Accelerated Long-Term Forgetting as a Candidate Behavioral Marker of Hippocampal Network Vulnerability: A Critical Review of Implications for Epilepsy, Cognitive Aging, and Preclinical Neurodegeneration

Memory impairment is a common cognitive comorbidity of epilepsy and can substantially affect quality of life. Most memory testing tasks measure learning and memory over about 20 to 30 minutes, which may not capture the complexity of long-term memory formation. Because long-term memories continue to consolidate over hours or days, weeks, or longer, more comprehensive evaluation methods may be needed to assess whether memories persist over time.This raises an important question: Do conventional memory assessments adequately assess the longevity of memory? One issue is accelerated long-term forgetting (ALF), characterized by relatively intact learning and short-delay recall, followed by disproportionately rapid forgetting over longer intervals. ALF has been studied most extensively in epilepsy and has been associated with abnormalities involving the hippocampus and related memory networks. In temporal lobe epilepsy, accelerated memory decay has been demonstrated between conventional delayed and longer-term recall. Impaired systems consolidation is a leading explanation, with possible contributions from sleep disruption, interictal epileptiform activity, and broader network dysfunction. However, substantial methodological variability across studies, including differences in learning procedures, retention intervals, outcome measures, and definitions of abnormal forgetting, limits comparison and interpretation of findings.This review integrates current knowledge from diverse areas, including epilepsy, neuroscience, sleep studies, brain imaging, and aging. It discusses the role of ALF as a measure of memory deficits, explores its biological basis, and assesses the strengths and limitations of existing research. We also consider whether ALF could serve as a candidate behavioral marker of hippocampal network vulnerability. Before this role can be established, extended-delay memory paradigms require greater methodological standardization and prospective multimodal validation. Understanding memory persistence as a key component of cognitive function may help refine memory assessment tools, improve understanding of neurological conditions, and develop new approaches to assessing cognitive health in patients with epilepsy and other neurological conditions.