The relationship between semantic and episodic memory: evidence from a case of severe anterograde amnesia.

It is increasingly being recognized that new declarative, consciously accessible information can be learned in anterograde amnesia, but it is not clear whether this learning is supported by episodic or semantic memory. We report a case of a 55-year-old man who experienced severe amnesia after limited damage to the medial temporal lobe following neurosurgical complications. His general cognitive performance and knowledge of new French words and public events that occurred before and after the onset of amnesia were assessed. Performance remained satisfactory on post-morbid vocabulary and public events, with a drop in performance observed for very recent public events only, while knowledge of very recent vocabulary was comparable to that of the control subjects. The implications of these findings for our understanding of the underlying learning mechanisms are discussed. This is the first report of acquisition of consciously accessible postmorbid knowledge of public events in a patient with severe amnesia.

Isolated bilateral fornix anterior columns infarction with acute amnesia and fiber tracts damage, a case report.

Isolated fornix anterior column infarction has rarely been described and is difficult to assess accurately using conventional magnetic resonance imaging (MRI). We report the case of a 75-year-old female who experienced acute anterograde amnesia. MRI performed within 24 h after amnesia onset showed an isolated infarction of the bilateral anterior columns of the fornix on diffusion-weighted imaging (DWI). Her symptoms persisted for up to 50 days, and diffusion tensor imaging (DTI) showed disruption of the fiber tracts of the fornix. when acute amnesia syndrome onset, fornix anterior column infarction should be considered, and optimized DWI and DTI methods are needed to study the fornix in vivo in future research.

Digital dementia in the internet generation: excessive screen time during brain development will increase the risk of Alzheimer's disease and related dementias in adulthood.

Converging evidence from biopsychosocial research in humans and animals demonstrates that chronic sensory stimulation (via excessive screen exposure) affects brain development increasing the risk of cognitive, emotional, and behavioural disorders in adolescents and young adults. Emerging evidence suggests that some of these effects are similar to those seen in adults with symptoms of mild cognitive impairment (MCI) in the early stages of dementia, including impaired concentration, orientation, acquisition of recent memories (anterograde amnesia), recall of past memories (retrograde amnesia), social functioning, and self-care. Excessive screen time is known to alter gray matter and white volumes in the brain, increase the risk of mental disorders, and impair acquisition of memories and learning which are known risk factors for dementia. Chronic sensory overstimulation (i.e., excessive screen time) during brain development increases the risk of accelerated neurodegeneration in adulthood (i.e., amnesia, early onset dementia). This relationship is affected by several mediating/moderating factors (e.g., IQ decline, learning impairments and mental illness). We hypothesize that excessive screen exposure during critical periods of development in Generation Z will lead to mild cognitive impairments in early to middle adulthood resulting in substantially increased rates of early onset dementia in later adulthood. We predict that from 2060 to 2100, the rates of Alzheimer's disease and related dementias (ADRD) will increase significantly, far above the Centres for Disease Control (CDC) projected estimates of a two-fold increase, to upwards of a four-to-six-fold increase. The CDC estimates are based entirely on factors related to the age, sex, race and ethnicity of individuals born before 1950 who did not have access to mobile digital technology during critical periods of brain development. Compared to previous generations, the average 17-19-year-old spends approximately 6 hours a day on mobile digital devices (MDD) (smartphones, tablets, and laptop computers) whereas individuals born before 1950 at the same age spent zero. Our estimates include the documented effects of excessive screen time on individuals born after 1980, Millennials and Generation Z, who will be the majority of individuals ≥65 years old. An estimated 4-to-6-fold increase in rates of ADRD post-2060 will result in widespread societal and economic distress and the complete collapse of already overburdened healthcare systems in developed countries. Preventative measures must be set in place immediately including investments and interventions in public education, social policy, laws, and healthcare.

Comparative Study of the Effect of a DNA Methyltransferase Inhibitor and a Histone Deacetylase Inhibitor on Memory Formation Processes in Anterograde Amnesia.

The participation of DNA methylation and histone acetylation in the mechanisms of anterograde amnesia and memory recovery was studied on grape snails trained in conditioned food aversion. Anterograde amnesia developed 10 days after memory reconsolidation impairment with an NMDA glutamate receptor antagonist and was characterized by long-term memory formation impairment upon repeated training. DNA methyltransferase inhibitor injections to snails 1 h before repeated training, as well as 15 min or 4 h after repeated training, caused rapid formation of memory that persisted for at least 10 days. Injections of histone deacetylase inhibitor before repeated training also induced the formation of a stable long-term memory. However, administration of histone deacetylase inhibitor 15 min after repeated training initiated a temporary memory recovery. Injections of the inhibitor 4 h after repeated training were ineffective. These results indicate that histone-dependent chromatin remodeling and DNA methylation are selectively involved in the mechanisms of anterograde amnesia and memory recovery.

The Role of DNA Methylation and Activity of Neurotransmitter Receptors in the Mechanisms of Specific Anterograde Amnesia and Memory Recovery.

Impairment of reconsolidation of conditioned food aversion memory led to the development of a specific anterograde amnesia: repeated training of amnestic snails did not induce long-term memory formation. DNA demethylation caused by injections of DNA methyltransferase inhibitor (DNAMT) during repeated training led to long-term memory formation. Injections of an NMDA glutamate receptor antagonist or a serotonin receptor antagonist prevented memory formation induced by administration of DNAMT inhibitor and repeated training. We hypothesize that methylation-dependent repression of neuronal genes underlies anterograde amnesia. Demethylation eliminated the blockade of these genes and created conditions for long-term memory formation, the induction mechanisms of which involve neurotransmitter receptors.

[Transient Global Amnesia in the Reykjavik area].

BACKGROUND: Transient Global Amnesia (TGA) is a benign syndrome characterized by sudden anterograde memory loss, that resolves spontaneously within 24 hours. TGA appears without other focal neurological symptoms. The aim of this study was to study TGA in the greater Reykjavik-area. METHODS: We retrospectively analysed the medical history of patients with a diagnosis of TGA (ICD-10 G45.4) at the University Hospital in Iceland in 2010-2021. Medical records were reviewed, and information about year and age at diagnosis, sex, symptoms, precipitating events, imaging results and risk factors were collected. Statistical processing was performed with Excel and Rstudio. RESULTS: Overall, 348 attacks of TGA were identified with a mean frequency of 29 attacks/year, where 9.9% had an earlier history of TGA. The mean age was 64.1, with 50% of subjects between 58-70 years old. The sex distribution was equal (49.9% female). Possible precipitating events were found in 53.7% of cases, with physical activity being the most common one (24.4%), followed by sudden temperature change and emotional stress. In 96% of patients a computerized tomography was performed (no sign of acute changes were found), and magnetic resonance imaging (MRI) in 36.2% of cases. MRI showed restricted diffusion in the hippocampal area in 10.3% of cases. DISCUSSION: TGA is not a rare but a benign syndrome. Our findings regarding age, sex distribution and precipitating events were in accordance with other studies. TGA is thought to result from a temporary hippocampal dysfunction supported by the clinical presentation and MRI findings. The cause of TGA is however still unknown.

Relevance of a Novel Circuit-Level Model of Episodic Memories to Alzheimer's Disease.

The medial temporal lobe memory system has long been identified as the brain region showing the first histopathological changes in early Alzheimer's disease (AD), and the functional decline observed in patients also points to a loss of function in this brain area. Nonetheless, the exact identity of the neurons and networks that undergo deterioration has not been determined so far. A recent study has identified the entorhinal and hippocampal neural circuits responsible for encoding new episodic memories. Using this novel model we describe the elements of the episodic memory network that are especially vulnerable in early AD. We provide a hypothesis of how reduced reelin signaling within such a network can promote AD-related changes. Establishing novel associations and creating a temporal structure for new episodic memories are both affected in AD. Here, we furnish a reasonable explanation for both of these previous observations.

A Study of the Participation of NMDA Glutamate Receptors in the Mechanisms of Specific Anterograde Amnesia Reversion.

We studied the involvement of NMDA glutamate receptors in the mechanisms of anterograde amnesia. It was found that repeated training of amnestic animals treated with D-cycloserine, a potent agonist of the glycine site of NMDA receptors, did not lead to consolidation of long-term memory, while expression of short-term memory was more pronounced in comparison with control animals that received saline before repeated training. It was shown that D-cycloserine in amnestic snails did not affect the food reactions caused by the presentation of a conditioned stimulus during the reminder (without combination with the unconditioned stimulus). It is assumed that NMDA glutamate receptors in amnestic animals are involved in the neural plasticity mechanisms that underlie short-term memory, but their activation does not influence the anterograde amnesia processes and does not lead to the formation or recovery of long-term memory.

The Rhesus Monkey Hippocampus Critically Contributes to Scene Memory Retrieval, But Not New Learning.

Humans can recall a large number of memories years after the initial events. Patients with amnesia often have lesions to the hippocampus, but human lesions are imprecise, making it difficult to identify the anatomy underlying memory impairments. Rodent studies enable great precision in hippocampal manipulations, but not investigation of many interleaved memories. Thus it is not known how lesions restricted to the hippocampus affect the retrieval of multiple sequentially encoded memories. Furthermore, disagreement exists as to whether hippocampal inactivations lead to temporally graded or ungraded amnesia, which could be a consequence of differences between rodent and human studies. In the current study, rhesus monkeys of both sexes received either bilateral neurotoxic hippocampal lesions or remained unoperated controls and were tested on recognition and new learning of visual object-in-place scenes. Monkeys with hippocampal lesions were significantly impaired at remembering scenes that were encoded before the lesion. We did not observe any temporal gradient effect of the lesion on memory recognition, with recent and remote memories being equally affected by the lesion. Monkeys with hippocampal lesions showed no deficits in learning new scenes. Thus, the hippocampus, like other cortical regions, may be engaged in the acquisition and storage of new memories, but the role of the damaged hippocampus can be taken over by spared hippocampal tissue or extra-hippocampal regions following a lesion. These findings illustrate the utility of experimental paradigms for studying retrograde and anterograde amnesia that make use of the capacity of nonhuman primates to rapidly acquire many distinct visual memories.SIGNIFICANCE STATEMENT Recalling old memories, creating new memories, and the process by which memories transition from temporary to permanent storage all may rely on the hippocampus. Whether the hippocampus is necessary for encoding and retrieval of multiple related visual memories in primates is not known. Monkeys that learned many visual memory problems before precise lesions of the hippocampus were impaired at recalling those memories after hippocampal damage regardless of when the memories were formed, but could learn new memory problems at a normal rate. This suggests the hippocampus is normally vital for retrieval of complex visual memories regardless of their age, and also points to the importance of investigating mechanisms by which memories may be acquired in the presence of hippocampal damage.

Autobiographical memory, future imagining, and the medial temporal lobe.

In two experiments, patients with damage to the medial temporal lobe (MTL) and healthy controls produced detailed autobiographical narratives as they remembered past events (recent and remote) and imagined future events (near and distant). All recent events occurred after the onset of memory impairment. The first experiment aimed to replicate the methods of Race et al. [Race E, Keane MM, Verfaellie M (2011) J Neurosci 31(28):10262-10269]. Transcripts from that study were kindly made available for independent analysis, which largely reproduced the findings from that study. Our patients produced marginally fewer episodic details than controls. Patients from the earlier study were more impaired than our patients. Patients in both groups had difficulty in returning to their narratives after going on tangents, suggesting that anterograde memory impairment may have interfered with narrative construction. In experiment 2, the experimenter used supportive questioning to help keep participants on task and reduce the burden on anterograde memory. This procedure increased the number of details produced by all participants and rescued the performance of our patients for the distant past. Neither of the two patient groups had any special difficulty in producing spatial details. The findings suggest that constructing narratives about the remote past and the future does not depend on MTL structures, except to the extent that anterograde amnesia affects performance. The results further suggest that different findings about the status of autobiographical memory likely depend on differences in the location and extent of brain damage in different patient groups.

Retrograde Personal Semantic Memory During Post-Traumatic Amnesia and Following Emergence.

OBJECTIVES: Anecdotal reports suggest that following traumatic brain injury (TBI) retrograde memories are initially impaired and recover in order of remoteness. However, there has been limited empirical research investigating whether a negative gradient in retrograde amnesia-relative preservation of remote over recent memory-exists during post-traumatic amnesia (PTA) compared with the acute phase post-emergence. This study used a repeated-measures design to examine the pattern of personal semantic (PS) memory performance during PTA and within two weeks of emergence to improve understanding of the nature of the memory deficit during PTA and its relationship with recovery. METHODS: Twenty patients with moderate-severe TBI and 20 healthy controls (HCs) were administered the Personal Semantic Schedule of the Autobiographical Memory Interview. The TBI group was assessed once during PTA and post-emergence. Analysis of variance was used to compare the gradient across lifetime periods during PTA relative to post-emergence, and between groups. RESULTS: PS memory was significantly lower during PTA than post-emergence from PTA, with no relative preservation of remote memories. The TBI group was still impaired relative to HCs following emergence from PTA. Lower overall PS memory scores during PTA were associated with increased days to emerge from PTA post-interview. CONCLUSIONS: These results suggest a global impairment in PS memory across lifetime periods particularly during PTA, but still present within 2 weeks of emergence from PTA. PS memory performance may be sensitive to the diffuse nature of TBI and may, therefore, function as a clinically valuable indicator of the likely time to emerge from PTA. (JINS, 2018, 24, 1064-1072).

Persistent anterograde amnesia due to the artery of Percheron occlusion: a case report.

Bilateral thalamic infarction involving the artery of Percheron (AOP) can cause diagnostic difficulties due to the varying clinical presentations. AOP infarcts presented with isolated memory impairment are not common and the factors affecting the persistence of memory disorders are still unknown. A 41-year-old male patient was hospitalized with acute unconsciousness. MRI disclosed bilateral paramedian thalamic infarction The patient had isolated memory deficit and his anterograde amnesia continued without any change in the past decade. More cases might answer the questions concerning the intra- and extra-thalamic structures responsible for the amnesic syndrome and the factors affecting the persistence of the symptoms.

Anterograde Amnesia Induced by Disruption of Consolidation or Reconsolidation of Long-Term Memory.

Mechanisms of amnesia caused by impairment of consolidation or reconsolidation of conditioned food aversion memory with protein synthesis inhibitor cycloheximide were studied in Helix lucorum. Cycloheximide injection during training or memory reconsolidation in trained snails produced amnesia. In both cases, repeated training 10 days after amnesia induction led to short-term memory formation, while long-term memory was not formed, despite the fact that the number of conditioned and reinforcing stimuli combinations was higher than during initial training. The possibility of formation of short-term memory not transforming into long-term memory is one of the key characteristics of anterograde amnesia. Our findings data and experimental model can be used for analysis of specific molecular mechanisms of anterograde amnesia.

Profound anterograde amnesia following routine anesthetic and dental procedure: a new classification of amnesia characterized by intermediate-to-late-stage consolidation failure?

Anterograde amnesia caused by bilateral hippocampal or diencephalon damage manifests in characteristic symptoms of preserved intellect and implicit learning, and short span of awareness with complete and rapid forgetting of episodic material. A new case, WO, 38-year-old male with anterograde amnesia, in the absence of structural brain changes or psychological explanation is presented, along with four comparison cases from the extant literature that share commonalities between them including preserved intellect, span of awareness greater than working memory, and complete forgetting within hours or days following successful learning, including notably for both explicit and implicit material. WO's amnesia onset coincided with anesthetic injection and root canal procedure, with extended vasovagal-like incident. The commonalities between the five cases presented may suggest a shared biological mechanism involving the breakdown of intermediate-to-late-stage consolidation that does not depend on the structural integrity of the hippocampi. Speculation on the mechanism of consolidation breakdown and diagnostic implications are discussed.

The role of executive functions in long-term memory: case report.

The role of executive functions in long-term memory has been studied. We describe a single-case study, consisting of a 45-year-old male patient, hospitalized for right frontal stroke. After the stroke, the patient had memory alterations in everyday activities. However, performance in short-term memory tests was not significantly altered. Long-term memory assessments included pre- and post-stroke episodic, semantic, and procedural memories. Specific skills involved in the acquisition of new learning (auditory-verbal and visual reproduction) were also evaluated, as well as executive functions. The results evidence that short-term memory was not affected. Regarding long-term memory, significant differences were observed between pre- and post-stroke knowledge, the former being better preserved, which reveals anterograde amnesia. Pre-stroke long-term memory was also affected, but only with respect to episodic knowledge, with semantic and procedural memories preserved (episodic retrograde amnesia). Executive functions were altered as well, which could have been a factor affecting the acquisition and consolidation of new learning, despite the fact that short-term memory was not significantly altered. Therefore, executive functions might be a determinant factor in the acquisition of new learning, regardless of short-term memory processes, at least partially. According to the results of the present study, alterations in these functions might lead to anterograde amnesia. This entails the need to evaluate executive functions as an intrinsic part of memory evaluation.

Toxic-Induced Encephalopathy Following Chemsex in a Young HIV-Positive Male: A Complex Case of Acute Cognitive Impairment with Anterograde Amnesia and Behavioral Alterations.

BACKGROUND: A broadened clinical spectrum of concomitant complications emerges among the escalating incidence of substance use, particularly within the 'chemsex' context. This case exemplifies the profound neurotoxic repercussions and neurological risk of chemsex in a young HIV-positive male and addresses the multifaceted challenges of such evolving paradigms in substance utilization. CLINICAL FINDING: After consuming cannabis, poppers, methamphetamine, and cocaine, a 28-year-old HIV-positive male exhibited significant neurological and cognitive impairment. The initial presentation included dysarthria and profound anterograde amnesia. Laboratory findings showed leukocytosis with a PCR of 3 mg/dl - elevated cerebrospinal fluid protein levels with no cells. Urine toxicology returned positive for cannabis and amphetamines. A brain CT scan revealed bilateral and symmetrical hippocampi and pale globes hypodensity, indicative of toxic-metabolic encephalopathy. MRI further identified lesions in the globus pallidus, cerebellum, and hippocampi. Following the detection of toxic encephalopathy, Initial neuropsychological was performed screening using the Montreal Cognitive Assessment (MoCA), which highlighted immediate memory deficits. An in-depth neuropsychological assessment conducted 3 weeks later included the Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV), the Rey Auditory Verbal Learning Test (RAVLT), and tests for visuospatial skills, motor functions, and memory recall. The evaluations revealed pronounced anterograde amnesia, persistent long-term memory inconsistencies, and notable executive function challenges, detailed in Table 1. CONCLUSIONS: The detailed analysis of this case underpins the severe neurological consequences that can manifest from heavy substance use. Comprehensive diagnostic evaluations, including neuroimaging and neuropsychological assessments, are crucial in elucidating the full spectrum of substance-induced cognitive impairments. There is an urgent need for enhanced public awareness and preventative measures, especially in the context of chemsex, to bring forth multifaceted health, social, and government implications that modern society must adeptly navigate.

Cholecystokinin B receptor agonists alleviates anterograde amnesia in cholecystokinin-deficient and aged Alzheimer's disease mice.

BACKGROUND: As one major symptom of Alzheimer's disease (AD), anterograde amnesia describes patients with an inability in new memory formation. The crucial role of the entorhinal cortex in forming new memories has been well established, and the neuropeptide cholecystokinin (CCK) is reported to be released from the entorhinal cortex to enable neocortical associated memory and long-term potentiation. Though several studies reveal that the entorhinal cortex and CCK are related to AD, it is less well studied. It is unclear whether CCK is a good biomarker or further a great drug candidate for AD. METHODS: mRNA expressions of CCK and CCK-B receptor (CCKBR) were examined in two mouse models, 3xTg AD and CCK knock-out (CCK-/-) mice. Animals' cognition was investigated with Morris water maze, novel object recognition test and neuroplasticity with in-vitro electrophysiological recording. Drugs were given intraperitoneally to animals to investigate the rescue effects on cognitive deficits, or applied to brain slices directly to explore the influence in inducement of long-term potentiation. RESULTS: Aged 3xTg AD mice exhibited reduced CCK mRNA expression in the entorhinal cortex but reduced CCKBR expression in the neocortex and hippocampus, and impaired cognition and neuroplasticity comparable with CCK-/- mice. Importantly, the animals displayed improved performance and enhanced long-term potentiation after the treatment of CCKBR agonists. CONCLUSIONS: Here we provide more evidence to support the role of CCK in learning and memory and its potential to treat AD. We elaborated on the rescue effect of a promising novel drug, HT-267, on aged 3xTg AD mice. Although the physiological etiology of CCK in AD still needs to be further investigated, this study sheds light on a potential pharmaceutical candidate for AD and dementia.

A Dive Into Oblivion: A Case of Transient Global Amnesia.

Transient global amnesia (TGA) is an uncommon neurologic disorder that consists of a sudden and temporary loss of memory, both present and past. Its causes and risk factors are not well known. We describe a case of a 58-year-old woman who was brought to the emergency department (ED) with sudden onset loss of memory and disorientation after a dive in the ocean. She presented memory deficits with incapacity to retain new memories and amnesia for the previous 24 hours. All exams ordered were normal, including computed tomography of the brain and laboratory analysis. After six hours of close monitoring in the ED, she gradually started to retain short-term memories and was discharged after 48 hours with no memory or other deficits. The diagnosis of TGA was made based on the clinical presentation and the patient's rapid improvement. Follow-up neurology consultation and further testing did not demonstrate any evidence to exclude this diagnosis. Further research is needed on this topic to allow the identification of risk factors and causes to prevent it.

The Weight of Bariatric Surgery: Wernicke-Korsakoff Syndrome after Vertical Sleeve Gastrectomy-A Case Series.

In this case series, the simultaneous occurrence of Wernicke's encephalopathy (WE) and dry beriberi was reported in three patients who underwent vertical sleeve gastrectomy (VSG) between May 2021 and May 2023. All patients were obese women who underwent vertical sleeve gastrectomy (VSG) without immediate postoperative complications, but two weeks later, hyperemesis and subsequent encephalopathy with ocular movement abnormalities and weakness were observed over the following thirty days. Patients were referred to neurology, where due to the high suspicion of WE, thiamine replacement therapy was initiated; meanwhile, diagnostic neuroimaging and blood tests were conducted. Neurological and psychiatric evaluations and neuroconduction studies were performed to assess the clinical evolution and present sequelae. One year after diagnosis, all patients exhibited affective and behavioral sequelae, anterograde memory impairment, and executive functioning deficits. Two patients met the criteria for Korsakoff syndrome. Additionally, peripheral nervous system sequelae were observed, with all patients presenting with sensorimotor polyneuropathy. In conclusion, Wernicke's encephalopathy requires a high diagnostic suspicion for timely intervention and prevention of irreversible sequelae, which can be devastating. Therefore, raising awareness among medical professionals regarding the significance of this disease is essential.