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Background: The VALCODIS (Valencian Cognitive Diseases Study) cohort was designed and studied at the Hospital Universitari i Politècnic La Fe (Valencia, Spain) for the research of cognitive diseases, especially in the search for new biomarkers of Alzheimer's disease (AD). Methods: Participants in the VALCODIS cohort had cerebrospinal fluid (CSF) and blood samples, neuroimaging, and neuropsychological tests. The ApoE genotype was evaluated to identify its relationship with CSF biomarkers and neuropsychological tests in AD and non-AD participants. Results: A total of 1249 participants were included. They were mainly AD patients (n = 547) but also patients with other dementias (frontotemporal lobar dementia (n = 61), Lewy body dementia without AD CSF signature (n = 10), vascular dementia (n = 24) and other specific causes of cognitive impairment (n = 442), and patients with subjective memory complaints (n = 165)). In the ApoE genotype evaluation, significant differences were found for Aß42 levels between genotypes in both AD and non-AD patients, as well as a negative correlation between tau values and a cognitive test in non-carriers and ε4 heterozygous. Conclusions: The VALCODIS cohort provides biologically diagnosed patients with demographical, clinical and biochemical data, and biological samples for further studies on early AD diagnosis. Also, the ApoE genotype evaluation showed correlations between CSF biomarkers and neuropsychological tests.

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BACKGROUND: The number of people with cognitive deficits and diseases, such as stroke, dementia, or attention-deficit/hyperactivity disorder, is rising due to an aging, or in the case of attention-deficit/hyperactivity disorder, a growing population. Neurofeedback training using brain-computer interfaces is emerging as a means of easy-to-use and noninvasive cognitive training and rehabilitation. A novel application of neurofeedback training using a P300-based brain-computer interface has previously shown potential to improve attention in healthy adults. OBJECTIVE: This study aims to accelerate attention training using iterative learning control to optimize the task difficulty in an adaptive P300 speller task. Furthermore, we hope to replicate the results of a previous study using a P300 speller for attention training, as a benchmark comparison. In addition, the effectiveness of personalizing the task difficulty during training will be compared to a nonpersonalized task difficulty adaptation. METHODS: In this single-blind, parallel, 3-arm randomized controlled trial, 45 healthy adults will be recruited and randomly assigned to the experimental group or 1 of 2 control groups. This study involves a single training session, where participants receive neurofeedback training through a P300 speller task. During this training, the task's difficulty is progressively increased, which makes it more difficult for the participants to maintain their performance. This encourages the participants to improve their focus. Task difficulty is either adapted based on the participants' performance (in the experimental group and control group 1) or chosen randomly (in control group 2). Changes in brain patterns before and after training will be analyzed to study the effectiveness of the different approaches. Participants will complete a random dot motion task before and after the training so that any transfer effects of the training to other cognitive tasks can be evaluated. Questionnaires will be used to estimate the participants' fatigue and compare the perceived workload of the training between groups. RESULTS: This study has been approved by the Maynooth University Ethics Committee (BSRESC-2022-2474456) and is registered on ClinicalTrials.gov (NCT05576649). Participant recruitment and data collection began in October 2022, and we expect to publish the results in 2023. CONCLUSIONS: This study aims to accelerate attention training using iterative learning control in an adaptive P300 speller task, making it a more attractive training option for individuals with cognitive deficits due to its ease of use and speed. The successful replication of the results from the previous study, which used a P300 speller for attention training, would provide further evidence to support the effectiveness of this training tool. TRIAL REGISTRATION: ClinicalTrials.gov NCT05576649; https://clinicaltrials.gov/ct2/show/NCT05576649. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/46135.

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Increasing pieces of evidence have supported those chemicals from industrial, agricultural wastes and organoleptic activities play important role in the development of neurological disorders. The frequency of neurological disorders is increased to a much extent in recent years with the advancements in science and technology. Google Scholar, PubMed, and Scopus databases were selected to search the relevant information by using keywords including "Heavy metals", "Neurotoxicity", "Glutathione", "Glutathione AND Neurodegenerative disorders" etc. Heavy metals are particularly recognized as a major resource of toxicities during the stage of early pregnancy where a fetus gets exposed to them from maternal activities and circulation. As infants have a weak immune system and cannot respond to the specific challenge as faced by the body during mercury, zinc, iron, and cadmium exposure. Daily diet and drinking habits in addition to industrial activities also form a major field of study under investigation. This study aims to investigate the role of these metals in the accumulation of pollutants in the brain, liver, and kidneys hence leading to serious consequences. Moreover, their prevalence in teenagers that are under the age of ten years is being observed that leads them to learn, writing, and intellectual abilities. Males are more affected due to their hormonal differences. The role of the GST gene in the development of cognitive conditions and its phenotypes has been discussed thoroughly in this review. The mutations of GST lead to the accumulation of peroxides and superoxides which exacerbate oxidative damage to cells. Binding of toxic metals to GSH genes and the role of glutathione transferase genes is was demonstrated in this review.

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INTRODUCTION: Accumulated vascular damage contributes to the onset and progression of vascular dementia and possibly to Alzheimer's disease. Here we evaluate the feasibility and utility of using retinal imaging of microvascular markers to identify older adults at risk of cognitive disease. METHODS: The "Eye Determinants of Cognition" (EyeDOC) study recruited a biracial, population-based sample of participants from two sites: Jackson, MS, and Washington Co, MD. Optical coherence tomographic angiography (OCTA) was used to capture vessel density (VD) from a 6 × 6 mm scan of the macula in several vascular layers from 2017 to 2019. The foveal avascular zone (FAZ) area was also estimated. Image quality was assessed by trained graders at a reading center. A neurocognitive battery of 10 tests was administered at three time points from 2011 to 2019 and incident mild cognitive impairement (MCI)/dementia cases were ascertained. Linear mixed-effects models were used to evaluate associations of retinal vascular markers with cognitive factor score change over time. RESULTS: Nine-hundred and seventy-six older adults (mean age of 78.7 (± 4.4) years, 44% black) were imaged. Gradable images were obtained in 55% (535/976), with low signal strength (66%) and motion artifact (22%) being the largest contributors to poor quality. Among the 297 participants with both high-quality images and no clinically significant retinal pathology, the average decline in global cognitive function factor score was -0.03 standard deviations per year. In adjusted analyses, no associations of VD or FAZ with longitudinal changes in either global cognitive function or with incident MCI/dementia were found. CONCLUSIONS: In this large biracial community sample of older adults representative of the target population for retinal screening of cognitive risk, we found that obtaining high-quality OCTA scans was infeasible in a nearly half of older adults. Among the select sample of healthier older adults with scans, OCTA markers were not predictive of cognitive impairment.

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HIV associated neurocognitive impairment afflicts roughly half of infected individuals on antiretroviral therapy. This disease currently has no treatment. We have previously shown that type I interferon is induced by and partially controls infection and neuropathogenesis in mice infected by chimeric HIV, EcoHIV. Here we investigate the intentional ligation of the pattern recognition receptor Toll-like receptor 3 (TLR3) by polyinosinic-polycytidylic acid (poly I:C) for its ability to prevent or control infection and associated cognitive disease in EcoHIV infected mice. We tested topical, injection, and intranasal application of poly I:C in mice during primary infection through injection or sexual transmission or in established infection. We measured different forms of HIV DNA and RNA in tissues by real-time PCR and the development of HIV-associated cognitive disease by the radial arm water maze behavioral test. Our results indicate that poly I:C blocks primary EcoHIV infection of mice prior to reverse transcription and reduces established EcoHIV infection. Prevention or control of viral replication by poly I:C prevents or reverses HIV associated cognitive disease in mice. These findings indicate that poly I:C or other innate immune agonists may be useful in control of HIV cognitive disease.

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Obesity and cognitive decline can occur in association. Brain dysmetabolism and insulin resistance might be common underlying traits. We aimed to examine the effect of high-fat diet (HFD) on cognitive decline, and of cognitive impairment on food intake and body-weight, and explore efficacy of chronic intranasal insulin (INI) therapy. We used control (C) and triple transgenic mice (3×Tg, a model of Alzheimer's pathology) to measure cerebral mass, glucose metabolism, and the metabolic response to acute INI administration (cerebral insulin sensitivity). Y-Maze, positron emission-computed tomography, and histology were employed in 8 and 14-month-old mice, receiving normal diet (ND) or HFD. Chronic INI therapy was tested in an additional 3×Tg-HFD group. The 3×Tg groups overate, and had lower body-weight, but similar BMI, than diet-matched controls. Cognitive decline was progressive from HFD to 3×Tg-ND to 3×Tg-HFD. At 8 months, brain fasting glucose uptake (GU) was increased by C-HFD, and this effect was blunted in 3×Tg-HFD mice, also showing brain insulin resistance. Brain mass was reduced in 3×Tg mice at 14 months. Dentate gyrus dimensions paralleled cognitive findings. Chronic INI preserved cognition, dentate gyrus and metabolism, reducing food intake, and body weight in 3×Tg-HFD mice. Peripherally, leptin was suppressed and PAI-1 elevated in 3×Tg mice, correlating inversely with cerebral GU. In conclusion, 3×Tg background and HFD exert additive (genes*lifestyle) detriment to the brain, and cognitive dysfunction is accompanied by increased food intake in 3×Tg mice. PAI-1 levels and leptin deficiency were identified as potential peripheral contributors. Chronic INI improved peripheral and central outcomes.

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The progressive supranuclear palsy is a progressive neurodegenerative disease characterized by Parkinsonism, oculomotor abnormalities, early postural instability and cognitive impairment. Neurodegeneration in PSP is associated with tau protein, but the mechanisms by which tau abnormalities lead to cell dysfunction and death are not well understood. Neuro-behavioural problems related to the fear and loss of autonomy can determinate many bioethical implications. Careful planning involving patients' families, academic and industry researchers were necessary to ensure improvement in quality of life.

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The TGF-ß superfamily signaling is involved in a variety of biological processes during embryogenesis and in adult tissue homeostasis. Faulty regulation of the signaling pathway that transduces the TGF-ß superfamily signals accordingly leads to a number of ailments, such as cancer and cardiovascular, metabolic, urinary, intestinal, skeletal, and immune diseases. In recent years, a number of studies have elucidated the essential roles of TGF-ßs and BMPs during neuronal development in the maintenance of appropriate innervation and neuronal activity. The new advancement implicates significant roles of the aberrant TGF-ß superfamily signaling in the pathogenesis of neurological disorders. In this review, we compile a number of reports implicating the deregulation of TGF-ß/BMP signaling pathways in the pathogenesis of cognitive and neurodegenerative disorders in animal models and patients. We apologize in advance that the review falls short of providing details of the role of TGF-ß/BMP signaling or mechanisms underlying the pathogenesis of neurological disorders. The goal of this article is to reveal a gap in our knowledge regarding the association between TGF-ß/BMP signaling pathways and neuronal tissue homeostasis and development and facilitate the research with a potential to develop new therapies for neurological ailments by modulating the pathways.

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A Western diet, high in saturated fats, has been linked to the development of cognitive impairment. Lycopene has recently received considerable attention for its potent protective properties demonstrated in several models of nervous system dysfunction. However, it remains unclear whether lycopene exerts protective effects on cognition. The present study aimed to investigate the protective effects of lycopene on learning and memory impairment and the potential underlying mechanism in rats fed a high-fat diet (HFD). One-month-old male rats were fed different diets for 16 weeks (n=12 per group), including a standard chow diet (CD), a HFD, or a HFD plus lycopene (4mg/kg, oral gavage in the last three weeks). Behavioral testing, including the Morris water maze (MWM), object recognition task (ORT), and anxiety-like behavior in an open field (OF), were assessed at week 16. The dendritic spine density and neuronal density in the hippocampal CA1 subfield were subsequently measured. The results indicate that HFD consumption for 16 weeks significantly impaired spatial memory (P<0.001), working memory (P<0.01), and object recognition memory (P<0.01), decreased the dendritic spine density (P<0.001), damaged pyramidal neurons in the CA1 subfield (P<0.001) compared with the CD group. However, lycopene significantly attenuated learning and memory impairments and prevented the reduction in dendritic spine density (P<0.001). Thus, this study indicated that lycopene helps to protect HFD induced cognitive dysfunction.

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The offered methodological principles of the geriatric analysis in medicine enables to plan economic parameters of social protection of the population, necessary amount of medical help financing, to define a structure of the qualified medical personnel training. It is shown that personal health and cognitive longevity of the person depend on the adequate system geriatric analysis and use of biological parameters monitoring in time. That allows estimate efficiency of the combined individual treatment. The geriatric analysis and in particular its genetic-mathematical component aimed at reliability and objectivity of an estimation of the person life expectancy in the country and in region due to the account of influence of mutagen factors as on a gene of the person during his live, and on a population as a whole.

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Expression of hypoxia-inducible factor 1a (HIF1a) is increased under several pathological conditions such as hyperactive mechanistic target of rapamycin complex 1 (mTORC1) in tuberous sclerosis complex (TSC). Hyperactive mTORC1 and the resulting increased dendritic complexity of neurons are shared molecular and cellular alterations in several neurological disorders associated with cognitive disabilities. Despite some evidence that HIF1a contributes to dendritic overgrowth in vitro, it remains unknown whether increased HIF1a in TSC neurons could contribute to their increased dendritic complexity. To address this use in vivo, we generated TSC neurons by deleting Tsc1 in newborn olfactory bulb (OB) neurons of conditional Tsc1 transgenic mice using neonatal electroporation. In addition to their increased dendritic complexity, Tsc1(null) neurons have been reported to display increased Hif1a mRNA level and HIF1a transcriptional activity. We found that Tsc1(null)-dependent dendritic overgrowth was prevented by knocking down HIF1a or expressing a dominant negative HIF1a. In addition, overexpressing HIF1a in wild-type developing neurons resulted in increased dendritic complexity in vivo. These data highlight that an increase in HIF1a levels contributes to abnormal dendritic patterning in developing neurons under normal conditions and hyperactive mTORC1 conditions as in TSC.

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