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Community-dwelling people with Mild Cognitive Impairment self-reporting not to be meeting recommended physical activity levels participated in this study to (a) determine compliance of wearing (thigh-worn) accelerometers, (b) describe physical activity levels and sedentary behavior, and (c) determine the validity of the Physical Activity Scale for the Elderly (PASE) compared with activPAL accelerometers. A total of 79 people had valid accelerometer data (median [interquartile range]: age, 71 [54–75] years). Compliance was 86.81%. Participants were sedentary for 10.6 hr per day and engaged in a median of 9 min per day of moderate-intensity physical activity. Fair correlations were found between the PASE and total stepping time per day (r =.35, p <.01), total number of steps per day (r =.36, p <.01), and number of steps in stepping activities completed for ≤1 min (r =.42, p <.01). The PASE and Standing time (r =.04, p =.724) and PASE and Sitting time (r =.04, p =.699) had little to no relationship. The use of thigh-worn accelerometers for this population is achievable. People with Mild Cognitive Impairment have high levels of sedentary behavior and minimal engagement in moderate-intensity physical activity. The PASE has fair, positive criterion validity with activity-based outcomes measured by activPAL accelerometers but not with sedentary behavior, which is high for this population. [ABSTRACT FROM AUTHOR]

As rates of obesity continue to rise, so does the impact of obesity on cognitive function. Engaging in physical activity is one pathway through which individuals can help maintain cognitive function. This study examined whether any link between exercise and cognitive function was associated with weight characteristics. Data from 6,012 participants in the Health and Retirement Study were used. The association between participation in light or moderate physical activity and better cognitive function was particularly strong for overweight or obese adults and less so for those who were normal weight. Overall, the findings suggested that while being physically active is associated with better cognitive function regardless of weight, the associations were stronger for individuals who were overweight/obese compared with those who were normal weight. Given the results were particularly pronounced for waist circumference (relative to body mass index), further research should be conducted to examine if individuals with greater abdominal adiposity may benefit most from staying active in terms of their cognitive function. [ABSTRACT FROM AUTHOR]

Context: A healthy, 22-year-old, male NCAA Division I baseball shortstop was experiencing confusion, chest pain, and tightness during an off-season intersquad scrimmage. The patient did not have any significant medical history or mechanism of head injury. After initial evaluation from the athletic trainer, the patient's cognitive status began to quickly decline. The emergency action plan was put in place rapidly and referred the patient to the local emergency clinic. Case Presentation: Upon arrival at the emergency department, an electrocardiogram was performed to rule out myocardial infarction or stroke. The first electrocardiogram results returned negative for any cardiac pathology, but a stroke alert was called. The patient was then transported to a level II trauma center due to continual cognitive decline. The patient was diagnosed with transient ischemic attack (TIA) secondary to an undiagnosed patent foramen ovale (PFO) that would later be diagnosed with further evaluation 2 months after the initial TIA incident. After multiple diagnostic and laboratory tests, the PFO went undetected until a 2D echocardiogram was performed and evaluated by a cardiologist. Management and Outcomes: After the confirmation of the congenital defect, surgical intervention was performed to correct the PFO using catheterization. Despite multiple preparticipation examinations, electrocardiograms, and examination of past family history, the PFO went undetected until the patient experienced symptoms of TIA. The discovery of PFO in this 22-year-old athletic individual is unusual because traditional screening techniques (electrocardiogram and preparticipation examinations) failed to detect the congenital defect. Conclusions: Due to the emergent and timely actions of the athletic trainer, the patient has made a full recovery and is able to compete fully in athletic events. This case study amplifies the need for athletic trainers at all sporting events, updated and reviewed emergency action plans, rapid recognition of TIA in athletic individuals, and return-to-play protocol for an athletic individual after TIA. [ABSTRACT FROM AUTHOR]

The Timed Up-and-Go (TUG) test has been combined with different verbal/cognitive tasks (i.e., TUG dual task [TUGdt]) as a form of motor-cognitive testing. However, it is still unclear how different TUGdt conditions affect gait among older adults. Thirty community-dwelling older adults, with mean age of 73 years, participated in the study. Data were collected using marker-free video recordings. Gait parameters were extracted using a semiautomatic deep learning system. Comparisons of execution time and gait parameter outcomes were made under TUG and three types of TUGdt test conditions: TUGdt-naming animals, TUGdt-months backwards, and TUGdt-serial 7s. Statistical analyses were based on mean values of the gait parameters for each participant and TUG condition, including TUGdt gait cost, that is, the relative difference between TUGdt and TUG. All the investigated TUGdt conditions resulted in varying degrees of gait parameter changes. Under TUGdt conditions, participants took shorter and slower steps, with TUGdt-serial 7s causing the largest interference. [ABSTRACT FROM AUTHOR]

Emerging evidence suggests muscarinic acetylcholine receptors represent novel targets to treat alcohol use disorder. In this review, we draw from literature across medicinal chemistry, molecular biology, addiction and learning/cognition fields to interrogate the proposition for muscarinic receptor ligands in treating various aspects of alcohol use disorder, including cognitive dysfunction, motivation to consume alcohol and relapse. In support of this proposition, we describe cholinergic dysfunction in the pathophysiology of alcohol use disorder at a network level, including alcohol‐induced adaptations present in both human post‐mortem brains and reverse‐translated rodent models. Preclinical behavioural pharmacology implicates specific muscarinic receptors, in particular, M4 and M5 receptors, as potential therapeutic targets worthy of further interrogation. We detail how these receptors can be selectively targeted in vivo by the use of subtype‐selective allosteric modulators, a strategy that overcomes the issue of targeting a highly conserved orthosteric site bound by acetylcholine. Finally, we highlight the intense pharma interest in allosteric modulators of muscarinic receptors for other indications that provide an opportunity for repurposing into the alcohol use disorder space and provide some currently unanswered questions as a roadmap for future investigation. [ABSTRACT FROM AUTHOR]

Aging-related cognitive impairment, mainly Alzheimer's disease (AD), has been widely studied. However, effective prevention and treatment methods are still lacking. In recent years, researchers have observed beneficial effects of plant-based supplements, such as flavonoids, on cognitive protection. This provides a new clue for the prevention of cognitive dysfunction. Studies have shown that dietary flavonoids have neuroprotective effects, but the mechanism is not clear. In this review, we systematically reviewed the research progress on the effects of dietary flavonoids on gut microbes and their metabolites, and concluded that flavonoids could improve cognitive function through the gut-brain axis. Flavonoids can be absorbed through the intestine, cross the blood-brain barrier, and enter the brain tissue. Flavonoids can inhibit the expression and secretion of inflammatory factors in brain tissue, reduce the damage caused by oxidative stress, clear neural damage proteins and inhibit neuronal apoptosis, thereby ameliorating age-related cognitive disorders. Future work will continue to explore the gut-brain axis and target genes regulated by flavonoids. In addition, clinical research and its mechanisms need to be further explored to provide solutions or advise for patients with cognitive impairment. [ABSTRACT FROM AUTHOR]

Interrogative suggestibility has been suggested to grow in situations of isolation. The current study aimed to test this assumption for the first time in an experimental approach. We hypothesized that ostracism increases suggestibility, and assumed this relationship to be mediated by cognitive impairments or social uncertainty. To test these hypotheses, we conducted two studies. We manipulated the state of ostracism (vs. inclusion) using the O-Cam (Study 1) and Cyberball paradigm (Study 2), and measured suggestibility using the Gudjonsson Suggestibility Scale. Results revealed an indirect link between inclusionary status and suggestibility. More precisely, there was no direct relationship between ostracism and suggestibility. However, ostracism induced weaker cognitive performances and this translated to increased suggestibility. Social uncertainty, on the other hand, did not serve as effective mediator. These findings indicate that each situation that is accompanied by (temporary) cognitive impairments, as is ostracism, might have the power to raise interrogative suggestibility. [ABSTRACT FROM AUTHOR]

Objectives: Late-onset rheumatoid arthritis (LORA), which has been increasing in recent years, lacks evidence for initial treatment. Japanese rheumatology experts recognized this gap and addressed it by developing consensus statements on the first clinical application of LORA. Methods: These statements were created following an introductory discussion about treatment fundamentals, which included a review of existing literature and cohort data. The steering committee created a draft, which was refined using a modified Delphi method that involved panel members reaching a consensus. The panel made decisions based on input from geriatric experts, clinical epidemiologists, guideline developers, patient groups, and the LORA Research Subcommittee of the Japan College of Rheumatology. Results: The consensus identified four established facts, three basic approaches, and six expert opinions for managing LORA. Methotrexate was recommended as the primary treatment, with molecular-targeted agents being considered if treatment goals cannot be achieved. An emphasis was placed on assessing the lives of older patients due to challenges in risk management and methotrexate accessibility caused by comorbidities or cognitive decline. Conclusions: The experts substantiated and refined 13 statements for the initial treatment of LORA. To validate these claims, the next is to conduct a registry study focusing on new LORA cases. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) and Down syndrome (DS) share a common therapeutic target, the dual-specificity, tyrosine phosphorylation activated kinase 1A (DYRK1A). Abnormally active DYRK1A is responsible for cognitive disorders (memory, learning, spatial localization) observed in both conditions. In DS, DYRK1A is overexpressed due to the presence of the DYRK1A gene on chromosome 21. In AD, calcium-activated calpains cleave full-length DYRK1A (FL-DYRK1A) into a more stable and more active, low molecular weight, kinase (LMW-DYRK1A). Genetic and pharmacological experiments carried out with animal models of AD and DS strongly support the idea that pharmacological inhibitors of DYRK1A might be able to correct memory/learning disorders in people with AD and DS. Starting from a marine sponge natural product, Leucettamine B, Perha Pharmaceuticals has optimized, through classical medicinal chemistry, and extensively characterized a small molecule drug candidate, Leucettinib-21. Regulatory preclinical safety studies in rats and minipigs have been completed and formulation of Leucettinib-21 has been optimized as immediate-release tablets. Leucettinib-21 is now undergoing a phase 1 clinical trial (120 participants, including 12 adults with DS and 12 patients with AD). The therapeutic potential of DYRK1A inhibitors in AD and DS is presented. [ABSTRACT FROM AUTHOR]

Extracts made from plants are complex mixtures of substances with varying compositions depending on the plant material and method of manufacture. This complexity makes it difficult for scientists and clinicians to interpret findings from pharmacological and clinical research. We performed a narrative review summarizing information on ginkgo biloba leaf extract, its composition, pharmacological data and clinical evidence supporting its administration for the treatment of Alzheimer's disease (AD). Medicinal products containing ginkgo biloba leaf extract which are manufactured in compliance with the requirements of the European Pharmacopoeia are approved as medicinal products for the treatment of dementia and related conditions by drug regulatory agencies in Europe, Asia and South America. As multicomponent mixtures, they may affect various targets in the pathogenesis of AD, the most common form of dementia. Pharmacodynamic studies demonstrate the effects of EGb 761 and individual constituents on various pathophysiological features of experimentally induced cognitive impairment and neurodegeneration that could contribute to its clinical efficacy. The safety and efficacy in the treatment of AD and cognitive decline has been studied in randomized, placebo-controlled clinical trials. Most of the studies that investigate the effects of ginkgo biloba extract (GbE) used the special extract EGb 761, which makes it the best-researched plant preparation worldwide. It is therefore the only herbal alternative to standard-of-care anti-dementia drugs. However, the mechanism of action has not been fully elucidated yet, and the clinical studies in AD show heterogeneity. [ABSTRACT FROM AUTHOR]

Background: Older adults with dementia who are on polypharmacy are more vulnerable to the use of potentially inappropriate medications (PIM), which can significantly increase the risk of adverse events and drug-related problems (DRPs). Objective: This systematic review and meta-analysis were conducted to map the prevalence of PIM use, polypharmacy, and hyper-polypharmacy among older adults with cognitive impairment or dementia attending memory clinics. Methods: Ovid MEDLINE, Ovid EMBASE, Scopus, Cochrane Library, EBSCOhost CINAHL, and Ovid International Pharmaceutical Abstracts (IPA) were systematically searched from inception to April 22, 2024. Observational studies assessing the PIMs use among older adults with CI or dementia were screened. A random- effects meta-analysis was conducted to pool the prevalence estimates. Results: Of 5,787 identified citations, 11 studies including 4,571 participants from 8 countries were included. Among all the included studies the pooled prevalence of PIM use was 38% (95% confidence interval (CIn): 27– 50%), highlighting a notable range from 20% to 78%. The analysis identified anticholinergics, benzodiazepines, and non-benzodiazepine sedatives as the most common PIMs. Subgroup analysis revealed a higher pooled prevalence of PIM in the USA (39%; 95% CIn: 10– 78, I2 (%) = 98, 3 studies) and Australia (36%, 95% CIn: 12– 70, I2 (%) = 96, 2 Studies). Additionally, pooled prevalence of polypharmacy and hyper-polypharmacy was reported as (60%; 95% CIn: 46– 73, I2 (%) = 95, 3 studies), and (The prevalence of hyper-polypharmacy was 17.6%; 1 study) respectively. Conclusions: The definition of PIMs significantly impacts study results, often more than geographical variations. The variability in criteria and tools like the Beers or Screening Tool of Older Persons' Prescriptions (STOPP) criteria across studies and regions leads to differing prevalence rates. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is the most common neurodegenerative disorder which primarily involves memory and cognitive functions. It is increasingly recognized that motor involvement is also a common and significant aspect of AD, contributing to functional decline and profoundly impacting quality of life. Motor impairment, either at early or later stages of cognitive disorders, can be considered as a proxy measure of cognitive impairment, and technological devices can provide objective measures for both diagnosis and prognosis purposes. However, compared to other neurodegenerative disorders, the use of technological tools in neurocognitive disorders, including AD, is still in its infancy. Objective: This report aims to evaluate the role of technological devices in assessing motor involvement across the AD spectrum and in other dementing conditions, providing an overview of the existing devices that show promise in this area and exploring their clinical applications. Methods: The evaluation involves a review of the existing literature in the PubMed, Web of Science, Scopus, and Cochrane databases on the effectiveness of these technologies. 21 studies were identified and categorized as: wearable inertial sensors/IMU, console/kinect, gait analysis, tapping device, tablet/mobile, and computer. Results: We found several parameters, such as speed and stride length, that appear promising for detecting abnormal motor function in MCI or dementia. In addition, some studies have found correlations between these motor aspects and cognitive state. Conclusions: Clinical application of technological tools to assess motor function in people with cognitive impairments of a neurodegenerative nature, such as AD, may improve early detection and stratification of patients. [ABSTRACT FROM AUTHOR]

Background: Semantic intrusion errors (SIEs) are both sensitive and specific to PET amyloid-β (Aβ) burden in older adults with amnestic mild cognitive impairment (aMCI). Objective: Plasma Aβ biomarkers including the Aβ42/40 ratio using mass spectrometry are expected to become increasingly valuable in clinical settings. Plasma biomarkers are more clinically informative if linked to cognitive deficits that are salient to Alzheimer's disease (AD). Methods: This study included 119 older adults enrolled in the 1Florida Alzheimer's Disease Research Center (ADRC), 45 aMCI participants scored below the established Aβ42/40 ratio cut-off of 0.160 using the Quest AD-Detect™ assay indicating Aβ positivity (Aβ+), while 50 aMCI participants scored above this cut-off indicating Aβ negative status (Aβ–). Additionally, 24 cognitively unimpaired (CU) persons scored above the cut-off of 0.160 (Aβ–). Results: The aMCI plasma Aβ+ group evidenced the greatest percentage of SIEs, followed by the aMCI Aβ–. The CU Aβ– group exhibited the lowest percentage of SIEs. After adjustment for global cognitive impairment, aMCI plasma Aβ+ continued to demonstrate greater SIEs on tests tapping the failure to recover from proactive semantic interference (frPSI) as compared to the aMCI Aβ–group. Using pre-established cut-offs for frPSI impairment, 8.3% of CU Aβ– participants evidenced deficits, compared to 37.8% of aMCI Aβ–, and 74.0% of aMCI Aβ+. Conclusions: SIEs reflecting frPSI were associated with aMCI Aβ+ status based on the Aβ42/40 ratio. Results suggest the importance of SIEs as salient cognitive markers that map onto underlying AD pathology in the blood. [ABSTRACT FROM AUTHOR]

Objective: Cognitive impairment in Parkinson's disease (PD) can show a very heterogeneous trajectory among patients. Here, we explored the mechanisms involved in the expression and prediction of different cognitive phenotypes over 4 years. Methods: In 2 independent cohorts (total n = 475), we performed a cluster analysis to identify trajectories of cognitive progression. Baseline and longitudinal level II neuropsychological assessments were conducted, and baseline structural magnetic resonance imaging, resting electroencephalogram and neurofilament light chain plasma quantification were carried out. Linear mixed‐effects models were used to study longitudinal changes. Risk of mild cognitive impairment and dementia were estimated using multivariable hazard regression. Spectral power density from the electroencephalogram at baseline and source localization were computed. Results: Two cognitive trajectories were identified. Cluster 1 presented stability (PD‐Stable) over time, whereas cluster 2 showed progressive cognitive decline (PD‐Progressors). The PD‐Progressors group showed an increased risk for evolving to PD mild cognitive impairment (HR 2.09; 95% CI 1.11–3.95) and a marked risk for dementia (HR 4.87; 95% CI 1.34–17.76), associated with progressive worsening in posterior‐cortical‐dependent cognitive processes. Both clusters showed equivalent clinical and sociodemographic characteristics, structural magnetic resonance imaging, and neurofilament light chain levels at baseline. Conversely, the PD‐Progressors group showed a fronto‐temporo‐occipital and parietal slow‐wave power density increase, that was in turn related to worsening at 2 and 4 years of follow‐up in different cognitive measures. Interpretation: In the absence of differences in baseline cognitive function and typical markers of neurodegeneration, the further development of an aggressive cognitive decline in PD is associated with increased slow‐wave power density and with a different profile of worsening in several posterior‐cortical‐dependent tasks. ANN NEUROL 2024;96:981–993 [ABSTRACT FROM AUTHOR]

Memory impairment is one of the main characteristics of postoperative cognitive dysfunction. It remains elusive how postoperative pathological changes of the brain link to the memory impairment. The clinical setting of perioperation was mimicked via partial hepatectomy under sevoflurane anaesthesia together with preoperative restraint stress (Hep‐Sev‐stress) in mice. Memory changes were assessed with fear conditioning. The medial prefrontal cortex (mPFC)‐dorsal hippocampus connectivity was evaluated with injecting neurotracer 28 days before surgery. Astrocytic activation was limited via injecting AAV‐GFAP‐hM4Di‐eGFP into the mPFC. Astrocytic and microglial phagocytosis of synapses were visualised with co‐labelling hippocampal neuronal axon terminals with PSD‐95 and S100β or Iba1. Neuroinflammation and oxidative stress status were also detected. Hep‐Sev‐stress impaired the memory consolidation (mean [standard error], 49.91 [2.55]% vs. 35.40 [3.97]% in the contextual memory, p = 0.007; 40.72 [2.78]% vs. 27.77 [2.22]% in cued memory, p = 0.002) and the cued memory retrieval (39.00 [3.08]% vs. 24.11 [2.06]%, p = 0.001) in mice when compared with these in the naïve controls. Hep‐Sev‐stress damaged the connectivity from the dorsal hippocampus to mPFC but not from the mPFC to the dorsal hippocampus and increased the astrocytic but not microglial phagocytosis of hippocampal neuronal axon terminals in the mPFC. The intervention also induced neuroinflammation and oxidative stress in the dorsal hippocampus and the mPFC in a regional‐dependent manner. Limiting astrocyte activation in the mPFC alleviated memory consolidation impairment induced by Hep‐Sev‐stress. Postoperative memory consolidation was impaired due to astrocytic phagocytosis‐induced connectivity injury from the dorsal hippocampus to the medial prefrontal cortex. [ABSTRACT FROM AUTHOR]

Background and Aims: Studies on adolescent alcohol use and cognition are often unable to separate the potential causal effects of alcohol use on cognition from shared etiological influences, including genetic influences or other substance use comorbidities also known to be associated with cognition, such as nicotine use. The present study aimed to fill this gap and clarify the relationship between adolescent alcohol use and young adult cognition by accounting for both measured and unmeasured confounders. Design: A random effects model accounting for nesting in families was used to control for measured confounders. Next, co‐twin comparisons were conducted within the full sample and in monozygotic twin pairs (MZ) to control for unmeasured genetic and environmental confounders shared by co‐twins. Participants/Setting: Participants were 812 individuals (58.6% female, 361 complete pairs, 146 MZ pairs) from the longitudinal FinnTwin12 study in Finland. Measurements Adolescent alcohol use was indexed with measures of frequency of use and intoxication averaged across ages 14 and 17. Cognitive outcomes were measured at average age 22 and included Trail Making Test, California Stroop test, Wechsler Adult Intelligence subtests (Vocabulary, Block Design, Digit Symbol), Digit Span subtest of Wechsler Memory Scale, Mental Rotation Test and Object Location Memory test. Covariates included sex, parental education, general cognitive ability, current alcohol use and nicotine use. Findings Greater frequency of alcohol use and frequency of intoxication across adolescence was associated with decreased vocabulary scores in the co‐twin control [freq: stnd beta = −0.12, 95% confidence interval (CI) = −0.234, −0.013] and MZ only co‐twin control models (freq: stnd beta = −0.305, 95% CI = –0.523, −0.087; intox: stnd beta = −0.301, 95% CI = ‐0.528, −0.074). Conclusions: In Finland, there appears to be little evidence that adolescent alcohol use causes cognitive deficits in young adulthood, except modest evidence for association of higher adolescent alcohol use with lower young adult vocabulary scores. [ABSTRACT FROM AUTHOR]

Background & Objective: Oral stage dysphagia mostly caused by frontal lobe lesions. We investigated the relationship between oral hesitation and cognitive impairment after frontal lobe stroke. Methods: We consecutively collected 946 patients with stroke from January 2016 to December 2020. Among them, 38 patients had only frontal lobe lesions. Video fluoroscopic swallowing study (VFSS) was performed in 5 stages from water to solid food. Patients who progressed to solid food are very rare, so we focused on liquid and soft food. Diagnosis of stroke was limited to cases in which cerebral infarction or haemorrhage had been verified by magnetic resonance imaging (MRI). Cognitive impairment was evaluated by MMSE in patients with frontal lobe lesions. Result: Of the total 946 patients, 35 patients with frontal lobe lesions were enrolled in the study. Of them, 22 were judged to have cognitive impairment. The oral hesitation of the liquid component was analysed, and a conclusion was drawn that the group with cognitive impairment showed significant oral hesitation than the group without cognitive impairment. On the other hand, in the case of soft food, it was found that there was no correlation between cognition and oral hesitation. Conclusion: It was confirmed that oral hesitation during swallowing in patients with frontal lobe stroke had a meaningful relationship with cognition, and oral hesitation during swallowing was significantly higher in liquid swallowing rather than soft food. [ABSTRACT FROM AUTHOR]

Objectives: The feared possible self refers to an imagined version of self that one is afraid of being or becoming. Previous evidence has shown that dysfunctional reasoning (i.e., inferential confusion) is associated with obsessive‐compulsive disorder (OCD) symptoms, which is partially mediated by a feared self. However, the evidence is reliant on non‐clinical samples and a general measure of the feared self. Methods: Using a cross‐sectional design, the current study attempted to replicate and extend this literature in a sample clinically diagnosed with OCD (n = 350) to assess the pathway from inferential confusion to OCD symptoms when feared self is accounted for as a mediator, particularly the individual dimensions of feared self (i.e., corrupted, culpable, and malformed feared selves). Participants completed a structured clinical interview for DSM‐5, as well as measures of inferential confusion (Dysfunctional Reasoning Processes Task), obsessive beliefs, feared self, OCD symptoms, and psychological distress. Results: Inferential confusion directly, and indirectly through the feared corrupted self, affected OCD symptoms, even after adjusting for obsessive beliefs, psychological distress, and comorbidity. However, the feared culpable and malformed selves did not play a role in this pathway. Conclusions: The study underscores that the feared corrupted self links inferential confusion to OCD symptoms, translating to the need to consider both dysfunctional reasoning processes and this specific feared self in clinical settings when treating OCD. Furthermore, the study provides more support for the inference‐based approach (IBA) to OCD. [ABSTRACT FROM AUTHOR]

Depression and delirium are common and serious problems for surgical patients, particularly in high-risk groups such as older adults. Screening for depression in peri-operative settings has gained more focus as clinicians recognize the importance of identifying and addressing barriers to recovery. A meta-analysis of nearly 5 million patients from five continents found that patients with depression are at double the risk of postoperative delirium compared to those without depression. However, the effectiveness of traditional medications for depression in preventing delirium is uncertain. The causal relationship between depression and delirium is complex and may involve multiple factors, making it difficult to determine the exact cause. Despite this, depression can be a predictor of delirium and offers an opportunity for diagnosis and treatment in the peri-operative period to improve patients' quality of life. The peri-operative period is seen as an opportunity to optimize patients' health conditions and implement interventions to improve long-term outcomes. While more research is needed to determine the efficacy and safety of interventions for depression and delirium, the association between the two conditions provides motivation to improve peri-operative care. [Extracted from the article]

The prevalence of dementia is increasing globally, with an estimated 139 million people expected to be living with dementia by 2050. Across numerous countries, substandard care for people with dementia is evident, with quality improvement needed. Recently, a focus on patient-reported experience measures (PREMs) has been utilised in healthcare services as a method of evaluating the care experiences provided and determining areas of improvement. The literature is scarce regarding the feasibility and acceptability of implementing PREMs with people with moderate to advanced dementia. This scoping review aimed to identify PREMs that have been used with vulnerable populations including people with cognitive impairment, mental health concerns, and children, outline dimensions included, and determine adaptions made to the PREMs to improve acceptability of the instruments for vulnerable populations. A database search of Medline was conducted to identify 36 studies including 32 PREMs. The PREMs identified covered a range of dimensions, most frequently care effectiveness, care environment, and patient involvement. The most common adaption to the PREMs was simplification of wording and sentence structure. Several measures conflated patient outcomes and patient satisfaction with patient experience, limiting utility for improving patient experience specifically. While several PREMs have been used with people with dementia, challenges in their implementation and their applicability to specific settings limit their use more broadly. Evidently, there is a need for development of a PREM for people with moderate to advanced dementia that is applicable across healthcare settings and is appropriately adapted for varying cognitive and communicative barriers. [ABSTRACT FROM AUTHOR]

Aim: To clarify the concept of fear of childbirth among pregnant women and to examine its current measure tools. Background: Fear of childbirth is a psychological symptom, prevalent among pregnant women, which negatively impacts women's health and well‐being. It has become an increasingly concerning issue in perinatal mental health. However, due to its poor conceptualization, it presents difficulty in conducting reliable assessments and identifying risk factors. Methods: The Walker and Avant approach to concept analysis guided this review. Six bibliographic databases were systematically searched for published research from their inception date to May 2023. Additional records were identified by manually searching the reference lists of relevant studies. Quantitative and qualitative studies investigating fear of childbirth in pregnant women were included. Results: Three critical attributes have been identified: cognitive impairments, affective disorders and somatic symptoms. Antecedents include perceived a real or anticipated threat of pregnancy or its outcomes, low perceived self‐coping ability and unmet social support needs. Consequences include processing and avoiding behaviours. This study also identified the dimensions of fear of childbirth, including 6 primary categories and 14 subcategories. The content of five scales was analysed and none covered all domains. Conclusions: The current analysis provides healthcare providers with a more comprehensive framework to assess and identify fear of childbirth. Further research is needed to develop a suitable instrument that covers all the attributes and dimensions of this concept and assesses its severity. Impact: This conceptual analysis provides a comprehensive insight into the phenomenon of fear of childbirth. This will help family members, healthcare providers and policymakers to identify the psychological needs of pregnant women and improve the quality of antenatal care. Patient or Public Contribution: Not applicable as no new data were generated. [ABSTRACT FROM AUTHOR]

Aim: The purpose of this study was to estimate the extent to which neurodevelopmental disorders (NDD's) symptoms (motor, sensory, attention and executive function) are associated with aspects of social function among school aged children. Methods: This cross-sectional study included 39 children aged 6–9 years old (71.8% boys) who were referred to child development centers due to motor, sensory, and/or cognitive difficulties. The parents completed NDD's symptoms questionnaires: Developmental Coordination Disorder Questionnaire; Child Sensory Profile-2; Attention Deficit Hyperactive Disorder (ADHD) Rating Scale and the Behavior Rating Inventory of Executive Function. They also completed the Social Skills Improvement System and a social participation measure. Results: Analysis demonstrated low to moderate correlations between social functioning aspects and the majority of NDD's symptoms. Executive functioning was the only predictor of social skills and social participation and accounted for most of the variability of behavioral problems, alongside a small contribution of ADHD symptoms. Conclusion: The findings contribute to the accumulating body of knowledge regarding social abilities of children with NDD's and suggest new information as to the effect of executive functions in this domain. Along with conducting a routine evaluation of social skills among children suspected to have NDD's, executive functions should also be comprehensively evaluated. [ABSTRACT FROM AUTHOR]

The societal hallmark of the Covid‐19 pandemic was a set of mitigation measures such as lockdowns and curfews. The cognitive impact on the public of the resulting spatial, social and temporal constraints is still being investigated. While pandemic time has been extensively studied and mostly described as slowed down and elongated, opposite experimental patterns across national and social contexts leave open an important explanatory gap in order to understand which factor has been causally fundamental in determining the phenomenology of the crisis. In this paper, we use a quantitative questionnaire developed for measuring temporal and social disorientation on a sample of 3306 respondents during an acute phase of restrictions in France. We show that social disorientation greatly contributed to the temporal disruptions experienced during the pandemic. This result reinforces the importance for public authorities to address the compounding effect of feeling isolated during crises. [ABSTRACT FROM AUTHOR]

We assessed whether symptomatic neurocognitive impairment (NCI) and asymptomatic NCI -of which the clinical relevance is debated- affect HIV control and the role of ART adherence in this relationship. Observational study on the relationship between NCI and viral control during the 2 years before and the 2 after the neurocognitive evaluation (NCE) of 322 PLWH on ART. Viral load (VL) was defined as undetectable, very low-level (VLLV), low-level (LLV), or high-level viremia (HLV), and classified overtime as persistent (p; ≥2 consecutive values in the same worst category), viral failure (VF; ≥1 HLV requiring ART changes), or optimal control. Adherence was the proportion of days covered by ART. Frascati criteria were used. Adjusted models were performed for factors associated with viral control. Mediation analyses informed causality in the path from NCI to viral control through adherence. Sensitivity analyses were focused on the year following NCE for only participants with optimal viral control before. Among the participants (53 ± 10 years, CD4 + T-cells 630/µL), 41.6% and 10.8% presented asymptomatic and symptomatic NCI. Over 3,304 VLs, 8.4% and 22.1% of participants had VF and pLLV/pVLLV. Both symptomatic and asymptomatic NCI were independently associated with VF (aRRR = 8.5; aRRR = 4.3) and pVLLV/pLLV (aRRR = 4.3; aRRR = 2.1). Specific cognitive domains showed independent associations with VL categories (models' P < 0.001). Adherence partially mediated these relationships (models' P < 0.001). Sensitivity analysis confirmed these findings. Prevalence and severity of poor viral control increased as the severity of NCI increased, with ART adherence mediating this relationship. The current "asymptomatic" attribution used by Frascati's criteria could overlook clinical risks. [ABSTRACT FROM AUTHOR]

Age-related cognitive decline is a prominent concern in older adults and selenium (Se) deficiency has been found to be associated with cognitive deficits. For the first time, the present study explored the association between Se intake and cognitive performance in older people with/without cognitive impairment using the data from the National Health and Nutrition Examination Survey 2011–2014. Weighted linear regression models were conducted to evaluate the association between dietary Se/total Se intakes and cognitive assessments. A total of 2387 participants were included. The significant positive association between dietary Se/total Se intakes and total scores of cognitive functioning tests existed only in the older people with low cognitive performance (p < 0.001), not in those with normal cognitive performance. In conclusion, Se intake was beneficial for cognitive decline only in the low cognition older people but failed in normal cognition older people. [ABSTRACT FROM AUTHOR]

Introduction: Retinal nerve fiber layer (RNFL) thickness is a promising biomarker of axonal loss and a potential outcome predictor in Multiple Sclerosis (MS). Cognitive impairment (CoI) exhibits a high prevalence in patients with MS (pwMS), even in the early phases of the disease. Our aim was to explore the role of RNFL thickness as a predictor of physical and cognitive disability in pwMS. Methods: All newly diagnosed pwMS referred to the MS centre of the University-Hospital "Policlinico-San Marco" between 2015–2019 were evaluated at baseline and at 3 years. RNFL and ganglion cell layer (GCL) thickness for right (r.e.) and left eyes (l.e.) were measured with Optical Coherence Tomography (OCT). Disability level and cognitive profile were assessed, using the Expanded Disability Status Scale (EDSS) and the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) battery, respectively. Results: We consecutively enrolled 487 pwMS, including 68 (14.0%) with primary progressive MS (PPMS). At baseline, RNFL and GCL were bilaterally thinner in PPMS (r.e. 90.4 ± 12.7; l.e. 90.2 ± 13.5, and r.e. 80.1 ± 11.2; l.e. 80.3 ± 12.6, respectively) compared to relapsing–remitting MS (RRMS) (r.e. 94.6 ± 13.1; l.e. 94.3 ± 14.8, and r.e. 85.1 ± 9.5; l.e. 84.9 ± 9.3, respectively) (p < 0.01). Both groups exhibited reduced RNFL and GCL thickness, worse cognitive performance and higher EDSS scores at 3-years follow-up compared with baseline. RNFL thickness ≤ 88.0 μm was an independent predictor of CoI (OR = 5.32; 95% CI = 1.84–9.12; p = 0.02) and disability worsening (OR = 3.18; 95% CI = 1.21–10.33; p = 0.05). Discussion: RNFL thickness, as a biomarker of neurodegeneration, could be considered a predictive biomarker of cognitive degeneration and physical disability in MS. [ABSTRACT FROM AUTHOR]

Background: Chronic systemic inflammation is linked to cognitive decline pathogenesis. This study investigates the association between systemic inflammation markers and cognitive decline progression in a clinical cohort. Methods: This prospective observational cohort study enrolled 295 participants. Cognitive decline progression was defined by an increase in clinical dementia rating (CDR) scores. The study examines the correlation between systemic inflammation markers, including systemic Inflammation Response Index (SIRI), systemic Immune-Inflammation Index (SII), prognostic Inflammatory and Nutritional Index (PIV), and cognitive impairment progression. Results: The presence of the APOE 4 allele and diabetes mellitus was associated with elevated PIV levels (P < 0.05). Additionally, AD patients had the highest SII levels, indicating increased inflammation compared to individuals with MCI and SCD (P < 0.05). After a mean follow-up of 17 months, 117 patients (51.31%) experienced cognitive decline progression. AD diagnosis, CDR, and SII were significant predictors of cognitive decline progression (All P < 0.05). Conclusion: This study highlights the clinical significance of elevated systemic inflammation markers in identifying individuals at risk of cognitive decline. Addressing inflammation may offer a promising approach to improving cognitive health and mitigating age-related cognitive decline. [ABSTRACT FROM AUTHOR]

Background: Emerging data associated subjective cognitive complaints (SCC) with a heightened risk of future cognitive decline in Parkinson´s Disease (PD). Objective: To determine whether SCC may predict the development of cognitive impairment in PD patients at baseline. Methods: Over 4 years, major aspects of motor and non-motor symptoms were assessed. SCC were evaluated by non-motor symptoms scale domain-5 (NMSS5). The predictor value of SCC in cognitive change was assessed with univariate linear regression analyses, with NMSS5 at baseline as predictor. Change in cognition (ΔMoCA) was calculated by subtracting Montreal Cognitive Assessment Scale (MoCA) scores at baseline from scores obtained at reassessment and employed as the outcome. We replicated these analyses by employing alterations in MoCA subdomains as outcomes. Results: 134 patients were evaluated at baseline, of those 73 PD patients were reassessed four years later. In our study, SCC didn´t act as a predictor for future cognitive decline. However, baseline NMSS5 was associated significantly with variation in attention, naming, and orientation domains. Conclusion: Our findings did not support that SCC in PD patients acts as a predictor of global cognitive decline. However, our findings enhance comprehension of how SCC correlates with performance in distinct cognitive areas, thereby providing better guidance for patients on their current complaints. [ABSTRACT FROM AUTHOR]

The cerebral vasculature plays a significant role in the development of Alzheimer's disease (AD), however, the specific association between them remains unclear. In this paper, based on the benefits of photoacoustic imaging (PAI), including label-free, high-resolution, in vivo imaging of vessels, we investigated the structural changes of cerebral vascular in wild-type (WT) mice and AD mice at different ages, analyzed the characteristics of the vascular in different brain regions, and correlated vascular characteristics with cognitive behaviors. The results showed that vascular density and vascular branching index in the cortical and frontal regions of both WT and AD mice decreased with age. Meanwhile, vascular lacunarity increased with age, and the changes in vascular structure were more pronounced in AD mice. The trend of vascular dysfunction aligns with the worsening cognitive dysfunction as the disease progresses. Here, we utilized in vivo PAI to analyze the changes in vascular structure during the progression of AD, elucidating the spatial and temporal correlation with cognitive impairment, which will provide more intuitive data for the study of the correlation between cerebrovascular and the development of AD. [ABSTRACT FROM AUTHOR]

Motivation has long been considered key to sending adolescents with mental or substance use disorders in the direction of recovery. But how do you motivate an adolescent, to whom motivational approaches may feel like a call to battle — or even worse, an excuse for running away? Lauren Sbarbaro, Ph.D., a psychologist licensed in alcohol and drug treatment who trained at Hazelden, shared some insights with attendees at the Cape Cod Symposium on Addictive Disorders (CCSAD) in Hyannis, Massachusetts in September. [ABSTRACT FROM AUTHOR]

Prolactin (PRL) assumes a pivotal role during the postpartum phase, particularly within the hippocampus—a region densely populated with receptors for stress hormones, where stress significantly inhibits adult hippocampal neurogenesis (AHN). The reduction in neurogenesis is implicated in the pathogenesis of anxiety and depression. Mothers are at an increased risk of developing depression when exposed to chronic stress. Therefore, it is imperative to investigate the potential role of PRL in depression-like behaviors stemming from prolonged postpartum stress, and to explore any underlying mechanisms. Despite pup separation (PS) being a natural postpartum care practice, the impact of various PS methods on lactating dams remains uncertain. Lactating C57BL/6J mice, from postpartum day (PPD) 1 to PPD 21, underwent no PS (NPS), brief PS (15 min per day, PS15), or long PS (180 min per day, PS180), followed by 21 days of chronic restraint stress (CRS). Behavioral tests were conducted, and measurements included serum PRL concentration, PRL-R expression, and AHN in the hippocampus. Dams with CRS exhibited cognitive decline, depressive- and anxiety-like behaviors, and reduced PRL secretion, correlating with lower levels of AHN. PS15 dams displayed lower levels of depressive- and anxiety-like behaviors and cognitive decline compared to NPS and PS180 dams. Significantly, PS15 dams exhibited higher levels of AHN, PRL-R expression in the hippocampus, and serum PRL concentration. This study collectively reveals reduced serum PRL and AHN in dams with cognitive decline and depressive- and anxiety-like behaviors after CRS. Brief PS confers resistance to behavioral deficits after CRS, increasing serum PRL concentration and reversing AHN decrease in dams. [ABSTRACT FROM AUTHOR]

For the last two decades, the aromatic aldehyde 5‐hydroxymethyl‐furfural (5‐HMF) has been the subject of several investigations for its pharmacologic potential. In 2004, the Safo group reported that 5‐HMF has potent antisickling activity by targeting and ameliorating the primary pathophysiology of hypoxia‐induced sickling of erythrocytes (red blood cells [RBC]). Following the encouraging outcome of the preclinical and phase I/II clinical studies of 5‐HMF for the treatment of sickle cell disease (SCD), there have been multiple studies suggesting 5‐HMF has several other biological or pharmacologic activities, including anti‐allergic, antioxidant, anti‐hypoxic, anti‐ischemic, cognitive improvement, anti‐tyrosinase, anti‐proliferation, cytoprotective, and anti‐inflammatory activities. The wide range of its effects makes 5‐HMF a potential candidate for treating a variety of diseases including cognitive disorders, gout, allergic disorders, anemia, hypoxia, cancers, ischemia, hemorrhagic shock, liver fibrosis, and oxidative injury. Several of these therapeutic claims are currently under investigation and, while promising, vary in terms of the strength of their evidence. This review presents the research regarding the therapeutic potential of 5‐HMF in addition to its sources, physicochemical properties, safety, absorption, distribution, metabolism, and excretion (ADME) profiles. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether individuals with subjective cognitive decline (SCD) have changes in whole-brain network characteristics and intracerebral node characteristics in the structural network, and whether there is a difference between SCD with and without Apolipoprotein E4 (APOEε4). Methods: This cross-sectional study included 36 individuals without SCD without APOEε4 (healthy control, HC group), 21 individuals with SCD with APOEε4 (APOEε4+ group), and 33 individuals with SCD without APOEε4 (APOEε4-group). The white matter structural network was constructed using the fractional anisotropy (FA) based deterministic fiber tracking method. Graph theory was used to analyze the whole-brain network characteristics and intracerebral node characteristics of the three groups. Results: Regarding the whole-brain network characteristics, all three groups exhibited small-worldness in their structural networks. The clustering coefficient (Cp) and local efficiency (Eloc) in the APOEε4+ and APOEε4- groups were significantly lower than in the HC group (p < 0.05), but no significant difference in Cp or Eloc was observed between the APOEε4+ and APOEε4- groups. Regarding intracerebral node characteristics, there were significant differences in some brain regions, mainly the default mode network (DMN), the occipital lobe, the temporal lobe, and subcortical regions. The change in intracerebral node characteristics was different between the APOEε4+ group and the APOEε4- group. Conclusions: Individuals with SCD demonstrate changes in whole-brain network characteristics and intracerebral node characteristics in the structural network. Moreover, differences exist between APOEε4+ and APOEε4- individuals. [ABSTRACT FROM AUTHOR]

While many studies have demonstrated a relationship between depression and cognitive deficits, most have neglected to include measurements of performance validity. This study examined the relationship between depression and cognition after accounting for noncredible performance. Participants were veterans referred for outpatient clinical evaluation. The first set of regression analyses (N = 187) included age, sex, and education in Model 1, Beck Depression Inventory-2 (BDI-2) added in Model 2, and pass/failure of Test of Memory Malingering (TOMM) added in Model 3 as predictors of 12 neuropsychological test indices. The second set of analyses (N = 559) mirrored the first but with Major Depressive Disorder (MDD) diagnosis in Models 2 and 3. In the first analyses, after including TOMM in the model, only the relationship between BDI-2 and verbal fluency remained significant, but this did not survive a Bonferroni correction. In the second analyses, after including TOMM and Bonferroni correction, MDD diagnosis was a significant predictor only for CVLT-II Short Delay Free Recall. Therefore, the relationship between depression and cognition may not be driven by frank cognitive impairment, but rather by psychological mechanisms, which has implications for addressing depressed individuals' concerns about their cognitive functioning and suggest the value of providing psychoeducation and reassurance. [ABSTRACT FROM AUTHOR]

Confrontation naming measures are commonly used for both diagnostic and clinical research purposes in populations of known or suspected neurodegenerative disorders. The Boston Naming Test (BNT) is the most widely used measure of confrontation naming but has been criticized for outdated and culturally biased content. A new naming measure, the Multilingual Naming Test (MiNT), has been developed that may address these limitations, but research regarding its validity and diagnostic performance relative to existing instruments is limited. The current study examined how the BNT and MiNT performed in a sample of older adults evaluated in an interprofessional memory disorders clinic. Eighty-six individuals (50.0% women) met the inclusion criteria and were included in the study. The average age of participants was 74.2 years (SD = 7.7), and the average education was 16.7 years (SD = 2.5). Most participants were non-Hispanic White (94.2%), and the remaining participants were Hispanic or Black. All participants completed a comprehensive evaluation in English and were administered both the BNT and the MiNT. The strength of agreement as indexed by CCC (.67) was modest for the sample as a whole. Eighty-seven-point five percent classification agreement for impaired vs. normal naming performance was obtained. Eleven cases showed disagreement between BNT and MiNT classification of impairment, with seven of these being borderline score cases. Overall, the results suggest that the MiNT performs similarly at the identification of naming impairments as the BNT, though performance may diverge across different diagnostic groups and may be influenced by age. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was the measurement of the test–retest reliability of n-back in Chinese stroke patients. Methods: Seventy-five sub-acute stroke patients performed n-back twice in three days. The test–retest reliability of n-back was analyzed by correlation coefficient. Results: The n-back had excellent test–retest reliability in stroke patients. Pearson or Spearman coefficients ranged from 0.81 to 0.88. The intra-class correlation coefficients ranged from 0.72 to 0.87. The Chinese version of Montreal Cognitive Assessment-Basic (MoCA-BC) score was significantly correlated with the performance of n-back. MoCA-BC and n-back accuracy were significantly related in the Mild Cognitive Impairment (MCI) group (r = 0.60 in 1-back, p =.002; r = 0.43 in 2-back, p =.040). However, MoCA-BC was correlated with reaction time (RT) in the Cognitively Normal (CN) group (r = –0.44 in 1-back, p =.003; r = –0.36 in 2-back, p =.018). The test–retest reliability of CN group was mostly higher than that of MCI group RT: 0.71–0.76 in MCI, 0.80–0.88 in CN; accuracy: 0.80–0.85 in MCI, 0.75–0.86 in CN). The practice effect was observed in the CN group instead of the MCI group. Conclusions: This study indicated that the test–retest reliability of n-back was high in stroke patients. N-back was correlated with cognition. It was preferable to conduct subgroup analyses according to the level of cognitive assessment of patients with stroke. [ABSTRACT FROM AUTHOR]

Background: Pediatric patients with kidney failure often experience cognitive delays. However, academic delay (being more than one grade level below age-appropriate grade, or in special education) after pediatric kidney transplantation (KTx) has not been explored. We sought to identify patient characteristics associated with a higher risk of academic delay 1 year post-KTx. Methods: We used the United Network for Organ Sharing (UNOS) database to identify children aged 6–17 years who received a primary KTx between 2014 and 2021 and had a functioning graft 1 year after KTx. The primary outcome was the patient's academic progress at 1 year post-transplant. The secondary outcome was change in academic progress between transplant and 1-year follow-up: onset of new delay, resolution of pre-existing delay, persistence of delay, or no delay at either timepoint. Binomial and multinomial mixed effects logistic regression models were used to predict each outcome based on patient characteristics. Results: The study included 2197 patients, of whom 14% demonstrated academic delay at 1 year post-KTx, 4% demonstrated a new onset of academic delay, 5% demonstrated a resolution of academic delay, and 10% demonstrated persistent academic delay. Patients undergoing transplantation at a younger age, receiving a deceased donor kidney, experiencing longer waitlist times, and undergoing KTx for vascular or other disease indications for KTx were more likely to experience academic delays, including new-onset academic delays. Conclusions: Academic delays are frequently reported among pediatric KTx recipients. Additional academic support may help resolving or preventing academic delay for at-risk subgroups of children undergoing KTx. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) is a demyelinating disease of the central nervous system. Caffeine, as the most widely consumed psychoactive substance, has been suggested to have potential effects on the clinical course and disability levels of MS patients. This study aimed to review the current evidence on the effects of coffee/caffeine in patients with MS. Methods: This study followed the Joanna Briggs Institute (JBI) Manual for Evidence Synthesis and PRISMA 2020 statement. Clinical evidence regarding the effects of caffeine/coffee in MS patients was considered. A systematic search was performed in PubMed, Scopus, Web of Science, and Embase in October 2023, and updated via handsearching in March 2024. JBI's critical appraisal tools were utilized to scrutinize the risk of bias. Results: Out of 297 screened records, eight studies were eventually found to meet our inclusion criteria. The sample size of the studies varied between 12 and 1372 and the study designs were retrospective cohort, RCT, single-blind crossover trial, single-arm pilot study (each one study), and cross-sectional (four studies). No significant association between the level of disability and coffee/caffeine intake has been reported, although it was reported to be associated with cognitive improvements. Discussion: Evidence indicates an association between coffee/caffeine consumption, and improved cognitive outcomes in patients with MS, while there is no considerable relationship with the disease disability. Considering the limitations of the evidence, such as the small number of studies, and great diversity in study designs, the findings of this study should translate to clinical practice with caution. [ABSTRACT FROM AUTHOR]

Beta-glucan (BG), a polysaccharide comprised of interfacing glucose monomers joined via beta-glycosidic linkages, can be defined as a type of dietary fiber with high specificity based on its interaction with the gut microbiota. It can induce similar interindividual microbiota responses, thereby having beneficial effects on the human body. In this paper, we review the four main sources of BG (cereals, fungi, algae, and bacteria) and their differences in structure and content. The interaction of BG with gut microbiota and the resulting health effects have been highlighted, including immune enhancement, regulation of serum cholesterol and insulin levels, alleviation of obesity and improvement of cognitive disorders. Finally, the application of BG in food products and its beneficial effects on the gut microbiota of consumers were discussed. Although some of the mechanisms of action remain unclear, revealing the beneficial functions of BG from the perspective of gut microbiota can help provide theoretical support for the development of diets that target the regulation of microbiota. [ABSTRACT FROM AUTHOR]

Long COVID, or Post-Acute Sequelae of COVID-19 (PASC), was characterized by persistent symptoms such as fatigue, shortness of breath, and cognitive impairments. These symptoms, emerging one to 2months post-infection and persisting for several months, cannot be attributed to other diagnoses. The pathophysiology of long COVID remained elusive; however, emerging studies suggested multiple potential mechanisms, including the reactivation of Epstein-Barr virus, persistent SARS-CoV-2 reservoirs, neuroinflammation, and vascular damage, which may contribute to its development. Long COVID affected multiple organ systems, including respiratory, circulatory, and nervous systems, leading to a range of functional impairments. Additionally, it showed a profound impact on mental health, manifesting as anxiety and depression, which significantly degraded the quality of life. The absence of definitive treatments underscored the importance of prevention. Recent evidence indicated that early antiviral intervention--particularly with small-molecule drugs such as Metformin, Ensitrelvir, Molnupiravir, and Nirmatrelvir--may effectively reduce the incidence of longCOVID. This underscored the promising role of small-molecule compounds in mitigating long-term COVID-19 consequences, offering a novel preventive strategy against long COVID and its extensive impacts on patients. [ABSTRACT FROM AUTHOR]

Objectives: Subjective cognitive decline (SCD) as a stage between healthy cognition and early neurocognitive disorders, has been proposed to be helpful in the diagnosis of prodromal neurocognitive disorders. To investigate the prevalence of SCD and the related risk factors on the prevalence. Methods: A cross-sectional study involving 1,120 elderly subjects residing in Baotou, China. From June 2021 to June 2023, the data were gathered by research assistants with training utilizing standardized questionnaires. The following factors were evaluated: subjective cognitive decline, physical and cognitive activity levels, past medical history, demographics, instrumental activities of daily living, and cognitive function. Risk factors of SCD were used chi-square tests and multivariate logistic regression analysis. Results: The prevalence of SCD was 43.8%. Permanent residence, marital status, BMI, dietary habits, average sleep duration per night, smoking, diabetes, coronary heart disease, and visual impairment were significantly associated with SCD (p < 0 0.05). Multivariable logistic regression analysis showed obesity, vegetarian-based, smoking for a long time, diabetes and coronary heart disease, visual impairment, no spouse, and average sleep duration per night <6 h were independent risk factors for SCD. Based on the gender analysis, the difference in marital status, dietary habits, average sleep duration per night, smoking, drinking, and hypertension was statistically significant (p < 0.001). Conclusion: The prevalence of subjective cognitive decline was high among elder adults. We discovered significant differences in the prevalence or risk factors for SCD between men and women based on their sex. This study provides a more theoretical basis for the early prevention and screening of cognitive impairment diseases in the elderly population. [ABSTRACT FROM AUTHOR]

Background: Schizophrenia is a debilitating mental disorder affecting about 1% of the global population, characterized by significant cognitive impairments and a strong hereditary component. Carnitine, particularly Levo-carnitine and its derivatives, plays a crucial role in cellular metabolism and mitochondrial function, with evidence suggesting a link between levo-carnitine deficiency and schizophrenia pathology. This study aims to investigate the causal relationship between different subtypes of levo-carnitine and the susceptibility to schizophrenia using Mendelian randomization analysis. Methods: Forward Mendelian randomization analysis was conducted using levo-carnitine and its derivatives as exposure and schizophrenia as the outcome. Candidate data were obtained from the Open-GWAS database. Instrumental variables were identified as single nucleotide polymorphisms closely associated with exposure and harmonized with the outcome data after removing confounders and outliers. Mendelian randomization analysis was performed using inverse variance weighting as the primary approach, and sensitivity analysis was conducted to assess the reliability and robustness of the results. Finally, a reverse Mendelian randomization analysis was carried out using the same analytical procedures. Results: The Mendelian randomization results indicate a significant negative causal relationship between isovaleryl-levo-carnitine and schizophrenia (P < 0.05), but no significant associations in other groups (P > 0.05). Additionally, the reverse Mendelian randomization analysis did not identify any causal relationship between schizophrenia and levo-carnitine related exposures (P > 0.05). Sensitivity analyses, including pleiotropy and heterogeneity analysis, did not reveal any potential bias in the Mendelian randomization results (P > 0.05). Conclusion: The results suggest that elevated levels of isovaleryl-levo-carnitine may potentially mitigate the risk of developing schizophrenia, highlighting the prospective therapeutic and preventive implications of isovaleryl-levo-carnitine in the clinical management of schizophrenia. [ABSTRACT FROM AUTHOR]

Background: The prevalence of cognitive diseases, including Alzheimer's disease and other forms of dementia, poses a significant global health challenge due to the limited availability of effective therapeutic options. Recent years have witnessed a growing emphasis in research on the exploration of natural compounds and their derivatives as prospective therapeutic agents for cognitive impairments. Main body Xanthotoxin, a furanocoumarin compound derived from botanical sources, exhibits promising therapeutic promise in several neurological conditions such as depression, neuronal inflammation, Alzheimer's disease, vascular cognitive impairment, epilepsy, and Parkinson's disease. This potential stems from its notable neuroprotective, antioxidant, and anti-inflammatory characteristics. The present study offers a comprehensive examination of the acquisition of XAT from both natural sources and synthetic means. It delves into the significance of XAT in the treatment of cognitive disorders and delineates potential avenues for future research in the domain of XAT and cognitive disorders. Conclusion: Ongoing research and advancements in the field of XAT have the potential to enhance its use as a potent therapeutic intervention for cognitive impairments, consequently enhancing the holistic welfare of those afflicted by these incapacitating disorders. [ABSTRACT FROM AUTHOR]

Elderly individuals display metabolite alterations that may contribute to development of cognitive impairment following surgery and anesthesia. However, these relationships remain largely unexplored. The study aims to assess the S-methyl-5-thioadenosine (MTA) is associated with postoperative delayed neurocognitive recovery (dNCR). We assess altered metabolites following anesthesia/surgery in both mice and patients to identify blood biomarkers of dNCR. Preoperative and postoperative plasma metabolites are determined by widely targeted metabolomics. The brains of mice with anesthesia/surgery show decreased MTA and activated MTA phosphorylase. Mice also show that preoperative administration of MTA can prevent inflammation and cognitive decline. In clinical patients, we detect lower preoperative serum MTA levels in those who developed dNCR. Both low preoperative and postoperative blood MTA levels are associated with increased risk of postoperative dNCR. These results suggest that anesthesia/surgery induces cognitive decline through methionine synthesis pathways and that MTA could be a perioperative predictor of dNCR. Low blood S-methyl-5-thioadenosine (MTA) levels are associated with postoperative delayed neurocognitive recovery (dNCR) and thus could be used as a potential perioperative predictor. [ABSTRACT FROM AUTHOR]

Background: Analysis of selected research cohorts has highlighted an association between plasma neurofilament light (NfL) protein and cross-sectional cognitive impairment as well as longitudinal cognitive decline. However, the findings have yielded inconsistent results regarding its possible application in clinical practice. Despite its potential prognostic significance, the role of plasma NfL in daily clinical practice with unselected patients suffering from cognitive impairment remains largely unexplored. Methods: This retrospective, cross-sectional and longitudinal monocentric study enrolled 320 patients with Alzheimer's disease ([AD], n = 158), dementia with Lewy body ([DLB], n = 30), frontotemporal dementia ([FTD], n = 32), non-neurodegenerative diseases ([NND], n = 59) or subjective cognitive decline ([SCD], n = 41). Plasma NfL levels were measured at baseline on the Simoa platform. AD, DLB, and FTD patients were also analyzed altogether as a 'degenerative conditions' subgroup, whereas SCD and NND were grouped as a 'non-degenerative conditions' subgroup. We assessed the relationship between plasma NfL levels and cross-sectional cognitive performance, including global cognition and six specific cognitive domains. A subset of 239 patients had follow-up mini-mental state examinations (MMSE) up to 60 months. Models were adjusted on age, education level, glomerular filtration rate and body mass index. Results: In 320 patients, baseline plasma NfL levels were negatively associated with global cognition (β=-1.28 (-1.81 ; -0.75) P < 0.001), memory (β=-1.48 (-2.38 ; -0.59), P = 0.001), language (β=-1.72(-2.49 ; -0.95) P < 0.001), praxis (β=-2.02 (-2.91 ; -1.13) P < 0.001) and executive functions (β=-0.81, P < 0.001). Across diagnosis, plasma NfL levels were negatively associated with cross-sectional global cognition in all but the SCD subgroup, specifically with executive functions and memory in AD (respectively β=-0.71(-1.21 ; -0.211), P = 0.005 and β=-1.29 (-2.17 ; -0.42), P = 0.004), and with attention in LBD (β=-0.81(-1.16 ; -0.002), P = 0.03). Linear mixed-effects models showed that plasma NfL predicted MMSE decline in the global population (βPlasmaNfLxTime=-0.15 (-0.26 ; -0.04), P = 0.006), as in the neurodegenerative condition subgroup (βPlasmaNfLxTime=-0.21 (-0.37 ; − 0.06), P = 0.007), but not in non-neurodegenerative condition subgroup. Conclusion: In our clinical cohort, plasma NfL was associated with faster cognitive decline in neurodegenerative dementia, which corroborates data obtained in research cohorts. Yet, plasma NfL was not predictive of accelerated cognitive decline in individuals without neurodegeneration, suggesting its use as a neurodegeneration-specific predictive biomarker. [ABSTRACT FROM AUTHOR]

Background: With the recent surge in the utilization of electronic health records for cognitive decline, the research community has turned its attention to conducting fine-grained analyses of dementia onset using advanced techniques. Previous works have mostly focused on machine learning-based prediction of dementia, lacking the analysis of dementia progression and its associations with risk factors over time. The black box nature of machine learning models has also raised concerns regarding their uncertainty and safety in decision making, particularly in sensitive domains like healthcare. Objective: We aimed to characterize the progression of health conditions, such as chronic diseases and neuropsychiatric symptoms, of the participants in Mayo Clinic Study of Aging (MCSA) from initial mild cognitive impairment (MCI) diagnosis to dementia onset through network analysis. Methods: We used the data from the MCSA, a prospective population-based cohort study of cognitive aging, and examined the changing association among variables (i.e., participants' health conditions) from the first visit of MCI diagnosis to the visit of dementia onset using network analysis. The number of participants for this study are 97 with the number of visits ranging from 2 visits (30 months) to 7 visits (105 months). We identified the network communities among variables from three-fold collection of instances: (i) the first MCI diagnosis, (ii) progression to dementia, and (iii) dementia diagnosis. We determine the variables that play a significant role in the dementia onset, aiming to identify and prioritize specific variables that prominently contribute towards developing dementia. In addition, we explore the sex-specific impact of variables in relation to dementia, aiming to investigate potential differences in the influence of certain variables on dementia onset between males and females. Results: We found correlation among certain variables, such as neuropsychiatric symptoms and chronic conditions, throughout the progression from MCI to dementia. Our findings, based on patterns and changing variables within specific communities, reveal notable insights about the time-lapse before dementia sets in, and the significance of progression of correlated variables contributing towards dementia onset. We also observed more changes due to certain variables, such as cognitive and functional scores, in the network communities for the people who progressed to dementia compared to those who does not. Most changes for sex-specific analysis are observed in clinical dementia rating and functional activities questionnaire during MCI onset are followed by chronic diseases, and then by NPI-Q scores. Conclusions: Network analysis has shown promising potential to capture significant longitudinal changes in health conditions, spanning from the MCI diagnosis to dementia progression. It can serve as a valuable analytic approach for monitoring the health status of individuals in cognitive impairment assessment. Furthermore, our findings indicate a notable sex difference in the impact of specific health conditions on the progression of dementia. [ABSTRACT FROM AUTHOR]

Schizophrenia is a severe psychiatric disorder with high heritability, characterized by positive and negative symptoms as well as cognitive abnormalities. Dysfunction in glutamate synapse is strongly implicated in the pathophysiology of schizophrenia. However, the precise role of the perturbed glutamatergic system in contributing to the cognitive abnormalities of schizophrenia at the synaptic level remains largely unknown. Although our previous work found that Opcml promotes spine maturation and Opcml-deficient mice exhibit schizophrenia-related cognitive impairments, the synaptic mechanism remains unclear. By using whole-cell patch clamp recording, we found that decreased neuronal excitability and alterations in intrinsic membrane properties of CA1 PNs in Opcml-deficient mice. Furthermore, Opcml deficiency leads to impaired glutamatergic transmission in hippocampus, which is closely related to postsynaptic AMPA/NMDA receptors dysfunction, resulting in the disturbances of E/I balance. Additionally, we found that the aripiprazole which we used to ameliorate abnormal cognitive behaviors also rescued the impaired glutamatergic transmission in Opcml-deficient mice. These findings will help to understand the synaptic mechanism in schizophrenia pathogenesis, providing insights into schizophrenia therapeutics with glutamatergic disruption. [ABSTRACT FROM AUTHOR]

Mitochondria, the cellular powerhouses with bacterial evolutionary origins, play a pivotal role in maintaining neuronal function and cognitive health. Several viruses have developed sophisticated mechanisms to target and disrupt mitochondrial function which contribute to cognitive decline and neurodegeneration. The interplay between viruses and mitochondria might be traced to their co-evolutionary history with bacteria and may reflect ancient interactions that have shaped modern mitochondrial biology. [ABSTRACT FROM AUTHOR]

Diabetic encephalopathy (DE) is a severe complication of diabetes, but its pathogenesis remains unclear. This study aimed to investigate the roles and underlying mechanisms of high glucose (HG)- and advanced glycosylation end product (AGE)-induced oxidative stress (OS) in the cognitive decline in DE. The DE mouse model was established using a high-fat diet and streptozotocin, and its cognitive functions were evaluated using the Morris Water Maze, novel object recognition, and Y-maze test. The results revealed increased reactive oxygen species (ROS) generation, mitophagy inhibition, and decreased prohibitin 2 (PHB2) expression in the hippocampal neurons of DE mice and HG- or AGE-treated HT-22 cells. However, overexpression of PHB2 reduced ROS generation, reversed mitophagy inhibition, and improved mitochondrial function in the HG- or AGE-treated HT-22 cells and ameliorated cognitive decline, improved mitochondrial structural damage, and reversed mitophagy inhibition of hippocampal neurons in DE mice. Further analysis revealed that the Kelch-like ECH-associated protein 1 (Keap1)–nuclear factor erythroid 2-related factor 2 (Nrf2) pathway was involved in the HG- or AGE-mediated downregulation of PHB2 in HT-22 cells. These results demonstrate that HG- or AGE-induced OS inhibits the mitophagy of hippocampal neurons via the Keap1–Nrf2–PHB2 pathway, thereby contributing to the cognitive decline in DE. [ABSTRACT FROM AUTHOR]