Did H.M. exhibit accelerated long-term forgetting? Measuring forgetting in amnesia.

The early investigations of patient H.M. inaugurated the modern era of memory research. During the 1970s and 1980s, a key debate over whether H.M. with bilateral medial temporal lobe lesions exhibited accelerated long-term forgetting attracted an increasing interest in forgetting research among amnestic patients. Huppert and Piercy (1979) examined H.M.'s performance in visual recognition at 10-minute, 1-day, and 7-day intervals and suggested that H.M. was subjected to rapid forgetting compared with Korsakoff patients and healthy participants reported in Huppert and Piercy (1978). In contrast, Freed et al. (1987) employed the same experimental paradigm and concluded that forgetting rates in H.M. did not differ from those in healthy controls. These incompatible findings highlighted a methodological challenge in measuring forgetting in the cross-group comparison design, where closely equalising the initial performance between patient and control groups is usually suggested. The re-analysis in this viewpoint, using both linear- and nonlinear-based modelling, reconciled the discrepancy between the aforementioned studies. Our results indicated that the rate of forgetting in H.M. did not differ from that in healthy controls, regardless of whether the initial performance was closely matched. Here, we suggest that the cross-group comparisons in forgetting studies do not necessarily seek a perfect match in initial performance unless the risks of confounding encoding and retrieval processes can be effectively controlled.

Anatomo-functional changes in neural substrates of cognitive memory in developmental amnesia: Insights from automated and manual Magnetic Resonance Imaging examinations.

Despite bilateral hippocampal damage dating to the perinatal or early childhood period and severely impaired episodic memory, patients with developmental amnesia continue to exhibit well-developed semantic memory across the developmental trajectory. Detailed information on the extent and focality of brain damage in these patients is needed to hypothesize about the neural substrate that supports their remarkable capacity for encoding and retrieval of semantic memory. In particular, we need to assess whether the residual hippocampal tissue is involved in this preservation, or whether the surrounding cortical areas reorganize to rescue aspects of these critical cognitive memory processes after early injury. We used voxel-based morphometry (VBM) analysis, automatic (FreeSurfer) and manual segmentation to characterize structural changes in the brain of an exceptionally large cohort of 23 patients with developmental amnesia in comparison with 32 control subjects. Both the VBM and the FreeSurfer analyses revealed severe structural alterations in the hippocampus and thalamus of patients with developmental amnesia. Milder damage was found in the amygdala, caudate, and parahippocampal gyrus. Manual segmentation demonstrated differences in the degree of atrophy of the hippocampal subregions in patients. The level of atrophy in CA-DG subregions and subicular complex was more than 40%, while the atrophy of the uncus was moderate (-24%). Anatomo-functional correlations were observed between the volumes of residual hippocampal subregions in patients and selective aspects of their cognitive performance, viz, intelligence, working memory, and verbal and visuospatial recall. Our findings suggest that in patients with developmental amnesia, cognitive processing is compromised as a function of the extent of atrophy in hippocampal subregions. More severe hippocampal damage may be more likely to promote structural and/or functional reorganization in areas connected to the hippocampus. In this hypothesis, different levels of hippocampal function may be rescued following this variable reorganization. Our findings document not only the extent, but also the limits of circuit reorganization occurring in the young brain after early bilateral hippocampal damage.

The effects of treatment, clinical and demographic factors on recovery of orientation after ECT: A care network study.

BACKGROUND: Time to reorientation after electroconvulsive therapy (ECT) has been shown to predict retrograde amnesia and is a useful measure for monitoring patients over the acute treatment course. This study investigated the effects of treatment, clinical and demographic factors on the recovery of orientation after ECT. METHODS: Data from 555 ECT patients across two different clinical CARE Network sites were analysed. The main outcome variable was recovery of orientation on the 10-Item Orientation Questionnaire assessed after every ECT treatment. A linear mixed-effects repeated measures model was used to predict the recovery of orientation across the ECT course based on multiple factors, including age, gender, electrode montage, ECT number and frequency, diagnosis, and baseline cognitive impairment. RESULTS: Type of ECT demonstrated a significant effect (F(2, 2341) = 48.414, p = 0.000): individuals who received right unilateral (RUL) ultrabrief ECT or bifrontal ECT had higher orientation scores compared to those who received RUL brief pulse ECT. Older age groups and female patients had lower orientation scores. Baseline global cognitive functioning significantly influenced orientation scores (F(3, 2339) = 43.597, p = 0.000), with individuals with no or mild cognitive impairment exhibiting higher scores. LIMITATIONS: The study involved a retrospective analysis of de-identified data, which may have introduced inherent biases with missing data. CONCLUSIONS: This large-scale retrospective, real-world study showed that recovery of orientation after ECT was most affected by ECT type, though age, gender, and baseline level cognitive impairment also affected outcomes. These findings can inform the interpretation of post ECT orientation scores, facilitating its monitoring and optimisation of patient outcomes.

Anoxic Brain Injury: A Subtle and Often Overlooked Finding in Non-Fatal Intimate Partner Strangulation.

BACKGROUND: A paucity of literature exists dedicated to the identification of anoxic brain injury in patients that survive non-fatal intimate partner strangulation (NF-IPS). While some individuals report experiencing symptoms of brain hypoxia followed by a loss of consciousness, other individuals report symptoms of brain hypoxia prior to amnesia, rendering some unable to recall loss of consciousness (LOC). OBJECTIVE: Using a standardized clinical assessment tool, the purpose of this retrospective analysis is to describe anoxic brain injury symptom prevalence in a sample of patients reporting NF-IPS. METHODS: One hundred and ninety-one unique patients, reporting a total of 267 strangulation events, were assessed by a member of the Shasta Community Forensic Care Team utilizing the Strangulation Hypoxia Anoxia Symptom TBI Assessment (SHASTA) tool. The sample is 98% female and includes adult patients ages 18-68. Examination records were categorized based on the presence or absence of hypoxia and anoxia symptoms. This manuscript utilizes the STROBE checklist. RESULTS: Amnesia was reported in 145 of the 267 strangulations (54.3%). Of those, 74 reported LOC (51.0%) while 71 did not recall LOC (49.0%). CONCLUSIONS: Within our sample, 49% of patients with amnesia did not recall losing consciousness, demonstrating that LOC is an imperfect measure of anoxia for patients following NF-IPS. Healthcare providers examining NF-IPS patients should inquire about additional symptoms of hypoxia and amnesia, which can be captured on the SHASTA tool.

Drawing promotes memory retention in a patient with sleep-related anterograde amnesia.

Drawing is a powerful tool to enhance memory in healthy participants and patients with probable dementia. Here, we investigated whether the drawing effect could extend to patient CT, a young woman with severe anterograde amnesia. Following surgery for a midline tumor involving her septum pellucidium and extending down into her fornices bilaterally, CT experienced a severe case of sleep-related amnesia. She can remember information encountered throughout the day, but when waking up in the morning or following a nap she forgets information learned prior to sleep. Here, we tested CT and 21 age-matched controls in a 3-day within-subjects design, during which participants encoded words by either drawing or writing them down. Memory for encoded words was tested in two conditions that each followed a 12-h delay, once after a night of sleep, and once after 12 h of wake. Despite her severe memory impairment, CT showed a drawing effect that was comparable to controls in both sleep and wake conditions. Whereas CT's memory for written words was consistently impaired relative to controls, her memory for drawn words was at the lower control range following a waking delay and above chance following a sleep delay. We suggest that amnesic patients may benefit from the drawing effect due to the recruitment of brain regions outside of the hippocampal system for encoding and consolidation. Furthermore, in control participants, sleep benefited memory for written words, but not for drawn words, suggesting that sleep preferentially consolidates memories that are more dependent on the hippocampal system.

Human retrograde amnesia and memory consolidation.

This paper reports a reassessment of published literature on the question of whether retrograde amnesia data from patients with severe trauma supports the idea that there is ongoing consolidation of long-lasting memories. That is, memory consolidation continues for decades with older memories being increasingly consolidated, and, thus, more protected from forgetting. Our analysis was limited to patients with specific traumas rather than neurodegenerative conditions that can be complicated by the additional presence of significant anterograde amnesia. These constraints were used because trauma patients have a definitive start to their amnesia allowing comparison of their memories before this event, unlike when there is an undefined amnesia onset. Our results revealed that the standard account of retrograde amnesia only fits part of the data, with more than half not conforming to this account. Specifically, damage to different brain areas was associated with different patterns of retrograde amnesia. Those cases where the standard retrograde amnesia account was held tended to involve damage to the hippocampus and temporal lobes, as expected. Future directions to better understand the influence of retrograde amnesia and memory consolidation are suggested.

Beyond Repressed Memory: Current Alternative Solutions to the Controversy.

Debates surrounding the origin of recovered memories of child abuse have traditionally focused on two conflicting arguments, namely that these memories are either false memories or instances of repressed memories (i.e., reflecting the idea that people can unconsciously block traumatic autobiographical experiences and eventually regain access). While scientific evidence for the first is clearly established, the second is the subject of a controversy in the academic, clinical, and legal fields. This controversy rages on today. In this introductory article to our topic "Beyond Repressed Memory: Current Alternative Solutions to the Controversy," we present alternative and more parsimonious explanations for repressed memories that we sorted into three categories: cognitive, motivational, and biological factors. Our aim is to provide a timely overview to help clinical and legal professionals, academics, and the general public to move beyond the idea that traumatic memories can be unconsciously repressed.

Judges and lawyers' beliefs in repression and dissociative amnesia may imperil justice: further guidance required.

This article examines continuing misunderstanding about memory function especially for trauma, across three UK samples (N = 717). Delayed allegations of child sexual and physical abuse are prevalent in Western legal systems and often rely upon uncorroborated memory testimony to prove guilt. U.K. legal professionals and jurors typically assess the reliability of such memory recall via common sense, yet decades of scientific research show common sense beliefs often conflict with science. Recent international surveys show controversial notions of repression and accurate memory recovery remain strongly endorsed. In historical cases, these notions may lead to wrongful convictions. The current study surveyed the U.K. public, lawyers, and mental health professionals' beliefs about repression, dissociative amnesia and false memories. Study findings give unique data on judges' and barristers' beliefs. Overall, the study findings reinforce international scientists' concerns of a science - knowledge-gap. Repression was strongly endorsed by lay, legal and clinical participants (> 78%) as was dissociative amnesia (> 87%). Moreover, suboptimal professional legal education and juror guidance may increase misunderstanding. Correcting beliefs about memory function, and extending the contribution of memory science in the courtroom remains an important quest for cognitive scientists.

Forgetfulness in adult attention-deficit/hyperactivity disorder masks transient epileptic amnesia: a case report.

Background: Inattention due to attention-deficit/hyperactivity disorder (ADHD) can lead to forgetfulness. Transient epileptic amnesia (TEA) can cause forgetfulness, similar to ADHD. We report a patient with ADHD who developed TEA. Case Presentation: The patient was a 40-year-old woman with ADHD. She has been prone to forgetfulness since childhood. Two years before visiting our outpatient clinic, she had begun to occasionally forget events that had occurred several days earlier. However, she was largely unaware of the emergence of new amnestic symptoms. She had also begun to experience various other amnestic symptoms 2 months before she visited our clinic, which prompted her to visit our outpatient clinic. The combination of a detailed interview, electroencephalography (EEG) examination, and consideration of TEA enabled us to diagnose her with TEA and provide treatment accordingly. In our patient, daily forgetfulness due to ADHD delayed the recognition of new additional forgetfulness attributed to TEA. Conclusion: Psychiatrists need to consider TEA when patients with ADHD present with changes in or exacerbation of forgetfulness.

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.

A Case With Bilateral Hippocampal Infarction Resembling Transient Global Amnesia.

Transient global amnesia (TGA) is a benign and transient condition with a sudden short-term amnesia. One of the conditions resembling TGA is hippocampal infarction, which requires relapse prevention treatments. In this report, we present a case with bilateral hippocampal infarction in whom distinguishing these two conditions was difficult for up to 1 week from the onset. A 60-year-old female visited our hospital with sudden onset retrograde and anterograde amnesia. Thin-slice magnetic resonance imaging (MRI) with 2-mm thickness revealed hyperintense signals on diffusion-weighted imaging (DWI) with signal loss on apparent diffusion coefficient (ADC) on both sides of the hippocampus. MRI with 5-mm thickness on day 7 revealed persistent restricted diffusion on both sides, one of which was still with decreased ADC values. Based on this finding, the diagnosis of bilateral hippocampal infarction was reached, and the relapse-preventive antiplatelet was continued. This case implied the potential difficulty of distinguishing cases with TGA and those with hippocampal infarction based on MRI findings within the first several days after onset. Thin-slice brain MRI, careful search of potential cardiovascular risks, and follow-up MRI ≥ 7 days after onset will be helpful to reach a correct diagnosis in cases with sudden amnesia.

Brouillet's Une leçon clinique à la Salpêtrière as an epistemic tool in Charcot's research on hysterical amnesia.

Much has been written, mostly in overly critical terms, about Jean-Martin Charcot's use of images in his hysteria research. Besides the images of patients Charcot produced for his clinical research, one other image has preoccupied present-day scholars-André Brouillet's painting Une leçon clinique à la Salpêtrière. Unveiled at the 1887 Salon in Paris, this life-sized painting depicts Charcot lecturing on hysteria to his male audience while presenting a swooning female patient. For many present-day critics, Brouillet's painting symbolizes Charcot's purported misuse of his female hysteria patients. Contrary to such interpretations, this article shows that Brouillet's painting did not merely serve as an iconic visual representation of Charcot's hysteria research but was also used by Charcot as an active epistemic tool in his research on hysterical amnesia. Through a close reading of Charcot's only published lecture on hysterical amnesia, which he held on December 22, 1891, I analyze the process through which Charcot generated new medical insights into hysterical amnesia. I thereby trace the decisive role that Une leçon clinique played in this process.

Clinical Heterogeneity in Alzheimer's Disease: A Possible New Amnesic Phenotype.

We rediscovered a phenotype of AD known in the early 1900s as presbyophrenia, but then forgotten, and renamed as confabulation-misidentification phenotype. The phenotype includes diencephalic amnesia whose prototype is Korsakoff syndrome. The main features are anterograde and retrograde amnesia with marked disorientation and confabulation, executive impairments, reduced insight and attention deficits, misidentification, minor hallucination and other delusions, behavioral disturbances, and early anxiety. In this article, we summarize what we have discovered about the new phenotype and what is still missing to confirm this diencephalic variant of AD.

Retrograde and semantic amnesia in a case of post-treatment Lyme disease syndrome: did something lead to a psychogenic memory loss? A single-case study.

OBJECTIVE: To describe a case of Post-Treatment Lyme Disease Syndrome (PTLDS) with an atypical cognitive profile. METHOD: A 41-year-old PTLDS patient underwent comprehensive neuropsychological testing and psychological assessment. RESULTS: The patient exhibited impaired intensive attention but preserved selective attention. Executive functions were normal. Short-term and anterograde memory were intact, while retrograde and semantic memory were significantly impaired. The patient also experienced identity loss, specific phobias, dissociative symptoms, and depressed mood. CONCLUSIONS: Severe episodic-autobiographical and retrograde semantic amnesia was consistent with some reports of dissociative amnesia. Loss of identity and phobias were also highly suggestive of a psychogenic mechanism underlying amnesia.

Dopaminergic psychostimulants cause arousal from isoflurane-induced sedation without reversing memory impairment in rats.

BACKGROUND: Dopaminergic psychostimulants can restore arousal in anaesthetised animals, and dopaminergic signalling contributes to hippocampal-dependent memory formation. We tested the hypothesis that dopaminergic psychostimulants can antagonise the amnestic effects of isoflurane on visuospatial working memory. METHODS: Sixteen adult Sprague-Dawley rats were trained on a trial-unique nonmatching-to-location (TUNL) task which assessed the ability to identify a novel touchscreen location after a fixed delay. Once trained, the effects of low-dose isoflurane (0.3 vol%) on task performance and activity, assessed by infrared beam breaks, were assessed. We attempted to rescue deficits in performance and activity with a dopamine D1 receptor agonist (chloro-APB), a noradrenergic reuptake inhibitor (atomoxetine), and a mixed dopamine/norepinephrine releasing agent (dextroamphetamine). Anaesthetic induction, emergence, and recovery from anaesthesia were also investigated. RESULTS: Low-dose isoflurane impaired working memory in a sex-independent and intra-trial delay-independent manner as assessed by task performance, and caused an overall reduction in activity. Administration of chloro-APB, atomoxetine, or dextroamphetamine did not restore visuospatial working memory, but chloro-APB and dextroamphetamine recovered arousal to levels observed in the baseline awake state. Performance did not differ between induction and emergence. Animals recovered to baseline performance within 15 min of discontinuing isoflurane. CONCLUSIONS: Low-dose isoflurane impairs visuospatial working memory in a nondurable and delay-independent manner that potentially implicates non-hippocampal structures in isoflurane-induced memory deficits. Dopaminergic psychostimulants counteracted sedation but did not reverse memory impairments, suggesting that isoflurane-induced amnesia and isoflurane-induced sedation have distinct underlying mechanisms that can be antagonised independently.

Temporal organization of narrative recall is present but attenuated in adults with hippocampal amnesia.

Studies of the impact of brain injury on memory processes often focus on the quantity and episodic richness of those recollections. Here, we argue that the organization of one's recollections offers critical insights into the impact of brain injury on functional memory. It is well-established in studies of word list memory that free recall of unrelated words exhibits a clear temporal organization. This temporal contiguity effect refers to the fact that the order in which word lists are recalled reflects the original presentation order. Little is known, however, about the organization of recall for semantically rich materials, nor how recall organization is impacted by hippocampal damage and memory impairment. The present research is the first study, to our knowledge, of temporal organization in semantically rich narratives in three groups: (1) Adults with bilateral hippocampal damage and severe declarative memory impairment, (2) adults with bilateral ventromedial prefrontal cortex (vmPFC) damage and no memory impairment, and (3) demographically matched non-brain-injured comparison participants. We find that although the narrative recall of adults with bilateral hippocampal damage reflected the temporal order in which those narratives were experienced above chance levels, their temporal contiguity effect was significantly attenuated relative to comparison groups. In contrast, individuals with vmPFC damage did not differ from non-brain-injured comparison participants in temporal contiguity. This pattern of group differences yields insights into the cognitive and neural systems that support the use of temporal organization in recall. These data provide evidence that the retrieval of temporal context in narrative recall is hippocampal-dependent, whereas damage to the vmPFC does not impair the temporal organization of narrative recall. This evidence of limited but demonstrable organization of memory in participants with hippocampal damage and amnesia speaks to the power of narrative structures in supporting meaningfully organized recall despite memory impairment.

Effect of curcumin-donepezil combination on spatial memory, astrocyte activation, and cholinesterase expressions in brain of scopolamine-treated rats.

BACKGROUND: The study investigated the effect of co-administration of curcumin and donepezil on several markers of cognitive function (such as spatial memory, astrocyte activation, cholinesterase expressions) in the brain cortex and hippocampus of scopolamine-treated rats. METHOD AND RESULTS: For seven consecutive days, a pre-treatment of curcumin (50 mg/kg) and/or donepezil (2.5 mg/kg) was administered. On the seventh day, scopolamine (1 mg/kg) was administered to elicit cognitive impairment, 30 min before memory test was conducted. This was followed by evaluating changes in spatial memory, cholinesterase, and adenosine deaminase (ADA) activities, as well as nitric oxide (NO) level were determined. Additionally, RT-qPCR for glial fibrillary acidic protein (GFAP) and cholinesterase gene expressions was performed in the brain cortex and hippocampus. Also, GFAP immunohistochemistry  of the brain tissues for neuronal injury were performed in the brain cortex and hippocampus. In comparison to the control group, rats given scopolamine had impaired memory, higher levels of acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and ADA activities, as well as elevated markers of oxidative stress. In addition to enhanced GFAP immunoreactivity, there was also overexpression of the GFAP and BChE genes in the brain tissues. The combination of curcumin and donepezil was, however, observed to better ameliorate these impairments in comparison to the donepezil-administered rat group. CONCLUSION: Hence, this evidence provides more mechanisms to support the hypothesis that the concurrent administration of curcumin and donepezil mitigates markers of cognitive dysfunction in scopolamine-treated rat model.

The association between dietary intake of fats and transient global amnesia (TGA).

BACKGROUND: Different types of dietary fat may influence memory and cognitive functions. This study aimed to investigate the association between dietary fat intake and transient global amnesia (TGA). METHODS: This case-control study was conducted using Persian Sabzevar cohort data on 258 individuals with TGA and 520 individuals without amnesia in Sabzevar Iran. The food frequency questionnaire (FFQ) was used to assess the intake of dietary fats of the participants. All study participants were screened for TGA by a neurologist and their status was determined based on the diagnostic symptoms defined by the Kaplan and Hodges criteria. RESULTS: There was an inverse association between the risk of TGA and dietary intake of alpha-linolenic acid (ALA) (OR = 0.94, CI95%:0.88-0.99, P = 0.01). Also, a positive association was observed between TGA and dietary intake of n-6 fatty acids (OR = 1.18, CI 95%: 1.04-1.33, P = 0.01). The results remained significant after adjustment for age, sex, education, job, marital status, physical activity, BMI, and calorie intake. CONCLUSION: Omega-3 fatty acids may have beneficial effects; however, omega-6 fatty acids may have adverse effects on the risk of amnesia. Further longitudinal studies are warranted.

Severe Dissociative Experiences beyond Detachment in a Large Clinical Sample of Inpatients with Post-Traumatic Stress Disorder: Diagnostic and Treatment Implications.

INTRODUCTION: The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) contains a dissociative subtype of post-traumatic stress disorder (PTSD) characterized by depersonalization and derealization. Yet, there is evidence that dissociative symptoms in PTSD go beyond this kind of detachment dissociation and that some patients present with additional compartmentalization dissociation in the form of auditory-verbal hallucination, amnesia, and identity alteration. METHODS: Hence, in this study, we examined latent profiles of childhood trauma (Childhood Trauma Questionnaire), PTSD (Impact-of-Event Scale-Revised), and pathological dissociation (Dissociative Experiences Scale-Taxon; DES-T) in a large sample of severely traumatized inpatients with PTSD (N = 1,360). RESULTS: Results support a three-class solution of the latent profile analysis with a PTSD class, a dissociative subtype class, and a third class characterized by more complex and more severe dissociative symptoms. Importantly, in our inpatient sample of patients with severe PTSD, the latter class was found to be the most prevalent. Both the exploratory character of our retrospective analysis of clinical routine data and the use of the DES-T limit the generalizability of our findings, which require methodologically more rigorous replication. CONCLUSION: In severe PTSD, dissociative symptoms beyond detachment are highly prevalent. Diagnostic and treatment implications are discussed.

Overview of Hepatitis B Vaccine Non-Response and Associated B Cell Amnesia: A Scoping Review.

BACKGROUND: The advent of the hepatitis B vaccine has achieved tremendous success in eradicating and reducing the burden of hepatitis B infection, which is the main culprit for hepatocellular carcinoma-one of the most fatal malignancies globally. Response to the vaccine is achieved in about 90-95% of healthy individuals and up to only 50% in immunocompromised patients. This review aimed to provide an overview of hepatitis B vaccine non-response, the mechanisms involved, B cell amnesia, and strategies to overcome it. METHODS: Databases, including Google Scholar, PubMed, Scopus, Cochrane, and ClinicalTrials.org, were used to search and retrieve articles using keywords on hepatitis B vaccine non-response and B cell amnesia. The PRISMA guideline was followed in identifying studies, screening, selection, and reporting of findings. RESULTS: A total of 133 studies on hepatitis B vaccine non-response, mechanisms, and prevention/management strategies were included in the review after screening and final selection. Factors responsible for hepatitis B vaccine non-response were found to include genetic, immunological factors, and B cell amnesia in healthy individuals. The genetic factors were sex, HLA haplotypes, and genetic polymorphisms in immune response markers (cytokines). Non-response was common in conditions of immunodeficiency, such as renal failure, haemodialysis, celiac disease, inflammatory bowel disease, hepatitis C co-infection, and latent hepatitis B infection. Others included diabetes mellitus and HIV infection. The mechanisms involved were impaired immune response by suppression of response (T helper cells) or induced suppression of response (through regulatory B and T cells). DISCUSSION: A comprehensive and careful understanding of the patient factors and the nature of the vaccine contributes to developing effective preventive measures. These include revaccination or booster dose, vaccine administration through the intradermal route, and the use of adjuvants in the vaccine.