22 results about "Cognitive deficit" patented technology

The present composition comprises magnesium-L-threonate and a neurotransmitter such as, but not limited to phosphatidylserine and optionally, at least one of vitamin C, vitamin B6, and vitamin D3. The composition has been shown to increase at least one of memory or cognition in clinical study subjects. The present disclosure is further directed to methods of identifying and a subject with a memory or cognitive deficiency and administering a therapeutically effective amount of a formula comprising magnesium-L-threonate and a neurotransmitter to improve the memory and / or cognitive deficiency. In some implementations, the magnesium-L-threonate is Magtein®. It is also intended that any other neurotransmitter that results in a synergistic composition of the magnesium-L-threonate and the neurotransmitter by administered to improve a subject's memory and / or cognition.

New 3-phenoxy-3-phenylpropanamine derivatives, compositions thereof and their use as a medicament in the treatment of nervous system disorders associated with cognitive deficits and behavioural dysfunctions, in particular fragile X syndrome and Rett syndrome.

Smell loss (hyposmia) is a common cognitive deficit perceived clinically as a nasal abnormality but, in reality, it is a deficit of complex biochemical detection and processing of externally generated chemical events. A major mechanism initiating hyposmia involves abnormalities of growth of human olfactory cells through altered growth factor stimulation of stem cell activity. While several growth factors are involved well known signaling substances generate and perpetuate this process; among these substances are cAMP and cGMP. We have hypothesized a role for cAMP in taste and olfaction as a growth factor necessary for stem cell maturation. We have thus measured cAMP and cGMP in parotid saliva of 19 normal subjects and 144 patients with hyposmia to evaluate roles for these signals in cognition. Results indicate that patients secrete significantly less cAMP (0.40+ / −0.03 pmol / mg protein (Mean+ / −SEM); patients; 0.67+ / −0.09, normals, p<0.005) and significantly less cGMP (0.072+ / −0.003, patients; 0.100+ / −0.007, normals, p<0.005) than do normals. While parotid gland secretions relate directly to taste bud growth factors many substances secreted in saliva are similar to those secreted in nasal mucus. The present results indicate aberrant signaling in saliva may serve both as a marker for hyposmia and as an indicator of a mechanism which interferes with olfactory system function.

The present disclosure relates to compositions and methods for preventing or treating a cognitive deficit in a subject. The compositions comprise a barley extract as an active ingredient.

This invention relates to the field of molecular biology, specifically to the application of PRAS40 protein as a therapeutic target for Alzheimer's disease. This invention combines Western blotting, computer-generated virtual docking, and surface plasmon resonance (SPR) techniques to confirm that PRAS40 protein is a key target influencing the pathological progression of AD. Experimental results show that specific intervention (elimination or reduction) of PRAS40 protein levels is sufficient to significantly improve cognitive deficits and pathological characteristics in AD model mice, providing a clear molecular target for subsequent screening and development of novel anti-AD drugs.

A method of reducing an APOE ε4 mediated cognitive deficit is provided and comprises administering to a subject in need thereof an effective amount of a recombinant vaccinia virus complement control protein (hrVCP) polypeptide having a modified amino acid sequence including one or more amino acid substitutions to an amino acid sequence as set forth in SEQ ID NO: 2, wherein the one or more amino acid substitutions are selected from the group consisting of H98Y, E102K, E108K, E120K, and combinations thereof, provided at least one of the substitutions is E102K. Methods of treating dementia characterized by an APOE ε4 mediated cognitive deficit and methods of reducing complement activation mediated by APOE ε4 are further provided an include administration of the hrVCP polypeptide.

Here, the Inventors show that chronic IL- 1 -induced H2A.X signaling, which mediated DNA DSB response, in hippocampal neurons is a critical driver of cognitive deficits in chronic low grade neuroinflammation. They show that mice chronically infected with the brain- persisting T. gondii parasite display deficits in spatial memory consolidation without general memory loss. Extensive mapping of the neuroinflammatory landscape, beyond a latent T. gondii infection elicited type 1-like neuroinflammation, display elevated production of IL-1α and IL-1β in the hippocampus. Using a mouse model to specifically delete the IL-1 receptor from excitatory neurons, they uncovered that neuronal IL-1 signaling is required for the spatial memory deficits caused by latent T. gondii infection. By singling out a chronic exposure to IL- ip they found that IL-1β signaling in neurons indeed impairs spatial memory. Moreover, they showed that chronic exposure to IL-1β increases DNA DSB levels in neurons, and that neuronal H2A.X-dependent DSB response mediates the IL-1β-induced memory deficits. Importantly, neuronal DSBs were also increased upon T. gondii infection and the deficit in hippocampus- dependent spatial memory caused by T. gondii infection was prevented by the abrogation of neuronal H2A.Xdependent signaling. These results highlight the instrumental role of cytokine- induced DSB-dependent signaling in spatial memory defects elicited by a chronic infectious neuroinflammatory process. Accordingly, the present invention relates to a method of treating a subject suffering from cognitive deficit comprising administering to said subject a therapeutically effective amount of an inhibitor of IL- 1 -induced H2A.X signaling.

The present invention relates to the field of treat age-related cognitive declines. In this study, the inventors report that GPR158, which localizes at the PC, is required for OCN- dependent autophagy induction in hippocampal neurons. Consistently, the mobilization of key autophagy players by OCN in hippocampal neurons requires core PC-proteins. In aged hippocampi, neuronal PC present an abnormal morphology, correlated with a reduction of the major core ciliary proteins levels. Conversely, restoration of their levels in aged hippocampi is sufficient to improve autophagy and cognitive deficits. Lastly, they show that core PC-proteins are required to integrate the rejuvenating effects of OCN in the hippocampus, thereby ameliorating age-related cognitive deficits. Altogether, these findings demonstrate a new paradigm for the neuron / systemic milieu communication and significantly advance our understanding of the regulatory mechanism mediating the rejuvenating effects of the pro-youth blood factor, OCN, in hippocampal neurons. This study also provides the foundation for novel therapeutic strategies to treat age-related cognitive decline, as well as neurological deficits in ciliopathies. Thus, the present invention relates to an activator of the primary cilia (PC) for use in the restoration and / or improvement of cognitive functions in a subject in need thereof.

The present invention relates to a compound of formula (I) wherein R1 represents a (C3-C8)cycloalkyl group, a bridged (C6-C10)cycloalkyl group, a fused phenyl group, a substituted phenyl group, a R′-L- group, wherein L is either a single bond or a (C1-C3)alkanediyl group, and R′ represents, a (C3-C8)heterocycloalkyl group, or a (C3-C8)heteroaryl u group, or a R″-L- group wherein L is a (C1-C3)alkanediyl group, and R″ is an optionally substituted phenyl group; R2 is selected from the group consisting of a hydrogen atom and a (C1-C3)alkyl group; R5 represents a hydrogen atom, a (C1-C4)alkyl group or a (C3-C6)cycloalkyl group or any of its pharmaceutically acceptable salt. The present invention further relates to a composition comprising a compound of formula (I) and a process for manufacturing said compound as well as its synthesis intermediates. It also relates to said compound for use as a medicament, in particular in the treatment and / or prevention of cognitive deficits and neuroinflammation associated with Down syndrome; Alzheimer's disease; dementia; tauopathies; Parkinson's disease; CDKL5 Deficiency Disorder; Phelan-McDermid syndrome; autism; type 1 and type 2 diabetes; abnormal folate and methionine metabolism; osteoarthritis and tendinopathy; Duchenne muscular dystrophy; cancers and leukemias; neuroinflammation, anemia, infections caused by unicellular parasites, viral infections and for regulating body temperature.

The present disclosure relates to methods and compositions for treating traumatic brain injury (TBI) and TBI-associated impairments and improving outcome in subjects that have sustained traumatic brain injury comprising administering to the subject a sgp130 or an agent that promotes the binding of sgp130 and sIL-6R and / or reduces sIL-6R mediated trans-signaling. The present disclosure also relates to methods and kits for identifying a subject that is at risk of developing a TBI-associated impairment (e.g., headache, depression, cognitive deficits, and seizure) or monitoring the responsiveness to a treatment regimen for a TBI-associated impairment in the subject, using biomarkers (e.g., white blood cells indices (e.g., Neutrophil-Lymphocyte Ratio (NLR), absolute lymphocyte counts), sIL-6R, sgp130, IL-6, sgp130:sIL-6R ratio, sIL-2Ra, IL-2, sIL-2Ra:IL-2 ratio, TNFα, TNFRI, and TNFRI:TNFα ratio).

N-([1,1'-biaryl]-4-yl)-N-((1-hydroxycycloalkyl)methyl)-2-(aryl)cyclopropane-1-carboxamide compounds (I) and derivatives are G-protein coupled receptor (GPR) 88 modulators for use in the treatment of a disease mediated by GPR88. Indications include Tourette's Syndrome, Huntington's Disease (HD), Addiction, Parkinson's Disease (PD), Schizophrenia, and Attention Deficit Hyperactivity Disorder (ADHD), choreiform movements, tardive dyskinesia, speech delay, learning disabilities, depression, hyperkinetic movement disorders characterised by chorea and / or dystonia, psychosis, cognitive deficits in schizophrenia, affective disorders, bipolar disorder, Alzheimer's disease, basal ganglia disorders, and tardive dyskinesia.

New 3-phenoxy-3-phenylpropanamine derivatives, compositions thereof and their use as a medicament in the treatment of nervous system disorders associated with cognitive deficits and behavioural dysfunctions, in particular fragile X syndrome and Rett syndrome.

The present disclosure relates to methods and compositions for treating traumatic brain injury (TBI) and TBI-associated impairments and improving outcome in subjects that have sustained traumatic brain injury comprising administering to the subject a sgp130 or an agent that promotes the binding of sgp130 and sIL-6R and / or reduces sIL-6R mediated trans-signaling. The present disclosure also relates to methods and kits for identifying a subject that is at risk of developing a TBI-associated impairment (e.g., headache, depression, cognitive deficits, and seizure) or monitoring the responsiveness to a treatment regimen for a TBI-associated impairment in the subject, using biomarkers (e.g., white blood cells indices (e.g., Neutrophil-Lymphocyte Ratio (NLR), absolute lymphocyte counts), sIL-6R, sgp130, IL-6, sgp130:sIL-6R ratio, sIL-2Ra, IL-2, sIL-2Ra:IL-2 ratio, TNFα, TNFRI, and TNFRI:TNFα ratio).

The present application relates to the technical field of motor design, in particular to a motor reverse design method and system based on a proxy model and active learning, comprising the following steps: S1, defining multi-working-condition targets and an initial design space; S2, constructing a high-precision forward proxy model; S3, reverse optimization solution based on a two-stage hybrid strategy; S4, optimization solution based on an active learning self-adaptive correction mechanism until the error converges, outputting a final motor candidate scheme. The present application introduces an active learning mechanism to address the prediction distortion problem caused by the sparsity of high-performance area samples in reverse design, improves the training set by dynamically backfilling real finite element simulation samples, makes up for the cognitive defects of the proxy model in unknown areas, effectively improves the generalization accuracy and scheme feasibility of extreme performance areas, and provides reliable technical support for efficient and accurate motor design.

An orally disintegrating pharmaceutical tablet comprising: between 0.1 and 21 wt % of cariprazine or its pharmaceutically acceptable salts, between 0.1 and 15 wt % of a disintegrant, between 0.1 and 5 wt % of colloidal silicon dioxide, between 0.1 and 10 wt % of a taste masking agent, between 0.1 and 5 wt % of a lubricant, and up to 100 wt % of a diluent, the percentage being expressed with regard to the total weight of the pharmaceutical tablet. Said composition for use in the treatment and / or prevention of pathological conditions which require the modulation of dopamine receptors, selected from the group of psychoses, drug abuse, cognitive impairment accompanying schizophrenia, mild-to-moderate cognitive deficits, dementia, psychotic states associated with dementia, eating disorders, attention deficit disorders, hyperactivity disorders in children, psychotic depression, bipolar disorder, paranoid and delusional disorders, dyskinetic disorders, anxiety, sexual dysfunction, sleep disorders, emesis, aggression and autism.

The present application discloses a neuromodulation system for cognitive impairment. The system includes: a cognitive behavioral assessment module for identifying the cognitive deficit areas that need to be improved in the target object; an imaging data acquisition module for collecting and preprocessing the task-state nuclear magnetic resonance data and T1-weighted structural images of the target object; a brain region activation analysis module for determining potential neuromodulation targets based on the preprocessed task-state nuclear magnetic resonance data; a brain network analysis module for identifying key nodes related to cognitive deficits; a stimulation target screening module for determining individualized stimulation targets for the target object based on the potential neuromodulation targets and key nodes of the target object; a time-domain interference electrical stimulation simulation and implementation module for performing electrical stimulation on the individualized stimulation targets; and a dynamic feedback adjustment module for dynamically adjusting the stimulation parameters to enhance the personalized regulation effect. By using the present application, specific brain regions directly related to cognitive impairment can be determined, thereby enhancing the targeting and accuracy of treatment.

The present invention relates to new uses of a 5-HT4 receptor agonist, specifically Isopropyl-3-{5-[1-(3-methoxypropyl)piperidin-4-yl]-[1,3,4]oxadiazol-2-yl}-1H-indazole (Compound-1) or a pharmaceutically acceptable salts thereof, for the treatment of dementia due to menopause, senile dementia, cognitive deficits associated with schizophrenia, depression, chemotherapy-induced cognitive impairment, and behavioral and psychological symptoms of dementia such as apathy / indifference, agitation, aggression, depression, anxiety, irritability / lability, dysphoria, aberrant motor behavior, delusions, hallucinations, elation / euphoria, psychosis, disinhibition, sleep and night time behavior disorders or appetite and eating disorders. The present invention further provides use of the 5-HT4 receptor agonist in the manufacture of medicament intended for the treatment of the disorders described herein.

The present invention relates to new uses of a 5-HT4 receptor agonist, specifically Isopropyl-3 - { 5- [ 1 -(3 - methoxypropyl) piperidin-4-yl] - [ 1,3,4] oxadiazol-2-yl } - 1 H- indazole (Compound- 1) or a pharmaceutically acceptable salts thereof, for the treatment of dementia due to menopause, senile dementia, cognitive deficits associated with schizophrenia, depression, chemotherapy-induced cognitive impairment and behavioural and psychological symptoms of dementia such as apathy / indifference, agitation, aggression, depression, anxiety, irritability / lability, dysphoria, aberrant motor behaviour, delusions, hallucinations, elation / euphoria, psychosis, disinhibition, sleep and night time behaviour disorders or appetite and eating disorders. The present invention further provides use of the said compounds in the manufacture of medicament intended for the treatment of the disorders described herein.

Aspects of the invention are directed to methods of stimulating or promoting neurogenesis by administering to a subject of a composition comprising a cyclodextrin and a polyethylene glycol to alleviate learning, memory and cognitive deficits present in subjects afflicted with various brain disorders or from neurodegenerative disorder associated with aging.

A method for treating Gulf War Illness (GWI) involves administering a therapeutically effective amount of a dominant negative tumor necrosis factor (DN-TNF) protein variant to a subject in need thereof. The DN-TNF variant is one that is modified with one to seven specific amino acid substitutions relative to the amino acid sequence of wtTNF and demonstrates a mechanism of selectively inhibiting soluble TNF (solTNF) without affecting transmembrane TNF (tmTNF) signaling. The method, exemplified by XPro1595 (pegipanermin), alleviates GWI symptoms, including depression, neuropathic pain, anxiety, and cognitive deficits, as shown in preclinical models. By targeting solTNF-driven neuroinflammation, this approach offers a novel therapeutic strategy for GWI.

The present invention relates to the use of HIP / PAP proteins or derivatives thereof in therapy and prophylaxis, in particular to the use of said HIP / PAP proteins or derivatives thereof in the treatment of cognitive disorders associated with one or more anxiety disorders in an individual in need thereof, and for improving cognitive function in an individual affected by a nervous system condition associated with one or more anxiety disorders, or for alleviating cognitive deficits in a subject suffering from a condition selected from the group consisting of obsessive-compulsive disorder, attention deficit disorder, Lewy body dementia, early onset dementia, epilepsy-related cognitive dysfunction, frontotemporal dementia, posterior cortical atrophy, Huntington's disease (HD), Parkinson's disease, bipolar affective disorder, substance abuse, attention deficit disorder, etc. A psychiatric disorder and an SARS-CoV-2 infection; and for the prevention and / or treatment of diet-induced cognitive and anxiety deficits in an individual in need thereof, in particular for the prevention and / or treatment of cognitive and anxiety deficits caused by high fat diet.

Compositions of compounds with SGLT2i activity in combination with compounds having BHB activity. These can be used in methods of treatment for a variety of human diseases such as cognitive deficits, Alzheimer's, kidney disease, heart failure and aortic aneurysms and dissection. The methods allow therapeutic levels of both SGLT2i and BHB activity to be achieved and maintained for as many hours per day as deemed optimal for the patient in need of therapy.