Mortalidad asociada al trastorno neurocognitivo y dependencia en personas mayores de 55 años. Revisión sistemática / Mortality associated with neurocognitive disorder and dependence in people over 55 years of age. Systematic review

Introducción El creciente envejecimiento poblacional trae consigo un aumento de la incidencia del trastorno neurocognitivo (TNC) así como diversas situaciones generadoras de dependencia. Objetivo Analizar mediante una revisión sistemática la relación que existe entre TNC y dependencia con el riesgo de mortalidad en personas mayores. Métodos Se realizó una búsqueda bibliográfica de los estudios longitudinales publicados en Pubmed y Scopus abordando la relación entre TNC, dependencia para las actividades básicas de la vida diaria (ABVD) y mortalidad publicados entre los años 1995 y 2021 De los 1040 artículos encontrados, se seleccionaron 10 estudios. Resultados Se observó que las cohortes de personas mayores con TNC presentaron riesgo de mortalidad asociado a la afectación de las ABVD (test de Barthel) y a las puntuaciones de Mini-Mental State Examination siguiendo una tendencia lineal significativa. Otros factores asociados al riesgo de mortalidad fueron: niveles bajos de educación, vivir solo y presentar fragilidad. Es clara la vinculación entre los tres términos utilizados en la búsqueda de este trabajo y, sin embargo, destaca que haya pocos estudios longitudinales que los analicen conjuntamente. Conclusiones Los resultados hallados subrayan la importancia de realizar evaluaciones del estado cognitivo y funcional mediante escalas validadas, ya que ambas áreas se asocian con la mortalidad. La evaluación de la dependencia y de la función cognitiva en adultos mayores debe considerarse tanto en la investigación como en la práctica clínica, ya que aportarían información sobre su posible relación con la mortalidad. (AU)

Introduction The increasing aging of the population brings with it an increase in the incidence of neurocognitive disorder (NCD) as well as various situations that generate dependence. Objective To analyze by means of a systematic review the relationship between NCD and dependence with the risk of mortality in the elderly. Methods A bibliographic search of longitudinal studies published in Pubmed and Scopus addressing the relationship between NCI, dependence for basic activities of daily living (ADL) and mortality published between 1995 and 2021 was performed. Of the 1040 articles found, 10 studies were selected. Results It was observed that cohorts of elderly people with NCI presented mortality risk associated with ABVD impairment (Barthel test) and Mini-Mental State Examination scores following a significant linear trend. Other factors associated with mortality risk were low levels of education, living alone, and frailty. Conclusions The results underline the importance of performing assessments of cognitive and functional status using validated scales, since both areas are associated with mortality. The link between the three terms used in the search for this work is clear, but it is noteworthy that there are few longitudinal studies that analyze them together. The assessment of dependence and cognitive function in older adults should be considered in both research and clinical practice as it would provide information on their possible relationship with mortality. (AU)

The neuroprotective effect of near infrared light therapy in aged mice with postoperative neurocognitive disorder by upregulating IRF7.

BACKGROUND: Postoperative neurocognitive disorder (PND) is a common central nervous system complication after undergoing surgery and anesthesia especially in elderly patients, while the therapeutic options are very limited. This study was carried out to investigate the beneficial effects of transcranial near infrared light (NIRL) which was employed to the treatment of PND and propose the involved mechanisms. METHODS: The PND mice were established through left carotid artery exposure under isoflurane anesthesia and received transcranial NIRL treatment. Behavioral testing was performed to evaluate the cognitive function of PND mice after transcranial NIRL therapy. Changes in the transcriptomic profiles of prefrontal cortex (PFC) and hippocampus (HP) were identified by next generation sequencing (NGS), and the molecular mechanisms involved were examined by both in vivo mouse model and in vitro cell culture studies. RESULTS: We found that transcranial NIRL therapy effectively ameliorated learning and memory deficit induced by anesthesia and surgery in aged mice. Specifically, we identified down-regulation of interferon regulatory factor 7 (IRF7) in the brains of PND mice that was mechanistically associated with increased pro-inflammatory M1 phenotype of microglia and elevated neuroinflammatory. NIRL treatment produced protective effects through the upregulation of IRF7 expression and reversing microglial phenotypes from pro-inflammatory to neuroprotective, resulting in reduced brain damage and improved cognitive function in PND mice. CONCLUSION: Our results indicate that transcranial NIRL is an effective and safe therapy for PND via alleviating neuroinflammation, and IRF7 plays a key transcription factor in regulating the M1-to-M2 switch of microglia.

Postoperative neurocognitive disorders: A clinical guide.

For years, postoperative cognitive outcomes have steadily garnered attention, and in the past decade, they have remained at the forefront. This prominence is primarily due to empirical research emphasizing their potential to compromise patient autonomy, reduce quality of life, and extend hospital stays, and increase morbidity and mortality rates, especially impacting elderly patients. The underlying pathophysiological process might be attributed to surgical and anaesthesiological-induced stress, leading to subsequent neuroinflammation, neurotoxicity, burst suppression and the development of hypercoagulopathy. The beneficial impact of multi-faceted strategies designed to mitigate the surgical and perioperative stress response has been suggested. While certain potential risk factors are difficult to modify (e.g., invasiveness of surgery), others - including a more personalized depth of anaesthesia (EEG-guided), suitable analgesia, and haemodynamic stability - fall under the purview of anaesthesiologists. The ESAIC Safe Brain Initiative research group recommends implementing a bundle of non-invasive preventive measures as a standard for achieving more patient-centred care. Implementing multi-faceted preoperative, intraoperative, and postoperative preventive initiatives has demonstrated the potential to decrease the incidence and duration of postoperative delirium. This further validates the importance of a holistic, team-based approach in enhancing patients' clinical and functional outcomes. This review aims to present evidence-based recommendations for preventing, diagnosing, and treating postoperative neurocognitive disorders with the Safe Brain Initiative approach.

Prevalence of internet addiction and psychological factors in adolescents during the covid-19 pandemic / Prevalência de dependência da internet e fatores psicológicos em adolescentes durante a pandemia de covid-19 / Prevalencia de la adicción a internet y factores psicológicos en adolescentes durante la pandemia de la covid-19

Addictive behaviors related to Internet are becoming more common and this tool has been essential once it enables home office, entertainment, homeschooling, and easy access to information. Despite the easiness brought by technology, the exaggerated use has affected users in different ways, including in the development of psychiatric disorders. This study aimed to assess internet addiction, depression, anxiety, attention-deficit/hyperactivity disorder (ADHD), attention, impulsivity, and stress in 48 adolescents (26 young women and 22 young men), aged from 15 to 18 years, with a mean age of 16.74 (0.61), mostly students of public schools, during COVID-19, to investigate correlations between these variables according to sex and sociodemographic aspects. To assess the factors, the Internet Addiction Test (IAT); the Swanson, Nolan, and Pelham Rating Scale (SNAP-IV) Questionnaire ; the Depression, Anxiety, and Stress scale for brazilian adolescents (EDAE-A); the Barratt Impulsiveness Scale (BIS-11); and a sociodemographic questionnaire were applied. The data collection was performed in schools located in southern Brazil. The results indicated that 12 out of 48 adolescents were considered addicted to the Internet. Moreover, Internet addiction was a predictor of depression in regression analysis (p<0.001). In addition, participants classified as more addicted to the Internet scored lower averages in general attention (p<0.035) and higher averages in behavioral symptoms of inattention and ADHD (p<0.050), stress (p<0.003), anxiety (p<0.016), and depression (p<0.015), with effect sizes ranging from moderate to high. Therefore, the intense internet use by adolescents might cause psychological consequences such as depression in adolescents. Family support and professional intervention might help in the reduction of symptoms and consequences of internet addiction as well as in its prevention.(AU)

A dependência de internet é cada vez mais comum, pois essa ferramenta tem se tornado imprescindível, uma vez que possibilita home office, entretenimento, educação domiciliar e fácil acesso às informações. No entanto, o uso exagerado da tecnologia afeta os usuários de diversas formas, inclusive no desenvolvimento de transtornos psiquiátricos. Este estudo visou avaliar a dependência de internet, depressão, ansiedade, hiperatividade, atenção, impulsividade e estresse em 48 adolescentes (26 meninas e 22 meninos) de 15 a 18 anos, com idade média de 16,74 (0,61), estudantes de escolas públicas do Sul do Brasil durante a covid-19, para investigar correlações entre as variáveis anteriores de acordo com gênero e aspectos sociodemográficos. Para avaliar, aplicou-se o Internet Addiction Test (IAT), um teste de atenção, escala SNAP IV, escala de depressão, ansiedade e estresse para adolescentes (EDAE-A), escala de impulsividade de Barratt e um questionário sociodemográfico. Os resultados indicaram que 12 adolescentes foram considerados viciados em internet, e que a dependência desta foi preditora da depressão na análise de regressão (p < 0,001). Ainda, os participantes classificados como adictos tiveram médias mais baixas em atenção geral (p < 0,035) e mais altas em sintomas comportamentais de desatenção e hiperatividade (p < 0,050), estresse (p < 0,003), ansiedade (p < 0,016) e depressão (p < 0,015), com efeitos que variaram de moderado a alto. Portanto, o uso intenso da internet por adolescentes pode ter consequências psicológicas, como a depressão. Bom apoio familiar e intervenção profissional podem ajudar na redução dos sintomas e consequências, bem como na prevenção da dependência.(AU)

La adicción a Internet es cada vez más habitual, puesto que esta herramienta es esencial para el trabajo remoto, el entretenimiento, la educación domiciliar y el fácil acceso a la información. Sin embargo, su uso exagerado afecta a la vida de las personas de diferentes maneras, incluso en el desarrollo de trastornos psiquiátricos. El objetivo de este estudio fue evaluar la adicción a Internet, depresión, ansiedad, hiperactividad, atención, impulsividad y estrés en 48 adolescentes (26 muchachas y 22 muchachos), de entre 15 y 18 años, con una edad promedio de 16,74 (0,61), en su mayoría estudiantes de escuelas públicas del Sur de Brasil, durante la pandemia de la COVID-19, para investigar las correlaciones entre las variables mencionadas según género y aspectos sociodemográficos. Para evaluar los factores, se aplicaron el Test de Adicción a Internet (TAI), un test de atención, la escala SNAP IV, la Escala de Depresión, Ansiedad y Estrés para adolescentes (EDAE-A), la escala de impulsividad de Barratt y un cuestionario sociodemográfico. Los resultados indicaron que 12 adolescentes fueron considerados adictos a Internet, además, la adicción a Internet fue un predictor de la depresión en el análisis de regresión (p<0,001). Igualmente, los participantes clasificados como más adictos a Internet tuvieron promedios más bajos en atención general (p<0,035), y más altos en síntomas conductuales de falta de atención e hiperactividad (p<0,050), estrés (p<0,003), ansiedad (p<0,016) y depresión (p<0,015), con efectos que varían de moderado a alto. Por lo tanto, el uso intenso podría producir consecuencias psicológicas como la depresión en los adolescentes. Tener un buen apoyo familiar e intervención profesional puede ayudar a reducir los síntomas y las consecuencias de la adicción a Internet, así como prevenirla.(AU)

Complementary and Alternative Medicine Approaches in Alzheimer Disease and Other Neurocognitive Disorders.

As our population ages, there is interest in delaying or intervening in cognitive decline. While newer agents are under development, agents in mainstream use do not impact the course of diseases that cause cognitive decline. This increases interest in alternative strategies. Even as we welcome possible new disease-modifying agents, they are likely to remain costly. Herein, we review the evidence behind other complementary and alternative strategies for cognitive enhancement and prevention of cognitive decline.

Transcutaneous electrical acupoint stimulation for the prevention of perioperative neurocognitive disorders in geriatric patients: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: To evaluate whether transcutaneous electrical acupoint stimulation (TEAS) decreases rates of perioperative neurocognitive disorders (PND) when used as an adjuvant method during perioperative period in geriatric patients since the new definition was released in 2018. METHODS: Six databases [Chinese National Knowledge Infrastructure, VIP Database for Chinese Technical Periodicals, WanFang Database, PubMed, EMBASE, and Cochrane Library] were systematically searched. Data analysis was performed using RevMan 5.4.1 software (Copenhagen: The Nordic Cochrane Centre, the Cochrane Collaboration, 2020). Risk ratios (RR) with 95% confidence interval were calculated using a random effects model. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. RESULTS: 13 randomized clinical trials (999 patients) in total were included. TEAS had positive effects on preventing the incidence of PND (RR: 0.43; 0.31, 0.61; P < .001; low certainty) [postoperative delirium within 7 days (RR: 0.39; 0.26, 0.59; P < .001), delayed neurocognitive recovery within 3 months (RR: 0.51; 0.33, 0.78; P = .002)]. TEAS could also improve the scores of the confusion assessment method (CAM) (Mean difference: -1.30; -2.14, -0.46; P = .003; low certainty). Limited evidence suggested that TEAS could reduce the serum levels of biochemical indicator (S100ß) (SMD = -1.08, -1.67, -0.49, P < .001; I2  = 83%; very low certainty) as well as anesthetic requirements (remifentanil) (SMD: -1.58; -2.54, -0.63; P = .001; I2  = 87%; very low certainty). Subgroup analysis indicated that different protocols of TEAS had significant pooled benefits (TEAS used only in surgery and in combination with postoperative intervention) (RR: 0.45; 0.31, 0.63; P < .001). Acupoint combination (LI4 and PC6) in the TEAS group had more significantly advantages (RR: 0.34; 0.17, 0.67; P = .002). TEAS group had a lower incidence of PND in different surgery type (orthopedic surgery and abdominal surgery) (RR: 0.43; 0.30, 0.60; P < .001), as well as with different anesthetic modality (intravenous anesthesia and intravenous and inhalational combined anesthesia) (RR: 0.38; 0.23, 0.61; P < .001). CONCLUSION: In terms of clinical effectiveness, TEAS appeared to be beneficial for prophylaxis of PND during a relatively recent period, noting the limitations of the current evidence.

Is the Snoezelen method a non-pharmacological alternative for patients with neurocognitive disorders? / La méthode Snoezelen : une alternative thérapeutique chez les patients ayant des troubles cognitifs ?

Neuropsychiatric disorders are one of the frequent complications of neurocognitive disease, and have an impact on the quality of life of patients and caregivers. Non-phamacologic interventions are recommended as first-line treatment. The Snoezelen method is a multisensory stimulation method based on the assumption that acting on sensoriality can improve neuropsychiatric symptoms and thus quality of life, but its level of evidence is controversial. To explore this, we performed a systematic literature review of randomized controlled articles focusing on the use of the Snoezelen method in patients with cognitive disorders. Eighteen studies were included. The clinical outcomes studied were multiple (behavior, mood, cognition, functional capacities and biomedical parameters). When the Snoezelen method was compared to the "standard activities" group, it appears to be effective on short-term behavior. This was more negligible when the method was compared to others non-pharmacological interventions. Although the Snoezelen method could be effective on mood, cognition, and functional abilities, its level of evidence remains low. Furthers mixed studies (quantitative and qualitative) would be an interesting approach to delve into this topic in the most holistic way by integrating the patients, the caregivers and the cost of the method.

La prise en soin des symptômes neuropsychiatriques de patients ayant des troubles neurocognitifs est basée sur des traitements non médicamenteux. Certains auteurs suggèrent que la méthode Snoezelen pourrait être une alternative thérapeutique. L'objectif de cette revue de littérature était de faire une recherche systématique des essais contrôlés et randomisés ayant analysé l'effet de la méthode Snoezelen sur les patients âgés ayant des troubles cognitifs. Le processus de sélection a permis d'inclure 18 études, ayant des méthodologies hétérogènes. Dans plusieurs études, la méthode Snoezelen pourrait avoir un effet bénéfique, à court terme, sur les troubles du comportement, sur l'humeur, la cognition, ou les capacités fonctionnelles. Cependant, la méthode Snoezelen ne semblait pas être supérieure à d'autres interventions non médicamenteuses et certaines études montraient des résultats discordants. Finalement, le niveau de preuve d'efficacité de la méthode Snoezelen reste faible et des études mixtes (quantitatives et qualitatives) seraient intéressantes à mener pour évaluer l'intérêt de la méthode Snoezelen sur des profils spécifiques de patients ayant des troubles neurocognitifs.

Complementary and Integrative Medicine for Neurocognitive Disorders and Caregiver Health.

PURPOSE OF REVIEW: Integrative medicine is the practice of combining conventional medical treatments with "alternative" or "complementary" therapies. Integrative psychiatry is a holistic, person-centered approach to neuropsychiatric disorders that emphasizes a person's physical, emotional, interpersonal, behavioral, nutritional, environmental, and spiritual dimensions to achieve well-being. Older adults are more prone to physical injury, interpersonal loss, chronic illnesses, and physical and cognitive decline that can manifest as anxiety, depression, with functional decline and inability to care for self. Additionally, stress of caring for older adults with dementia can adversely affect caregivers' health. Although integrative approaches are perceived as safer and less stigmatizing, it is important to understand the risks and benefits of such therapies for older adults with neurocognitive disorders and their caregivers. RECENT FINDINGS: Here, we summarize the results of the recent clinical trials and meta-analyses that provide evidence for integrative approaches to treating older adults with cognitive disorders and their caregivers which include the use of diet and supplements, and mind-body therapies. Dietary and mind-body therapies have become increasingly popular and show the strongest evidence of effectiveness for cognitive disorders and caregiver stress. Vitamins and supplements are the most popular integrative intervention, but there is mixed evidence supporting their use and the concern for herb (supplement)-drug interactions. While there is increasing popularity of integrative treatments, information to guide clinicians providing care for older adults remains limited, with variable scientific rigor of the available RCTs for a large number of commonly used integrative interventions particularly for cognitive disorders and caregiver stress and well-being.

Vitamin C deficiency induces hypoglycemia and cognitive disorder through S-nitrosylation-mediated activation of glycogen synthase kinase 3ß.

Vitamin C (VC, l-ascorbic acid) is an essential nutrient that plays a key role in metabolism and functions as a potent antioxidant in regulating the S-nitrosylation and denitrosylation of target proteins. The precise function of VC deprivation in glucose homeostasis is still unknown. In the absence of L-gulono-1,4-lactone oxidoreductase, an essential enzyme for the last step of VC synthesis, VC deprivation resulted in persistent hypoglycemia and subsequent impairment of cognitive functions in female but not male mouse pups. The cognitive disorders caused by VC deprivation were largely reversed when these female pups were given glucose. VC deprivation-induced S-nitrosylation of glycogen synthase kinase 3ß (GSK3ß) at Cys14, which activated GSK3ß and inactivated glycogen synthase to decrease glycogen synthesis and storage under the feeding condition, while VC deprivation inactivated glycogen phosphorylase to decrease glycogenolysis under the fasting condition, ultimately leading to hypoglycemia and cognitive disorders. Treatment with Nω-Nitro-l-arginine methyl ester (l-NAME), a specific inhibitor of nitric oxide synthase, on the other hand, effectively prevented S-nitrosylation and activation of GSK3ß in female pups in response to the VC deprivation and reversed hypoglycemia and cognitive disorders. Overall, this research identifies S-nitrosylation of GSK3ß and subsequent GSK3ß activation as a previously unknown mechanism controlling glucose homeostasis in female pups in response to VC deprivation, implying that VC supplementation in the prevention of hypoglycemia and cognitive disorders should be considered in the certain groups of people, particularly young females.

Transcranial Photobiomodulation Therapy Ameliorates Perioperative Neurocognitive Disorder Through Modulation of Mitochondrial Function in Aged Mice.

Perioperative neurocognitive disorder (PND) is a serious nervous system complication characterized by progressive cognitive impairment, especially in geriatric population. However, the neuropathogenesis of PND is complex, and there are no approved disease-modifying therapeutic options. Mitochondrial dysfunction has been demonstrated to contribute to the occurrence and development of PND. Transcranial near-infrared (tNIR) light treatment helps to improve mitochondrial dysfunction and enhance cognition, but its effect on PND remains unclear. Here, we evaluated the effect of tNIR light treatment on PND caused by anesthesia and surgery in aged mice. We built the PND models with 18-month C57BL/6 male mice by exploratory laparotomy under isoflurane inhalation anesthesia, and treated by tNIR light with wavelength 810 nm for 2 weeks. The short-term and long-term changes in cognitive function were analyzed by behavioral tests. We further explored the effects of tNIR light on mitochondria, synapses, neurons, and signaling pathways through different experimental methods. The results demonstrated that the cognitive impairment and mitochondrial dysfunction in PND mice were ameliorated after tNIR light treatment. Further experiments demonstrated that photobiomodulation therapy (PBMT) increased synapse-related protein expression, neuronal survival, and protected synapse from depletion. Moreover, downregulated sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) were increased after tNIR light treatment. Our results suggested that tNIR light was an effective treatment of PND through PBMT effect, accompanied by synaptic and neuronal improvement. The improvement of mitochondrial dysfunction mediated by SIRT1/PGC-1α signaling pathway might participate in this process. Those findings might provide a novel and noninvasive therapeutic target for PND.

One-Year Follow-Up of Healthy Older Adults with Electroencephalographic Risk for Neurocognitive Disorder After Neurofeedback Training.

BACKGROUND: In healthy older adults, excess theta activity is an electroencephalographic (EEG) predictor of cognitive impairment. In a previous study, neurofeedback (NFB) treatment reinforcing reductions theta activity resulted in EEG reorganization and cognitive improvement. OBJECTIVE: To explore the clinical applicability of this NFB treatment, the present study performed a 1-year follow-up to determine its lasting effects. METHODS: Twenty seniors with excessive theta activity in their EEG were randomly assigned to the experimental or control group. The experimental group received an auditory reward when the theta absolute power (AP) was reduced. The control group received the reward randomly. RESULTS: Both groups showed a significant decrease in theta activity at the training electrode. However, the EEG results showed that only the experimental group underwent global changes after treatment. These changes consisted of delta and theta decreases and beta increases. Although no changes were found in any group during the period between the posttreatment evaluation and follow-up, more pronounced theta decreases and beta increases were observed in the experimental group when the follow-up and pretreatment measures were compared. Executive functions showed a tendency to improve two months after treatment which became significant one year later. CONCLUSION: These results suggest that the EEG and behavioral benefits of this NFB treatment persist for at least one year, which adds up to the available evidence contributing to identifying factors that increase its efficacy level. The relevance of this study lies in its prophylactic features of addressing a clinically healthy population with EEG risk of cognitive decline.

Alterations in Brain Cannabinoid Receptor Levels Are Associated with HIV-Associated Neurocognitive Disorders in the ART Era: Implications for Therapeutic Strategies Targeting the Endocannabinoid System.

HIV-associated neurocognitive disorders (HAND) persist despite the advent of antiretroviral therapy (ART), suggesting underlying systemic and central nervous system (CNS) inflammatory mechanisms. The endogenous cannabinoid receptors 1 and 2 (CB1 and CB2) modulate inflammatory gene expression and play an important role in maintaining neuronal homeostasis. Cannabis use is disproportionately high among people with HIV (PWH) and may provide a neuroprotective effect for those on ART due to its anti-inflammatory properties. However, expression profiles of CB1 and CB2 in the brains of PWH on ART with HAND have not been reported. In this study, biochemical and immunohistochemical analyses were performed to determine CB1 and CB2 expression in the brain specimens of HAND donors. Immunoblot revealed that CB1 and CB2 were differentially expressed in the frontal cortices of HAND brains compared to neurocognitively unimpaired (NUI) brains of PWH. CB1 expression levels negatively correlated with memory and information processing speed. CB1 was primarily localized to neuronal soma in HAND brains versus a more punctate distribution of neuronal processes in NUI brains. CB1 expression was increased in cells with glial morphology and showed increased colocalization with an astroglial marker. These results suggest that targeting the endocannabinoid system may be a potential therapeutic strategy for HAND.

Protective effects of Lycium barbarum polysaccharide on ovariectomy­induced cognition reduction in aging mice.

Women experience cognitive decline as they age due to the decrease in estrogen levels following menopause. Currently, effective pharmaceutical treatments for age­related cognitive decline are lacking; however, several Traditional Chinese medicines have shown promising effects. Lycium barbarum polysaccharides (LBPs) were found to exert a wide variety of biological activities, including anti­inflammatory, antioxidant and anti­aging effects. However, to the best of our knowledge, the neuroprotective actions of LBP on cognitive impairment induced by decreased levels of estrogen have not yet been determined. To evaluate the effects of LBP on learning and memory impairment in an animal model of menopause, 45 female ICR mice were randomly divided into the following three groups: i) Sham; ii) ovariectomy (OVX); and iii) OVX + LBP treatment. The results of open­field and novel object recognition tests revealed that mice in the OVX group had learning and memory impairments, and lacked the ability to recognize and remember new objects. Notably, these deficits were attenuated following LBP treatment. Immunohistochemical staining confirmed the protective effects of LBP on hippocampal neurons following OVX. To further investigate the underlying mechanism of OVX in mice, mRNA sequencing of the hippocampal tissue was performed, which revealed that the Toll­like receptor 4 (TLR4) inflammatory signaling pathway was significantly upregulated in the OVX group. Moreover, reverse transcription­quantitative PCR and immunohistochemical staining demonstrated that OVX induced hippocampal injury, upregulated the expression levels of TLR4, myeloid differentiation factor 88 and NF­κB, and increased the expression of TNF­α, IL­6 and IL­1ß inflammatory factors. Conversely, LBP treatment downregulated the expression levels of mRNAs and proteins associated with the TLR4/NF­κB signaling pathway, decreased the inflammatory response and reduced neuronal injury in mice that underwent OVX. In conclusion, the findings of the present study indicated that oral LBP treatment may alleviate OVX­induced cognitive impairments by downregulating the expression levels of mRNAs and proteins associated with the TLR4/NF­κB signaling pathway, thereby reducing neuroinflammation and damage to the hippocampal neurons. Thus, LBP may represent a potential agent for the prevention of learning and memory impairments in patients with accelerated aging caused by estrogen deficiency.

LncRNA-MYL2-2 and miR-124-3p Are Associated with Perioperative Neurocognitive Disorders in Patients after Cardiac Surgery.

BACKGROUND: Perioperative neurocognitive disorders (PND) resulting from cardiac surgery is a complication with high morbidity and mortality. However, the pathogenesis is unknown. METHODS: For the sake of investigating the risk factors and mechanism of PND, we collected the characteristics and neurological scores of patients undergoing cardiac surgery in the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University and Affiliated Hospital of Southwest Medical University from Jan 1, 2016 to Dec 11, 2018. RESULTS: We found that age and left atrial thrombus are independent risk factors for PND after cardiac surgery. Furthermore, the serum of 29 patients was collected on the 7th day after cardiac surgery for detecting the expression of lncRNA-MYL2-2 and miR-124-3p. Increased lncRNA-MYL2-2 and decreased miR-124-3p in serum were associated with the decline of patients' cognition. CONCLUSIONS: LncRNA-MYL2-2 and miRNA-124-3p may jointly participate in the occurrence and development of PND after cardiac surgery. These important findings are advantaged to further understand the pathogenesis of PND and prevent it, provide new biomarkers for the diagnosis and monitoring of PND.

Dietary interventions and cognition: A systematic review of clinical trials.

Prevalence of Alzheimer's Disease and other forms of dementia is increasing in accordance with the increase of life expectancy and the resulting world population aging, while an effective pharmaceutical treatment is pending. These facts underline the need for development of targeted interventions that could decrease the incidence of dementia. Dietary supplementation, especially sources of ω-3 fatty acids and polyphenols such as fish oil and blueberries respectively, have been reported to have a beneficial effect on cognitive functioning. The aim of this review is to summarize the most recent findings of clinical studies investigating the effect of dietary supplementation on cognitive performance and identify potential effective interventions. For this purpose, PubMed, Scopus and Google Scholar research was conducted and a total of ten studies met the selection criteria. Four of these studies investigated the effect of ω-3 fatty acid supplementation. Two of these presented significant benefits in certain domains of cognitive functions (such as working memory, space imagery efficiency perceptual speed), in full scale IQ as well as prevention of hippocampal atrophy while the remaining two did not report any improvements. Two more studies investigated the effect of polyphenol supplementation and reported minor benefits in spatial memory as well as enhanced stimulation of certain brain regions. One study compared the effect of fish oil and blueberry supplementation as well as their combination and presented cognitive benefits for both fish oil and blueberries but not for their simultaneous administration. Finally, three more studies investigated the effect of DW 2009 soybean, ashwagandha and a nutraceutical formulation and reported cognitive benefits in attention, memory and global cognition respectively for their intervention groups. In total, eight studies investigated interventions on people with Mild Cognitive Impairment or Subjective Cognitive Impairment and all of them reported significant cognitive benefits in some cognitive domains. On the contrary, the remaining two studies included individuals with diagnosed dementia reported minimal to hardly any benefits. Conclusively, the interventions of the studies reviewed seem promising for individuals at risk of dementia, but not for those who are already diagnosed with dementia. However, further research is required to validate their effect as well as determine recommended doses.

Mindfulness-based stress reduction for HIV-associated neurocognitive disorder: Rationale and protocol for a randomized controlled trial in older adults.

The symptom burden of HIV-associated neurocognitive disorder (HAND) is high among older individuals, and treatment options are limited. Mindfulness-based stress reduction (MBSR) has potential to improve neurocognitive performance, psychosocial wellbeing, and quality of life, but empirical studies in this growing vulnerable population are lacking. In this trial, participants (N = 180) age 55 and older who are living with HIV infection, are on combination antiretroviral therapy with suppressed viral loads, and yet continue to experience behavioral and cognitive symptoms of HAND, are randomized to MBSR or to a waitlist control arm that receives MBSR following a 16-week period of standard care. Primary outcomes (attention, executive function, stress, anxiety, depression, everyday functioning, quality of life) and potential mediators (affect, mindfulness) and moderators (social support, loneliness) are assessed at baseline and weeks 8, 16, and 48 in both groups, with an additional assessment at week 24 (post-MBSR) in the crossover control group. Assessments include self-report and objective measures (e.g., neuropsychological assessment, neurological exam, clinical labs). In addition, a subset of participants (n = 30 per group) are randomly selected to undergo fMRI to evaluate changes in functional connectivity networks and their relationship to changes in neuropsychological outcomes. Forthcoming findings from this randomized controlled trial have the potential to contribute to a growing public health need as the number of older adults with HAND is expected to rise.

Identification of Neuropsychiatric Copy Number Variants in a Health Care System Population.

Importance: Population screening for medically relevant genomic variants that cause diseases such as hereditary cancer and cardiovascular disorders is increasing to facilitate early disease detection or prevention. Neuropsychiatric disorders (NPDs) are common, complex disorders with clear genetic causes; yet, access to genetic diagnosis is limited. We explored whether inclusion of NPD in population-based genomic screening programs is warranted by assessing 3 key factors: prevalence, penetrance, and personal utility. Objective: To evaluate the suitability of including pathogenic copy number variants (CNVs) associated with NPD in population screening by determining their prevalence and penetrance and exploring the personal utility of disclosing results. Design, Setting, and Participants: In this cohort study, the frequency of 31 NPD CNVs was determined in patient-participants via exome data. Associated clinical phenotypes were assessed using linked electronic health records. Nine CNVs were selected for disclosure by licensed genetic counselors, and participants' psychosocial reactions were evaluated using a mixed-methods approach. A primarily adult population receiving medical care at Geisinger, a large integrated health care system in the United States with the only population-based genomic screening program approved for medically relevant results disclosure, was included. The cohort was identified from the Geisinger MyCode Community Health Initiative. Exome and linked electronic health record data were available for this cohort, which was recruited from February 2007 to April 2017. Data were collected for the qualitative analysis April 2017 through February 2018. Analysis began February 2018 and ended December 2019. Main Outcomes and Measures: The planned outcomes of this study include (1) prevalence estimate of NPD-associated CNVs in an unselected health care system population; (2) penetrance estimate of NPD diagnoses in CNV-positive individuals; and (3) qualitative themes that describe participants' responses to receiving NPD-associated genomic results. Results: Of 90 595 participants with CNV data, a pathogenic CNV was identified in 708 (0.8%; 436 women [61.6%]; mean [SD] age, 50.04 [18.74] years). Seventy percent (n = 494) had at least 1 associated clinical symptom. Of these, 28.8% (204) of CNV-positive individuals had an NPD code in their electronic health record, compared with 13.3% (11 835 of 89 887) of CNV-negative individuals (odds ratio, 2.21; 95% CI, 1.86-2.61; P < .001); 66.4% (470) of CNV-positive individuals had a history of depression and anxiety compared with 54.6% (49 118 of 89 887) of CNV-negative individuals (odds ratio, 1.53; 95% CI, 1.31-1.80; P < .001). 16p13.11 (71 [0.078%]) and 22q11.2 (108 [0.119%]) were the most prevalent deletions and duplications, respectively. Only 5.8% of individuals (41 of 708) had a previously known genetic diagnosis. Results disclosure was completed for 141 individuals. Positive participant responses included poignant reactions to learning a medical reason for lifelong cognitive and psychiatric disabilities. Conclusions and Relevance: This study informs critical factors central to the development of population-based genomic screening programs and supports the inclusion of NPD in future designs to promote equitable access to clinically useful genomic information.

[Effects of pony-assisted therapy on the behavior of older people with neurocognitive disorders living in nursing homes]. / Effets de la thérapie assistée par le poney sur le comportement des personnes âgées ayant des troubles neurocognitifs vivant en Ehpad.

CONTEXT: Experienced in psychomotricity in two nursing homes, pony-assisted therapy shows first positive effects on psycho-behavioral symptoms. Recognized in the field of disability and psychiatry, this form of therapy is not developed in gerontology. OBJECTIVES: To measure the effects of this therapy on the behavior of elderly people with neurocognitive disorders living in long-term care and especially on the involvement in this activity. Anxiety and apathy were chosen as the measurement criteria. METHODS: An intervention study with an experimental cross-study design was conducted over two months for 23 subjects. An intervention group was studied during a period with TAP and a period without TAP. Another group without intervention was also studied. All participants were assessed before and after intervention with the NPI-R scale. The engagement during two TAP sessions and one animation time was also evaluated with the ECPAI scale. RESULTS: In the crossover study, positive engagement is more important in participant/pony interaction than in participant/facilitator interaction (p<0.01). The ECPAI score reflecting apathetic behavior was significantly decreased during interaction with the animal than in the interaction with the facilitator in patients undergoing therapy (p<0.01). The ECPAI score reflecting engagement is greater in pony interaction for participants in therapy than in the control group in facilitator interaction (p<0.01). There is no significant change in the scores for the anxiety and apathy items on the NPI-R scale. CONCLUSION: TAP participates in the positive engagement of the elderly people in the interaction with the animal. These results are consistent with the conclusions of the studies on animal mediation and confirm the clinical observations collected. TAP could work by improving self-esteem and valuing all of the person's preserved abilities.

Ligustrazine ameliorates lipopolysaccharide­induced neurocognitive impairment by activating autophagy via the PI3K/AKT/mTOR pathway.

Autophagy is a lysosome­mediated cell content­dependent degradation pathway that leads to enhanced inflammation in an uncontrolled state. This study examined the role of autophagy in lipopolysaccharide (LPS)­induced brain inflammation and the effects of the traditional Chinese medicine ligustrazine on LPS­induced neurocognitive impairment in rats. Furthermore, the molecular mechanisms by which ligustrazine influences neurocognitive impairments were explored. The production of the inflammatory mediators interleukin (IL)­1ß and tumor necrosis factor (TNF)­α was analyzed using ELISAs, and the expression levels of the autophagy marker microtubule­associated protein light chain 3 (LC3) II/I were analyzed using western blotting. LPS exposure upregulated the expression of IL­1ß and TNF­α and downregulated the expression of LC3 II/I. Ligustrazine activated autophagy by preventing the expression of phosphoinositide 3­kinase (PI3K), phosphorylated protein kinase B (p­AKT), and phosphorylated mammalian target of rapamycin (p­mTOR). The present results suggest that ligustrazine improved LPS­induced neurocognitive impairments by activating autophagy and ameliorated neuronal injury by regulating the PI3K/AKT/mTOR signaling pathway. These findings provide an important reference for the prevention and treatment of neuroinflammation.

Neurocognitive sequelae after carbon monoxide poisoning and hyperbaric oxygen therapy.

Carbon monoxide (CO) has been the leading cause of poisoning mortality in many countries and hyperbaric oxygen (HBO) is a widely accepted treatment for CO poisoning. However, some patients with CO poisoning will still develop neurocognitive sequelae regardless of HBO therapy, which can persist since CO poisoning or be present days to weeks after a recovery from CO poisoning. HBO has been used in the prevention and treatment of neurocognitive sequelae after CO poisoning, and some mechanisms are also proposed for the potential neuroprotective effects of HBO on the neurocognitive impairment after CO poisoning, but there is still controversy on the effectiveness of HBO on neurocognitive sequelae after CO poisoning. In this paper, we briefly introduce the neurocognitive sequelae after CO poisoning, summarize the potential predictive factors of neurocognitive sequelae, and discuss the use of HBO in the treatment and prevention of neurocognitive sequelae after CO poisoning.