Accelerated long-term forgetting across neuropsychiatric disorders: A review of mechanisms and a neurobiological perspective of forgetting.

Accelerated long-term forgetting (ALF) is the rapid loss of newly-learnt information, typically noticeable after ~30minutes, and observed across diverse neuropsychiatric disorders including epilepsy, Alzheimer's disease (AD), Parkinson's disease (PD), traumatic brain injury, stroke, and genetic conditions such as 22q11.2 deletion syndrome. Traditionally, ALF has been attributed to impaired memory consolidation or acquisition, with emphasis on hippocampal dysfunction or epileptic activity. However, these explanations are insufficient, as ALF also occurs in individuals without hippocampal damage or seizure activity. This review critiques these historical perspectives and proposes a unifying framework: that ALF may, to some degree, stem from hyperactive intrinsic forgetting mechanisms, rather than solely impaired consolidation. Drawing from recent research on memory engrams, synaptic plasticity, and forgetting, the review highlights the role of synaptic remodelling, neurotransmission, glial cell activity, actin cytoskeleton dynamics, hippocampal neurogenesis, and dopaminergic signalling in modulating engram accessibility, and thus memory persistence. Disruption in these pathways - evident across multiple neuropsychiatric conditions - may converge to produce ALF as a shared cognitive symptom. This reframing suggests that ALF may in part represent a maladaptive form of active forgetting, driven by disease-specific disruptions to otherwise adaptive neurobiological processes. Furthermore, ALF is framed as one end of a broader "forgetting continuum," with downregulated forgetting contributing to memory persistence (in conditions such as PTSD, autism savant syndrome, or highly superior autobiographical memory) on the other. Understanding ALF through this lens may unify its presence across diverse conditions and open avenues for targeted therapeutic interventions that aim to modulate memory persistence by addressing the brain's intrinsic forgetting machinery.

• Publication year

  2025

• Venue

  Neuroscience and Biobehavioral Reviews

• Publication date

  2025-11-01

• Fields of study

  Medicine, Psychology

• Identifiers
  DOI 10.1016/j.neubiorev.2025.106461PMID 41213445
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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