Memory Disorders Research Articles

Oxidative Stress-mediated Loss of Hippocampal Parvalbumin Interneurons Contributes to Memory Precision Decline After Acute Sleep Deprivation.

Sleep is pivotal to memory consolidation, and sleep deprivation (SD) after learning can impede this process, leading to memory disorders. In the present study, we aimed to explore the effects of acute sleep deprivation (ASD) on memory disorders and the underlying mechanisms. ASD model was induced by subjecting the mice to 6h of SD following fear conditioning training. Different cohorts were used for behavioral, biochemical, and electrophysiological tests. Here, we showed that memory precision decline was induced by ASD, concomitant with a notable elevation in oxidative stress within PV interneurons, loss of PV, and disturbed neuronal oscillation in the CA1 region. Notably, chemogenetic activation of PV interneurons effectively ameliorated abnormal gamma oscillation and memory precision decline observed in ASD mice. Meanwhile, chemogenetic inhibition of PV interneurons successfully mimicked the abnormal brain oscillations and memory precision decline observed in ASD mice. Additionally, prior administration of the antioxidant medication N-acetylcysteine effectively reversed memory precision decline and mitigated PV loss and abnormal oscillation triggered by ASD. Collectively, our findings indicated that ASD increased oxidative stress in PV interneurons, thereby disrupting neural oscillation in the CA1 and ultimately leading to memory precision decline.

Effect of JM-20 on Age-Related Cognitive Impairment in Mice.

The decline in cognitive function associated with aging significantly impacts the well-being of elderly individuals and their families. This decline is a major recognized risk factor for neurodegenerative diseases, notably Alzheimer's disease. Animal models of aging provide a platform for evaluating drugs concerning aspects like memory and oxidative stress. JM-20 has demonstrated protective effects on short-term memory acquisition and consolidation, along with antioxidant properties and modulation of Acetylcholinesterase activity. This study assesses the potential protective JM-20 against cognitive decline and age-related memory loss. For the study, aged mice exhibiting aging-associated damage were initially selected. Experimental groups were then formed, and the effect of 8mg/kg of JM-20 was evaluated for 40 days on aging-related behavior, such as spatial memory, novelty recognition memory, ambulatory activity, and anxiety. Subsequently, animals were sacrificed, and the hippocampal region was extracted for redox studies and to assess acetylcholinesterase activity. Results indicated that JM-20 at 8mg/kg reversed damage to spatial working and reference memory, exhibiting performance comparable to untreated young adult animals. Furthermore, JM-20 preserved the enzymatic activity of superoxide dismutase, catalase, and total sulfhydryl levels in age-related cognitive impairment in mice, indicating a potent protective effect against oxidative events at the brain level. However, only young, healthy animals showed decreased acetylcholinesterase enzyme activity. These findings provide preclinical pharmacological evidence supporting the neuroprotective activity of JM-20, positioning it as a promising therapeutic candidate for treating memory disorders associated with aging.

Highly prevalent geriatric medications and their effect on β-amyloid fibril formation.

The unprecedented increase in the older population and ever-increasing incidence of dementia are leading to a "silver tsunami" in upcoming decades. To combat multimorbidity and maintain daily activities, elderly people face a high prevalence of polypharmacy. However, how these medications affect dementia-related pathology, such as Alzheimer's β-amyloid (Aβ) fibrils formation, remains unknown. In the present study, we aimed to analyze the medication profiles of Alzheimer's disease (AD; n = 124), mild cognitive impairment (MCI; n = 114), and non-demented (ND; n = 228) patients to identify highly prevalent drugs and to determine the effects of those drugs on Aβ fibrils formation. Study subjects (≥ 65 years) were recruited from an academic geriatric practice that heavily focuses on memory disorders. The disease state was defined based on the score of multiple cognitive assessments. Individual medications for each subject were listed and categorized into 10 major drug classes. Statistical analysis was performed to determine the frequency of individual and collective drug classes, which are expressed as percentages of the respective cohorts. 10 µM monomeric β-amyloid (Aβ) 42 and fibrillar Aβ (fAβ) were incubated for 6-48h in the presence of 25 µM drugs. fAβ was prepared with a 1:10 ratio of Aβ42 to Aβ40. The amount of Aβ fibrils was monitored using a thioflavin T (Th-T) assay. Neuronal cells (N2A and SHSY-5Y) were treated with 25 µM drugs, and cell death was measured using a lactose dehydrogenase (LDH) assay. We noticed a high prevalence (82-90%) of polypharmacy and diverse medication profiles including anti-inflammatory (65-77%), vitamin and mineral (64-72%), anti-cholesterol (33-41%), anti-hypersensitive (35-39%), proton pump inhibitor (23-34%), anti-thyroid (9-21%), anti-diabetic (5-13%), anti-constipation (9-11%), anti-coagulant (10-13%), and anti-insomnia (9-20%) drugs in the three cohorts. Our LDH assay with 18 highly prevalent drug components showed toxic effects of Norvasc, Tylenol, Colace, and Plavix on N2A cells, and of vitamin D and Novasc on SH-SY5Y cells. All these drugs except Colace significantly reduced the amount of Aβ fibril when incubated with Aβ42 for a short period (6h). However, Lipitor, vitamin D, Levothyroxine, Prilosec, Flomax, and Norvasc prominently reduce the amount of fibrils when incubated with monomeric Aβ42 for a longer period (48h). Furthermore, our disaggregation study with fAβ showed consistent results for cholecalciferol (vitamin D), omeprazole (Prilosec), clopidogrel hydrogensulfate (Flomax), levothyroxine, and amlodipine (Norvasc). The chemical structures of these four efficient molecules contain polyphenol components, a characteristic feature of the structures of polyphenolic inhibitors of Aβ fibrillation. A higher polypharmacy incidence was observed in an elderly population of 228 ND, 114 MCI, and 124 AD patients. We found that several highly recommended drug components, including vitamin D3, Levothyroxine, Prilosec, Flomax, and Norvasc, efficiently reduce the amount of fibrils formed by monomeric Aβ42 and existing preformed Aβ fibrils in vitro. However, only Levothyroxine was able to prevent Aβ-mediated toxicity to SH-SY5Y cells. Our study suggested that these drugs likely function as polyphenolic inhibitors of Aβ.

Study on the Pilot-Scale Technology of Ginkgolide B Synthesis by Coprinus comatus

Ginkgo biloba extract (EGB) has been approved by the Food and Drug Administration in the United States for clinical studies on memory disorders. Ginkgolide B (GB) is the major terpene lactone component of EGB and is a specific and potent antagonist of platelet-activating factor (PAF). In a previous study, we reported the medium composition for the conversion of ginkgolides to GB by Coprinus comatus. In the present study, we applied the response surface methodology (RSM) to optimize the conversion conditions in a 20 L fermenter and applied HPLC-MS/MS, circular dichroism (CD) and infrared (IR) spectroscopy analyses, and nuclear magnetic resonance (NMR) to further confirm the sample structure. The optimal conversion conditions consisted of 12.7 L/min of ventilation, a 156 h conversion time, a 132 rpm rotating speed, a 0.04 MPa fermenter pressure, and a 27.8 °C conversion temperature. Under the optimal conditions, the GB conversion rate was 98.62%, and the GB content of the sample was higher than 98%. HPLC-MS/MS, CD, IR, and NMR analyses showed that the molecular formula of the sample was C20H24O10 and the chemical structure of the sample was in good agreement with the standard GB. Our current study lays the groundwork for the industrial production of GB.

Association of Seizure Foci and Location of Tau and Amyloid Deposition and Brain Atrophy in Patients With Alzheimer Disease and Seizures.

Alzheimer disease (AD) is associated with a 2 to 3-fold increased risk of developing late-onset focal epilepsy, yet it remains unclear how development of focal epilepsy in AD is related to AD pathology. The objective of this study was to examine spatial relationships between the epileptogenic zone and tau deposition, amyloid deposition, and brain atrophy in individuals with AD who developed late-onset, otherwise unexplained focal epilepsy. We hypothesized that if network hyperexcitability is mechanistically linked to AD pathology, then there would be increased tau and amyloid deposition within the epileptogenic hemisphere. In this cross-sectional study, we performed tau and amyloid PET imaging, brain MRI, and overnight scalp EEG in individuals with early clinical stages of AD who developed late-onset, otherwise unexplained focal epilepsy (AD-Ep). Participants were referred from epilepsy and memory disorders clinics at our institutions. We determined epilepsy localization based on EEG findings and seizure semiology. We quantified tau deposition, amyloid deposition, and atrophy across brain regions and calculated asymmetry indices for these measures. We compared findings in AD-Ep with those in a control AD group without epilepsy (AD-NoEp). The AD-Ep group included 8 individuals with a mean age of 69.5 ± 4.2 years at PET imaging. The AD-NoEp group included 14 individuals with a mean age of 71.7 ± 9.8 years at PET imaging. In AD-Ep, we found a highly asymmetric pattern of tau deposition, with significantly greater tau in the epileptogenic hemisphere. Amyloid deposition and cortical atrophy were also greater in the epileptogenic hemisphere, although the magnitudes of asymmetry were reduced compared with tau. Compared with AD-NoEp, the AD-Ep group had significantly greater tau asymmetry and trends toward greater asymmetry of amyloid and atrophy. AD-Ep also had significantly greater amyloid burden bilaterally and trends toward greater tau burden within the epileptogenic hemisphere, compared with AD-NoEp. Our results reveal a spatial association between the epileptogenic focus and tau deposition, amyloid deposition, and neurodegeneration in early clinical stages of AD. Within the limitations of a cross-sectional study with small sample sizes, these findings contribute to our understanding of the clinicopathologic heterogeneity of AD, demonstrating an association between focal epilepsy and lateralized pathology in AD.

Different Markers of Semantic–Lexical Impairment Allow One to Obtain Different Information on the Conversion from MCI to AD: A Narrative Review of an Ongoing Research Program

Background: In this narrative review, we have surveyed results obtained from a research program dealing with the role of semantic memory disorders as a predictor of progression from mild cognitive impairment (MCI) to Alzheimer’s disease (AD). Objectives: In this research program, we have taken into account many different putative markers, provided of a different complexity in the study of the semantic network. These markers ranged from the number of words produced on a semantic fluency task to the following: (a) the discrepancy between scores obtained on semantic vs. phonemic word fluency tests; (b) the presence, at the single-word level, of features (such as a loss of low typical words on a category verbal fluency task) typical of a degraded semantic system; or (c) the presence of more complex phenomena (such as the semantic distance between consecutively produced word pairs) concerning the organization of the semantic network. In the present review, all these studies have been presented, providing separate subsections for (a) methods, (b) results, and (c) a short discussion. Some tentative general conclusions have been drawn at the end of the review. We found that at baseline all these markers are impaired in MCI patients who will later convert to AD, but also that they do not necessarily show a linear worsening during the progression to AD and allow one to make different predictions about the time of development of AD. Our conclusions were that, rather than searching for the best marker of conversion, we should use a range of different markers allowing us to obtain the information most appropriate to the goal of our investigation.

Astrocytes and Memory: Implications for the Treatment of Memory-related Disorders.

Memory refers to the imprint accumulated in the brain by life experiences and represents the basis for humans to engage in advanced psychological activities such as thinking and imagination. Previously, research activities focused on memory have always targeted neurons. However, in addition to neurons, astrocytes are also involved in the encoding, consolidation, and extinction of memory. In particular, astrocytes are known to affect the recruitment and function of neurons at the level of local synapses and brain networks. Moreover, the involvement of astrocytes in memory and memory-related disorders, especially in Alzheimer's disease (AD) and post-traumatic stress disorder (PTSD), has been investigated extensively. In this review, we describe the unique contributions of astrocytes to synaptic plasticity and neuronal networks and discuss the role of astrocytes in different types of memory processing. In addition, we also explore the roles of astrocytes in the pathogenesis of memory-related disorders, such as AD, brain aging, PTSD and addiction, thus suggesting that targeting astrocytes may represent a potential strategy to treat memory-related neurological diseases. In conclusion, this review emphasizes that thinking from the perspective of astrocytes will provide new ideas for the diagnosis and therapy of memory-related neurological disorders.

Clinical and Demographic Profile of Syrian Patients with Malignant Glioma: A Six-Month Retrospective Analysis

This study presents a retrospective analysis of glioblastoma cases admitted to Tishreen University Hospital in Lattakia, Syria, between February and August 2024. The study examines the several potential risk factors including age, sex, genetic predispositions, and lifestyle factors such as smoking and alcohol consumption. It also explores the most commonly encountered tumor grade and the presence of various neurological symptoms, as well as treatment outcomes. A total of 30 glioblastoma were enrolled in this study, 63% of which were males, and the highest age incidence was between 40 and 50 years. Only 6% had a family history of glioblastoma, and 66% of the patients were smokers. Memory disorders, visual impairments, and headaches were common symptoms, with 100% of the patients reporting nausea and vomiting. Glioblastoma diagnosis was primarily established through MRI with contrast (76%), and the predominant treatment modality was surgery combined with radiotherapy and chemotherapy (80%). Post-treatment relapse occurred in 26% of the patients, with a median remission period of four months. These findings provide important insights into the clinical characteristics and treatment outcomes of glioblastoma patients in this region.

High Behavioral Reactivity to Novelty as a Susceptibility Factor for Memory and Anxiety Disorders in Streptozotocin-Induced Neuroinflammation as a Rat Model of Alzheimer's Disease.

Individual differences in responsiveness to environmental factors, including stress reactivity and anxiety levels, which differ between high (HR) and low (LR) responders to novelty, might be risk factors for development of memory and anxiety disorders in sporadic Alzheimer's disease (sAD). In the present study, we investigated whether behavioral characteristics of the HR and LR rats, influence the progression of sAD (neuroinflammation, β-amyloid peptide, behavioral activity related to memory (Morris water maze) and anxiety (elevated plus maze, white and illuminated open field test) in streptozotocin (STZ)-induced neuroinflammation as a model of early pathophysiological alterations in sAD. Early (45 days) in disease progression, there was a more severe impairment of reference memory and higher levels of anxiety in HRs compared with LRs. Behavioral depression in HRs was associated with higher expression of β-amyloid deposits, particularly in the NAcS, and activation of microglia (CD68+ cells) in the hypothalamus, as opposed to less inflammation in the hippocampus, particularly in CA1, compared with LRs in late (90 days) sAD progression. Our findings suggest that rats with higher behavioral activity and increased responsivity to stressors show more rapid progression of disease and anxiety disorders compared with low responders to novelty in the STZ-induced sAD model.

Memory impairment after one year of the acute episode of Covid-19 infection

Abstract Introduction Memory impairment is one of the most frequently reported sequelae of COVID-19 infection. The aim of our study was to estimate the risk of memory disorders one year after the acute episode of COVID-19 infection in the Tunisian population of Monastir. Methods This is a cohort study conducted in Monastir University Hospital. The study included two groups: Exposed subjects were randomly selected among those with a positive diagnosis of COVID-19 between September 2021 and January 2022. The non exposed group was selectd among subjects with a negative COVID-19 diagnosis during the same period and who had no COVID infection during the following year. The Mac Nair scale was used to assess memory impairment after one year of follow up. Results Our study included 140 subjects diagnosed with Covid-19 and 139 subjects who had never been in contact with this virus. The incidence rate of memory impairment at one year post-Covid-19 infection was 17.9% (IC95% [11.5 - 24.2%]), whereas in the non exposed group it was 9.4% (IC95% [4.45% -14.5%]). Multivariate analysis revealed that the group exposed to Covid-19 had a significantly higher Mac-Nair Total score after one year of the acute episode of infection compared with the non exposed group (exp β = 1.25, IC95% [1.10; 1.42]). The other main predictors of memory impairment in the study population were age (exp β = 1.006, IC95% [1.001; 1.01]), diabetes (exp β = 1.67, IC95% [1.44; 1.95]), history of anxiety and depression ((exp β = 1.71, IC95% [1.35; 2.17]) and obesity (exp β = 1.25, IC95% [1.10; 1.42]), whereas vaccination with two or more doses prior to COVID-19 infection (exp β = 0.84, IC95% [0.74; 0.96]) and male gender (exp β = 0.65, IC95% [ 0.57; 0.73]) were found to be protective against these disorders. Conclusions Our study allowed us to estimate the risk of long-term memory disorders following Covid-19 infection. This could help better guide preventive measures to reduce the incidence of these disorders. Key messages • The incidence rate of memory impairment at one year post-Covid-19 infection was 17.9%. • The main other predictors of memory impairment were age, female gender, diabetes, history of anxiety and depression and obesity whereas vaccination prior to COVID-19 infection was a protective factor.

The Digitized Memory Clinic.

Several major challenges, including an ageing population and declining workforce and the implementation of recent breakthrough therapies for Alzheimer disease, are prompting a necessary rethink of how people with neurodegenerative dementias are diagnosed and medically managed. Digital health technologies could play a pivotal part in this transformation, with new advances enabling the collection of millions of data points from a single individual. Possible applications include unobtrusive monitoring that aids early detection of disease and artificial intelligence-based health advice. To translate these advances to meaningful benefits for people living with a disease, technologies must be implemented within a system that retains the physician expert as a central figure in decision-making. This Perspective presents a new framework, termed the Digitized Memory Clinic, for the diagnostic pathway of neurodegenerative dementias that incorporates digital health technologies with currently available assessment tools, such as fluid and imaging biomarkers, in an interplay with the physician. The Digitized Memory Clinic will manage people across the entire disease spectrum, from the detection of risk factors for cognitive decline and the earliest symptoms to dementia, and will replace the present paradigm of a pure 'brick-and-mortar' memory clinic. Important ethical, legal and societal barriers associated with the implementation of digital health technologies in memory clinics need to be addressed. The envisioned Digitized Memory Clinic aims to improve diagnostics and enable precise disease-tracking prognostication for individuals with memory disorders and to open new possibilities, such as precision medicine for prevention and treatment.

Alzheimer's disease and other memory disorders in the age of AI: reflection and perspectives on the 120th anniversary of the birth of Dr. John von Neumann.

Two themes are coming to the forefront in this decade: Cognitive impairment of an aging population and the quantum leap in developing artificial intelligence (AI). Both can be described as growing exponentially and presenting serious challenges. Although many questions have been addressed about the dangers of AI, we want to go beyond the fearful aspects of this topic and focus on the possible contribution of AI to solve the problem of chronic disorders of the elderly leading to cognitive impairment, like Alzheimer's disease, Parkinson's disease, and Lewy body dementia. Our second goal is to look at the ways in which modern neuroscience can influence the future design of computers and the development of AI. We wish to honor the memory of Dr. John von Neumann, who came up with many breakthrough details of the first electronic computer. Remarkably, Dr. von Neumann dedicated his last book to the comparison of the human brain and the computer as it stood in those years of the mid-1950s. We will point out how his ideas are more relevant than ever in the age of supercomputers, AI and brain implants.

Low Cardiac Output And Brain Function In The Prognosis Of Adult Patients With Heart Failure

Objective: Synthesize the best evidence from the literature describing the relationship between low expenditure and brain function in the prognosis of adult patients with heart failure. Methods: Descriptive integrative review, which performed a search in limited databases from 2009 to 2019, using MeSH and DeCS terms, such as Heart Failure, cardiac output, cognitive dysfunction, memory disorders in the analysis of 20 articles found. Results: It was identified that there is evidence that patients with heart failure suffer from prevalent mental disorders associated with numerous processes, including attention and learning deficits, decreased psychomotor speed, memory dysfunction, difficulties in solving problems and decreased executive function which worsens the prognosis because it is associated with poor adherence to treatment and lower quality of life Conclusion: In heart failure, cognitive resources decrease and cognitive demands increase, therefore, nursing must establish strategies for promotion and prevention, timely detection that comprehensively address the patient, aiming to improve self-care, in order to control medication, therapeutic regimens. and dietary, to ensure adherence to treatment and thus improve the quality of life of the patient and his family.

Memory-enhancing activity of verapamil in murine models of stress

Purpose: To evaluate the benefit of verapamil on stress-induced memory impairment in mice. Methods: Forty-eight (48) mice were used in this study. They were divided into two equal groups based on the two models of stress used in this study (sleep deprivation and hypoxia). Each model was further divided into 4 groups of six animals each. The mice in the sleep deprivation model were suspended on a platform above water while in the hypoxic model, mice were locked in an airless container for 20 min daily throughout the experiment. As for the intervention, 25 and 50 mg/kg verapamil were preadministered via the oral route to study groups, except the normal control group and negative control group in both models. After seven-day stress and intervention, the mice were subjected to behavioural tests (Y-maze and object recognition tests), biochemical assays (for acetylcholinesterase activity) and histochemical analysis. Results: Stress caused a significant (p < 0.05) impairment in the consolidation and retrieval of working and recognition memories. Also, acetylcholinesterase activity was significantly (p < 0.05) enhanced in the stressed groups when compared to control groups. Similarly, the histological analysis revealed a significant decline in population (p < 0.05), distribution and density of viable neurons in specific areas of the hippocampus and prefrontal cortex. These alterations were significantly (p < 0.05) attenuated in verapamil-treated groups almost in a dose-dependent pattern. Conclusion: Verapamil displays significant memory-enhancing effects in two (2) murine models of stress. Antihypertensives should therefore be considered a viable prospect in the management of stress-related memory disorders after additional studies have been done to establish the mechanisms of action.

Exploring the septum pellucidum: Short review of anatomical insights and the clinical impact of septum pellucidum and cavum septi pellucidi

BackgroundThe septum pellucidum (SP) is a thin, triangular, and delicate structure in the brain. It consists of two layers of white and gray matter and topographically is located between the lateral ventricles. The SP is part of the limbic system, which involves emotions, behavior, and memory. AimThis concise review provides an overview of the anatomy, development, and clinical significance of the SP, with a specific focus on cavum septi pellucidi (CSP). It also discusses its implications for brain function and its potential link to neurological disorders. ConclusionsAs an essential structure within the limbic system, the SP and its associated variations, like CSP, offer valuable insights into brain development and function, particularly concerning emotions, memory, and psychiatric disorders. Understanding the role of the septum pellucidum and its developmental anomalies may shed light on various neuropsychiatric conditions and help guide future research and clinical practices.

Proinflammatory factors inhibition and fish oil treatment: A promising therapy for neonatal seizures

Brain injury is one of the most important causes of infant mortality and chronic neurological disabilities. Hypoxia is an acute brain injury which led to various cognitive, behavioral, and memory disorders throughout life. Previous studies reported neuroprotective possibilities for fish oil (FO) in brain-injured situations. In this study, we evaluated the effect of the FO diet during the lactation period on seizure activity, behavioral performance, histomorphometry, and inflammatory changes in the brains of hypoxia rats. Male Wistar rats were randomly divided in to 4 groups: Sham (intact rats), hypoxia, FO and FO+hypoxia groups. Hypoxia was induced by keeping neonate rats at PND12 in a hypoxic chamber (7 % oxygen and 93 % nitrogen intensity) for 15 minutes. In the FO groups, rats received oral FO (1 ml/day) for 12 days during the lactation period. Seizure activity was assessed by measuring the number of tonic-clonic seizures and seizure thresholds. Novel object recognition tests (NORT), rotarod, and open field tests were used to measure behavioral performances. A Histological study was performed to evaluate histomorphometric changes in the hippocampus and cerebellum. The gene expression of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) was measured using RT-PCR. Findings showed that the number of tonic-clonic seizures, atrophy, and cell death in the hippocampus and cerebellum, the gene expression of TNF-α and IL-1β in the hippocampus, and behavioral disorders were significantly increased in the hypoxia rats compared to the sham group. Administration of FO in the hypoxia groups significantly decreased the gene expression of TNF-α and IL-1β, the number of tonic-clonic seizures, and neuronal cell death in the hippocampus and cerebellum compared to the hypoxia groups. Furthermore, it can improve behavioral tasks and cognitions.

Ameliorating Effect of S-Allyl Cysteine (Black Garlic) on 6-OHDA Mediated Neurotoxicity in SH-SY5Y Cell Line

Therapeutic approaches based on isolated compounds derived from natural products are more common in preventing diseases involving inflammation and oxidative stress at present. S-allyl cysteine (SAC) is a promising garlic-derived organosulfur compound with many positive effects in cell models and living systems. SAC has biological activity in various fields, enclosing healing in learning and memory disorders, neurotrophic effects, and antioxidant activity. In this study, we purposed to identify the neuroprotective activity of SAC toward 6-OHDA-induced cell demise in the SH-SY5Ycell line. For this purpose, 6-OHDA-induced cytotoxicity, and biochemical, and gene expression changes were evaluated in SH-SY5Y cells. SH-SY5Y cells grown in cell culture were treated with SAC 24hours before and after 6-OHDA application. Then, cell viability, antioxidant parameters, and gene expressions were measured. Finally, immunofluorescence staining analysis was performed. Our results showed that SAC increased cell viability by 144% at 80µg/mL with pre-incubation (2hours). It was observed that antioxidant levels were significantly increased and oxidative stress marker levels were decreased in cells exposed to 6-OHDA after pre-treatment with SAC (p<0.05). SAC supplementation also suppressed the increase in pro-inflammation levels (TNF-α/IL1/IL8) caused by 6-OHDA (p < 0.05). While 8-OHdG and Nop10 expressions were observed at a mild level in SAC pretreatment depending on the dose, 8-OHdG, and Nop10 expressions were observed at a moderate level in SAC treatment after 6-OHDA application (p<0.05). Our findings demonstrate the positive effect of pretreatment with SAC on SH-SY5Y cells injured by 6-OHDA, suggesting that SAC may be beneficial for neuroprotection in regulating oxidative stress and neuronal survival in an in vitro model of Parkinson's disease.

Cognitive outcomes and psychological symptoms in an Italian cohort with post-acute COVID-19 condition (PACC)

BackgroundWe aim to investigate the proportion of patients (pts) with long-term cognitive outcomes (CO) of PACC and identify associated features. MethodsWe assessed participants through a neuropsychological assessment. The chi-square test was used for comparisons according with time of NPA (within or beyond 6 months since COVID19) and with previously hospitalization status (hospitalized patients, PH; not hospitalized patients, nPH). Results520 participants: mean age 54 years (SD 12), 53 % female, 14 years of education (SD 3.4), 35 % with >1 comorbidity, 48 % previously hospitalized. Overall, we found CO in 89 % of pts, in particular 88 % evaluated in w6M and 89 % in b6M (p = 0.801) while 90 % and 87 % in nPH and PH, respectively (p = 0.239). By fitting multivariable analysis, PH for COVID19 and female gender were associated with an increased risk of an altered PSQI [Odd Ratio, OR 2.48, 95 % CI 1.54 to 3.99, p < 0.001 and OR 2.59, 95 % CI 1.60 to 4.17, p < 0.001, respectively) and BAI [F vs M: OR 1.67, 95 % CI 1.16 to 2.40, p = 0.005). ConclusionsWe show a substantial proportion of PACC-CO; hospitalization leads to impaired memory, anxiety and sleep disorders. Women seem to be at higher risk for anxious-depressive symptoms and worse sleep quality than men.

Joint administration of sub-threshold doses of the acetylcholinesterase inhibitor donepezil with those of the NMDA receptor antagonist ketamine improved rats’ recognition memory abilities

Alzheimer’s Disease (AD) is a serious progressive neurodegenerative illness conducting to the decay of cognitive functions. A few drugs have been approved for the therapy of AD, including the acetylcholinesterase inhibitors (AChEIs) like donepezil. Their efficiency, however, is modest and their application is associated with toxicity. Recently, the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine, a rapidly acting antidepressant, has been proposed as a potential agent for the treatment of AD. The present study was designed to investigate the effects exerted by the combination of sub-threshold doses of donepezil with those of ketamine on rats’ recognition memory abilities. For these experiments, the object recognition task (ORT) and the object location task (OLT), two procedures assessing non-spatial and spatial recognition memory respectively in rodents were used. Post-training acute administration of inactive doses of donepezil (0.3 mg/kg) and ketamine (1 mg/kg) counteracted non-spatial and spatial recognition memory impairments. The present findings, although preliminary, propose that the combined administration of ketamine and donepezil could represent a new strategy for the therapy of memory disorders, a common feature of AD patients.

Suspected Pseudobulbar Affect in Neurodegenerative Disease.

To investigate the association between suspected pseudobulbar affect (PBA), clinical diagnosis, cognitive testing, and self-reported mood in older adults presenting for evaluation of dementia. Patients presenting to an outpatient memory disorders clinic (N=311). We used traditional and novel network modeling approaches to examine associations between neuropsychological (NP) tests, patient and clinician rating scales, and the Center for Neurological Study-Lability Scale (CNS-LS) among patients with suspected AD (n=133) and other neurocognitive diagnosis (n=178). We then examined differences in test performance between patients with and without suspected PBA (CNS-LS cut-off of ≥ 13), while accounting for demographic and psychiatric covariates with propensity score matching. Group differences were assessed with Bayesian models. Prevalence of suspected PBA in AD was slightly less than half (44.4%) and at a similar rate in other dementias (e.g., 46.9% in CVD and 45.5% in LBD). In network models, the CNS-LS was associated with higher anxiety and better word list recall. After accounting for covariates, AD patients with suspected PBA performed better on word list recall βM=0.40, 95% CI [0.15, 0.66], and committed fewer false positive errors on recognition βM=-1.51, 95% CI [-2.34, -0.59] than AD patients without suspected PBA. There were no differences in patients with any other diagnostic impression, nor group differences on other NP measures. Patients with suspected PBA and AD diagnosis had better memory recall and recognition than those without suspected PBA, suggesting that impaired emotional regulation may be an early sign of AD in patients with less prominent memory decline. Better understanding PBA in neurodegenerative diseases, including prevalence and comorbidity with psychiatric conditions, could help with early identification, education, and initiation of treatment.