensitivity. Effects persisted at ≥1 month but weakened in at-risk groups. Conclusions ALF is strongly detected in the preclinical stage of AD, especially at a 1-week delay across different materials and retrieval methods. Long-delay memory tests may enhance the sensitivity of neuropsychological assessments for detecting early cognitive issues in the early stages of the AD continuum.