Correlates Of Cognitive Dysfunction Research Articles

Discovery of a novel piperazine derivative, cmp2: a selective TRPC6 activator suitable for treatment of synaptic deficiency in Alzheimer’s disease hippocampal neurons

Alzheimer disease (AD) is characterized by progressive loss of memory. Synaptic loss is now the best correlate of cognitive dysfunction in patients with Alzheimer’s disease. Thus, restoration or limitation of synapse loss is a promising strategy for pharmacotherapy of AD. N–N substituted piperazines are widely used chemical compounds for drug interventions to treat different illnesses including CNS diseases such as drug abuse, mental and anxiety disorders. Piperazine derivatives are small molecules that are usually well tolerated and cross blood brain barrier (BBB). Thus, disubstituted piperazines are good tools for searching and developing novel disease-modifying drugs. Previously, we have determined the piperazine derivative, 51164, as an activator of TRPC6 in dendritic spines. We have demonstrated synaptoprotective properties of 51164 in AD mouse models. However, 51164 was not able to cross BBB. Within the current study, we identified a novel piperazine derivative, cmp2, that is structurally similar to 51164 but is able to cross BBB. Cmp2 binds central part of monomeric TRPC6 in similar way as hypeforin does. Cmp2 selectively activates TRPC6 but not structurally related TRPC3 and TRPC7. Novel piperazine derivative exhibits synaptoprotective properties in culture and slices and penetrates the BBB. In vivo study indicated cmp2 (10 mg/kg I.P.) reversed deficits in synaptic plasticity in the 5xFAD mice. Thus, we suggest that cmp2 is a novel lead compound for drug development. The mechanism of cmp2 action is based on selective TRPC6 stimulation and it is expected to treat synaptic deficiency in hippocampal neurons.

Abstract #1412888: Cognitive Dysfunction in Panhypopituitarism and Correlation of Cognitive Dysfunction with Duration of Illness

To identify cognitive dysfunction in any treated patient of panhypopituitarism, to identify the realm of cognitive dysfunction in panhypopituitarism, to correlate the cognitive dysfunction with the duration of illness. Study Design: Cross sectional observational study. Study population: Patients admitted in the hospital with Panhypopituitarism during the period from January 2019 to June 2022. Sample Size 50 nos. Assessment of cognitive function was done using Addenbrokes cognitive examination. The results showed majority of the patients were in higher age group, females were majority in the study population. The diagnoses of the conditions presented by the patients showed majority of them having Pituitary adenoma (36 %), followed by Empty Sella syndrome (12%). The duration of illness showed that majority (26 %) of the patients had the disease for 2.5 years, followed by 1.5 years (24%) and 6 months (22%). The ACE score before showed low mean score of 81.1 and after the treatment mean score increased to 92.7. The delta score of mean difference between the ACE score before and after showed mean score of 11.6. The range of value of ACE before majority (72 %) were between 81 to 86. The range of ACE score after the treatment showed major improvement in the ACE score, as majority were in 89 to 92 (52%) and 93 to 96 (48%). There was definitive cognitive improvement before and after treatment. The association between ACE score before treatment and illness duration showed that the ACE score gets lower when the duration of illness of increases. This inverse relationship was statistically significant. The association between ACE score after treatment and illness duration showed that the ACE score gets lower when the duration of illness of increases. This inverse relationship was statistically significant. The association of Attention/Memory against ACE mean scores before and after treatment was shown to have significantly higher score than rest of the variables. The mean ratio is 0.146± 0.06. Majority (53 %) of the patients had scores between 0.07 to 0.11, followed by 0.12 to 0.19 (24 %) and 12 % each having 0.20 to 0.24 and 0.25 to .31 score. The correlation between ACE delta score and duration of illness showed that there was direct positive correlation these two factors. The correlation ‘r’ value is 0.109 or else it can be expressed as 10.9% of the changes seen in the ACE delta score can be attributed to the duration of illness. This study has found a direct relationship between duration of illness and their deteriorating cognitive functions with significant improvement of cognitive function post treatment.

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Aims and Objectives: To identify cognitive dysfunction in any treated patient of panhypopituitarism, to identify the realm of cognitive dysfunction in panhypopituitarism, to correlate the cognitive dysfunction with the duration of illness Methods: Study Design: Cross sectional observational study. Study population: Patients admitted in the hospital with Panhypopituitarism during the period from January 2019 to June 2022. Sample Size 50 nos. Assessment of cognitive function was done using Addenbrokes cognitive examination. Results: The results showed majority of the patients were in higher age group, females were majority in the study population. The diagnosis of the conditions presented by the patients showed majority of them having Pituitary adenoma (36%), followed by Empty Sella syndrome (12%). The duration of illness showed that majority (26%) of the patients had the disease for 2.5 years, followed by 1.5 years (24%) and 6 months (22%). The ACE score before showed low mean score of 81.1 and after the treatment mean score increased to 92.7. The delta score of mean difference between the ACE score before and after showed mean score of 11.6. The range of value of ACE before majority (72%) were between 81 to 86. The range of ACE score after the treatment showed major improvement in the ACE score, as majority were in 89 to 92 (52%) and 93 to 96 (48%). There was definitive cognitive improvement before and after treatment. The association between ACE score before treatment and illness duration showed that the ACE score gets lower when the duration of illness of increases. This inverse relationship was statistically significant. The association between ACE score after treatment and illness duration showed that the ACE score gets lower when the duration of illness of increases. This inverse relationship was statistically significant. The association of Attention/Memory against ACE mean scores before and after treatment was shown to have significantly higher score than rest of the variables. The mean ratio is 0.146 ± 0.06. Majority (53%) of the patients had scores between 0.07 to 0.11, followed by 0.12 to 0.19 (24%) and 12% each having 0.20 to 0.24 and 0.25 to .31 score. The correlation between ACE delta score and duration of illness showed that there was direct positive correlation these two factors. The correlation ‘r’ value is 0.109 or else it can be expressed as 10.9% of the changes seen in the ACE delta score can be attributed to the duration of illness. Conclusion: This study has found a direct relationship between duration of illness and their deteriorating cognitive functions with significant improvement of cognitive function post treatment

CORRELATION OF COGNITIVE DYSFUNCTION AND COPD IN NORTH INDIA

CORRELATION OF COGNITIVE DYSFUNCTION AND COPD IN NORTH INDIA

A Review on P300 in Obsessive-Compulsive Disorder.

Neuropsychological studies indicate the presence of cognitive changes in patients with obsessive-compulsive disorder (OCD). Indeed, OCD may be included among the dysfunctions of the frontal lobes and their connections with the limbic system, associative cortex, and basal ganglia. P300 is a positive component of the human event-related potential (ERP); it is associated with processes of encoding, identification, and categorization constituting, as a whole, the superior cortical function of information processing. Thus, P300 explores several areas that are implicated in OCD pathophysiology. Our aim is to review all relevant studies on the P300 component of the human ERP in order to recognize any significant central nervous system (CNS) correlate of cognitive dysfunction in OCD. A PubMed-based literature search resulted in 35 articles assessing P300 in OCD and reporting neurophysiological correlates of response inhibition, cortical hyperarousal, and over-focused attention. A decreased P300 amplitude was reported in both adult and pediatric patients, with a trend toward normalization after pharmacological treatment. Source localization studies disclosed an association between P300 abnormalities and the functioning of brain regions involved in the pathophysiology of OCD. Moreover, studies converge on the evidence of neurophysiological dysfunction in the frontal areas with impairment of the normal inhibitory processes in OCD. At least some of these electrophysiological correlates might reflect the obsessive thoughts and compulsions that characterize this disorder. These findings may also support cognitive-behavioral therapy (CBT) approaches on over-focused attention and inflexibility of compulsive behaviors, which should be associated to pharmacological treatment in these patients.

Changes in resting-state functional connectivity in neuropsychiatric lupus: A dynamic approach based on recurrence quantification analysis

There is growing interest in dynamic approaches to functional brain connectivity (FC), and their potential applications in understanding atypical brain function. In this study, we assess the relative sensitivity of cross recurrence quantification analysis CRQA) to identify aberrant FC in patients with neuropsychiatric systemic lupus erythematosus (NPSLE) in comparison with conventional static and dynamic bivariate FC measures, as well as univariate (nodal) RQA. This technique was applied to resting-state fMRI data obtained from 45 NPSLE patients and 35 healthy volunteers (HC). Cross recurrence plots were computed for all pairs of 16 frontoparietal brain regions known to be critically involved in visuomotor control and suspected to show hemodynamic disturbance in NPSLE. Multivariate group comparisons revealed that the combination of six CRQA measures differentiated the two groups with large effect sizes (.214>η2>.061) in 40 out of the 120 region pairs. The majority of brain regions forming these pairs also showed group differences on nodal RQA indices (.146>η2>.09) Overall, larger values were found in NPSLE patients vs. HC with the exception of FC formed by the paracentral lobule. Determinism within five pairs of right-hemisphere sensorimotor regions (paracentral lobule, primary somatosensory, primary motor, and supplementary motor areas), correlated positively with visuomotor performance among NPSLE patients (p<.001). By comparison, group differences on static FC displayed large effect sizes in only 4 of the 120 region pairs (.126>η2>.061), none of which correlated significantly with visuomotor performance. Indices derived from dynamic, temporal-based FC analyses displayed large effect sizes in 11/120 region pairs (.11>η2>.063). These findings further support the importance of feature-based dFC in advancing current knowledge on correlates of cognitive dysfunction in a clinically challenging disorder, such as NPSLE.

COGNITIVE DYSFUNCTIONS IN A MINIMALLY VERBAL (MV) PATIENT WITH AUTISM SPECTRUM DISORDER (ASD)

The aim of this study was to examine the neurophysiological correlates of cognitive dysfunctions in a patient with the minimally verbal variant of Autism Spectrum Disorder (ASD + MV), who after reaching adulthood showed progressive deterioration of his cognitive skills. The patient was a 25-year-old male, diagnosed with ASD. He never developed spoken language, and communicated only by gesturing or writing on a computer. Our findings confirmed comorbidity of ASD and epilepsy, accompanied by dysfunction of cognitive control. We also found that spontaneous EEG and event-related potentials (ERPs) in a cued GO/NOGO task can be used to assess functional brain changes concomitant with ASD.

Brain Single Photon Emission Computed Tomography Scan (SPECT) and functional MRI in Systemic Lupus Erythematosus Patients with Cognitive Dysfunction: A Systematic Review.

Objective(s):Systemic lupus erythematosus (SLE) is an autoimmune disease with a wide range of clinical manifestations. Cognitive dysfunction is one of the manifestations that could present prior to the emergence of any other neuropsychiatric involvements in SLE. Cognitive dysfunction is a subtle condition occurring with a high frequency. However, there is no data on the correlation of cognitive dysfunction with central nervous system (CNS) imaging findings, in particular single-photon emission computed tomography scan (SPECT) and functional MRI. We decided to perform a systematic review of brain SPECT and fMRI in SLE patients with cognitive dysfunction. Methods:PubMed, Scopus, and Google Scholar databases were searched until April 2017 with the following keywords: “SLE OR systemic lupus erythematous OR lupus” AND “functional MRI OR functional magnetic resonance imaging OR fMRI OR SPECT or SCAN”. A total of 1,767articles were found. Two rheumatologists reviewed the articles and finally 14 articles were selected for the final systematic review. Results:The fMRI and SPECT imaging techniques could provide valuable information regarding the SLE patients with cognitive dysfunction at the early stages of the disease.Conclusion: Brain SPECT scan and fMRI are used as functional imaging tools in SLE. Both of these diagnostic modalities are sensitive in reflecting the subtle brain damages in SLE patients with cognitive dysfunction. Brain fMRI and SPECT scan could be significantly beneficial in the diagnosis and initial management of cognitive dysfunction in SLE. Nevertheless, prospective studies could be useful in confirming the application of these diagnostic modalities in the clinical setting.

Correlative study of cognitive dysfunction, activities of daily living and quality of life in patients with traumatic brain injury

Objective To investigate the current situation and correlation of cognitive dysfunction, activities of daily living (ADL) and quality of life in patients with traumatic brain injury (TBI) . Methods A total of 148 patients hospitalized in the Rehabilitation Department of the Second Affiliated Hospital of Kunming Medical University from January to December 2016 were included in this study. The Montreal cognitive assessment scale (MoCA) , modified Barthel Index scale (MBI) and WHO quality of life scale (WHO-QOL) were used to investigate the status of patients with traumatic brain injury. Results There were 78 of 148 patients with cognitive dysfunction and the incidence rate was 52.98%. Cognitive dysfunction after TBI was significantly positively related to the ADL ability (r=0.968, P<0.01) ; the visual space and executive function, attention, abstraction, delayed recall and orientation had the prediction effect on the ADL ability. Cognitive dysfunction after TBI was significantly positively related to the quality of life (r=0.973, P<0.01) ; cognitive items except the name could predict the quality of life. Conclusions There is a high incidence of cognitive dysfunction in patients with traumatic brain injury, which can affect their ADL ability and quality of life. It is necessary to take effective measures to improve the rehabilitation training of the cognitive function in early stage. Key words: Traumatic brain injury; Cognitive dysfunction; Activities of daily living; Quality of life

DTI Findings Correlated with Neurocognitive Impairments in Basal Ganglia Stroke: A Preliminary Study

Objective: Subcortical lesion involving basal ganglia can cause a wide range of behavioral and cognitive alterations largely attributed to disconnection of subcortical fibers; however, the underlying neural correlates of cognitive dysfunction based on the integrity of the white matter fiber has not yet been explored in stroke patients. Methods: The correlations among cognitive function and diffusion metrics of each subcortical fiber were investigated in nine basal ganglia stroke patients by diffusion tensor imaging (DTI) in our study. Results: Patient’s general cognitive and verbal working memory function correlated well with the integrity of the left superior longitudinal fasciculus (SLF), nonverbal attention with the right inferior longitudinal fasciculus (ILF), SLF, and frontostriatal (FS) fibers. On the other hand, nonverbal long-term memory correlated well with the integrity of the right ILF and FS fibers. Conclusions: Neurocognitive characteristics of patients with basal ganglia stroke seem to reflect the integrity of subcortical fiber connectivity.

EPA-0976 – Neural correlates of cognitive dysfunction in mood disorders

Objectives To define neural correlates of cognitive dysfunction in major depression and to disentangle the role of cognitive, default mode and limbic networks in emotional and cognitive problems of depressed patients Material and Methods We will review brain imaging studies of executive function and rumination in depression. We will also describe results of a recent study conducted in healthy volunteers (n=41) using cognitive tasks related to ruminative processes. During fMRI acquisition subjects were asked to read sentences and to engage in an analytical or an experiential self-referential task. Results Several studies using executive tasks related cognitive effort in depressed patients with increased activation of the dorsolateral prefrontal cortex. This hyperactivity of lateral prefrontal cortex is associated with abnormal deactivation of medial brain structures such as the medial prefrontal cortex. Consistent with this review, our study in healthy volunteers showed that subjects with High score in rumination showed lower activity in medial brain structures in relation with difficulties to differentiate analytical and experiential self-focus. Conclusion Overall these findings support the hypothesis of abnormal interaction in cognitive and default mode network in depression and may help to refine our understanding of how rumination promotes depression through maladaptive self-focus.

The correlation of cognitive dysfunction with serum brain-derived neurotrophic factor level in depression patients

Objective To investigate the characteristics of cognitive dysfunction in patients with depression, and identify the correlation between cognitive dysfunction and serum brain-derived neurotrophic factor(BDNF) level. Methods All participants including 73 depressed patients and 71 healthy controls were received clinical and cognitive assessments at admission, the depression group was divided into two groups by the score of Beijing version of the Montreal Cognitive Assessment (MoCA-BJ), one was depression with cognitive dysfunction group which had 36 cases, the other was depression without cognitive dysfunction group which had 37 cases.Concentration of BDNF was measured by the ELISA method. Results Cognitive impairments were found in numerous cognitive domains of depressed patients, including visuospatial and executive abilities, attention, delayed recall and orientation(P 0.05), and the levels were significantly lower than that in healthy people ((16.55±7.47)ng/ml, P 0.05). Conclusion Depression patients have cognitive dysfunction in numerous cognitive domains, including visuospatial and executive abilities, attention, delayed recall and orientation.Serum BDNF level is closely related with depression, while, it has no obvious relationship with cognition function in depression. Key words: Depression; Cognitive dysfunction; Brain-derived neurotrophic factor

Neurochemical correlates of cognitive dysfunction in patients with leukoaraiosis: a proton magnetic resonance spectroscopy study

Objectives: Leukoaraiosis (LA) is a common radiological finding in the elderly and may reflect cerebral small vessel disease (SVD). Although SVD has been identified as a major cause of vascular cognitive impairment or vascular dementia, the mechanisms for this association remain unclear. We therefore aimed to measure brain metabolites in LA using proton magnetic resonance spectroscopy (1H-MRS) as to determine the relationship between cognitive function and neurochemical white matter profile.Methods: We recruited 23 patients with LA and 23 age- and sex-matched healthy controls consecutively. Multi-voxel 1H-MRS was performed with a volume of interest located in centrum semiovale that contained mainly white matter voxels. Three main ratios of N-acetyl aspartate (NAA)/Cr, choline (Cho)/Cr and NAA/Cho were obtained. Spearman rank correlation coefficients were calculated between the cognitive function and the measured metabolite ratios.Results: We found significantly lower levels of NAA/Cho and NAA/Cr ratios in lesioned white matter in patients with LA than healthy controls (P<0·05). The ratios of NAA/Cho and NAA/Cr in normal appearing white matter (NAWM) were higher than lesioned white matter and lower than controls, but this difference was not significant (P>0·05). There was a positive relationship between Mini-Mental State Examination (MMSE) and NAA/Cho in NAWM (r = 0·417, P = 0·048), and also a positive relationship between MMSE and NAA/Cr in lesioned white matter (r = 0·551, P = 0·006) in patients with LA. A positive relationship between the Z scores of the executive function and NAA/Cho in lesioned white matter (r = 0·557, P = 0·006) was also found.Conclusion: The main finding of this study was a significant reduction in the ratios of NAA/Cr and NAA/Cho in lesioned white matter, which indicates a marker of neuronal loss or dysfunction in patients with LA, which was correlated with cognitive function. This relationship between cognitive function and metabolic changes suggests that 1H-MRS can be explored as a marker for cognitive dysfunction in patients with LA.

Correlation of cognitive dysfunction and diffusion tensor MRI measures in patients with mild and moderate multiple sclerosis

To compare the diffusion tensor imaging (DTI) measures of multiple sclerosis (MS) patients and healthy subjects in every brain voxel and to correlate them with Paced Auditory Serial Addition Test (PASAT) scores. Fractional anisotropy (FA), and mean, longitudinal, and transverse diffusivity are compared between control subjects and MS patients, which were subdivided as mildly and moderately impaired. In addition, PASAT scores are correlated for both MS groups with the diffusion measures. An optimized voxel based analysis (VBA) method, in terms of coregistration, atlas construction, and image smoothing, was thereby used. Diffusion differences between the control subjects and the patients with MS were found in the corpus callosum, inferior longitudinal fasciculus, cortico spinal tracts, forceps major, superior longitudinal fasciculus, and cingulum. In addition, we observed significant correlations of the FA and PASAT scores in the left inferior longitudinal fasciculus, the forceps minor, the capsula interna and externa, the genu of the corpus callosum, the left cingulum, the superior longitudinal fasciculus, and the corona radiata. Diffusion differences were observed between the mildly impaired MS patients and control subjects. In addition, different diffusion measures correlated with PASAT scores for cognitive decline in parietal, frontal, as well as temporal white matter (WM) regions.

Transcranial brain sonography findings related to neuropsychological impairment in multiple sclerosis

Cognitive dysfunction, fatigue and mood disorder contribute to the neuropsychological impairment that is common in multiple sclerosis (MS). The present paper reviews application of transcranial brain sonography (TCS) in MS patients and TCS findings related to neuropsychological dysfunction. TCS is a new neuroimaging method displaying tissue echogenicity of the brain through the intact skull. Whereas the cortex can not be discriminated from the subcortical white matter with TCS, subcortical brain structures such as ventricles and basal ganglia can be adequately displayed. Even though TCS proved sensitive and reliable in measuring widths of third and lateral ventricles in a number of neurodegenerative diseases, relatively few TCS studies on MS patients have been reported. Data of these studies suggest a good correlation of cognitive dysfunction and width of third ventricle which can be measured reliably with TCS. Moreover, abnormal TCS findings of basal ganglia were associated with cognitive impairment. However, TCS findings of midbrain structures, basal ganglia and ventricles did not correlate with fatigue or depression in MS patients. TCS has the advantages of low costs, short investigation times and unlimited repeatability. The use of third-ventricle and basalganglia TCS for predicting and monitoring neuropsychological impairment in MS patients, however, needs to be elucidated in further studies.

Neurophysiological correlates of delayed visual differentiation tasks in monkeys: the effects of the site of intracortical blockade of NMDA receptors.

A delayed visual differentiation task using stimuli of different colors was used in rhesus macaques to study the characteristics of visual recognition, short-term memory, and the responses of neurons recorded simultaneously in the visual and prefrontal areas of the cortex, along with their relationships with the site of intracortical (fields 17 or 46) perfusion of the glutamate receptor antagonist 2-amino-5-phosphonovaleric acid (APV). The behavioral characteristics and spike activity of individual cells in cortical fields 17 and 46 were recorded before and after perfusion with APV and after washing away of traces of APV. Multifactor dispersion analysis showed that the effect of APV in monkeys consisted of decreases in the probability of correct responses, leading to a decrease (two-fold) in the duration of short-term storage of information and a significant increase in the motor reaction time. The probability of correct solutions depended on the site of APV perfusion in the cortex, while the motor response time was independent of the perfusion site. Perfusion of field 46 with APV, unlike perfusion of field 17, altered the spike activity only of neurons in the prefrontal cortex, while no significant changes were seen in the neuron activity of the visual cortex. The actions of APV were accompanied by significant desynchronization of neuron activity in these two areas as compared with the level of synchronization in normal conditions; after traces of APV were washed away, the extent of desynchronization decreased. The neurophysiological correlates of cognitive dysfunctions associated with degradation of visual recognition and short-term memory due to modification of glutamatergic structures by blockade of NMDA receptors are discussed.

Electrophysiological correlates of cognitive dysfunction in multiple sclerosis

Electrophysiological correlates of cognitive dysfunction in multiple sclerosis

W83 Brain electric correlates of cognitive dysfunctions in schizophrenic patients

W83 Brain electric correlates of cognitive dysfunctions in schizophrenic patients