Accelerated Long-term Forgetting Research Articles

Detecting accelerated long-term forgetting remotely in a community sample of people with epilepsy: Evidence from the Crimes and Four Doors tests

People with epilepsy often report experiencing memory problems though these are not always detectable using standard neuropsychological measures. One form of difficulty that may be relatively prevalent in epilepsy is termed accelerated long-term forgetting (ALF), typically described as relatively greater loss of memory over days or weeks following initial encoding. The current study used remote assessment to examine memory and forgetting over one week in a broad community sample of people with epilepsy and healthy control participants, using two recently developed tests, one verbal (the Crimes test) and one visual (the Four Doors test). These were administered as part of a short battery of cognitive measures, run remotely with participants over Zoom. Across this community-derived sample, people with epilepsy reported more memory complaints and demonstrated significantly faster forgetting on both the verbal and visual tests. This difference was not attributable to level of initial learning performance and was not detectable through delayed recall on a standard existing test. Our results suggests that ALF may be more common than suspected in people with epilepsy, leading to a potentially important source of memory problems that are currently undetected by standard memory tests.

Could Accelerated Long-Term Forgetting Be a Feature of the Higher Rate of Memory Complaints Associated with Subjective Cognitive Decline? An Exploratory Study.

Recently, subjective cognitive decline (SCD) was proposed as an early risk factor for future Alzheimer's disease (AD). In this study, we investigated whether accelerated long-term forgetting (ALF), assessed with extended testing intervals than those adopted in clinical practice, might be a cognitive feature of SCD. Using an explorative MRI analysis of the SCD sample, we attempted to investigate the areas most likely involved in the ALF pattern. We recruited 31 individuals with SCD from our memory clinic and subdivided them based on their rate of memory complaints into mild SCDs (n = 18) and severe SCDs (n = 13). A long-term forgetting procedure, involving the recall of verbal and visuo-spatial material at four testing delays (i.e., immediate, 30 min, 24 h, and 7 days post-encoding) was used to compare the two sub-groups of SCDs with a healthy control group (HC; n = 16). No significant between-group difference was found on the standard neuropsychological tests, nor in the immediate and 30 min recall of the experimental procedure. By contrast, on the verbal test severe SCDs forgot significantly more than HCs in the prolonged intervals (i.e., 24 h and 7 days), with the greatest decline between 30 min and 24 h. Finally, in the whole SCD sample, we found significant associations between functional connectivity values within some cortical networks involved in memory (default mode network, salience network, and fronto-parietal network) and verbal long-term measures. Our preliminary findings suggest that long-term forgetting procedures could be a sensitive neuropsychological tool for detecting memory concerns in SCDs, contributing to early AD detection.

Impaired episodic verbal memory recall after 1 week and elevated forgetting in children after mild traumatic brain injury - results from a short-term longitudinal study.

There is preliminary evidence that children after traumatic brain injury (TBI) have accelerated long-term forgetting (ALF), i.e., an adequate learning and memory performance in standardized memory tests, but an excessive rate of forgetting over delays of days or weeks. The main aim of this study was to investigate episodic memory performance, including delayed retrieval 1 week after learning, in children after mild TBI (mTBI). This prospective study with two time-points (T1: 1 week after injury and T2: 3-6 months after injury), included data of 64 children after mTBI and 57 healthy control children aged between 8 and 16 years. We assessed episodic learning and memory using an auditory word learning test and compared executive functions (interference control, working memory, semantic fluency and flexibility) and divided attention between groups. We explored correlations between memory performance and executive functions. Furthermore, we examined predictive factors for delayed memory retrieval 1 week after learning as well as for forgetting over time. Compared to healthy controls, patients showed an impaired delayed recall and recognition performance 3-6 months after injury. Executive functions, but not divided attention, were reduced in children after mTBI. Furthermore, parents rated episodic memory as impaired 3-6 months after injury. Additionally, verbal learning and group, but not executive functions, were predictive for delayed recall performance at both time-points, whereas forgetting was predicted by group. Delayed recall and forgetting over time were significantly different between groups, both post-acutely and in the chronic phase after pediatric mTBI, even in a very mildly injured patient sample. Delayed memory performance should be included in clinical evaluations of episodic memory and further research is needed to understand the mechanisms of ALF.

Long-term forgetting is independent of age in healthy children and adolescents.

In clinical neuropsychology, the phenomenon of accelerated long-term forgetting (ALF) has advanced to be a marker for subtle but clinically relevant memory problems associated with a range of neurological conditions. The normal developmental trajectory of long-term memory, in this case, memory recall after 1 week, and the influence of cognitive variables such as intelligence have not extensively been described, which is a drawback for the use of accelerated long-term forgetting measures in pediatric neuropsychology. In this clinical observation study, we analyzed the normal developmental trajectory of verbal memory recall after 1 week in healthy children and adolescents. We hypothesized that 1-week recall and 1-week forgetting would be age-dependent and correlate with other cognitive functions such as intelligence and working memory. Sixty-three healthy participants between the ages of 8 and 16 years completed a newly developed auditory verbal learning test (WoMBAT) and the WISC-V intelligence test (General Ability Index, GAI). Using these tests, 1 week recall and 1 week forgetting have been studied in relation to GAI, verbal learning performance, and verbal working memory. Neither 1-week recall nor 1-week forgetting seems to be age-dependent. They are also not significantly predicted by other cognitive functions such as GAI or working memory. Instead, the ability to recall a previously memorized word list after 7 days seems to depend solely on the initial learning capacity. In the clinical setting, this finding can help interpret difficulties in free recall after 7 days or more since they can probably not be attributed to young age or low intelligence.

A Strategy for Allowing Earlier Diagnosis and Rigorous Evaluation of BACE1 Inhibitors in Preclinical Alzheimer's Disease.

Given continued failure of BACE1 inhibitor programs at symptomatic and prodromal stages of Alzheimer's disease (AD), clinical trials need to target the earlier preclinical stage. However, trial design is complex in this population with negative diagnosis of classical hippocampal amnesia on standard memory tests. Besides recent advances in brain imaging, electroencephalogram, and fluid-based biomarkers, new cognitive markers should be established for earlier diagnosis that can optimize recruitment to BACE1 inhibitor trials in presymptomatic AD. Notably, accelerated long-term forgetting (ALF) is emerging as a sensitive cognitive measure that can discriminate between asymptomatic individuals with high risks for developing AD and healthy controls. ALF is a form of declarative memory impairment characterized by increased forgetting rates over longer delays (days to months) despite normal storage within the standard delays of testing (20-60 min). Therefore, ALF may represent a harbinger of preclinical dementia and the impairment of systems memory consolidation, during which memory traces temporarily stored in the hippocampus become gradually integrated into cortical networks. This review provides an overview of the utility of ALF in a rational design of next-generation BACE1 inhibitor trials in preclinical AD. I explore potential mechanisms underlying ALF and relevant early-stage biomarkers useful for BACE1 inhibitor evaluation, including synaptic protein alterations, astrocytic dysregulation and neuron hyperactivity in the hippocampal-cortical network. Furthermore, given the physiological role of the isoform BACE2 as an AD-suppressor gene, I also discuss the possible association between the poor selectivity of BACE1 inhibitors and their side effects (e.g., cognitive worsening) in prior clinical trials.

Accelerated long-term forgetting in patients with acquired brain injury

ABSTRACT Objective Recent research suggests that patients with neurological disorders without overt seizures may also experience accelerated long-term forgetting (ALF). This term describes unimpaired learning and memory performance after standard retention intervals, but an excessive rate of forgetting over delays of days or weeks. The objective of this retrospective study was to investigate ALF in patients with an acquired brain injury (ABI) and to associate memory performance with executive functions. Methods Verbal memory performance (short-term recall, 30-min recall, 1-week recall) was assessed in 34 adult patients with ABI and compared to a healthy control group (n = 54) using an auditory word learning and memory test. Results Repeated measure analysis showed significant effects of time and group as well as interaction effects between time and group regarding recall and recognition performance. Patients with ABI had a significantly impaired 1-week recall and recognition performance compared to the healthy control group. Correlations between recall performance and executive functions were nonsignificant. Discussion Our results demonstrate that non-epileptic patients with ABI, especially patients with frontal and fronto-temporal lesions, are prone to ALF. Additionally, our data support the assumption that ALF results from a consolidation impairment since verbal recall and recognition were impaired in patients with ABI.

Accelerated long-term forgetting: from subjective memory decline to a defined clinical entity

ABSTRACT Subjective memory decline (SMD) might represent the preclinical phase of Alzheimer’s disease (AD), and has been reported in epileptic amnesia associated with accelerated long-term forgetting (ALF). We investigated ALF in SMD subjects by means of RAVLT recall and recognition and ROCF recall after 1-week retention and compared with a control group. Two-way ANOVAs for RAVLT and ROCF were conducted, and stepwise regression analysis was administered considering EMQ and DASS-21 as factors. SMD subjects performed significantly worse than controls at 1-week delay on RAVLT recall and recognition, but not on ROCF, and not associated with depression or memory complaints. SMD patients showed ALF, which is usually associated with temporomesial dysfunctions, representing a cognitive marker to assess objectively memory problems in SMD, and to undisclose initial neurodegenerative disease involving temporal structures usually compromised in AD. Therefore, SMD might no longer be “subjective,” but rather a specific and defined clinical entity.

Clinical Manifestations.

Accelerated Long-term Forgetting (ALF) is the phenomenon whereby material is retained normally over short intervals (minutes or hours) but forgotten abnormally rapidly over longer periods (days or weeks). ALF may be an early marker of cognitive decline, but little is known about its relationships with preclinical Alzheimer's disease pathology in older adults, and how memory selectivity may influence which material is forgotten. Participants in 'Insight 46', a sub-study of the MRC National Survey of Health and Development (British 1946 birth cohort), completed cognitive and neuroimaging assessments at two time-points (baseline at age ∼70; follow-up ∼2.4 years later). At follow-up, we assessed Complex Figure Drawing (copy; immediate recall; 30-minute recall; 7-day recall). Complex Figure items were categorized as 'outline' or 'detail' (Fig1), to test the hypothesis that forgetting the outline of the structure would be more sensitive to the effect of brain pathologies. ALF scores were calculated as the proportion of material retained after 7 days, relative to 30 minutes. Rates of cerebral atrophy between baseline and follow-up were quantified from T1-weighted MRI using the Brain Boundary Shift Integral (BBSI). β-amyloid status (positive/negative) was determined from 18F-Florbetapir-PET. Baseline serum neurofilament light (NfL) was quantified (Quanterix Simoa assay). Multivariable regression models were used to investigate the effects (mutually adjusted) of β-amyloid status, BBSI and NfL on ALF in n = 316 clinically-normal individuals (50% female; 22% β-amyloid positive; 30% APOE-ε4 carriers), and to explore interactions between these predictors, adjusting for potential confounders including prospectively-collected childhood cognitive ability and education. 'Outline' items were better retained than 'detail' (Fig1). β-amyloid-positive participants had poorer ALF scores for 'outline' (but not 'detail') items (Fig1C; Table 1). Unexpectedly, higher NfL was associated with scores for 'outline' items (Table 1). Greater rate of cerebral atrophy predicted poorer retention among participants with elevated β-amyloid and higher NfL (Table 1; Fig2). These results provide evidence of associations between biomarkers of brain pathologies and ALF in 73-year-olds. Interactions between different biomarkers merit further exploration. ALF may be a sensitive outcome measure for therapeutic trials in preclinical AD. Better retention of 'outline' (vs. 'detail') items illustrates the strategic role of memory selectivity.

4 Accelerated Long-Term Forgetting in Patients with Cerebrovascular Disease

Objective:Long-term forgetting rates may be more sensitive for detecting memory decrements compared to short-delay memory assessments (e.g., after 20-30 minutes). To date, much research has been performed on accelerated long-term forgetting (ALF) in epilepsy patients, but research in other patient groups is lacking. ALF may be promising in the field of cerebrovascular disease, as many of these patients experience cognitive complaints, yet do not show impaired performances on neuropsychological assessments.Participants and Methods:Here, I will present empirical findings on ALF in individuals after a TIA/minor stroke (n=30) and after stroke (n=91) using short- (20-30 min) and long-delay (1-week) memory testing.Results:After TIA/minor stroke, short-delay (2030 min) memory testing was unimpaired, but 1-week delayed testing showed an impaired performance compared to stroke-free controls. In the stroke group, ALF was present in 17% of the patients, compared to stroke-free controls, but more prevalent than rapid forgetting after short-delay memory testing.Conclusions:ALF is present in patients with cerebrovascular disease, despite normal acquisition rates. The relation with neuroimaging findings and the clinical relevance of these results will be discussed.

3 Towards Detecting a Pre-clinical Signature of Dementia: Accelerated Forgetting in Healthy Older Samples -Implications for Methodology, Future Ageing Studies and Early Identification of Dementia

Objective:Accelerated long-term forgetting (ALF) has been reported in healthy older individuals, and is a possible early marker for risk of developing Alzheimer’s disease (AD). The Verbal Associative Learning & Memory Test (VALMT; McGibbon & Jansari, 2013) addresses methodological weaknesses in existing clinical tests and has detected ALF in epilepsy within an hour. We used VALMT to investigate learning and forgetting in healthy older participants.Participants and Methods:Older (60-69yrs) and Younger (19-31yrs) participants were compared. Using VALMT, unrelated word-pairs were learned to criterion, then cued-recall was tested at delays of 5, 30 and 55 minutes. Unique pairs were tested at each delay. Subjective memory complaints data were gathered, and the Wechsler Memory Scale Logical Memory test (WMS-LM; a standard clinical measure) was administered.Results:VALMT identified a significant difference in delayed recall between Younger and Older groups by 55 minutes (d = 1.32). While 'fast-learning’ Older participants scored similarly to Younger participants, 'slow-learning’ Older participants were impaired at all delays. Forgetting rates suggested degradation of memory starts during early synaptic consolidation rather than later system-level consolidation. Increased subjective memory complaints were associated with reduced VALMT scores. By contrast, WMS-LM failed to identify significant differences between any groups, and did not correlate with memory complaints.Conclusions:We conclude VALMT may be better able than WMS-LM to identify subtle impairments in healthy older adults within a single clinical visit, and VALMT results better reflect subjective experience. Older slow-learners forget faster and report more subjective memory complaints, which may indicate a group at risk of developing AD.

Repeat testing enhances long-term verbal memory in children with epilepsy

ABSTRACT To (i) determine whether accelerated long-term forgetting (ALF) can be found using standardized verbal memory test materials in children with genetic generalized epilepsy (GGE) and temporal lobe epilepsy (TLE), and (ii) to establish whether ALF is impacted by executive skills and repeat testing over long delays. One hundred and twenty-three children aged 8 to 16, (28 with GGE, 23 with TLE, and 72 typically developing; TD) completed a battery of standardized tests assessing executive functioning and memory for two stories. Stories were recalled immediately and after a 30-min delay. To examine whether repeat testing impacts long-term forgetting, one story was tested via free recall at 1-day and 2-weeks, and the other at 2-weeks only. Recognition was then tested for both stories at 2-weeks. Children with epilepsy recalled fewer story details, both immediately and after 30-min relative to TD children. Compared to TD children, the GGE group, but not the TLE group, showed ALF, having significantly poorer recall of the story tested only at the longest delay. Poor executive skills were significantly correlated with ALF for children with epilepsy. Standard story memory materials can detect ALF in children with epilepsy when administered over long delays. Our findings suggest that (i) ALF is related to poor executive skills in children with epilepsy, and (ii) repeated testing may ameliorate ALF in some children.

Design and validation of the 1-week memory battery for assessing episodic memory and accelerated long-term forgetting in cognitively unimpaired subjects.

Subtle decline in memory is thought to arise in the preclinical phase of Alzheimer's disease (AD). However, detecting these initial cognitive difficulties cross-sectionally has been challenging, and the exact nature of the decline is still debated. Accelerated long-term forgetting (ALF) has been recently suggested as one of the earliest and most sensitive indicators of memory dysfunction in subjects at risk of developing AD. The objective of this study was to design and validate the 1-week memory battery (1WMB) for assessing episodic memory and ALF in cognitively unimpaired individuals. The 1WMB is unique in that it assesses multimodal memory and measures recall at both short delay (20 min) and at long term (1 week). Forty-five cognitively unimpaired subjects were assessed with 1WMB and standardized neuropsychological tests. Subjective cognitive decline (SCD), levels of anxiety and depression, and cognitive reserve were also measured. The tests of 1WMB showed a high internal consistency, and concurrent validity was observed with standard tests of episodic memory and executive functions. The analysis revealed a greater loss of information at 1 week compared to short-term forgetting (20 min). Performance in the 1WMB was affected by age and educational level, but was not associated with levels of anxiety and depression. Unlike standard tests, performance in the 1WMB correlated with measures of SCD. Our findings indicate that the 1WMB has good psychometric properties, and future studies are needed to explore its potential usefulness to assess cognitively unimpaired subjects at increased risk of developing AD. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Longer-term verbal and visual memory patterns in patients with temporal lobe and genetic generalized epilepsies.

To compare forgetting patterns between patients with temporal lobe (TLE) and generalized (GGE) epilepsies and to assess whether recall is associated with epileptic activity. Thirty-three patients with TLE (13 left, 17 right, and 3 nonlateralized TLE), 42 patients with GGE, and 57 healthy controls (HCs) were asked to recall words, verbal story material, and the Rey-Osterrieth complex figure at two delays. Accelerated long-term forgetting (ALF) was defined by group performance comparable to HCs at 30 min and worse recall than HCs after 4 weeks. ALF was assessed by comparing raw test scores in a two-way repeated measures analysis of variance (ANOVA) adjusted for the learning capacity. Compared to HCs, patients with R-TLE remembered fewer items of the word list after 30 min as well as after 4 weeks. Patients with L-TLE and GGE had comparable learning-adjusted performance to HCs at the 30 min delay but scored less after 4 weeks (group by delay interaction F(3, 124) = 3.2, P = 0.026, = 0.07). The epilepsy group (patients with TLE and GGE combined) performed as well as HCs at 30 min but worse after 4 weeks irrespective of experienced seizures during the 4-week delay or interictal bilateral (TLE) or generalized (GGE) activity before the study. We noted no statistically significant differences between patient and HC verbal story (group by delay interaction F(3, 124) = 0.7, P = 0.570, = 0.02) or complex figure (F(3, 124) = 0.8, P = 0.488, = 0.02) recall. Our data support verbal and visual memory impairment in both TLE and GGE with different performances between these groups in the task of word recall. We suggest the presence of ALF in patients with GGE and left TLE after adjusting for learning capacity. We could not confirm the influence of epileptic activity on long-term forgetting patterns. Future studies are required to better define domain-specific differences in memory impairment in TLE and GGE.

Classification of transient epileptic amnesia attacks: Two types of amnestic seizures, the pure amnesia type and partial amnesia type.

Transient epileptic amnesia (TEA) is a type of mesial temporal lobe epilepsy characterized by recurrent amnesia attacks. In 1998, Zeman et al. proposed the following diagnostic criteria for TEA: (1) recurrent, witnessed episodes of amnesia (TEA attacks); (2) other cognitive functions remain intact during attacks; and (3) evidence of epilepsy. It was also reported that patients with TEA often demonstrate two other types of memory symptoms: accelerated long-term forgetting (ALF) and autobiographical amnesia (AbA). Both ALF and AbA are persistent memory disorders, but transient epileptic seizures are not. We encountered two cases of TEA associated with two types of amnesia attacks. Therefore, we reviewed TEA cases in the literature to clarify the type of TEA attacks that occurred. Based on the extracted TEA cases, including our two cases, we found that there are two main types of TEA attacks, and we discussed their clinical features. We propose two main types of TEA attacks; that is, pure amnesia-type and partial amnesia-type seizures. Furthermore, we also propose that topographical amnesia mainly manifests as a type of amnesia attack, rather than as a chronic memory disturbance, such as ALF or AbA.

Accelerated long-term forgetting: A sensitive paradigm for detecting subtle cognitive impairment and evaluating BACE1 inhibitor efficacy in preclinical Alzheimer's disease.

Given a long preclinical stage of Alzheimer's disease (AD) continuum before the onset of dementia, there is a growing demand for tools capable of detecting the earliest feature of subtle cognitive impairment and optimizing recruitment to clinical trials for potentially disease-modifying therapeutic interventions such as BACE1 inhibitors. Now that all BACE1 inhibitor programs in symptomatic and prodromal AD populations have ended in failure, trials need to shift to target the earlier preclinical stage. However, evaluating cognitive efficacy (if any) in asymptomatic AD individuals is a great challenge. In this context, accelerated long-term forgetting (ALF) is emerging as a sensitive cognitive measure that can discriminate between presymptomatic individuals with high risks for developing AD and healthy controls. ALF is characterized by increased forgetting rates over extended delays (e.g., days, weeks, months) despite normal learning and short-term retention on standard memory assessments that typically use around 30-min delays. This review provides an overview of recent progress in animal model and clinical studies on this topic, focusing on the utility and underlying mechanism of ALF that may be applicable to earlier diagnosis and BACE1 inhibitor efficacy evaluation at a preclinical stage of AD.

Delayed episodic memory recall after one week is associated with executive functions and divided attention in pediatric epilepsy patients

AimRecent studies suggest that although children with epilepsy may show normal learning and memory performance, accelerated long-term forgetting (ALF) may become evident over time. Our study examined associations between delayed episodic memory performance (recall 1-week after learning) and executive functions. MethodA consecutive sample of children with a diagnosis of idiopathic epilepsy with focal or generalized seizures, without morphologic or metabolic abnormalities (n = 20, mean age: 11.70 years) was compared to an IQ-matched healthy control group (n = 20, mean age: 11.55 years). We also assessed parents’ and children’s rating of forgetting in everyday life and explored its association with delayed episodic memory recall. ResultsSimilar to results from recent studies of pediatric patients with temporal lobe epilepsy or genetic generalized epilepsy, our pediatric epilepsy patients showed a significantly elevated recall loss over time, although verbal learning, immediate and 30-minute recall was comparable to the matched control group. Additionally, delayed memory recall in patients was moderately associated with their subjective rating of forgetting, as well as with executive functions (verbal fluency and switching) and divided attention. InterpretationWe assume that executive functions play a crucial role in deep memory encoding, facilitating stronger and more enduring memory traces. Given that approximately 20% of epilepsy patients – compared to a healthy reference sample – had a significantly reduced delayed recall and due to the clinical relevance of long-term memory, age-appropriate standard norms for free memory recall after 1-week are desirable.

Accelerated long-term forgetting of recall and recognition memory in people with epilepsy

PurposePersons with epilepsy (PWE) report memory deficits as one of the most distressing aspects of their disorder. Recently, a long-term memory deficit known as Accelerated Long-Term Forgetting (ALF) has been described in PWE. ALF is characterized by the initial retention of learned information, followed by an accelerated rate of memory decay. However, the rate of ALF varies widely across literature and it is unclear how it impacts different memory retrieval types. The current study aimed to capture the time course of ALF on both free recall and recognition memory using a movie-based task in PWE. MethodsA sample of 30 PWE and 30 healthy comparison (HC) subjects watched a nature documentary and were tested on their recall and recognition of the film’s content immediately after viewing and at delays of 24 hours, 48 hours, and 72 hours. Participants also rated the confidence they had in their recognition memory trial responses. ResultsFor recall, PWE exhibit ALF at 72 hours (β = −19.840, SE = 3.743, z(226) = −5.301, p < 0.001). For recognition, PWE had decreased performance compared to controls at the 24-hour (β = −10.165, SE = 4.174, z(224) = −3.166, p = 0.004), 48-hour (β = −8.113, SE = 3.701, z(224) = −2.195, p = 0.044), and 72-hour (β = −10.794, SE = 3.017, z(224) = −3.295, p = 0.003) delays. The PWE group showed positive correlations (tau = 0.165, p < 0.001) between confidence ratings and accuracy, with higher confidence reflecting successful recognition. PWE were 49% less likely to answer either retrieval type correctly at 72 hours (OR 0.51, 95% CI [0.35, 0.74], p < 0.001). Left hemispheric seizure onset decreased the odds of successful retrieval by 88% (OR 0.12, 95% CI [0.01, 0.42], p = 0.019). ConclusionsThese findings provide evidence of ALF in PWE, with a differential impact on recall and recognition memory. This further supports the call to include ALF assessments in standard memory evaluations in PWE. Additionally, identifying the neural correlates of ALF in the future will be important in developing targeted therapies to alleviate the burden of memory impairment for PWE.

Atrophy of the hippocampal CA1 subfield relates to long-term forgetting in focal epilepsy.

The mechanisms underlying accelerated long-term forgetting (ALF) in patients with epilepsy are still under investigation. We examined the contribution of hippocampal subfields and their morphology to long-term memory performance in patients with focal epilepsy. We prospectively assessed long-term memory and performed magnetic resonance imaging in 80 patients with focal epilepsy (61 with temporal lobe epilepsy and 19 with extratemporal lobe epilepsy) and 30 healthy controls. The patients also underwent electroencephalography recording. Verbal and visuospatial memory was tested 30 s, 10min, and 1week after learning. We assessed the volumes of the whole hippocampus and seven subfields and deformation of the hippocampal shape. The contributions of the hippocampal volumes and shape deformation to long-term forgetting, controlling for confounding factors, including the presence of interictal epileptiform discharges, were assessed by multiple regression analyses. Patients with focal epilepsy had lower intelligence quotients and route recall scores at 10min than controls. The focal epilepsy group had smaller volumes of both the right and left hippocampal tails than the control group, but there were no statistically significant group differences for the volumes of the whole hippocampus or other hippocampal subfields. Multiple regression analyses showed a significant association between the left CA1 volume and the 1-week story retention (β=7.76; Bonferroni-corrected p=0.044), but this was not found for the whole hippocampus or other subfield volumes. Hippocampal shape analyses revealed that atrophy of the superior-lateral, superior-central, and inferior-medial regions of the left hippocampus, corresponding to CA1 and CA2/3, was associated with the verbal retention rate. Our results suggest that atrophy of the hippocampal CA1 region and its associated structures disrupts long-term memory consolidation in focal epilepsy. Neuronal cell loss in specific hippocampal subfields could be a key underlying cause of ALF in patients with epilepsy.

Accelerated forgetting in healthy older samples: Implications for methodology, future ageing studies, and early identification of risk of dementia.

Accelerated long-term forgetting (ALF) has been reported in healthy older individuals, and is a possible early marker for risk of developing Alzheimer's disease (AD). The Verbal Associative Learning and Memory Test (VALMT) addresses methodological weaknesses in existing clinical tests and has detected ALF in epilepsy within an hour. We used VALMT to investigate learning and forgetting in healthy Older participants. Older (60-69 years) and Younger (19-31 years) participants were compared. Using VALMT, unrelated word pairs were learnt to criterion, then cued-recall tested at delays of 5, 30, and 55 min. Unique pairs were tested at each delay. Subjective memory complaints data was gathered, and the Wechsler Memory Scale Logical Memory test (WMS-LM; a standard clinical measure) was administered. VALMT identified a significant difference in delayed recall between Younger and Older groups by 55 min (d = 1.32). While "fast-learning" Older participants scored similarly to Younger participants, "slow-learning" Older participants were impaired at all delays. Forgetting rates suggested degradation of memory starts during early synaptic consolidation rather than later system-level consolidation. Increased subjective memory complaints were associated with reduced VALMT scores. By contrast, WMS-LM failed to identify significant differences between any groups, and did not correlate with memory complaints. We conclude that VALMT may be better able than WMS-LM to identify subtle impairments in healthy older adults within a single clinical visit, and VALMT results better reflect subjective experience. Older slow-learners forget faster and report more subjective memory complaints, which may indicate a group at risk of developing AD.

Accelerated long-term forgetting in children with temporal lobe epilepsy: A timescale investigation of material specificity and executive skills

Recently, children with temporal lobe epilepsy (TLE) were found to be at risk of accelerated long-term forgetting (ALF). In this study, we examined the temporal trajectory of ALF, while exploring the relationship between ALF, executive skills, and epilepsy variables. Fifty-one children, (23 with TLE and 28 typically developing) completed a battery of neuropsychological tests of verbal and visual memory, executive skills, and two experimental memory tasks (verbal and visual) involving recall after short (30-min) and extended (1-day and 2-week) delays. Side of seizure focus and hippocampal integrity were considered. On the visual task (Scene Memory), children with TLE performed comparably to typically developing children following a 30-min and 1-day delay, although worse than typically developing children at 2 weeks: ALF was observed in children with right TLE focus. The two groups did not differ on the experimental verbal memory task. Children with TLE also had worse performance than typically developing children on standardized verbal memory test and on tests of executive skills (i.e., verbal generativity, inhibition, working memory, complex attention). Only complex attention was associated with visual ALF. ALF was present for visuo-spatial materials in children with TLE at two weeks, and children with right TLE were most susceptible. A relationship was identified between complex attention and long-term forgetting. The findings extend our understanding of difficulties in long-term memory formation experienced by children with TLE.