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Journal Article 2013; 34(7): 635-642 PubMed PMID: 24464001 Citation  Keywords:  Aged, Apolipoprotein E2:genetics, Apolipoprotein E4:genetics, Cognition:drug effects, Cognition Disorders:epidemiology, Dementia:epidemiology, Estrogen Replacement Therapy:methods, Female, Humans, Middle Aged, Polymorphism, Genetic, Postmenopause:drug eff.   

OBJECTIVE: The results of many studies revealed that estrogen plus progestogen therapy (EPT) may modify dementia development risk in relation to the apolipoprotein E gene (APOE) polymorphisms. However, the mechanism and subsequently clinical importance of such an effect are still unexplained. The objective of this study was to explore the influence of EPT on cognitive functioning of women in their postmenopausal life in relation to APOE polymorphism.

METHODS: The group of 214 women was recruited (106 out of this group with EPT) to the study. The inclusion criteria were: minimum two years after the last menstruation, FSH concentration over 30 U/ml and no dementia signs on Montreal Cognitive Assessment (MoCA). Computerized battery of Central Nervous System Vital Signs (CNS VS) test was used to diagnostic cognitive functions. APOE genotype was performed by multiplex PCR. Statistical analysis was performed using two-way analysis of variance in STATISTICA software.

RESULTS & CONCLUSION: The women after menopause have reduced neurocognitive index (NCI) and cognitive functions. NCI and all studied cognitive functions of the patients depended significantly on APOE polymorphisms. The presence of APOE4 corresponded with decreased cognitive functions as opposed to APOE2 which was present in women with better level of cognitive functions. Constantly using EPT correlated with three cognitive functions: memory, verbal memory and processing speed, which were significantly worse for women taking EPT than not taking ones. The interaction between APOE polymorphisms and EPT application was significant only for processing speed. EPT applying women with ε2/ε3 and ε4 obtained better scores in processing speed than women not taking EPT with these APOE polymorphisms. The opposite situation concerned women with ε3/ε3, women taking EPT achieved worse processing scores in comparison with those not taking EPT. It should be noted that APOE polymorphism assessment may be a factor in predicting the effect of EPT on cognitive functioning in postmenopausal period....

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Journal Article 2011; 32(5): 727-732 PubMed PMID: 22167136 Citation  Keywords:  Animals, Antidepressive Agents:pharmacokinetics, Aryl Hydrocarbon Hydroxylases:metabolism, Brain:drug effects, Cognition:drug effects, Dextromethorphan:blood, Dopamine Agents:pharmacokinetics, Drug Interactions, Drug Therapy, Combination, Enzyme Activatio.   

OBJECTIVES: The drug-drug interactions can result in alterations of the therapeutical responses. The present study was designed to investigate possible pharmacokinetic interactions between the cognitive agent memantine and the antidepressant fluoxetine combined often in treatments of cognitive disorders including Alzheimer disease. The attention was focused on changes of the cytochrome P450 2D2 isoenzyme activity in two animal models.

METHODS AND DESIGN: The tested drugs were administered alone or in a combination to rat males and their effects on the 2D2 isoenzyme activity was determined after in vivo administration. The levels of marker dextromethorphan, its 2D2 specific metabolite dextrorphan were analyzed in plasma of rats and using the model of isolated perfused rat liver in the perfusion medium. The dextromethorphan/dextrorphan (DEM/DEX) metabolic ratios were determined as a sign of inhibitory influences on CYP2D2.

RESULTS: The analyses showed elevation of DEM/DEX metabolic ratio after all treatments: a) memantine, b) fluoxetine and c) memantine+fluoxetine, however the results were not completely identical. The intensity of inhibitory effects on the CYP2D2 activity were: memantine < memantine + fluoxetine < fluoxetine.

CONCLUSION: The results presented suggest that the clinical pharmacotherapeutical approach to combine memantine with fluoxetine is from the point of view of pharmacokinetic drug-drug interaction on the level of CYP2D2 isoenzyme safe and even of benefit as memantine could elicit a suppression of the inhibitory influence of fluoxetine....

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Controlled Clinical Trial 2011; 32(4): 464-468 PubMed PMID: 21876511 Citation  Keywords:  Cognition:drug effects, Electroencephalography, Evoked Potentials, Visual:drug effects, Flavonoids:administration & dosage, Humans, Nonheme Iron Proteins:drug effects, Phenols:administration & dosage, Photic Stimulation:methods, Placebos, Polyphenols, Sac.   

OBJECTIVE: Several natural polyphenols exert effects upon the cardiovascular as well as nervous system. In vitro and animal studies suggest that polyphenols may potentially affect the human cognitive function. The aim was to study the effect of Provinols™, the polyphenolic compounds isolated from red wine, upon the human higher brain functions.

MATERIAL AND METHODS: The accuracy of space memory was assessed by means of visually-guided and memory-guided saccadic eye movements. The EEG and blood pressure were registered also. The healthy undergraduates served as subjects. They were divided into the control, placebo and Provinols™ groups. The amplitudes of saccades, EEG spectral density, evoked potentials time-locked to saccadic onset and blood pressure were analyzed in control condition and 2 hours later, after administration of placebo, Provinols™ (4 mg/kg of body weight) or nothing.

RESULTS: After the Provinols™ administration the memory-guided saccades were significantly more accurate and the significant decrease in the slow EEG bands, alpha power mainly, was registered over the broad regions of temporo-parietal cortex. No changes in saccadic eye movement related potentials as well as in blood pressure were found after the single dose Provinols™ administration.

CONCLUSIONS: Even a single dose of the Provinols™ was able to affect positively the space memory for limited time duration. The improvement in space memory function and/or the positive role of attentional mechanisms may be taken into account mainly. More sensitive analysis of the particular participation of attentional and memory components demands the further study....

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Journal Article 2010; 31(2): 265-269 PubMed PMID: 20424578 Citation  Keywords:  Acromegaly:complications, Adult, Arthralgia:drug therapy, Cognition:drug effects, Female, Follow-Up Studies, Growth Hormone:antagonists & inhibitors, Headache:drug therapy, Humans, Interpersonal Relations, Male, Middle Aged, Motor Activity:drug effects, O.   

OBJECTIVES: Acromegaly is a chronic disease caused by excessive growth hormone secretion resulting in bone and soft tissue overgrowth. Body image changes as well as systemic complications may considerably influence patients' psychological health and disturb everyday activities. The aim of this study was to determine the effect of octreotide treatment on somatic and psychological symptoms of acromegaly, and thus on patients' quality of life.

MATERIALS AND METHODS: The study was conducted on 15 patients with acromegaly. The average duration of octreotide therapy was 5.6 years (1-10 years). The respondents created a list of subjective signs and symptoms of acromegaly before treatment and reported changes observed during therapy. The psychological examination was performed with appropriate test scales assessed patients' self-efficacy, emotional control, psychological gender and their life satisfaction.

RESULTS: The most important changes observed during octreotide therapy were associated with head and joint pain relief and reduction of physical limitations. The patients also noticed the improvement of cognitive functions and interpersonal relations. The study revealed average life satisfaction in the group. The patients on the one hand demonstrated high self-efficacy and on the other hand - intensive repression of emotions. The undifferentiated sex-role schema dominated in group.

CONCLUSIONS: The study proved a significance of octreotide therapy in acromegalic patients' life. In spite of chronic disease, all the respondents reported good quality of life (average life satisfaction). Additionally, their high self-efficacy helps to cope with the disease. Nevertheless, undifferentiated sex role schema in the study group suggests lack of behavioral flexibility and high emotional repression predicts negative somatic consequences....

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Journal Article 2008; 29(6): 822-830 PubMed PMID: 19112414 Citation  Keywords:  Anesthesia, General:psychology, Animals, Brain:drug effects, Cognition:drug effects, Consciousness:drug effects, Humans, Psychophysiology,.   

: An explanation of consciousness is one of the major unsolved problems of modern science. The modern view of consciousness arose in the nineteenth century; the view presumed that mental activity correlates with distinct physical states. Is the problem of consciousness real? Crick and Koch made a tentative assumption that all different aspects of consciousness (pain, seeing, thinking, emotion, self-consciousness) are connected by a basic common mechanism. The next step towards understanding involved the neuronal theories of consciousness (correlates of consciousness), often referred as the NNC (neural correlates of consciousness). Many neuroscientists presume that consciousness must have a neuronal correlate. The neuroscience of anaesthesia can be defined as studying the effect of anaesthetic agents on consciousness and the preconsciousness brain mechanisms of cognitive function. Some of these mechanisms, such as recognition of the novel stimuli, are still present in deep anaesthesia, during continuous suppression. Anaesthesia is not "an all or nothing" phenomenon and consciousness awareness with explicit memory represents only one part of the spectrum of cognitive functions. The introduction of safe general anaesthesia represents one of the most important, although under-appreciated, advances in modern surgery. There is some difficulty in defining the term "consciousness" in relation to the anaesthetic state. The difference in brain activity between those under anaesthesia and those not under any such influence....

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Clinical Trial 2008; 29(4): 500-506 PubMed PMID: 18766158 Citation  Keywords:  Adult, Antidepressive Agents:therapeutic use, Cognition:drug effects, Depressive Disorder, Major:drug therapy, Estradiol:blood, Female, Follicle Stimulating Hormone:blood, Humans, Korea, Luteinizing Hormone:blood, Menopause:psychology, Middle Aged, Postme.   

OBJECTIVES: A hypo-estrogenic status, as that occurring with menopause, has been proposed to negatively affect cognitive function in post-menopause women. Nevertheless, little is known about the improvement of cognitive functions during antidepressant treatment in post-menopausal women with major depressive disorder (MDD) and its relation with hormonal changes. Hence, this study aimed to investigate the role of menopausal status including the level of sex hormones on cognitive function during antidepressant treatment.

DESIGN AND SETTINGS: Thirty-nine female patients (n=17 in pre-menopause; n=22 in post-menopause) with MDD based on DSM-IV criteria and who were not on hormonal replacement therapies participated in a prospective, 6-week, open-label naturalistic study. All patients were recruited in a university-based hospital. The Hamilton rating scale for Depression (HAMD), Montgomery-Asberg Depression Rating Scale (MADRS) and the Cognitive Failure Questionnaire (CFQ) were administered at baseline, week 1, week 3, and week 6. Levels of follicle stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2) were collected at baseline visit.

RESULTS: Cognitive functioning improved during antidepressant treatment in the overall sample (P=0.00001). In post-menopausal women, E2 levels were strongly correlated with CFQ scores at each measurement. After controlling for depression severity, E2 levels maintained a significant association with the baseline CFQ scores (regression analysis: beta= -0.55 P=0.010; correlation: R= -0.54). In addition, the reduction of CFQ scores during antidepressant treatment was significantly associated with E2 levels (P=0.021), independently from the improvement of depressive symptoms, which however had a strong effect (P=0.0003). Nevertheless, we failed to find any association of CFQ score with sex hormones in pre-menopausal women.

MAIN FINDINGS: In post-menopausal women, the CFQ scores were correlated with E2 levels and the reduction of CFQ score during antidepressant treatment was also dependent on E2 levels, even controlling for depressive symptoms severity.

CONCLUSION: The present study further supports a crucial role of E2 on the cognitive function in post-menopause women. Moreover, our results suggest that E2 may influence the improvement of cognitive function in post-menopause women with MDD, during treatment with antidepressants....

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Journal Article 2007; 28(Suppl 4): 10-11 PubMed PMID: 18030257 Citation  Keywords:  Aged:psychology, Alcohol Drinking:psychology, Cardiovascular System:drug effects, Central Nervous System Depressants:pharmacology, Cognition:drug effects, Ethanol:pharmacology, Humans, Neuropsychological Tests,.   

: The studies on the effect of moderate alcohol consumption on mental capacity in elderly and inflammatory markers in coronary heart disease are reviewed....

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Clinical Trial 2006; 27(6): 833-838 PubMed PMID: 17187010 Citation  Keywords:  Adolescent, Androgen Antagonists:therapeutic use, Autistic Disorder:drug therapy, Chelating Agents:therapeutic use, Child, Child Behavior:drug effects, Cognition:drug effects, Female, Humans, Leuprolide:therapeutic use, Male, Metals, Heavy:urine, Severity.   

BACKGROUND: A medical hypothesis has suggested that some autism spectrum disorders (ASDs) may result from interactions between the methionine cycle-transsulfuration and androgen pathways following exposure to mercury.

METHODS: The IRB of the Institute for Chronic Illnesses approved the present study. A novel treatment was utilized combining LUPRON (leuprolide acetate, TAP Pharmaceuticals, Inc.) and CHEMET (meso-2, 3-dimercaptosuccinic acid--DMSA, McNeil Consumer Products Company) on 11 consecutive children with ASDs.

RESULTS: A significant (p<0.01) overall improvement from the 70-79th percentile of severity (median baseline score=87) at baseline to the 40-49th percentile of severity (median end of study period score=63) at the end of the study was observed for patients treated for a median of approximately 4 months. Significant improvements in sociability, cognitive awareness, behavior, and clinical symptoms/behaviors of hyperandrogenemia were also observed. Significant decreases in blood androgens and increases in urinary heavy metal concentrations were observed. Minimal drug adverse effects were found.

CONCLUSION: This study provides the first clinical evidence for the benefit that combined anti-androgen and anti-heavy metal therapy may have on some children with ASDs. Additional studies should examine androgen and heavy metal mechanisms of action in ASDs, and future ASD treatment protocols should consider androgens and heavy metals....

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