Cognitive Function Disorders Research Articles

The Effect of Nocturnal Blood Pressure Changes on the Cognitive State of Patients With Parkinson’s Disease

This article has been retracted by the authors. Background: Recent data have revealed that cognitive involvement occurs, more or less, in every stage of idiopathic Parkinson’s disease (IPD), which is definitely going to cause radical changes in this traditional understanding. The effects of blood pressure changes during the night on the cognitive states of patients with IPD are not known for sure. The purpose of this study was to research the effects of blood pressure changes during the night on cognitive state of patients with IPD. Methods: A total of 30 patients, 14 females and 16 males, were followed with a diagnosis of IPD. Cognitive functions were assessed with an extensive neuropsychological test battery. Results: The fifth stage of Stroop test, test of line direction, test of face recognition and Hooper test were significantly different in dipper group when compared with the non-dipper group. Conclusion: Not having nocturnal blood pressure decrease in IPD can be accepted as a risk factor in terms of cognitive function disorders. J Neurol Res. 2015;5(3):207-212 doi: http://dx.doi.org/10.14740/jnr324w

Pharmacokinetics of cotinine in rats: A potential therapeutic agent for disorders of cognitive function

BackgroundAttention has been paid to cotinine (COT), one of the major metabolites of nicotine (NIC), for its pro-cognitive effects and potential therapeutic activities against Alzheimer's disease (AD) and other types of cognitive impairment. In order to facilitate pharmacological and toxicological studies on COT for its pro-cognitive activities, we conducted a pharmacokinetic (PK) study of COT in rats, providing important oral and intravenously (iv) PK information. MethodsIn this study, plasma samples were obtained up to 48h after COT was dosed to rats orally and iv at a dose of 3mg/kg. Plasma samples were prepared and analyzed using a sensitive liquid chromatography tandem mass spectrometry (LC–MS/MS) bioanalytical method, providing concentration profiles of COT and metabolites after oral and iv administrations. ResultsThe data were fitted into a one-compartment model and a two-compartment model for the oral and iv groups, respectively, providing important PK information for COT including PK profiles, half-life, clearance and bioavailability. The results suggested fast absorption, slow elimination and high bioavailability of COT in rats. ConclusionsSeveral important facts about the PK properties in rats suggested COT could be a potential pro-cognitive agent. Information about the pharmacokinetics of COT in rats revealed in this study is of great importance for the future studies on COT or potential COT analogs as agents for improving cognition.

Molecular mechanisms underlying the effects of statins in the central nervous system.

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, commonly referred to as statins, are widely used in the treatment of dyslipidaemia, in addition to providing primary and secondary prevention against cardiovascular disease and stroke. Statins’ effects on the central nervous system (CNS), particularly on cognition and neurological disorders such as stroke and multiple sclerosis, have received increasing attention in recent years, both within the scientific community and in the media. Current understanding of statins’ effects is limited by a lack of mechanism-based studies, as well as the assumption that all statins have the same pharmacological effect in the central nervous system. This review aims to provide an updated discussion on the molecular mechanisms contributing to statins’ possible effects on cognitive function, neurodegenerative disease, and various neurological disorders such as stroke, epilepsy, depression and CNS cancers. Additionally, the pharmacokinetic differences between statins and how these may result in statin-specific neurological effects are also discussed.

Сlinical and neurophysiological estimation of cognitive function in patients with chronic cerebral ischemia in a period of recovery after surgery

Objective – to estimate the peculiarities of the cognitive function disorders and cognitive evoked potentials (CEP) changes in patients with cerebrovascular deseasis (CVD) in post-operative period and period of recovery.Methods and subjects. 42 patients with chronic cerebral circulation impairment were examined. The patients were operated about the hemodynamic significantly stenosys in internal carotid or/and vertebral artery. The first clinical group included 20 patients, who had acute ischemic stroke; the second group comprised 22 patients without data on ischemic stroke in anamnesis. The methods used: clinical, neurological; neuropsychological testing (NPT), MRI, ultrasound study of the cerebral blood flow, EEG mapping, CEP P300.Results. All studies were conducted in the period of recovery 6 months – 2 years after operation: carotid endarterectomy (14), endovascular angioplasty with stenting (12). Positive changes in blood flow in the area of stenosis, and in the affected intracranial artery and its branches were observed after surgical removal of stenosis. As evidence of cognitive impairment using the results of the NPT decrease by 1.5 σ or more, as a sign of slowing of mental processes – significant increase of the latent period of P300 to 2 σ or more, a significant reduction in the amplitude and increase asymmetry of these indicators. It confirms the correlation of negative effect on the NPT-CEP indicators and next factors: elderly age, decreased blood flow in the proximal segments of the middle cerebral artery by more than 20% of the age norms, absence (significant decrease) in reserve capacity of cerebral blood flow, site of the lesion in the right hemisphere, the presence of seizures.Conclusions. Complex methodology of NTP-CEP allows to educe violations of cognitive functions for patients with CVD in the dynamics of surgery treatment and to control renewal.

PO-0836 Determination Of Cognitive Functioning Disorders Incidence In Children With Multiple Sclerosis

Aim Cognitive impairment is seen in patients with paediatric multiple sclerosis in more than 30% of cases. Altered functions with variable frequency are: attention, language (receptive, verbal fluency, naming), visual-spatial and motor functions, spatial memory, executive functions and abstract reasoning. The aim of this study is to determinate the cognitive functions disorders in children with multiple sclerosis. Methods A total of 21 individuals with paediatric MS (19 girls, 2 boys), ranging from 10–17 years of age (SD=14.90 ± 186) completed initial and follow-up neuropsychological testing at yearly interval. All the patients were given WISC-R, Raven’s Standard Progressive Matrices, Wisconsin Card Sorting, Stroop Test, Line Orientation Test and Verbal Fluency Results 55% of the patients had Interferon therapy, First attack age was 12.92 ± 2.36, total number of attacks was 2.68 ± 2.19. IQ assessment was as follows: 19.1% (n = 4) borderline, 47.6% (n = 10) average, 33.4% (n = 7) high average. After interferon therapy; patients showed increased reponse time with less mistakes in Stroop test (p Conclusion Cognitive impairment has a negative impact on patient’s life limiting social, academic activities. Early treatment with disease-modifying drugs seems to be advisable in order to prevent or delay the development of cognitive impairment.

MicroRNAs and synaptic plasticity--a mutual relationship.

MicroRNAs (miRNAs) are rapidly emerging as central regulators of gene expression in the postnatal mammalian brain. Initial studies mostly focused on the function of specific miRNAs during the development of neuronal connectivity in culture, using classical gain- and loss-of-function approaches. More recently, first examples have documented important roles of miRNAs in plastic processes in intact neural circuits in the rodent brain related to higher cognitive abilities and neuropsychiatric disease. At the same time, evidence is accumulating that miRNA function itself is subjected to sophisticated control mechanisms engaged by the activity of neural circuits. In this review, we attempt to pay tribute to this mutual relationship between miRNAs and synaptic plasticity. In particular, in the first part, we summarize how neuronal activity influences each step in the lifetime of miRNAs, including the regulation of transcription, maturation, gene regulatory function and turnover in mammals. In the second part, we discuss recent examples of miRNA function in synaptic plasticity in rodent models and their implications for higher cognitive function and neurological disorders, with a special emphasis on epilepsy as a disorder of abnormal nerve cell activity.

Hippocampal plasticity during the peripartum period: influence of sex steroids, stress and ageing.

The peripartum period is accompanied by dramatic changes in hormones and a host of new behaviours in response to experience with offspring. Both maternal experience and maternal hormones can have a significant impact upon the brain and behaviour. This review outlines recent studies demonstrating modifications in hippocampal plasticity across the peripartum period, as well as the putative hormonal mechanisms underlying these changes and their modulation by stress. In addition, the impact of reproductive experience upon the ageing hippocampus is discussed. Finally, we consider how these changes in hippocampal structure may play a role in postpartum cognitive function and mood disorders, as well as age-related cognitive decline.

PSYCHOEMOTIONAL STATUS FEATURES IN PATIENTS WITH THYROID GLAND PATHOLOGY

It is now well known that thyroid gland disorder (both excess and lack of thyroid hormones) may signifi­cantly influenced mental status, including emotions and cognition. Both central and peripheral nervous systems are affected. In hyperthyroidism nervous system lesion is associated with thyroid hormone toxic effect, metabo­lism increase and increased sensitivity to catecholamines. This state is manifested in emotional lability, quick transition from depression to euphoria. Different kinds of phobias and panic states may occur. Psychic disorders in hypothyroidism are the result of hypothyroid encephalopathy. Cognitive processes are hindered. Psychiatric diseases following the type of depression and paranoia may occur. In severe hypothyroidism exogenous or­ganic psychosis may develop. And despite all the achievements of euthyreosis patients may continue to have disorders of cognitive functions and emotional-affective distresses.

H03 Awareness Of Dysexecutive Function In Huntington Disease

<h3></h3> Patients with Huntington Disease (HD) show poor self-awareness of a variety of symptoms. Previous research in HD has primarily examined awareness of motor symptoms, whereas less attention has been given to unawareness of cognitive function and behavioural disorders. This study aim to assess self-awareness of executive deficits in HD and to explore the association between impaired awareness, cognition (executive function and memory) and evolution of the disease. Self-awareness was tested in 17 patients with HD (8 male, age=50.5 ± 9.8 years) at early stage of the disease (mean TFC 11.7) by comparing patient and family ratings using the Dysexecutive Questionnaire (DEX) with five-factor factorial structure (Inhibition, Intentionality, executive memory, negative and positive affect). Executive and memory functions were assessed by different standardised neuropsychological tests included in cognitive protocol Registry 3. Finally, we extracted the volume of the different striatal substructures (left and right caudate, putamen and nucleus accumbens) as a neuroanatomical signature of disease progression in HD. Statistical analysis revealed a significant discrepancy between the DEX-Family and DEX-Patient specifically in the second factor of DEX (intentionality). This factor contains items about disinhibition, aggression, euphoria, lack of insight and social conscience. We also found that poor insight in this area measured by DEX is significantly and specifically related with the atrophy of the left caudate. None of the cognitive tests that were administrated showed significant correlation with unawareness. Our results are consistent with previous literature, indicating that patients with HD generally overestimate their abilities. This study shows that the awareness of dysexecutive function in HD is not a general and uniform process, but is specific to certain symptoms (predominantly behaviours related with intentionality and disinhibition) and suggests the involvement of specific neuroanatomical substrates for unawareness in HD.

The relationship of serum cortisol levels with depression, cognitive function and sleep disorders in chronic kidney disease and hemodialysis patients.

In the present study, the relationships between cortisol, cognitive function, depressive behavior, and sleep quality in chronic kidney disease (CKD) and hemodialysis (HD) patients was investigated. Patients underwent history taking, physical examination, biochemical analysis, 24-h urine collection (for CKD patients only), measurement of dialysis adequacy (for HD patients only), evaluation of cognitive function, depressive behavior and sleep quality. Among study participants 58 had creatinine clearance ≥60 mL/min/1.73 m(2) (Group 1), 41 had creatinine clearance between 30 and 59 mL/min/1.73 m(2) (Group 2), 25 had creatinine clearance between 15 and 29 mL/min/1.73 m(2) (Group 3) and 12 had creatinine clearance <15 mL/min/1.73 m(2) (Group 4). 38 patients were regular HD patients (Group 5). The cortisol levels in Group 1, 2, 3, 4 and 5 patients were 472.3 ± 138.4, 490.2 ± 214.3, 541.6 ± 172.8, 569.9 ± 101.0 and 637.8 ± 153.7 nmol/L, respectively (P < 0.0001 for trend). In both non-dialysis patient group and dialysis patients linear regression analysis showed that cortisol was independently related with Beck depression inventory (BDI) score (P: 0.013 and 0.001, respectively) but not with cognitive function and sleep quality. In conclusion serum cortisol levels were independently associated with depressive behavior both in CKD and HD patients but not with cognitive function and sleep quality.

Neuroleptics and enrichment environment treatment in memory disorders and other central nervous system function observed in prenatally stressed rats.

It is believed that the most effective method of treatment in schizophrenia is pharmacotherapy, in particular, the use of atypical neuroleptics like aripiprazole (ARI) and olanzapine (OLA). Moreover, studies of many authors have shown that enriched living conditions and tobacco smoke exposure can also affect the cognitive functions that are disturbed in the course of schizophrenia. The aim of the study was to find whether tobacco smoke and enrichment living conditions have the influence on cognitive functions in the newborn offspring of prenatally stressed rats and whether drugs such as ARI (1.5 mg/kg intraperitoneally (i.p.)) and OLA (0.5 mg/kg ip) in single and chronic treatment modify those functions (Morris water maze). The study (in the same conditions) also analyses immobility time (Porsolt test) and motor activity of animals that received ARI and OLA. It has been shown that ARI and OLA as well as enriched environment reduce cognitive function disorders and modify cognitive functions in rats exposed to tobacco smoke. In turn, current research has shown that nicotine has increased cognitive function disorders compared to the previous study (animals without tobacco smoke exposure).

Efectos de un programa de intervención neuropsicológica basado en mindfulness sobre la enfermedad de Alzheimer: ensayo clínico aleatorizado a doble ciego

IntroductionThe purpose of this research was to assess effects of a mindfulness based neuropsychological intervention on the clinical course of Alzheimer's disease. Material and methodA two year randomized and double blind clinical trial was conducted on 127 probable Alzheimer's disease patients, according to NINCDS-ADRDA scale. Patients were grouped into three experimental groups (cognitive stimulation, progressive muscular relaxation, and mindfulness) plus a control group. All participants were receiving donepezil. Cognitive skills were assessed with CAMCOG and MMSE, functional area with RDRS-2, and NPI was used for psychopathology screening. Three treatment sessions per week were carried out for two years, and follow up measurements were taken every six months. ResultsThe global cognitive function, functionality and behavioral disorders measurements indicated that patients from the experimental group based on mindfulness were stable during the two years, while patients from the control group, as well as the other experimental groups, showed a mild but significant worsening of their mental capacities. ConclusionThe mindfulness based neuropsychological program showed better cognitive and functional stability, as well as significant improvement in the psychopathological condition of mild to moderate Alzheimer’ patients. These results support the idea that a mindfulness based intervention can produce a clinically relevant improvement in the treatment of dementia. More research is needed to confirm these data.

Exploring the indirect effects of catechol-O-methyltransferase (COMT) genotype on psychotic experiences through cognitive function and anxiety disorders in a large birth cohort of children.

Children reporting psychotic experiences (PEs) are at increased risk of developing psychosis in adulthood. Cognitive deficits and anxiety disorders often precede psychotic disorders and are associated with higher risk of PEs. While the high activity alleles of variants within COMT have been associated with cognitive deficits, and the low activity alleles with higher risk of anxiety disorders, no associations of COMT with PEs have been found. One possible explanation is that the association between COMT and PEs is indirect, through cognitive function and anxiety disorders. We examined whether the association between PEs and COMT (four single nucleotide polymorphisms and three haplotypes) is indirect, through cognition or anxiety disorders. 6,784 individuals from the Avon Longitudinal Study of Parents and Children (ALSPAC) were genotyped and completed neurocognitive assessments at ages 8 and 11, as well as semi-structured interviews for anxiety disorders and PEs at ages 10 and 12, respectively. Alleles rs2097603 and rs4680, and two COMT haplotypes, all indexing high activity, were indirectly associated with higher risk of PEs through impaired processing speed, IQ and attention. There was no evidence of a total effect of COMT on PEs, nor for an indirect effect through anxiety disorders. This is the first study to examine indirect effects of COMT on PEs. Evidence of an indirect association suggests a complex developmental pathway underlies the emergence of PEs in children, with possible implications for prevention/intervention strategies. Our findings provide additional support for processing speed and attention as endophenotypes in psychotic disorders.

Cognition in Microsurgically Treated Patients after Aneurysmal Haemorrhage

Aim: This research aimed to assess cognitive functions, depressive and anxious symptoms in patients after microsurgical treatment of ruptured intracranial aneurysm causing subarachnoid hemorrhage (SAH). Material and Methods: The prospective, controlled, randomized trailed was conducted. All patients were operated on by single neurosurgeon (KD). Preoperatively, patients were in good grade (Hunt-Hess I, II) There was no any focal neurological deficit and hydrocephalus postoperatively. The patients were tested in two-time points: 15 and 45 days after microsurgery with a battery of tests and questioners consisting of the Rivermead Behavioral Memory Test, the Sustained Attention to Response Task, the Trail Making Test, the Hayling Sentence Completion Test, the AC test of attention, the Cognitive Failure Questionnaire, the Beck Depression Inventory, the State-Trate Anxiety Inventory, the Wechsler Adult Intelligence Scale (verbal part) and the Alcohol Use Disorders Identification Test. Results were compared with sex, age, years of education and verbal IQ matched subjects undergoing discus hernia surgery. Results: Our results showed the presence of cognitive function disorder in the experimental group of patients with trend of being reduced as time passes by. There is a significant difference between experimental and control group with respect to results on cognitive functions tests and questioners of depressive and anxious symptoms at the second time-point. These results are in line with results obtained by other researchers engaged in SAH diagnosed subjects. Conclusion: The detailed neuropsychological assessment of operated patients who sustained SAH and were without focal neurological deficit postoperatively, showed their declination in cognitive function with presence of depressive and anxious symptoms.

Selenium and selenoprotein function in brain disorders

Selenoproteins are important for normal brain function, and decreased function of selenoproteins can lead to impaired cognitive function and neurological disorders. This review examines the possible roles of selenoproteins in Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and epilepsy. Selenium deficiency is associated with cognitive decline, and selenoproteins may be helpful in preventing neurodegeneration in AD. PD is associated with impaired function of glutathione peroxidase selenoenzymes. In HD, selenium deters lipid peroxidation by increasing specific glutathione peroxidases. Selenium deficiency increases risk of seizures in epilepsy, whereas supplementation may help to alleviate seizures. Further studies on the mechanisms of selenoprotein function will increase our understanding of how selenium and selenoproteins can be used in treatment and prevention of brain disorders.

High Content Image Analysis Identifies Novel Regulators of Synaptogenesis in a High-Throughput RNAi Screen of Primary Neurons

The formation of synapses, the specialized points of chemical communication between neurons, is a highly regulated developmental process fundamental to establishing normal brain circuitry. Perturbations of synapse formation and function causally contribute to human developmental and degenerative neuropsychiatric disorders, such as Alzheimer's disease, intellectual disability, and autism spectrum disorders. Many genes controlling synaptogenesis have been identified, but lack of facile experimental systems has made systematic discovery of regulators of synaptogenesis challenging. Thus, we created a high-throughput platform to study excitatory and inhibitory synapse development in primary neuronal cultures and used a lentiviral RNA interference library to identify novel regulators of synapse formation. This methodology is broadly applicable for high-throughput screening of genes and drugs that may rescue or improve synaptic dysfunction associated with cognitive function and neurological disorders.

Safety of nicergoline as an agent for management of cognitive function disorders.

Nicergoline is a semisynthetic ergot derivative and has a selective alpha-1A adrenergic receptor blocking property and also other additional mechanisms of actions, both in the brain and in the periphery. It is in clinical use for over three decades in over fifty countries for conditions such as cerebral infarction, acute and chronic peripheral circulation disorders, vascular dementia, and Alzheimer's disease and has been found to be beneficial in a variety of other conditions. However, concerns about its safety have been raised, especially after the European medicines agency's (EMEA's) restriction in the use of all ergot derivatives including nicergoline. But, most of the available literature and data suggest that the adverse events with nicergoline are mild and transient. Further, none of the available treatment options for cognitive disorders afford definitive resolution of symptoms. In this backdrop, we discuss the pharmacology of nicergoline with special emphasis on the safety of this compound, especially when used in patients suffering from cognitive function disorders.

EPA-1629 – Prevalence of delirium in geriatric inpatients of general hospital

World tendency towards overall age increase of the population leads to increase of elderly people among patients. Delirium (confusional state) is common in geriatric inpatients in general hospital. It is one of the most significant syndromes of cognitive dysfunction in people of senior age. The presence of delirium increases the duration of hospital stay, morbidity and mortality. To evaluate the prevalence of delirium amongst inpatients of senior age in different departments of general hospital. We have studied a total of 247 randomly selected inpatients. Of these, there were 113 patients in the Traumatology Department and 134 in the Neurology Department. Delirium was diagnosed based on the criteria of ICD-10. We used the Mini-mental state examination (MMSE) scale as a metric of the degree of the disorder of cognitive functions. 60 patients (24,3%) of the studied population were found to be delirious. There were 26,5% of delirious patients in the Traumatology Department and 22,4% in the Neurology Department. And the maximum prevalence of delirium was in the range of 81–85 years (39%). We present statistically significant results showing unequal prevalence of delirium amongst elderly inpatients of the two biggest departments of the general hospital. The large amount of delirious patients forces of medical professionals to pay more attention on psychiatric condition of patients.

Neurosteroid dehydroepiandrosterone and brain function

For last 30 years it became clear that DHEA and DHEAS are synthesized de novo in brain. Steroids synthesized in brain structures, were received the name "neurosteroids". In the review are submitted data on a biosynthesis and metabolism of DHEA(S) including its metabolism in fatty tissue where it serves as substrate for intracellular formation of its biologically active metabolites--estradiol and testosterone. The role of a sulfatase and sulfotransferase in mutual transformations of DHEA and DHEA-sulfate are analysed. Specific differences in DHEA synthesis in adrenals are surveyed. The adrenals of primates, both human beings and monkeys, produce free DHEA and DHEA-sulphate in large quantity. Their synthesis proceeds on Δ5-pathways: cholesterol-pregnenolone-17-hydroxypregnenolone-DHEA. Adrenals of other animas species, including rats and mice, don't synthesize DHEA. From the authors point of view, process of DHEAS penetration in brain structures include two mechanisms: transformation under steroid sulfatase action DHEAS in DHEA which freely gets through a blood-brain barrier and DHEAS passing through a hypothalamus which isn't protected by a blood-brain barrier. Results of researches on clinical application of DHEA as neurosteroid, with the analysis of its role in a course of Alzheimer's disease, distrurbances of cognitive function and other disorders of a CBS are presented also. The main neurobiological effects of DHEA(S) on brain structures which are studied on various models of animals include: neuroprotection, neurogenesis and neuronal survival, apoptosis, catecholamine synthesis and secretion. Neurosteroids have also antioxidant, anti-inflammatory and anti-glucocorticoid effects.

Risk of childhood injuries after prenatal exposure to maternal bereavement: a Danish National Cohort Study

ObjectivesThe aim of this study was to assess the risk of injuries among children exposed to a stressful life exposure (defined as bereavement) before conception or during fetal life.DesignPopulation-based cohort...