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.

Tongue coating-dependent superior temporal sulcus remodeling in amnestic mild cognitive impairment.

Tongue coating affects cognition, and cognitive decline at early stage also showed relations to functional and structural remodeling of superior temporal sulcus (STS) in amnestic mild cognitive impairment (aMCI). The potential correlation between disparate cognitive manifestations in aMCI patients with different tongue coatings, and corresponding mechanisms of STS remodeling remains uncharted. In this case-control study, aMCI patients were divided into thin coating (n = 18) and thick coating (n = 21) groups. All participants underwent neuropsychological evaluations and multimodal magnetic resonance imaging. Group comparisons were conducted in clinical assessments and neuroimaging measures of banks of the STS (bankssts). Generalized linear models were constructed to explore relationships between neuroimaging measures and cognition. aMCI patients in the thick coating group exhibited significantly poorer immediate and delayed recall and slower information processing speed (IPS) (P < 0.05), and decreased functional connectivity (FC) of bilateral bankssts with frontoparietal cortices (P < 0.05, AlphaSim corrected) compared to the thin coating group. It was found notable correlations between cognition encompassing recall and IPS, and FC of bilateral bankssts with frontoparietal cortices (P < 0.05, Bonferroni's correction), as well as interaction effects of group × regional homogeneity (ReHo) of right bankssts on the first immediate recall (P < 0.05, Bonferroni's correction). aMCI patients with thick coating exhibited poor cognitive performance, which might be attributed to decreased FC seeding from bankssts. Our findings strengthen the understanding of brain reorganization of STS via which tongue coating status impacts cognition in patients with aMCI.

Amnestic Syndrome in Memory Clinics: Similar Morphological Brain Patterns in Older Adults with and without Alzheimer's Disease.

Background: Amnestic syndrome of the hippocampal type (ASHT) in Memory Clinics is a presentation common to Alzheimer's disease (AD). However, ASHT can be found in other neurodegenerative disorders. Objective: To compare brain morphometry including hippocampal volumes between amnestic older adults with and without AD pathology and investigate their relationship with memory performance and cerebrospinal fluid (CSF) biomarkers. Methods: Brain morphometry of 92 consecutive patients (72.5±6.8 years old; 39% female) with Free and Cued Selective Recall Reminding Test (FCSRT) total recall < 40/48 was assessed with an automated algorithm and compared between AD and non-AD patients, as defined by CSF biomarkers. Results: AD and non-AD patients presented comparable brain morphology. Total recall was associated to hippocampal volume irrespectively from AD pathology. Conclusions: Brain morphometry, including hippocampal volumes, is similar between AD and non-AD older adults with ASHT evaluated in a Memory Clinic, underlying the importance of using molecular biomarkers for the diagnosis of AD.

Clinical Significance of the Plasma Biomarker Panels in Amyloid-Negative and Tau PET-Positive Amnestic Patients: Comparisons with Alzheimer's Disease and Unimpaired Cognitive Controls.

The purpose of this study was to investigate whether plasma biomarkers can help to diagnose, differentiate from Alzheimer disease (AD), and stage cognitive performance in patients with positron emission tomography (PET)-confirmed primary age-related tauopathy, termed tau-first cognitive proteinopathy (TCP) in this study. In this multi-center study, we enrolled 285 subjects with young-onset AD (YOAD; n = 55), late-onset AD (LOAD; n = 96), TCP (n = 44), and cognitively unimpaired controls (CTL; n = 90) and analyzed plasma Aß42/Aß40, pTau181, neurofilament light (NFL), and total-tau using single-molecule assays. Amyloid and tau centiloids reflected pathological burden, and hippocampal volume reflected structural integrity. Receiver operating characteristic curves and areas under the curves (AUCs) were used to determine the diagnostic accuracy of plasma biomarkers compared to hippocampal volume and amyloid and tau centiloids. The Mini-Mental State Examination score (MMSE) served as the major cognitive outcome. Logistic stepwise regression was used to assess the overall diagnostic accuracy, combining fluid and structural biomarkers and a stepwise linear regression model for the significant variables for MMSE. For TCP, tau centiloid reached the highest AUC for diagnosis (0.79), while pTau181 could differentiate TCP from YOAD (accuracy 0.775) and LOAD (accuracy 0.806). NFL reflected the clinical dementia rating in TCP, while pTau181 (rho = 0.3487, p = 0.03) and Aß42/Aß40 (rho = -0.36, p = 0.02) were significantly correlated with tau centiloid. Hippocampal volume (unstandardized ß = 4.99, p = 0.01) outperformed all of the fluid biomarkers in predicting MMSE scores in the TCP group. Our results support the superiority of tau PET to diagnose TCP, pTau181 to differentiate TCP from YOAD or LOAD, and NFL for functional staging.

Visual search for real-world scenes in patients with Alzheimer's disease and amnestic mild cognitive impairment.

BACKGROUND: Visual attention-related processes that underlie visual search behavior are impaired in both the early stages of Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI), which is considered a risk factor for AD. Although traditional computer-based array tasks have been used to investigate visual search, information on the visual search patterns of AD and MCI patients in real-world environments is limited. AIM: The objective of this study was to evaluate the differences in visual search behaviors among individuals with AD, aMCI, and healthy controls (HCs) in real-world scenes. MATERIALS AND METHODS: A total of 92 participants were enrolled, including 28 with AD, 32 with aMCI, and 32 HCs. During the visual search task, participants were instructed to look at a single target object amid distractors, and their eye movements were recorded. RESULTS: The results indicate that patients with AD made more fixations on distractors and fewer fixations on the target, compared to patients with aMCI and HC groups. Additionally, AD patients had longer fixation durations on distractors and spent less time looking at the target than both patients with aMCI and HCs. DISCUSSION: These findings suggest that visual search behavior is impaired in patients with AD and can be distinguished from aMCI and healthy individuals. For future studies, it is important to longitudinally monitor visual search behavior in the progression from aMCI to AD. CONCLUSION: Our study holds significance in elucidating the interplay between impairments in attention, visual processes, and other underlying cognitive processes, which contribute to the functional decline observed in individuals with AD and aMCI.

Thermodynamic model for memory.

A thermodynamic model for memory formation is proposed. Key points include: 1) Any thought or consciousness corresponds to a thermodynamic system of nerve cells. 2) The system concept of nerve cells can only be described by thermodynamics of condensed matter. 3) The memory structure is logically associated with the system structure or the normal structure of biology. 4) The development of our thoughts is processed irreversibly, and numerous states or thoughts can be generated. 5) Memory formation results from the reorganization and change of cellular structures (or memory structures), which are related to nerve cell skeleton and membrane. Their alteration can change the excitability of nerve cells and the pathway of neural impulse conduction. 6) Amnesia results from the loss of thermodynamic stability of the memory structure, which can be achieved by different ways. Some related phenomena and facts are discussed. The analysis shows that thermodynamics can account for the basic properties of memory.

Associations Between Free and Cued Selective Reminding Test and Cerebrospinal Fluid Biomarkers in Amnestic Mild Cognitive Impairment.

Background: The Free and Cued Selective Reminding Test (FCSRT), assessing verbal episodic memory with controlled learning and semantic cueing, has been recommended for detecting the genuine encoding and storage deficits characterizing AD-related memory disorders. Objective: The present study aims at investigating the ability of FCSRT in predicting cerebrospinal fluid (CSF) evidence of amyloid-ß positivity in subjects with amnestic mild cognitive impairment (aMCI) and exploring its associations with amyloidopathy, tauopathy and neurodegeneration biomarkers. Methods: 120 aMCI subjects underwent comprehensive neurological and neuropsychological examinations, including the FCSRT assessment, and CSF collection; CSF Aß42/40 ratio, p-tau181, and total-tau quantification were conducted by an automated CLEIA method on Lumipulse G1200. Based on the Aß42/40 ratio value, subjects were classified as either A+ or A-. Results: All FCSRT subitem scores were significantly lower in A+ group and significantly predicted the amyloid-ß status, with Immediate Total Recall (ITR) being the best predictor. No significant correlations were found between FCSRT and CSF biomarkers in the A- aMCI group, while in the A+ aMCI group, all FCSRT subitem scores were negatively correlated with CSF p-tau181 and total-tau, but not with the Aß42/40 ratio. Conclusions: FCSRT confirms its validity as a tool for the diagnosis of AD, being able to predict the presence of amyloid-ß deposition with high specificity. The associations between FCSRT subitem scores and CSF p-tau-181 and total-tau levels in aMCI due to AD could further encourage the clinical use of this simple and cost-effective test in the evaluation of individuals with aMCI.

Intense training prevents the amnestic effect of inactivation of dorsomedial striatum and induces high resistance to extinction.

A large body of evidence has shown that treatments that interfere with memory consolidation become ineffective when animals are subjected to an intense learning experience; this effect has been observed after systemic and local administration of amnestic drugs into several brain areas, including the striatum. However, the effects of amnestic treatments on the process of extinction after intense training have not been studied. Previous research demonstrated increased spinogenesis in the dorsomedial striatum, but not in the dorsolateral striatum after intense training, indicating that the dorsomedial striatum is involved in the protective effect of intense training. To investigate this issue, male Wistar rats, previously trained with low, moderate, or high levels of foot shock, were used to study the effect of tetrodotoxin inactivation of dorsomedial striatum on memory consolidation and subsequent extinction of inhibitory avoidance. Performance of the task was evaluated during seven extinction sessions. Tetrodotoxin produced a marked deficit of memory consolidation of inhibitory avoidance trained with low and moderate intensities of foot shock, but normal consolidation occurred when a relatively high foot shock was used. The protective effect of intense training was long-lasting, as evidenced by the high resistance to extinction exhibited throughout the extinction sessions. We discuss the possibility that increased dendritic spinogenesis in dorsomedial striatum may underly this protective effect, and how this mechanism may be related to the resilient memory typical of post-traumatic stress disorder (PTSD).

Episodic memory network characteristics in patients with amnestic mild cognitive impairment accompanied by executive function impairment.

OBJECTIVE: To explore the functional connectivity (FC) characteristics of the episodic memory network (EMN) in amnestic mild cognitive impairment (aMCI) patients with different levels of executive function (EF). METHODS: This study included 76 participants from the Alzheimer's Disease Neuroimaging Initiative database, comprising 23 healthy controls (HCs) and 53 aMCI patients. Based on EF levels, aMCI patients were categorized into aMCI-highEF and aMCI-lowEF groups. Cognitive function scores, pathological markers (cerebrospinal fluid ß-amyloid, total tau protein, phosphorylated tau protein, AV45-PET, and FDG-PET), and functional magnetic resonance imaging were collected and compared among the three groups. Seed-based FC analysis was used to examine differences in the EMN among the groups, and partial correlation analysis was employed to investigate the relationship between changes in FC and cognitive function scores as well as pathological markers. RESULTS: Compared to the aMCI-highEF group, the aMCI-lowEF group exhibited more severe cognitive impairment, decreased cerebral glucose metabolism, and elevated AV45 levels. Significant FC differences in the left superior temporal gyrus (STG) of the EMN were observed among the three groups. Post hoc analysis revealed that the aMCI-lowEF group had increased FC in the left STG compared to the HCs and aMCI-highEF groups, with statistically significant differences. Correlation analysis showed a significant negative correlation between the differences in FC in the left STG of aMCI-highEF and aMCI-lowEF groups and Rey Auditory Verbal Learning Test forgetting scores. Receiver operator characteristic curve analysis indicated an area under the curve of 0.741 for distinguishing between aMCI-highEF and aMCI-lowEF groups based on FC of left STG, with a sensitivity of 0.808 and a specificity of 0.667. CONCLUSION: aMCI-lowEF exhibits characteristic changes in FC within the EMN, providing theoretical support for the role of EF in mediating EMN alterations and, consequently, impacting episodic memory function.

The hippocampus supports precise memory for public events regardless of their remoteness.

The necessity of the human hippocampus and surrounding medial temporal lobe structures to semantic memory remains contentious. Impaired semantic memory following hippocampal lesions could arise either due to partially intertwined episodic memories and/or retrograde/anterograde effects. In this study, we tested amnesic individuals with lesions in hippocampus and surrounding medial temporal lobe (n = 7) and age-matched controls (n = 14) on their ability to precisely recall the dates of famous public events that occurred either before (i.e., pre-lifetime) or after participants' birth date (lifetime). We show that deficits in dating precision are greatest for recent lifetime events, consistent with the notion that recent event memory may be particularly intertwined with episodic memory. At the same time, individuals with medial temporal lobe lesions showed more subtle impairments in their ability to date pre-birth and remote lifetime events precisely. Together, these findings suggest that the hippocampus and surrounding medial temporal lobe structures are important for representational precision of semantic memories regardless of their remoteness.

Alterations in driving ability and their relationship with morphometric magnetic resonance imaging indicators in patients with amnestic mild cognitive impairment and Alzheimer's disease.

BACKGROUND: Drivers with dementia are at a higher risk of motor vehicle accidents. The characteristics of driving behaviour of patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) have not been fully elucidated. We investigated driving ability and its relationship with cognitive function and magnetic resonance imaging (MRI) morphometry indicators. METHODS: The driving abilities of 19 patients with AD and 11 with amnestic MCI (aMCI) were evaluated using a driving simulator. The association between each driving ability parameter and the Mini-Mental State Examination (MMSE) score or voxel-based specific regional analysis system for AD (VSRAD) was assessed. RESULTS: Patients with AD made a significantly higher number of operational errors than those with aMCI in attention allocation in the complex task test (P = 0.0008). The number of operational errors in attention allocation in the complex task test significantly and negatively correlated with MMSE scores in all participants (r = -0.4354, P = 0.0162). The decision time in the selective reaction test significantly and positively correlated with the severity and extent of medial temporal structural atrophy (r = 0.4807, P = 0.0372; r = 0.4862, P = 0.0348; respectively). CONCLUSION: An increase in the operational errors for attention allocation in the complex task test could be a potential indicator of progression from aMCI to AD. Atrophy of the medial temporal structures could be a potential predictor of impaired judgement in driving performance in aMCI and AD. A driving simulator could be useful for evaluating the driving abilities of individuals with aMCI and AD.

Combined in vivo MRI assessment of locus coeruleus and nucleus basalis of Meynert integrity in amnestic Alzheimer's disease, suspected-LATE and frontotemporal dementia.

BACKGROUND: The locus coeruleus (LC) and the nucleus basalis of Meynert (NBM) are altered in early stages of Alzheimer's disease (AD). Little is known about LC and NBM alteration in limbic-predominant age-related TDP-43 encephalopathy (LATE) and frontotemporal dementia (FTD). The aim of the present study is to investigate in vivo LC and NBM integrity in patients with suspected-LATE, early-amnestic AD and FTD in comparison with controls. METHODS: Seventy-two participants (23 early amnestic-AD patients, 17 suspected-LATE, 17 FTD patients, defined by a clinical-biological diagnosis reinforced by amyloid and tau PET imaging, and 15 controls) underwent neuropsychological assessment and 3T brain MRI. We analyzed the locus coeruleus signal intensity (LC-I) and the NBM volume as well as their relation with cognition and with medial temporal/cortical atrophy. RESULTS: We found significantly lower LC-I and NBM volume in amnestic-AD and suspected-LATE in comparison with controls. In FTD, we also observed lower NBM volume but a slightly less marked alteration of the LC-I, independently of the temporal or frontal phenotype. NBM volume was correlated with the global cognitive efficiency in AD patients. Strong correlations were found between NBM volume and that of medial temporal structures, particularly the amygdala in both AD and FTD patients. CONCLUSIONS: The alteration of LC and NBM in amnestic-AD, presumed-LATE and FTD suggests a common vulnerability of these structures to different proteinopathies. Targeting the noradrenergic and cholinergic systems could be effective therapeutic strategies in LATE and FTD.

Novel Panel of Long Noncoding RNAs as Diagnostic Biomarkers for Amnestic Mild Cognitive Impairment in Peripheral Blood.

Background: Long noncoding RNAs (lncRNAs) regulate the pathogenesis of Alzheimer's disease (AD). Objective: To identify lncRNAs in the peripheral blood as potential diagnostic biomarkers for amnestic mild cognitive impairment. Methods: In the discovery group, a microarray was used to screen for significant differences in lncRNA expression between patients with mild cognitive impairment (MCI) caused by AD and normal controls (NCs) (n = 10; MCI, 5; NC, 5). Furthermore, two analytic groups were assessed (analytic group 1: n = 10; amnestic MCI (aMCI), 5; NC, 5; analytic group 2: n = 30; AD, 10; aMCI, 10; NC, 10) and finalized in the validation group (n = 150; AD, 50; aMCI, 50; NC, 50). In the analytic and validation groups, real-time quantitative reverse-transcription polymerase chain reaction was used to identify differentially expressed lncRNAs between the aMCI and NC groups. Results: We identified 67 upregulated and 220 downregulated lncRNAs among the expression profiles. The panel with lncRNAs T324988, NR_024049, ENST00000567919, and ENST00000549762 displayed the highest discrimination ability between patients with aMCI and NCs. The area under the receiver operating characteristic curve of this combined model was 0.941, with a sensitivity of 92.00% and specificity of 84.00%. Conclusions: This study reports on a panel of four lncRNAs as promising biomarkers to diagnose aMCIs.

Prophylactic effects of apigenin against hyperglycemia-associated amnesia via activation of the Nrf2/ARE pathway in zebrafish.

The escalating focus on ageing-associated disease has generated substantial interest in the phenomenon of cognitive impairment linked to diabetes. Hyperglycemia exacerbates oxidative stress, contributes to ß-amyloid accumulation, disrupts mitochondrial function, and impairs cognitive function. Existing therapies have certain limitations, and apigenin (AG), a natural plant flavonoid, has piqued interest due to its antioxidant, anti-inflammatory, and anti-hyperglycemic properties. So, we anticipate that AG might be a preventive medicine for hyperglycemia-associated amnesia. To test our hypothesis, naïve zebrafish were trained to acquire memory and pretreated with AG. Streptozotocin (STZ) was administered to mimic hyperglycemia-induced memory dysfunction. Spatial memory was assessed by T-maze and object recognition through visual stimuli. Acetylcholinesterase (AChE) activity, antioxidant enzyme status, and neuroinflammatory genes were measured, and histopathology was performed in the brain to elucidate the neuroprotective mechanism. AG exhibits a prophylactic effect and improves spatial learning and discriminative memory of STZ-induced amnesia in zebrafish under hyperglycemic conditions. AG also reduces blood glucose levels, brain oxidative stress, and AChE activity, enhancing cholinergic neurotransmission. AG prevented neuronal damage by regulating brain antioxidant response elements (ARE), collectively contributing to neuroprotective properties. AG demonstrates a promising effect in alleviating memory dysfunction and mitigating pathological changes via activation of the Nrf2/ARE mechanism. These findings underscore the therapeutic potential of AG in addressing memory dysfunction and neurodegenerative changes associated with hyperglycemia.

News event memory in amnestic and non-amnestic MCI, heritable risk for dementia, and subjective memory complaints.

Robust and sensitive clinical measures are needed for more accurate and earlier detection of Alzheimer's disease (AD), for staging preclinical AD, and for gauging the efficacy of treatments. Mild impairment on episodic memory tests is thought to indicate a cognitive risk of developing AD and mild cognitive impairment (MCI), considered to be a transitional stage between normal aging and AD. Novel tests of semantic memory, such as memory for news events, are also impaired early on but have received little clinical attention even though they may provide a novel way to assess cognitive risk for AD. We examined memory for news events in older adults with normal cognition (NC, N = 34), amnestic MCI (aMCI, N = 27), or non-aMCI (N = 10) using the Retrograde Memory News Events Test (RM-NET). We asked if news event memory was sensitive to 1) aMCI and also non-aMCI, which has rarely been examined, 2) genetic risk for dementia (positive family history of any type of dementia, presence of an APOE-4 allele, or polygenic risk for AD), and 3) subjective memory functioning judgments about the past. We found that both MCI subgroups exhibited impaired RM-NET Lifespan accuracy scores together with temporally-limited retrograde amnesia. For the aMCI group amnesia extended back 45 years prior to testing, but not beyond that time frame. The extent of retrograde amnesia could not be reliably estimated in the small non-aMCI group. The effect sizes of having MCI on the RM-NET were medium for the non-aMCI group and large for the aMCI group, whereas the effect sizes of participant characteristics on RM-NET accuracy scores were small. For the combined MCI group (N = 37), news event memory was significantly related to positive family history of dementia but was not related to the more specific genetic markers of AD risk. For the NC group, news event memory was not related to any measure of genetic risk. Objective measures of past memory from the RM-NET were not related to subjective memory judgements about the present or the recent past in either group. By contrast, when individuals subjectively compared their present versus past memory abilities, there was a significant association between this judgment and objective measures of the past from the RM-NET (direct association for the NC group and inverse for the MCI group). The RM-NET holds significant promise for early identification of those with cognitive and genetic risk factors for AD and non-AD dementias.

The sign effect in temporal discounting does not require the hippocampus.

When considering future outcomes, humans tend to discount gains more than losses. This phenomenon, referred to as the temporal discounting sign effect, is thought to result from the greater anticipated emotional impact of waiting for a negative outcome (dread) compared to waiting for a positive outcome (mixture of savoring and impatience). The impact of such anticipatory emotions has been proposed to rely on episodic future thinking. We evaluated this proposal by examining the presence and magnitude of a sign effect in the intertemporal decisions of individuals with hippocampal amnesia, who are severely impaired in their ability to engage in episodic mental simulation, and by comparing their patterns of choices to those of healthy controls. We also measured loss aversion, the tendency to assign greater value to losses compared to equivalent gains, to verify that any reduction in the sign effect in the hippocampal lesion group could not be explained by a group difference in loss aversion. Results showed that participants with hippocampal amnesia exhibited a sign effect, with less discounting of monetary losses compared to gains, that was similar in magnitude to that of controls. Loss aversion, albeit greater in the hippocampal compared to the control group, did not account for the sign effect. These results indicate that the sign effect does not depend on the integrity of hippocampally mediated episodic processes. They suggest instead that the impact of anticipatory emotions can be factored into decisions via semantic future thinking, drawing on non-contextual knowledge about oneself.

Everyday amnesia: Residual memory for high confidence misses and implications for decision models of recognition.

Despite studying a list of items only minutes earlier, when reencountered in a recognition memory test, undergraduate participants often say with total confidence that they have not studied some of the items before. Such high confidence miss (HCM) responses have been taken as evidence of rapid and complete forgetting and of everyday amnesia (Roediger & Tekin, 2020). We investigated (a) if memory for HCMs is completely lost or whether a residual memory effect exists and (b) whether dominant decision models predict the effect. Participants studied faces (Experiments 1a, 2, and 3) or words (Experiment 1b), then completed a single-item recognition memory task, followed by either (a) a two-alternative forced-choice recognition task, in which the studied and nonstudied alternatives on each trial were matched for their previous old/new decision and confidence rating (Experiments 1 and 2) or (b) a second single-item recognition task in which the targets and foils were HCMs and high confidence correct rejections, respectively (Experiment 3). In each experiment, participants reliably distinguished HCMs from high-confidence correct rejections. The unequal variance signal detection and dual-process signal detection models were fit to the single-item recognition data, and the parameter estimates were used to predict the memory effect for HCMs. The dual-process signal detection model predicted the residual memory effect (as did another popular model, the mixture signal detection theory model). However, the unequal variance signal detection model incorrectly predicted a negative, or no, effect, invalidating this model. The residual memory effect for HCMs demonstrates that everyday amnesia is not associated with complete memory loss and distinguishes between decision models. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The Safety and Efficacy of Remimazolam Compared to Dexmedetomidine for Awake Tracheal Intubation by Flexible Bronchoscopy: A Randomized, Double-Blind, Controlled Trial.

Background: Remimazolam is a novel ultra-short-acting benzodiazepine sedative that has the potential to be an alternative for procedural sedation due to its rapid sedation and recovery, no accumulation effect, stable hemodynamics, minimal respiratory depression, anterograde amnesia effect, and specific antagonist. Here, we aimed to compare the safety and efficacy of remimazolam with dexmedetomidine for awake tracheal intubation by flexible bronchoscopy (ATI-FB). Methods: Ninety patients scheduled for ATI-FB were randomly divided into three groups, each consisting of 30 cases: dexmedetomidine 0.6 µg/kg + sufentanil (group DS), remimazolam 0.073 mg/kg + sufentanil (group R1S), or remimazolam 0.093 mg/kg + sufentanil (group R2S). The primary outcome was the success rate of sedation. Secondary outcomes were MOAA/S scores, hemodynamic and respiratory parameters, intubation conditions, intubation time, tracheal intubation amnesia, and adverse events. Results: The success rates of sedation in groups R2S and DS were higher than that in group R1S (93.3%, 86.7%, respectively, vs 58.6%; P = 0.002), and intubation conditions were better than those in group R1S (P < 0.05). Group R2S had shorter intubation times than groups R1S and DS (P = 0.003), and a higher incidence of tracheal intubation amnesia than group DS (P = 0.006). No patient in the three groups developed hypoxemia or hypotension, and there were no significant differences in oligopnea, PetCO2, or bradycardia (P > 0.05). Conclusion: In conclusion, both DS and R2S had higher success rates of sedation, better intubation conditions, and minor respiratory depression, but R2S, with its shorter intubation time, higher incidence of anterograde amnesia, and ability to be antagonized by specific antagonists, may be a good alternative sedation regimen for patients undergoing ATI-FB.

Coal-Derived Humic Substances: Insight into Chemical Structure Parameters and Biomedical Properties.

An investigation was carried out on humic substances (HSs) isolated from the coal of the Kansk-Achinsk basin (Krasnoyarsk Territory, Russia). The coal HSs demonstrate the main parameters of molecular structure inherent to this class of natural compounds. An assessment was performed for the chemical, microbiological, and pharmacological safety parameters, as well as the biological efficacy. The HS sample meets the safety requirements in microbiological purity, toxic metals content (lead, cadmium, mercury, arsenic), and radionuclides. The presence of 11 essential elements was determined. The absence of general, systemic toxicity, cytotoxicity, and allergenic properties was demonstrated. The coal HS sample was classified as a Class V hazard (low danger substances). High antioxidant and antiradical activities and immunotropic and cytoprotective properties were identified. The ability of the HS to inhibit hydroxyl radicals and superoxide anion radicals was revealed. Pronounced actoprotective and nootropic activities were also demonstrated in vivo. Intragastric administration of the HS sample resulted in the improvement of physical parameters in mice as assessed by the "swim exhaustion" test. Furthermore, intragastric administration in mice with cholinergic dysfunction led to a higher ability of animals with scopolamine-induced amnesia to form conditioned reflexes. These findings suggest that the studied HS sample is a safe and effective natural substance, making it suitable for use as a dietary bioactive supplement.

Dihydroergotamine Increases Histamine Brain Levels and Improves Memory in a Scopolamine-Induced Amnesia Model.

The beneficial effects of increasing histamine levels on memory have acquired special interest due to their applicability to psychiatric conditions that cause memory impairments. In addition, by employing drug repurposing approaches, it was demonstrated that dihydroergotamine (DHE), an FDA drug approved to treat migraines, inhibits Histamine N Methyl Transferase (HNMT), the enzyme responsible for the inactivation of histamine in the brain. For this reason, in the present work, the effect of DHE on histamine levels in the hippocampus and its effects on memory was evaluated, employing the scopolamine-induced amnesia model, the Novel Object Recognition (NOR) paradigm, and the Morris Water Maze (MWM). Furthermore, the role of histamine 1 receptor (H1R) and histamine 2 receptor (H2R) antagonists in the improvement in memory produced by DHE in the scopolamine-induced amnesia model was evaluated. Results showed that the rats that received DHE (10 mg/kg, i.p.) showed increased histamine levels in the hippocampus after 1 h of administration but not after 5 h. In behavioral assays, it was shown that DHE (1 mg/kg, i.p.) administered 20 min before the training reversed the memory impairment produced by the administration of scopolamine (2 mg/kg, i.p.) immediately after the training in the NOR paradigm and MWM. Additionally, the effects in memory produced by DHE were blocked by pre-treatment with pyrilamine (20 mg/kg, i.p.) administered 30 min before the training in the NOR paradigm and MWM. These findings allow us to demonstrate that DHE improves memory in a scopolamine-induced amnesia model through increasing histamine levels at the hippocampus due to its activity as an HNMT inhibitor.