Oculomotor evidence for neocortical systems but not cerebellar dysfunction in autism

PubMed Central

Minshew, Nancy J.; Luna, Beatriz; Sweeney, John A.

2010-01-01

Objective To investigate the functional integrity of cerebellar and frontal system in autism using oculomotor paradigms. Background Cerebellar and neocortical systems models of autism have been proposed. Courchesne and colleagues have argued that cognitive deficits such as shifting attention disturbances result from dysfunction of vermal lobules VI and VII. Such a vermal deficit should be associated with dysmetric saccadic eye movements because of the major role these areas play in guiding the motor precision of saccades. In contrast, neocortical models of autism predict intact saccade metrics, but impairments on tasks requiring the higher cognitive control of saccades. Methods A total of 26 rigorously diagnosed nonmentally retarded autistic subjects and 26 matched healthy control subjects were assessed with a visually guided saccade task and two volitional saccade tasks, the oculomotor delayed-response task and the antisaccade task. Results Metrics and dynamic of the visually guided saccades were normal in autistic subjects, documenting the absence of disturbances in cerebellar vermal lobules VI and VII and in automatic shifts of visual attention. Deficits were demonstrated on both volitional saccade tasks, indicating dysfunction in the circuitry of prefrontal cortex and its connections with the parietal cortex, and associated cognitive impairments in spatial working memory and in the ability to voluntarily suppress context-inappropriate responses. Conclusions These findings demonstrate intrinsic neocortical, not cerebellar, dysfunction in autism, and parallel deficits in higher order cognitive mechanisms and not in elementary attentional and sensorimotor systems in autism. PMID:10102406

Abnormal amyloid β42 expression and increased oxidative stress in plasma of CKD patients with cognitive dysfunction: A small scale case control study comparison with Alzheimer's disease.

PubMed

Vinothkumar, G; Kedharnath, C; Krishnakumar, S; Sreedhar, S; Preethikrishnan, K; Dinesh, S; Sundaram, A; Balakrishnan, D; Shivashekar, G; Sureshkumar; Venkataraman, P

2017-12-01

Cognitive dysfunction has been increasingly recognized in chronic kidney disease (CKD) patients. Senile plaques are important pathophysiological characteristic of cognitive dysfunction. The major component of plaques is the amyloid β (Aβ) peptide released from proteolytic cleavage of amyloid precursor protein (APP). Plasma Aβ has been a focus of the growing literature on blood based biomarkers for cognitive dysfunction. Oxidative stress is prevalent in CKD and it plays an important role in cognitive dysfunction. Increased oxidative stress leads to cause cleavage of APP and Aβ production. The aim of this study is to assess the antioxidant status and Aβ 42 levels in plasma of CKD patients with cognitive dysfunction compared to CKD without cognitive dysfunction. A total of 60 subjects divided into 30 CKD without cognitive dysfunction and 30 CKD with cognitive dysfunction based on neuropsychological assessment tests. To compare antioxidant status and Aβ 42 levels in plasma, the following groups such as healthy subjects (n = 30), normocytic normochromic anemia (n = 30) and Alzheimer's disease (AD, n = 10) patients were also maintained. Plasma Superoxide dismutase (SOD), Catalase (CAT), Glutathione peroxidase (GPx), Reduced glutathione (GSH) and lipid peroxidation (LPO) were determined by spectrophotometrically. Aβ level was determined by immunoblotting method. The parameters were statistically compared with healthy, normocytic normochromic anemia and AD subjects. Like AD subjects, significantly increased Aβ and LPO level while decreased SOD, CAT, GPx and GSH levels were observed in plasma of CKD patients with cognitive dysfunction when compared to healthy, CKD without cognitive dysfunction and normocytic normochromic anemic subjects. Results suggest that elevated plasma oxidative stress and Aβ were seen in CKD patients with cognitive dysfunction may be attributed to pathological changes within the brain.

Neurological and psychiatric disorders in thyroid dysfunctions. The role of nuclear medicine: SPECT and PET imaging.

PubMed

Lass, P; Slawek, J; Derejko, M; Rubello, D

2008-06-01

Thyroid dysfunctions may be accompanied by numerous neurological and psychiatric disorders. The most known is cognitive impairment and depression in hypothyroid patients, as well as an increased risk of cerebrovascular accidents. A separate, although a rare entity, is Hashimoto's encephalopathy. In hyperthyroidism there is an increased incidence of psychiatric disorders, including apathetic hyperthyroidism and hyperthyroid dementia. Functional imaging of cerebral blood flow and metabolism helped establish both global and/or regional decrease of both cerebral blood flow and metabolism in hypothyroidism, particularly in regions mediating attention, motor speed and visuospatial processing. Hypothyroid dementia may be mediated by neurocircuitry different from that in major depression. Less is known on flow/metabolism changes in hyperthyroidism. Global blood flow may be slightly increased, with regional deficits of blood flow, particular in hyperthyroid dementia. As presented above radionuclide functional imaging showed some metabolic patterns in thyroid dysfunctions, but still many issues remain unresolved. In particular little is known about the underlying pathology of cognitive impairment and depression in hypothyroidism, which may differ from ones in euthyroid patients. Also little is known about the reversibility of changes in cerebral blood flow following thyroid replacement therapy. In hyperthyroid patients functional imaging might contribute to elucidate the background of apathetic hyperthyroidism and potential different background of psychiatric complications.

Predictors of subjective versus objective cognitive functioning in patients with stable grades II and III glioma

PubMed Central

Gehring, Karin; Taphoorn, Martin J.B.; Sitskoorn, Margriet M.; Aaronson, Neil K.

2015-01-01

Background Studies in cancer and noncancer populations demonstrate lower than expected correlations between subjective cognitive symptoms and cognitive functioning as determined by standardized neuropsychological tests. This paper systematically examines the association between subjective and objective cognitive functioning in patients with low-grade glioma and the associations of these indicators of cognitive function with clusters of sociodemographic, clinical, and self-reported physical and mental health factors. Methods Multiple regression analyses with the subjective and 2 objective indicators of cognitive functioning as dependent variables and 4 clusters of predictor variables were conducted in 169 patients with predominantly low-grade glioma. Results Correlations between the subjective and the 2 objective cognitive indicators were negligible (0.04) to low (0.24). Objective cognitive deficits were predominantly associated with sociodemographic (older age, lower education, male sex) and clinical (left hemisphere tumor) variables, while lower ratings of subjective cognitive function were more closely related to self-reported mental health symptoms (fatigue, lower mental well-being), physical (motor) dysfunction and female sex. Self-reported communication deficits were associated significantly with both subjective and objective dysfunction. Conclusions We recommend that both subjective and objective measures of cognitive functioning, together with a measure of psychological distress, be used for comprehensive neuropsychological assessments of patients with glioma to determine which areas are most affected and which specific intervention strategies are most appropriate. PMID:26034638

A longitudinal analysis of cognitive dysfunction, coping, and depression in multiple sclerosis.

PubMed

Rabinowitz, Amanda R; Arnett, Peter A

2009-09-01

Using a longitudinal design, the authors examined coping and cognitive functioning in the development of depression in individuals with multiple sclerosis (MS). Coping style was evaluated in 2 conceptually distinct roles: as moderator and mediator of the impact of cognitive dysfunction on depression. Using indices derived from the COPE (C. S. Carver, M. F. Scheier, & J. K. Weintraub, 1989), the authors operationalized coping in 3 ways-as active, avoidant, and an index accounting for relative levels of both. Coping both moderated and partially mediated the relationship between cognitive dysfunction and depression. Moderation results suggest that the relationship between cognitive dysfunction and depression is dependent on coping style-adaptive coping protects individuals from experiencing depression related to their cognitive deficits; however, when individuals use maladaptive coping, cognitive dysfunction puts them at risk for depression. Mediational results suggest that cognitive dysfunction leads to depression partially due to cognitive dysfunction's effects on coping. That is, cognitive deficits may impair individuals' ability to use adaptive coping strategies, leaving them more likely to use maladaptive strategies. Clinical and theoretical implications of these findings are discussed.

Association Between Cognitive Complaints and Vulnerability to Environmental Distraction in Multiple Sclerosis.

PubMed

Randolph, John J; Randolph, Jennifer S; Wishart, Heather A

2017-02-01

Individuals with multiple sclerosis (MS) often report cognitive dysfunction, although neuropsychological evaluation findings may not correlate with subjective concerns. One factor that may explain this lack of correspondence is the controlled testing environment, which differs from busier settings where cognitive lapses are noted to occur. This study used a novel environmental manipulation to determine whether individuals with MS who report cognitive dysfunction are more vulnerable to the effects of auditory distraction during neuropsychological testing. Twenty-four individuals with clinically definite MS or clinically isolated syndrome were administered a cognitive battery during two counterbalanced auditory conditions: quiet/standard condition, and distraction condition with random office background noise. Participants were divided into high versus low cognitive complaint groups using a median split analysis of Perceived Deficits Questionnaire responses. Participants with more cognitive complaints showed a decrement in performance on the oral Symbol Digit Modalities Test during the distraction condition while those with fewer cognitive complaints demonstrated stable performance across conditions. These findings remained significant after controlling for education, premorbid intellect, fatigue, and depressed mood. These results suggest that individuals with MS with more cognitive complaints are vulnerable to environmental distraction, particularly regarding processing speed. Incorporating random environmental noise or other distraction conditions during selected measures may enhance the ecological validity of neuropsychological evaluation results in MS. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Efficacy of N-Butylphthalide and Hyperbaric Oxygen Therapy on Cognitive Dysfunction in Patients with Delayed Encephalopathy After Acute Carbon Monoxide Poisoning.

PubMed

Xiang, Wenping; Xue, Hui; Wang, Baojun; Li, Yuechun; Zhang, Jun; Jiang, Changchun; Pang, Jiangxia

2017-03-29

BACKGROUND Delayed encephalopathy after acute carbon monoxide (CO) poisoning (DEACMP) is one of the most serious complications after CO poisoning. This study was conducted to explore the efficacy of the combined application of N-Butylphthalide and hyperbaric oxygenation therapy (HBO) on cognitive dysfunction in patients with DEACMP. MATERIAL AND METHODS A total of 184 patients with DEACMP were randomly assigned to either receive HBO or N-Butylphthalide and HBO. Meanwhile, all patients received conventional treatment. The total remission rate (RR) was used to assess the clinical efficacy. The Mini-Mental State Examination (MMSE) was used to assess the cognitive function, and the National Institutes of Health Stroke Scale (NIHSS) was used to assess the neurological function. RESULTS Finally, there were 90 and 94 patients in the control and experimental groups, respectively. After eight weeks of treatment, the total RR in the experimental group (47.9%) was significantly higher than that in the control group (33.3%). Compared to the control group, significantly more patients in the experimental group had MMSE scores of 24-30. The lower NIHSS score in the experimental group showed that N-Butylphthalide had the effect of preservation and restoration of neurological function. No obvious drug toxicity or liver and kidney dysfunction was observed, and there was no significant change in the level of blood glucose and blood lipids. CONCLUSIONS These results indicated that the combined application of N-Butylphthalide and HBO could significantly improve the cognitive dysfunction of patients with DEACMP and have great clinical efficacy, which should be further studied.

Mild Cognitive Dysfunction Does Not Affect Diabetes Mellitus Control in Minority Elderly Adults

PubMed Central

Palta, Priya; Golden, Sherita H.; Teresi, Jeanne; Palmas, Walter; Weinstock, Ruth S.; Shea, Steven; Manly, Jennifer J.; Luchsinger, Jose A.

2015-01-01

OBJECTIVES To determine whether older adults with type 2 diabetes mellitus and cognitive dysfunction have poorer metabolic control of glycosylated hemoglobin, systolic blood pressure, and low-density lipoprotein cholesterol than those without cognitive dysfunction. DESIGN Prospective cohort study. SETTING A minority cohort in New York City previously recruited for a trial of telemedicine. PARTICIPANTS Persons aged 73.0 ± 3.0 (N = 613; 69.5% female; 82.5% Hispanic, 15.5% non-Hispanic black). MEASUREMENTS Participants were classified with executive or memory dysfunction based on standardized score cutoffs (<16th percentile) for the Color Trails Test and Selective Reminding Test. Linear mixed models were used to compare repeated measures of the metabolic measures and evaluate the rates of change in individuals with and without dysfunction. RESULTS Of the 613 participants, 331 (54%) had executive dysfunction, 202 (33%) had memory dysfunction, and 96 (16%) had both. Over a median of 2 years, participants with executive or memory dysfunction did not exhibit significantly poorer metabolic control than those without executive function or memory type cognitive dysfunction. CONCLUSION Cognitive dysfunction in the mild range did not seem to affect diabetes mellitus control parameters in this multiethnic cohort of older adults with diabetes mellitus, although it cannot be excluded that cognitive impairment was overcome through assistance from formal or informal caregivers. It is possible that more-severe cognitive dysfunction could affect control. PMID:25439094

Mild cognitive dysfunction does not affect diabetes mellitus control in minority elderly adults.

PubMed

Palta, Priya; Golden, Sherita H; Teresi, Jeanne; Palmas, Walter; Weinstock, Ruth S; Shea, Steven; Manly, Jennifer J; Luchsinger, Jose A

2014-12-01

To determine whether older adults with type 2 diabetes mellitus and cognitive dysfunction have poorer metabolic control of glycosylated hemoglobin, systolic blood pressure, and low-density lipoprotein cholesterol than those without cognitive dysfunction. Prospective cohort study. A minority cohort in New York City previously recruited for a trial of telemedicine. Persons aged 73.0 ± 3.0 (N = 613; 69.5% female; 82.5% Hispanic, 15.5% non-Hispanic black). Participants were classified with executive or memory dysfunction based on standardized score cutoffs (<16th percentile) for the Color Trails Test and Selective Reminding Test. Linear mixed models were used to compare repeated measures of the metabolic measures and evaluate the rates of change in individuals with and without dysfunction. Of the 613 participants, 331 (54%) had executive dysfunction, 202 (33%) had memory dysfunction, and 96 (16%) had both. Over a median of 2 years, participants with executive or memory dysfunction did not exhibit significantly poorer metabolic control than those without executive function or memory type cognitive dysfunction. Cognitive dysfunction in the mild range did not seem to affect diabetes mellitus control parameters in this multiethnic cohort of older adults with diabetes mellitus, although it cannot be excluded that cognitive impairment was overcome through assistance from formal or informal caregivers. It is possible that more-severe cognitive dysfunction could affect control. © 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.

Predictors and assessment of cognitive dysfunction resulting from ischaemic stroke

PubMed Central

Gottesman, Rebecca F; Hillis, Argye E

2013-01-01

Stroke remains a primary cause of morbidity throughout the world mainly because of its effect on cognition. Individuals can recover from physical disability resulting from stroke, but might be unable to return to their previous occupations or independent life because of cognitive impairments. Cognitive dysfunction ranges from focal deficits, resulting directly from an area of infarction or from hypoperfusion in adjacent tissue, to more global cognitive dysfunction. Global dysfunction is likely to be related to other underlying subclinical cerebrovascular disease, such as white-matter disease or subclinical infarcts. Study of cognitive dysfunction after stroke is complicated by varying definitions and lack of measurement of cognition before stroke. Additionally, stroke can affect white-matter connectivity, so newer imaging techniques, such as diffusion-tensor imaging and magnetisation transfer imaging, that can be used to assess this subclinical injury are important tools in the assessment of cognitive dysfunction after stroke. As research is increasingly focused on the role of preventable risk factors in the development of dementia, the role of stroke in the development of cognitive impairment and dementia could be another target for prevention. PMID:20723846

Disconnection as a Mechanism for Cognitive Dysfunction in Multiple Sclerosis

ERIC Educational Resources Information Center

Dineen, R. A.; Vilisaar, J.; Hlinka, J.; Bradshaw, C. M.; Morgan, P. S.; Constantinescu, C. S.; Auer, D. P.

2009-01-01

Disconnection of cognitively important processing regions by injury to the interconnecting white matter provides a potential mechanism for cognitive dysfunction in multiple sclerosis. The contribution of tract-specific white matter injury to dysfunction in different cognitive domains in patients with multiple sclerosis has not previously been…

Developing Interventions for Cancer-Related Cognitive Dysfunction in Childhood Cancer Survivors

PubMed Central

Ullrich, Nicole J.; Whelen, Megan J.; Lange, Beverly J.

2014-01-01

Survivors of childhood cancer frequently experience cancer-related cognitive dysfunction, commonly months to years after treatment for pediatric brain tumors, acute lymphoblastic leukemia (ALL), or tumors involving the head and neck. Risk factors for cancer-related cognitive dysfunction include young age at diagnosis, treatment with cranial irradiation, use of parenteral or intrathecal methotrexate, female sex, and pre-existing comorbidities. Limiting use and reducing doses and volume of cranial irradiation while intensifying chemotherapy have improved survival and reduced the severity of cognitive dysfunction, especially in leukemia. Nonetheless, problems in core functional domains of attention, processing speed, working memory and visual-motor integration continue to compromise quality of life and performance. We review the epidemiology, pathophysiology and assessment of cancer-related cognitive dysfunction, the impact of treatment changes for prevention, and the broad strategies for educational and pharmacological interventions to remediate established cognitive dysfunction following childhood cancer. The increased years of life saved after childhood cancer warrants continued study toward the prevention and remediation of cancer-related cognitive dysfunction, using uniform assessments anchored in functional outcomes. PMID:25080574

Controlled randomized clinical trial of spirituality integrated psychotherapy, cognitive-behavioral therapy and medication intervention on depressive symptoms and dysfunctional attitudes in patients with dysthymic disorder

PubMed Central

Ebrahimi, Amrollah; Neshatdoost, Hamid Taher; Mousavi, Seyed Ghafur; Asadollahi, Ghorban Ali; Nasiri, Hamid

2013-01-01

Background: Due to the controversy over efficacy of cognitive-behavioral therapy for chronic depression, recently, there has been an increasingly tendency toward therapeutic methods based on the cultural and spiritual approaches. The aim of this research was to compare efficacy of spiritual integrated psychotherapy (SIPT) and cognitive-behavioral therapy (CBT) on the intensity of depression symptoms and dysfunctional attitudes of patients with dysthymic disorder. Materials and Methods: This study had a mixed qualitative and quantitative design. In the first phase, SIPT model was prepared and, in the second phase, a double-blind random clinical trial was performed. Sixty-two patients with dysthymic disorder were selected from several centers include Nour and Alzahra Medical Center, Counseling Centers of Isfahan University of Medical Sciences and Goldis in Isfahan. The participants were randomly assigned to three experimental groups and one control group. The first group received 8 sessions treatment of SIPT, second groups also had 8 sessions of cognitive-behavioral therapy, which was specific to dysthymic disorder and third group were under antidepressant treatment. Beck depression inventory and dysfunctional attitudes scale were used to evaluate all the participants in four measurement stages. The data were analyzed using MANCOVA repeated measure method. Results: The results revealed that SIPT had more efficacy than medication based on both scales (P < 0.01); however, it was not different from CBT. SIPT was more effective on the modification of dysfunctional attitudes compared with CBT and medication (P < 0.05). Conclusion: These findings supported the efficacy of psychotherapy enriched with cultural capacities and religious teachings. PMID:24516853

Brain and Cognition Abnormalities in Long-Term Anabolic-Androgenic Steroid Users

PubMed Central

Kaufman, Marc J.; Janes, Amy C.; Hudson, James I.; Brennan, Brian P.; Kanayama, Gen; Kerrigan, Andrew R.; Jensen, J. Eric; Pope, Harrison G.

2015-01-01

Background Anabolic-androgenic steroid (AAS) use is associated with psychiatric symptoms including increased aggression as well as with cognitive dysfunction. The brain effects of long-term AAS use have not been assessed in humans. Methods This multimodal magnetic resonance imaging study of the brain compared 10 male weightlifters reporting long-term AAS use with 10 age-matched weightlifters reporting no AAS exposure. Participants were administered visuospatial memory tests and underwent neuroimaging. Brain volumetric analyses were performed; resting-state fMRI functional connectivity (rsFC) was evaluated using a region-of-interest analysis focused on the amygdala; and dorsal anterior cingulate cortex (dACC) metabolites were quantified by proton magnetic resonance spectroscopy (MRS). Results AAS users had larger right amygdala volumes than nonusers (P=0.002) and reduced rsFC between right amygdala and frontal, striatal, limbic, hippocampal, and visual cortical areas. Left amygdala volumes were slightly larger in AAS users (P=0.061) but few group differences were detected in left amygdala rsFC. AAS users also had lower dACC scyllo-inositol levels (P=0.004) and higher glutamine/glutamate ratios (P=0.028), possibly reflecting increased glutamate turnover. On a visuospatial cognitive task, AAS users performed more poorly than nonusers, with the difference approaching significance (P=0.053). Conclusions Long-term AAS use is associated with right amygdala enlargement and reduced right amygdala rsFC with brain areas involved in cognitive control and spatial memory, which could contribute to the psychiatric effects and cognitive dysfunction associated with AAS use. The MRS abnormalities we detected could reflect enhanced glutamate turnover and increased vulnerability to neurotoxic or neurodegenerative processes, which could contribute to AAS-associated cognitive dysfunction. PMID:25986964

Informant Perceptions of the Cause of Activities of Daily Living Difficulties in Parkinson's Disease.

PubMed

Benge, Jared F; Balsis, Steve

2016-01-01

Individuals with Parkinson's disease (PD) can have difficulties with activities of daily living (ADL) that stem from cognitive, motor, or affective manifestations of the disease. Accurately attributing ADL difficulty specifically to cognitive decline is critical when conducting a neuropsychological evaluation of a person with PD. Informant description of ADL performance is frequently used for this purpose, but there has been little work assessing informants' ability to attribute ADL dysfunction to a specific symptom source in PD. Fifty community dwelling individuals with PD completed cognitive, motor, and affective measures. A knowledgeable informant completed an ADL scale that asked about degree and perceived source of difficulty (cognitive, motor, affective) for each task. Informants indicated that motor dysfunction was the most common source of ADL difficulty, but the informants viewed difficulty with certain tasks, such as financial management, as particularly related to cognitive dysfunction. Informant reports of the source of ADL dysfunction (cognitive, motor, affective) were consistent with clinical measures of those specific dysfunctions. ADL dysfunction attributed to cognition specifically (χ(2) = 9.80, p = .01) was higher in those with measurable cognitive impairment. Informant reports of the sources of ADL dysfunction correlate with clinical measures of these symptoms, suggesting that informants may provide useful clinical information about the cause of ADL dysfunction in persons with PD.

Analysing UK clinicians' understanding of cognitive symptoms in major depression: A survey of primary care physicians and psychiatrists.

PubMed

McAllister-Williams, R Hamish; Bones, Kate; Goodwin, Guy M; Harrison, John; Katona, Cornelius; Rasmussen, Jill; Strong, Sarah; Young, Allan H

2017-01-01

Cognitive dysfunction occurs in depression and can persist into remission. It impacts on patient functioning but remains largely unrecognised, unmonitored and untreated. We explored understanding of cognitive dysfunction in depression among UK clinicians. A multi-step consultation process. Step 1: a multi-stakeholder steering committee identified key themes of burden, detection and management of cognitive dysfunction in depression, and developed statements on each to explore understanding and degree of agreement among clinicians. Step 2: 100 general practitioners (GPs) and 100 psychiatrists indicated their level of agreement with these statements. Step 3: the steering committee reviewed responses and highlighted priority areas for future education and research. There was agreement that clinicians are not fully aware of cognitive dysfunction in depression. Views of the relationship between cognitive dysfunction and other depressive symptom severities was not consistent with the literature. In particular, there was a lack of recognition that some cognitive dysfunction can persist into remission. There was understandable uncertainty around treatment options, given the current limited evidence base. However, it was recognised that cognitive dysfunction is an area of unmet need and that there is a lack of objective tests of cognition appropriate for depressed patients that can be easily implemented in the clinic. Respondents are likely to be 'led' by the direction of the statements they reviewed. The study did not involve patients and carers. UK clinicians should undergo training regarding cognitive dysfunction in depression, and further research is needed into its assessment, treatment and monitoring. Copyright © 2016 Elsevier B.V. All rights reserved.

Social Cognition Dysfunctions in Neurodegenerative Diseases: Neuroanatomical Correlates and Clinical Implications.

PubMed

Christidi, Foteini; Migliaccio, Raffaella; Santamaría-García, Hernando; Santangelo, Gabriella; Trojsi, Francesca

2018-01-01

Social cognitive function, involved in the perception, processing, and interpretation of social information, has been shown to be crucial for successful communication and interpersonal relationships, thereby significantly impacting mental health, well-being, and quality of life. In this regard, assessment of social cognition, mainly focusing on four key domains, such as theory of mind (ToM), emotional empathy, and social perception and behavior, has been increasingly evaluated in clinical settings, given the potential implications of impairments of these skills for therapeutic decision-making. With regard to neurodegenerative diseases (NDs), most disorders, characterized by variable disease phenotypes and progression, although similar for the unfavorable prognosis, are associated to impairments of social cognitive function, with consequent negative effects on patients' management. Specifically, in some NDs these deficits may represent core diagnostic criteria, such as for behavioral variant frontotemporal dementia (bvFTD), or may emerge during the disease course as critical aspects, such as for Parkinson's and Alzheimer's diseases. On this background, we aimed to revise the most updated evidence on the neurobiological hypotheses derived from network-based approaches, clinical manifestations, and assessment tools of social cognitive dysfunctions in NDs, also prospecting potential benefits on patients' well-being, quality of life, and outcome derived from potential therapeutic perspectives of these deficits.

Social Cognition Dysfunctions in Neurodegenerative Diseases: Neuroanatomical Correlates and Clinical Implications

PubMed Central

Santamaría-García, Hernando; Santangelo, Gabriella

2018-01-01

Social cognitive function, involved in the perception, processing, and interpretation of social information, has been shown to be crucial for successful communication and interpersonal relationships, thereby significantly impacting mental health, well-being, and quality of life. In this regard, assessment of social cognition, mainly focusing on four key domains, such as theory of mind (ToM), emotional empathy, and social perception and behavior, has been increasingly evaluated in clinical settings, given the potential implications of impairments of these skills for therapeutic decision-making. With regard to neurodegenerative diseases (NDs), most disorders, characterized by variable disease phenotypes and progression, although similar for the unfavorable prognosis, are associated to impairments of social cognitive function, with consequent negative effects on patients' management. Specifically, in some NDs these deficits may represent core diagnostic criteria, such as for behavioral variant frontotemporal dementia (bvFTD), or may emerge during the disease course as critical aspects, such as for Parkinson's and Alzheimer's diseases. On this background, we aimed to revise the most updated evidence on the neurobiological hypotheses derived from network-based approaches, clinical manifestations, and assessment tools of social cognitive dysfunctions in NDs, also prospecting potential benefits on patients' well-being, quality of life, and outcome derived from potential therapeutic perspectives of these deficits. PMID:29854017

Evaluating sub-clinical cognitive dysfunction and event-related potentials (P300) in clinically isolated syndrome.

PubMed

Kocer, Belgin; Unal, Tugba; Nazliel, Bijen; Biyikli, Zeynep; Yesilbudak, Zulal; Karakas, Sirel; Irkec, Ceyla

2008-12-01

This study investigated the presence of sub-clinical cognitive dysfunction in patients with clinically isolated syndrome (CIS) and the abnormalities of cognitive event-related potentials (ERPs). Subclinical cognitive dysfunction was assessed in 20 patients with CIS and in 20 healthy controls. Patients had impairments in verbal learning and long-term memory, evaluating attention, executive function and visuospatial skills, in decreasing order of frequency. SDLT and SIT were the most, and COWAT and BNT were the least affected tests. The N200 and P200 latencies were prolonged, and N100, N200 and P200 amplitudes were reduced in the patients relative to the controls, from the Fz, Cz and Pz electrode positions (p<0.05). Detailed cognitive testing is valuable in determining subclinical cognitive dysfunction in CIS patients. ERP abnormalities as well as abnormalities in detailed cognitivetesting in patients with CIS are helpful in the diagnosis of sub-clinical cognitive dysfunction.

Cognitive remission: a novel objective for the treatment of major depression?

PubMed

Bortolato, Beatrice; Miskowiak, Kamilla W; Köhler, Cristiano A; Maes, Michael; Fernandes, Brisa S; Berk, Michael; Carvalho, André F

2016-01-22

Cognitive dysfunction in major depressive disorder (MDD) encompasses several domains, including but not limited to executive function, verbal memory, and attention. Furthermore, cognitive dysfunction is a frequent residual manifestation in depression and may persist during the remitted phase. Cognitive deficits may also impede functional recovery, including workforce performance, in patients with MDD. The overarching aims of this opinion article are to critically evaluate the effects of available antidepressants as well as novel therapeutic targets on neurocognitive dysfunction in MDD. Conventional antidepressant drugs mitigate cognitive dysfunction in some people with MDD. However, a significant proportion of MDD patients continue to experience significant cognitive impairment. Two multicenter randomized controlled trials (RCTs) reported that vortioxetine, a multimodal antidepressant, has significant precognitive effects in MDD unrelated to mood improvement. Lisdexamfetamine dimesylate was shown to alleviate executive dysfunction in an RCT of adults after full or partial remission of MDD. Preliminary evidence also indicates that erythropoietin may alleviate cognitive dysfunction in MDD. Several other novel agents may be repurposed as cognitive enhancers for MDD treatment, including minocycline, insulin, antidiabetic agents, angiotensin-converting enzyme inhibitors, S-adenosyl methionine, acetyl-L-carnitine, alpha lipoic acid, omega-3 fatty acids, melatonin, modafinil, galantamine, scopolamine, N-acetylcysteine, curcumin, statins, and coenzyme Q10. The management of cognitive dysfunction remains an unmet need in the treatment of MDD. However, it is hoped that the development of novel therapeutic targets will contribute to 'cognitive remission', which may aid functional recovery in MDD.

Cognitive complaints and predictors of perceived cognitive dysfunction in adults with major depressive disorder: Findings from the Cognitive Dysfunction in Asians with Depression (CogDAD) study.

PubMed

Srisurapanont, Manit; Mok, Yee Ming; Yang, Yen Kuang; Chan, Herng-Nieng; Della, Constantine D; Zainal, Nor Zuraida; Jambunathan, Stephen; Amir, Nurmiati; Kalita, Pranab

2018-05-01

Several studies have described the presence of perceived cognitive dysfunction amongst Asian patients with major depressive disorder (MDD). To date, no study has been conducted investigating the predictors of perceived cognitive dysfunction amongst Asian MDD patients. This was a post-hoc analysis of the Cognitive Dysfunction in Asian patients with Depression (CogDAD) study. Descriptive statistics were used to describe the most common cognitive complaints by patients. Univariate and multivariate analyses were performed to determine variables associated with perceived cognitive dysfunction (Perceived Deficit Questionnaire-Depression, PDQ-D). The CogDAD study population is comprised of MDD patients with mild-to-moderate depression (Patient Health Questionnaire 9-item [PHQ-9]: 11.3 ± 6.9) who reported perceived cognitive dysfunction (PDQ-D = 22.6 ± 16.2). The most common cognitive complaints were: mind drifting (42.3%), trouble making decision (39.6%) and trouble concentrating (38.0%). Predictors of perceived cognitive dysfunction were: being Southeast Asians (vs. Taiwanese) (p < 0.001), current episode longer than 8 weeks (vs. 1-8 weeks) (p < 0.05), the presence of disability (vs. no disability) (p < 0.05), younger age (p < 0.01), and higher PHQ-9 total scores (p < 0.001). The causal relationship between predictive variables and PDQ-D could not be tested due to the cross-sectional nature of the study. Furthermore, a neuropsychological test was not included in the CogDAD study and use of concomitant medications, including anti-depressants, could have impacted patient's perceived cognitive ability. The present study results suggest a potential role for subjective cognitive assessment in patients with MDD who are young, with long durations of depression or severe depression. Copyright © 2018 Elsevier B.V. All rights reserved.

Therapeutic impact of rHuEPO on abnormal platelet APP, BACE 1, presenilin 1, ADAM 10 and Aβ expressions in chronic kidney disease patients with cognitive dysfunction like Alzheimer's disease: A pilot study.

PubMed

G, Vinothkumar; S, Krishnakumar; Sureshkumar; G, Shivashekar; S, Sreedhar; Preethikrishnan; S, Dinesh; A, Sundaram; D, Balakrishnan; Riya; P, Venkataraman

2018-08-01

Cognitive dysfunction is reported to be a major cause of morbidity in chronic kidney disease (CKD). The senile plaques (SPs) in the brain are one of the most pathophysiological characteristics of cognitive dysfunction and its major constituent amyloid β (Aβ) released from amyloid precursor protein (APP) by β (BACE1) and γ (presenilin 1) secretases . Platelets contain more than 95% of the circulating APP and implicate as a candidate biomarker for cognitive decline. Recombinant human erythropoietin (rHuEPO) is a standard therapy for anemia in CKD and also acts as a neuroprotective agent. The aim of the study is to determine the impact of rHuEPO therapy on platelet APP processing in CKD with Cognitive Dysfunction. A total of 60 subjects comprising of 30 CKD without cognitive dysfunction and 30 CKD with cognitive dysfunction based on neuropsychological assessment. APP, BACE1, Presenilin 1, ADAM 10 (α secretase) and Aβ expressions in platelets were determined by western blotting and lipid peroxidation (LPO) in platelet rich plasma (PRP) was done by spectrophotometrically. The parameters were statistically compared with Alzheimer's disease (AD), Normocytic normochromic anemic and healthy subjects. Significantly (p < 0.05) decreased APP, ADAM 10 while increased BACE1, Presenilin 1, Aβ and LPO were observed in CKD with cognitive dysfunction like AD subjects compared to other groups. The parameters were reassessed in CKD with cognitive dysfunction subjects after rHuEPO (100 IU/ kg, weekly twice, 6 months) therapy. All the parameters were retrieved significantly (p < 0.05) along with improved neuropsychological tests scoring after rHuEPO therapy. This study demonstrated that rHuEPO is an effective neuroprotective agent in the context of CKD associated cognitive dysfunction and proved its clinical usefulness. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Green tea consumption affects cognitive dysfunction in the elderly: a pilot study.

PubMed

Ide, Kazuki; Yamada, Hiroshi; Takuma, Norikata; Park, Mijong; Wakamiya, Noriko; Nakase, Junpei; Ukawa, Yuuichi; Sagesaka, Yuko M

2014-09-29

Green tea is known to have various health benefits for humans. However, the effect of green tea consumption on cognitive dysfunction remains to be clinically verified. We conducted a clinical study to investigate the effects of green tea consumption on cognitive dysfunction. Twelve elderly nursing home residents with cognitive dysfunction (Mini-Mental State Examination Japanese version (MMSE-J) score: <28) participated in the study (2 men, 10 women; mean age, 88 years). The participants consumed green tea powder 2 g/day for 3 months. After three months of green tea consumption, the participants' MMSE-J scores were significantly improved (before, 15.3 ± 7.7; after, 17.0 ± 8.2; p = 0.03). This result suggests that green tea consumption may be effective in improving cognitive function or reducing the progression of cognitive dysfunction; however, long-term large-scale controlled studies are needed to further clarify the effect.

Neuropsychological Functioning in College Students Who Misuse Prescription Stimulants

PubMed Central

Wilens, Timothy; Carrellas, Nicholas W.; Martelon, MaryKate; Yule, Amy M.; Fried, Ronna; Anselmo, Rayce; McCabe, Sean E.

2017-01-01

Background and Objectives Relatively little is known about the neuropsychological profiles of college students who misuse prescription stimulant medications. Methods Data presented are from college students aged 18 to 28 years who misused prescription stimulants prescribed for attention-deficit/hyperactivity disorder and controls (no prescription stimulant misuse). Students were assessed neuropsychologically using the self-report Behavioral Rating Inventory of Executive Functioning (BRIEF-A), the Cambridge Automated Neuropsychological Test and Battery (CANTAB), and other tests of cognitive functioning. The analyses included 198 controls (age 20.7 ± 2.6 years) and 100 prescription stimulant misusers (age 20.7 ± 1.7 years). Results On the BRIEF-A, misusers were more likely than controls to endorse greater dysfunction on 8 of 12 measures including Inhibition, Self Monitor, Initiation, Working Memory, and Plan/Organize, when adjusting for race and sex (all p’s <0.05). Similarly, when dichotomizing the BRIEF-A as abnormal (T score ≥ 65), misusers had more abnormalities on 5 of 9 subscales, as well as all major indices (p’s<0.05). Misusers also performed worse on several subtests of the CANTAB and standardized cognitive battery (p’s <0.05). A proxy of prescription stimulant misuse frequency was positively correlated with greater executive dysfunction on the BRIEF-A. Discussion and Conclusions These data demonstrate elevated risk for neuropsychological dysfunction among students who misuse prescription stimulants compared to non-misusing peers. The presence of ADHD contributed significantly to these cognitive findings. Students who misuse prescription stimulants should be screened for neuropsychological dysfunction. Scientific Significance These data may better elucidate the neuropsychological profile of college-aged prescription stimulant misusers. PMID:28494131

Cognitive-Behavioral Erectile Dysfunction Treatment for Gay Men

ERIC Educational Resources Information Center

Hart, Trevor A.; Schwartz, Danielle R.

2010-01-01

The purpose of the present paper is to assist cognitive-behavioral therapists who are treating erectile dysfunction among gay men. Little information is available to cognitive-behavioral therapists about the psychological and social effects of erectile dysfunction in this population, or how to incorporate the concerns of gay men with erectile…

Parental overprotection engenders dysfunctional attitudes about achievement and dependency in a gender-specific manner

PubMed Central

2013-01-01

Background It has been suggested that dysfunctional attitudes, cognitive vulnerability to depression, have developmental origins. The present study examined the effects of parental rearing on dysfunctional attitudes in three areas of life with special attention to gender specificity. Methods The subjects were 665 Japanese healthy volunteers. Dysfunctional attitudes were assessed by the 24-item Dysfunctional Attitude Scale, which has the Achievement, Dependency and Self-control subscales. Perceived parental rearing was assessed by the Parental Bonding Instrument, which has the Care and Protection subscales. Results Higher scores of the Achievement (β = 0.293, p < 0.01) and Dependency (β = 0.224, p < 0.05) subscales were correlated with higher scores of the Protection subscale in the combination of mother and daughter, but not in other combinations of parents and recipients. Scores of the Self-control subscale were not correlated with paternal or maternal rearing scores. Conclusions The present study suggests that parental overprotection engenders dysfunctional attitudes about achievement and dependency in a gender-specific manner. PMID:24365104

Cognitive dysfunction in multiple sclerosis: a review of recent developments.

PubMed

Bobholz, Julie A; Rao, Stephen M

2003-06-01

Nearly half of all patients diagnosed with multiple sclerosis will develop cognitive dysfunction, a symptom associated with significant decline in activities of daily living. The purpose of this review is to discuss recent literature investigating issues related to cognitive dysfunction in multiple sclerosis. Recent studies, examined in this review, have provided increased understanding regarding specific cognitive processes affected in multiple sclerosis, as well as a characterization of its natural history. Studies have also continued to emphasize the extent to which cognitive deficits in the condition are associated with decline in daily living skills. Recent concerns regarding driving performance have been documented among cognitively impaired individuals. Studies have also examined correlates of cognitive dysfunction, with particular emphasis on neuroimaging techniques reflecting disease activity or lesion burden. With increased understanding of neurobiological correlates of cognitive deficits, investigators have begun to examine potential treatments for managing cognitive dysfunction. This area of research has suggested that disease modifying medications can have an impact on magnetic resonance imaging disease activity by altering the cerebral demyelinating process resulting in a slower decline in cognitive functions over time and improved activities of daily living for patients with multiple sclerosis.

Garcinia kola seeds may prevent cognitive and motor dysfunctions in a type 1 diabetes mellitus rat model partly by mitigating neuroinflammation.

PubMed

Seke Etet, Paul F; Farahna, Mohammed; Satti, Gwiria M H; Bushara, Yahia M; El-Tahir, Ahmed; Hamza, Muaawia A; Osman, Sayed Y; Dibia, Ambrose C; Vecchio, Lorella

2017-04-15

Background We reported recently that extracts of seeds of Garcinia kola, a plant with established hypoglycemic properties, prevented the loss of inflammation-sensible neuronal populations like Purkinje cells in a rat model of type 1 diabetes mellitus (T1DM). Here, we assessed G. kola extract ability to prevent the early cognitive and motor dysfunctions observed in this model. Methods Rats made diabetic by single injection of streptozotocin were treated daily with either vehicle solution (diabetic control group), insulin, or G. kola extract from the first to the 6th week post-injection. Then, cognitive and motor functions were assessed using holeboard and vertical pole behavioral tests, and animals were sacrificed. Brains were dissected out, cut, and processed for Nissl staining and immunohistochemistry. Results Hyperglycemia (209.26 %), body weight loss (-12.37 %), and T1DM-like cognitive and motor dysfunctions revealed behavioral tests in diabetic control animals were not observed in insulin and extract-treated animals. Similar, expressions of inflammation markers tumor necrosis factor (TNF), iba1 (CD68), and Glial fibrillary acidic protein (GFAP), as well as decreases of neuronal density in regions involved in cognitive and motor functions (-49.56 % motor cortex, -33.24 % medial septal nucleus, -41.8 % /-37.34 % cerebellar Purkinje /granular cell layers) were observed in diabetic controls but not in animals treated with insulin or G. kola. Conclusions Our results indicate that T1DM-like functional alterations are mediated, at least partly, by neuroinflammation and neuronal loss in this model. The prevention of the development of such alterations by early treatment with G. kola confirms the neuroprotective properties of the plant and warrant further mechanistic studies, considering the potential for human disease.

Cognitive dysfunction in depression - pathophysiology and novel targets.

PubMed

Carvalho, Andre F; Miskowiak, Kamilla K; Hyphantis, Thomas N; Kohler, Cristiano A; Alves, Gilberto S; Bortolato, Beatrice; G Sales, Paulo Marcelo; Machado-Vieira, Rodrigo; Berk, Michael; McIntyre, Roger S

2014-01-01

Major depressive disorder (MDD) is associated with cognitive dysfunction encompassing several domains, including memory, executive function, processing speed and attention. Cognitive deficits persist in a significant proportion of patients even in remission, compromising psychosocial functioning and workforce performance. While monoaminergic antidepressants may improve cognitive performance in MDD, most antidepressants have limited clinical efficacy. The overarching aims of this review were: (1) to synthesize extant literature on putative biological pathways related to cognitive dysfunction in MDD and (2) to review novel neurotherapeutic targets for cognitive enhancement in MDD. We found that reciprocal and overlapping biological pathways may contribute to cognitive dysfunction in MDD, including an hyperactive hypothalamic-pituitary-adrenal axis, an increase in oxidative and nitrosative stress, inflammation (e.g., enhanced production of pro-inflammatory cytokines), mitochondrial dysfunction, increased apoptosis as well as a diminished neurotrophic support. Several promising neurotherapeutic targets were identified such as minocycline, statins, anti-inflammatory compounds, N-acetylcysteine, omega-3 poliunsaturated fatty acids, erythropoietin, thiazolidinediones, glucagon-like peptide-1 analogues, S-adenosyl-l-methionine (SAMe), cocoa flavonols, creatine monohydrate and lithium. Erythropoietin and SAMe had pro-cognitive effects in randomized controlled trials (RCT) involving MDD patients. Despite having preclinical and/or preliminary evidences from trials suggesting possible efficacy as novel cognitive enhancing agents for MDD, no RCT to date was performed for most of the other therapeutic targets reviewed herein. In conclusion, multiple biological pathways are involved in cognitive dysfunction in MDD. RCTs testing genuinely novel pro-cognitive compounds for MDD are warranted.

Cognitive dysfunction and functional magnetic resonance imaging in systemic lupus erythematosus.

PubMed

Barraclough, M; Elliott, R; McKie, S; Parker, B; Bruce, I N

2015-10-01

Cognitive dysfunction is a common aspect of systemic lupus erythematosus (SLE) and is increasingly reported as a problem by patients. In many cases the exact cause is unclear. Limited correlations between specific autoantibodies or structural brain abnormalities and cognitive dysfunction in SLE have been reported. It may be that the most appropriate biomarkers have yet to be found. Functional magnetic resonance imaging (fMRI) is a technique used in many other conditions and provides sensitive measures of brain functionality during cognitive tasks. It is now beginning to be employed in SLE studies. These studies have shown that patients with SLE often perform similarly to healthy controls in terms of behavioural measures on cognitive tasks. However, SLE patients appear to employ compensatory brain mechanisms, such as increased response in fronto-parietal regions, to maintain adequate cognitive performance. As there have been only a few studies using fMRI in SLE to investigate cognitive dysfunction, many questions remain unanswered. Further research could, however, help to identify biomarkers for cognitive dysfunction in SLE. © The Author(s) 2015.

Maternal Depressive Symptoms, Dysfunctional Cognitions, and Infant Night Waking: The Role of Maternal Nighttime Behavior

ERIC Educational Resources Information Center

Teti, Douglas M.; Crosby, Brian

2012-01-01

Mechanisms were examined to clarify relations between maternal depressive symptoms, dysfunctional cognitions, and infant night waking among 45 infants (1-24 months) and their mothers. A mother-driven mediational model was tested in which maternal depressive symptoms and dysfunctional cognitions about infant sleep predicted infant night waking via…

Dysfunctional Cognitions among Offspring of Individuals with Bipolar Disorder.

PubMed

Ruggero, Camilo J; Bain, Kathleen M; Smith, Patrick M; Kilmer, Jared N

2015-07-01

Individuals with bipolar disorder often endorse dysfunctional beliefs consistent with cognitive models of bipolar disorder (Beck, 1976; Mansell, 2007). The present study sought to assess whether young adult offspring of those with bipolar disorder would also endorse these beliefs, independent of their own mood episode history. Participants (N = 89) were young adult college students with a parent with bipolar disorder (n = 27), major depressive disorder (MDD; n = 30), or no mood disorder (n = 32). Semi-structured interviews of the offspring were used to assess diagnoses. Dysfunctional beliefs related to Beck and colleagues' (2006) and Mansell's (2007) cognitive models were assessed. Unlike offspring of parents with MDD or no mood disorder, those with a parent with bipolar disorder endorsed significantly more dysfunctional cognitions associated with extreme appraisal of mood states, even after controlling for their own mood diagnosis. Once affected by a bipolar or depressive disorder, offspring endorsed dysfunctional cognitions across measures. Dysfunctional cognitions, particularly those related to appraisals of mood states and their potential consequences, are evident in young adults with a parent who has bipolar disorder and may represent targets for psychotherapeutic intervention.

The influence of parenting on maladaptive cognitive schema: a cross-sectional research on a group of adults

PubMed Central

Pellerone, Monica; Iacolino, Calogero; Mannino, Giuseppe; Formica, Ivan; Zabbara, Simona Maria

2017-01-01

Background The literature emphasizes the role of early interpersonal experiences in the development of cognitive vulnerability; in particular, interruptions in early family relationships, parental unavailability and dysfunctional parenting are potential evolutionary precursors to negative cognitive style and emotional disorders. Materials and methods This study measured the relationship of retrospective ratings on parental bonding with cognitive patterns in a group of Italian adults. The objectives of this study were as follows: to analyze the influence of age and education level on cognitive domains; to verify whether being parents and living at home with parents affect both parenting style and cognitive domains; to investigate how the type of the maternal and paternal parenting independently affects cognitive styles; to measure the predictive variables for the use of cognitive dysfunctional patterns and to investigate age as a moderating variable of the relation between parenting styles and cognitive domains in a group of adult men and women. The research involved 209 adults (118 males and 91 females) living in Sicily (Italy) aged between 20 and 60 years (M = 37.52; SD = 11.42). The research lasted for 1 year. The instruments used were the Parental Bonding Instrument to measure the perception of parenting during childhood and the Young Schema Questionnaire-3 to investigate cognitive patterns. Results Data show that being a younger adult male with mother’s parenting style characterized by a lower level of nurturance is predictive of the disconnection and rejection domain, whereas, being a younger adult woman, with a higher level of maternal control is predictive of the impaired limits domain. Conclusion This study underlines that because mothers and fathers establish different bonds with their children, care and control by both parents might impact different domains of development. PMID:28203113

Subjective cognitive dysfunction in rehabilitation outpatients with musculoskeletal disorders or chronic pain.

PubMed

Schrier, Ernst; Geertzen, Jan H; Dijkstra, Pieter U

2017-08-01

Rehabilitation patients, without brain damage, sometimes complain about poor concentration and problems with their memory. The magnitude and associations, of this cognitive dysfunction, with different factors is unclear. To determine the magnitude of cognitive dysfunction in rehabilitation outpatient and to explore its associations with patient characteristics, diagnosis, surgery, pain, stress, anxiety and depression. Cross-sectional. Rehabilitation outpatients. Between July 2009 and January 2012, 274 rehabilitation outpatients were included and divided in 8 different groups through diagnosis. Cognitive functioning was assessed using the cognitive failure questionnaire and compared with the general Dutch population. Associations of gender, age, diagnosis, recent surgery, pain and stress coping ability with cognitive function was explored. Mediation of depression and anxiety was explored. The rehabilitation patients had a significantly higher score on the CFQ (mean 35.9±13.4) when compared to the general Dutch population (mean 31.8±11.1). Mean difference is 4.1, 95% confidence interval 2.60 to 5.60. In the stepwise linear regression analysis only gender, diagnosis and stress coping ability were significantly associated. A significant mediation effect was found of anxiety (P≤0.001) and depression (P≤0.005) between stress coping ability and cognitive function. Rehabilitation outpatients experience more cognitive problems in comparison to the general Dutch population. Reported dysfunction of cognition in rehabilitation outpatients are associated with stress coping ability and for a small amount to gender and diagnosis. The association of stress coping ability and cognitive dysfunction is mediated by depression and anxiety. Women tend to report more dysfunctional cognition compared to men. Patient characteristics, surgery and experienced pain have no significant influence on the experienced cognitive dysfunction. Cognitive problems reported by patients should be addressed by adapting the rehabilitation program, for instance write down instructions, repeat explanations and take more time for instructions. Cognitive problems in rehabilitation patients without brain damage is probably a stress coping problem and can be addressed by boosting resilience. Targeting depression or anxiety is another option of treatment cognition if those are mediating between stress coping and cognitive problems.

Structural correlates of cognitive deficit and elevated gamma noise power in schizophrenia.

PubMed

Suazo, Vanessa; Díez, Álvaro; Montes, Carlos; Molina, Vicente

2014-03-01

The aim of this study was to assess the relation between cognition, gray matter (GM) volumes and gamma noise power (amount of background oscillatory activity in the gamma band) in schizophrenia. We explored the relation between cognitive performance and regional GM volumes using voxel-based morphometry (VBM), in order to discover if the association between gamma noise power (an electroencephalography measurement of background activity in the gamma band) and cognition is observed through structural deficits related to the disease. Noise power, magnetic resonance imaging and cognitive assessments were obtained in 17 drug-free paranoid patients with schizophrenia and 13 healthy controls. In comparison with controls, patients showed GM deficits at posterior cingulate (bilateral),left inferior parietal (supramarginal gyrus) and left inferior dorsolateral prefrontal regions. Patients exhibited a direct association between performance in working memory and right temporal (superior and inferior gyri) GM densities. They also displayed a negative association between right anterior cerebellum volume and gamma noise power at the frontal midline (Fz) site. A structural deficit in the cerebellum may be involved in gamma activity disorganization in schizophrenia. Temporal structural deficits may relate to cognitive dysfunction in this illness. © 2013 The Authors. Psychiatry and Clinical Neurosciences © 2013 Japanese Society of Psychiatry and Neurology.

Cognitive dysfunction in Body Dysmorphic Disorder: New implications for nosological systems & neurobiological models

PubMed Central

Jefferies-Sewell, K; Chamberlain, SR; Fineberg, NA; Laws, KR

2017-01-01

Background Body dysmorphic disorder (BDD) is a debilitating disorder, characterised by obsessions and compulsions relating specifically to perceived appearance, newly classified within the DSM-5 Obsessive-Compulsive and Related Disorders grouping. Until now, little research has been conducted into the cognitive profile of this disorder. Materials and Methods Participants with BDD (n=12) and healthy controls (n=16) were tested using a computerised neurocognitive battery investigating attentional set-shifting (Intra/Extra Dimensional Set Shift Task), decision-making (Cambridge Gamble Task), motor response-inhibition (Stop-Signal Reaction Time Task) and affective processing (Affective Go-No Go Task). The groups were matched for age, IQ and education. Results In comparison to controls, patients with BDD showed significantly impaired attentional set shifting, abnormal decision-making, impaired response inhibition and greater omission and commission errors on the emotional processing task. Conclusions Despite the modest sample size, our results showed that individuals with BDD performed poorly compared to healthy controls on tests of cognitive flexibility, reward and motor impulsivity and affective processing. Results from separate studies in OCD patients suggest similar cognitive dysfunction. Therefore, these findings are consistent with the re-classification of BDD alongside OCD. These data also hint at additional areas of decision-making abnormalities that might contribute specifically to the psychopathology of BDD. PMID:27899165

Aspartic acid in the hippocampus: a biomarker for postoperative cognitive dysfunction

PubMed Central

Hu, Rong; Huang, Dong; Tong, Jianbin; Liao, Qin; Hu, Zhonghua; Ouyang, Wen

2014-01-01

This study established an aged rat model of cognitive dysfunction using anesthesia with 2% isoflurane and 80% oxygen for 2 hours. Twenty-four hours later, Y-maze test results showed that isoflurane significantly impaired cognitive function in aged rats. Gas chromatography-mass spectrometry results showed that isoflurane also significantly increased the levels of N,N-diethylacetamide, n-ethylacetamide, aspartic acid, malic acid and arabinonic acid in the hippocampus of isoflurane-treated rats. Moreover, aspartic acid, N,N-diethylacetamide, n-ethylacetamide and malic acid concentration was positively correlated with the degree of cognitive dysfunction in the isoflurane-treated rats. It is evident that hippocampal metabolite changes are involved in the formation of cognitive dysfunction after isoflurane anesthesia. To further verify these results, this study cultured hippocampal neurons in vitro, which were then treated with aspartic acid (100 μmol/L). Results suggested that aspartic acid concentration in the hippocampus may be a biomarker for predicting the occurrence and disease progress of cognitive dysfunction. PMID:25206795

Aspartic acid in the hippocampus: a biomarker for postoperative cognitive dysfunction.

PubMed

Hu, Rong; Huang, Dong; Tong, Jianbin; Liao, Qin; Hu, Zhonghua; Ouyang, Wen

2014-01-15

This study established an aged rat model of cognitive dysfunction using anesthesia with 2% isoflurane and 80% oxygen for 2 hours. Twenty-four hours later, Y-maze test results showed that isoflurane significantly impaired cognitive function in aged rats. Gas chromatography-mass spectrometry results showed that isoflurane also significantly increased the levels of N,N-diethylacetamide, n-ethylacetamide, aspartic acid, malic acid and arabinonic acid in the hippocampus of isoflurane-treated rats. Moreover, aspartic acid, N,N-diethylacetamide, n-ethylacetamide and malic acid concentration was positively correlated with the degree of cognitive dysfunction in the isoflurane-treated rats. It is evident that hippocampal metabolite changes are involved in the formation of cognitive dysfunction after isoflurane anesthesia. To further verify these results, this study cultured hippocampal neurons in vitro, which were then treated with aspartic acid (100 μmol/L). Results suggested that aspartic acid concentration in the hippocampus may be a biomarker for predicting the occurrence and disease progress of cognitive dysfunction.

Clinical Epidemiology, Evaluation, and Management of Dementia in Parkinson Disease.

PubMed

Safarpour, Delaram; Willis, Allison W

2016-11-01

The prevalence of neurodegenerative diseases such as Parkinson disease (PD) will increase substantially, due to the aging of the population and improved treatments leading to better disease-related outcomes. Dementia is the most common nonmotor symptom in PD, and most patients with PD will have cognitive dysfunction and cognitive decline in the course of their disease. The development of cognitive dysfunction in PD greatly limits the ability to participate in activities of daily living and can be a tipping point for nursing home placement or major caregiver stress. Understanding the different causes of dementia and how to reduce the incidence and impact of secondary cognitive dysfunction in PD are necessary skills for primary care physicians and neurologists. In this review, we discuss the clinical epidemiology of dementia in PD with an emphasis on preventable cognitive dysfunction, present tools for outpatient evaluation of cognitive dysfunction, and describe current pharmacological treatments for dementia in PD. © The Author(s) 2016.

Association Between Cognitive Function and Health Care Costs 3 Months and 6 Months After Initiating Antidepressant Medication for Depressive Disorders.

PubMed

Walker, Valery; Patel, Haridarshan; Kurlander, Jonathan L; Essoi, Breanna; Yang, Jiao; Mahableshwarkar, Atul R; Samp, Jennifer C; Akhras, Kasem S

2015-09-01

Major depressive disorder is one of the most common and disabling mental health disorders and is associated with substantial costs in terms of direct health care utilization and workplace productivity. Cognitive dysfunction, which alone substantially increases health care costs, is commonly associated with major depressive disorder. However, the health care costs of cognitive dysfunction in the context of depressive disorder are unknown. Recovery from mood symptoms is not always associated with resolution of cognitive dysfunction. Thus, cognitive dysfunction may contribute to health care burden even with successful antidepressant therapy.  To compare health care utilization and costs for patients with a depressive disorder with and without cognitive dysfunction, at 3 and 6 months after initiation of antidepressant medication.  This was an observational study, combining a cross-sectional patient survey, administered during a telephone interview, with health care claims data from a large, geographically diverse U.S. health plan. Included patients had at least 1 pharmacy claim for an antidepressant medication between August 1 and September 30, 2012, and no claim for any antidepressant during the 6 months prior to the index date. In addition to other criteria assessed in the claims data, patients confirmed a diagnosis of depression or major depressive disorder and the absence of any exclusionary neurological diagnoses possibly associated with cognitive impairment. Eligible patients were administered validated cognitive function assessments of verbal episodic memory (Hopkins Verbal Learning Test-Revised, Delayed and Total); attention (Digit Span Forward Maximum Sequence Length); working memory (Digit Span Backward Maximum Sequence Length); and executive function (D-KEFS-Letter Fluency Test). Based on comparison of scores with normative data, patients were assigned to cognitive dysfunction or cognitive normal cohorts. All-cause (all diagnoses) and depressive disorder-related health care utilization and costs (all from a payer perspective) were assessed 6 months prior (baseline) to antidepressant initiation and 3 months and 6 months after (follow-up) initiation of antidepressant medication. Health care utilization and costs included ambulatory (office and hospital outpatient), emergency room, inpatient hospital, pharmacy, other medical (e.g., laboratory and diagnostics), and total (all categories combined). All-cause and depressive disorder-related total costs during the 3- and 6-month follow-up periods were modeled with generalized linear modeling with gamma distribution and log link, while adjusting for potential confounders (age, race, gender, education, employment, and comorbidities). Of the 13,537 patients who were mailed an invitation, 824 (6%) were eligible and agreed to participate. Of these, 563 patients provided informed consent, completed the interview, maintained eligibility, and were included in the 3-month calculations. Among these, 255 (45%) were classified as having cognitive dysfunction. Mean patient age was 41.3 (± 12.5) years; 80% were female. Most patients were white and employed. More patients in the cognitive normal cohort were white (P  less than  0.001) and employed full time (P = 0.029), had higher education attainment (P  less than    0.001), and had fewer comorbidities (P = 0.007) than those in the cognitive dysfunction cohort. Over the first 3 months, patients with cognitive dysfunction had higher adjusted all-cause costs ($3,309 vs. $2,157, P = 0.002) and higher adjusted depressive disorder-related costs ($718 vs. $406, P  less than  0.001) than patients without cognitive dysfunction. At 6 months, data from 4 patients were removed from the analysis because of exclusionary diagnoses. Over 6 months, patients with cognitive dysfunction had higher adjusted all-cause costs ($4,793) than patients without cognitive dysfunction ($3,683, P = 0.034). Over 6 months, depressive disorder-related costs did not significantly differ between patients with ($771) and without cognitive dysfunction ($594, P = 0.071). The main drivers of all-cause costs were office visits, outpatient hospital visits, and inpatient costs, and the main driver of depressive disorder-related costs was inpatient costs. Cognitive dysfunction was associated with higher adjusted all-cause and depressive disorder-related costs 3 months after initiation of an antidepressant medication. This difference persisted for all-cause costs through 6 months. Identification and treatment of cognitive dysfunction in patients with depressive disorder might reduce health care costs.

Emerging pharmacotherapy for cancer patients with cognitive dysfunction

PubMed Central

2013-01-01

Advances in the diagnosis and multi-modality treatment of cancer have increased survival rates for many cancer types leading to an increasing load of long-term sequelae of therapy, including that of cognitive dysfunction. The cytotoxic nature of chemotherapeutic agents may also reduce neurogenesis, a key component of the physiology of memory and cognition, with ramifications for the patient’s mood and other cognition disorders. Similarly radiotherapy employed as a therapeutic or prophylactic tool in the treatment of primary or metastatic disease may significantly affect cognition. A number of emerging pharmacotherapies are under investigation for the treatment of cognitive dysfunction experienced by cancer patients. Recent data from clinical trials is reviewed involving the stimulants modafinil and methylphenidate, mood stabiliser lithium, anti-Alzheimer’s drugs memantine and donepezil, as well as other agents which are currently being explored within dementia, animal, and cell culture models to evaluate their use in treating cognitive dysfunction. PMID:24156319

Altered emotional interference processing in affective and cognitive-control brain circuitry in major depression

PubMed Central

Fales, Christina L.; Barch, Deanna M.; Rundle, Melissa M.; Mintun, Mark A.; Snyder, Abraham Z.; Cohen, Jonathan D.; Mathews, Jose; Sheline, Yvette I.

2008-01-01

Background Major depression is characterized by a negativity bias: an enhanced responsiveness to, and memory for, affectively negative stimuli. However it is not yet clear whether this bias represents (1) impaired top-down cognitive control over affective responses, potentially linked to deficits in dorsolateral prefrontal cortex function; or (2) enhanced bottom-up responses to affectively-laden stimuli that dysregulate cognitive control mechanisms, potentially linked to deficits in amygdala and anterior cingulate function. Methods We used an attentional interference task using emotional distracters to test for top-down versus bottom-up dysfunction in the interaction of cognitive-control circuitry and emotion-processing circuitry. A total of 27 patients with major depression and 24 controls were tested. Event-related functional magnetic resonance imaging was carried out as participants directly attended to, or attempted to ignore, fear-related stimuli. Results Compared to controls, patients with depression showed an enhanced amygdala response to unattended fear-related stimuli (relative to unattended neutral). By contrast, control participants showed increased activity in right dorsolateral prefrontal cortex (Brodmann areas 46/9) when ignoring fear stimuli (relative to neutral), which the patients with depression did not. In addition, the depressed participants failed to show evidence of error-related cognitive adjustments (increased activity in bilateral dorsolateral prefrontal cortex on post-error trials), but the control group did show them. Conclusions These results suggest multiple sources of dysregulation in emotional and cognitive control circuitry in depression, implicating both top-down and bottom-up dysfunction. PMID:17719567

Cognitive deficits are associated with poorer simulated driving in older adults with heart failure

PubMed Central

2013-01-01

Background Cognitive impairment is prevalent in older adults with heart failure (HF) and associated with reduced functional independence. HF patients appear at risk for reduced driving ability, as past work in other medical samples has shown cognitive dysfunction to be an important contributor to driving performance. The current study examined whether cognitive dysfunction was independently associated with reduced driving simulation performance in a sample of HF patients. Methods 18 persons with HF (67.72; SD = 8.56 year) completed echocardiogram and a brief neuropsychological test battery assessing global cognitive function, attention/executive function, memory and motor function. All participants then completed the Kent Multidimensional Assessment Driving Simulation (K-MADS), a driving simulator scenario with good psychometric properties. Results The sample exhibited an average Mini Mental State Examination (MMSE) score of 27.83 (SD = 2.09). Independent sample t-tests showed that HF patients performed worse than healthy adults on the driving simulation scenario. Finally, partial correlations showed worse attention/executive and motor function were independently associated with poorer driving simulation performance across several indices reflective of driving ability (i.e., centerline crossings, number of collisions, % of time over the speed limit, among others). Conclusion The current findings showed that reduced cognitive function was associated with poor simulated driving performance in older adults with HF. If replicated using behind-the-wheel testing, HF patients may be at elevated risk for unsafe driving and routine driving evaluations in this population may be warranted. PMID:24499466

Cognitive medicine - a new approach in health care science.

PubMed

Wallin, Anders; Kettunen, Petronella; Johansson, Per M; Jonsdottir, Ingibjörg H; Nilsson, Christer; Nilsson, Michael; Eckerström, Marie; Nordlund, Arto; Nyberg, Lars; Sunnerhagen, Katharina S; Svensson, Johan; Terzis, Beata; Wahlund, Lars-Olof; Georg Kuhn, H

2018-02-08

The challenges of today's society call for more knowledge about how to maintain all aspects of cognitive health, such as speed/attention, memory/learning, visuospatial ability, language, executive capacity and social cognition during the life course. Medical advances have improved treatments of numerous diseases, but the cognitive implications have not been sufficiently addressed. Disability induced by cognitive dysfunction is also a major issue in groups of patients not suffering from Alzheimer's disease or related disorders. Recent studies indicate that several negative lifestyle factors can contribute to the development of cognitive impairment, but intervention and prevention strategies have not been implemented. Disability due to cognitive failure among the workforce has become a major challenge. Globally, the changing aging pyramid results in increased prevalence of cognitive disorders, and the diversity of cultures influences the expression, manifestation and consequences of cognitive dysfunction. Major tasks in the field of cognitive medicine are basic neuroscience research to uncover diverse disease mechanisms, determinations of the prevalence of cognitive dysfunction, health-economical evaluations, and intervention studies. Raising awareness for cognitive medicine as a clinical topic would also highlight the importance of specialized health care units for an integrative approach to the treatment of cognitive dysfunctions.

Early Maladaptive Schemas and Cognitive Distortions in Adults with Morbid Obesity: Relationships with Mental Health Status.

PubMed

da Luz, Felipe Q; Sainsbury, Amanda; Hay, Phillipa; Roekenes, Jessica A; Swinbourne, Jessica; da Silva, Dhiordan C; da S Oliveira, Margareth

2017-02-28

Dysfunctional cognitions may be associated with unhealthy eating behaviors seen in individuals with obesity. However, dysfunctional cognitions commonly occur in individuals with poor mental health independently of weight. We examined whether individuals with morbid obesity differed with regard to dysfunctional cognitions when compared to individuals of normal weight, when mental health status was controlled for. 111 participants-53 with morbid obesity and 58 of normal weight-were assessed with the Mini-Mental State Examination, Young Schema Questionnaire, Cognitive Distortions Questionnaire, Depression, Anxiety and Stress Scale, and a Demographic and Clinical Questionnaire. Participants with morbid obesity showed higher scores in one (insufficient self-control/self-discipline) of 15 early maladaptive schemas and in one (labeling) of 15 cognitive distortions compared to participants of normal weight. The difference between groups for insufficient self-control/self-discipline was not significant when mental health status was controlled for. Participants with morbid obesity showed more severe anxiety than participants of normal weight. Our findings did not show clinically meaningful differences in dysfunctional cognitions between participants with morbid obesity or of normal weight. Dysfunctional cognitions presented by individuals with morbid obesity are likely related to their individual mental health and not to their weight.

Informed Consent and Cognitive Dysfunction After Noncardiac Surgery in the Elderly.

PubMed

Hogan, Kirk J; Bratzke, Lisa C; Hogan, Kendra L

2018-02-01

Cognitive dysfunction 3 months after noncardiac surgery in the elderly satisfies informed consent thresholds of foreseeability in 10%-15% of patients, and materiality with new deficits observed in memory and executive function in patients with normal test performance beforehand. At present, the only safety step to avoid cognitive dysfunction after surgery is to forego surgery, thereby precluding the benefits of surgery with removal of pain and inflammation, and resumption of normal nutrition, physical activity, and sleep. To assure that consent for surgery is properly informed, risks of both cognitive dysfunction and alternative management strategies must be discussed with patients by the surgery team before a procedure is scheduled.

Adaptive and regulatory mechanisms in aged rats with postoperative cognitive dysfunction

PubMed Central

Bi, Yanlin; Liu, Shuyun; Yu, Xinjuan; Wang, Mingshan; Wang, Yuelan

2014-01-01

Inflammation may play a role in postoperative cognitive dysfunction. 5′ Adenosine monophosphate-activated protein kinase, nuclear factor-kappa B, interleukin-1β, and tumor necrosis factor-α are involved in inflammation. Therefore, these inflammatory mediators may be involved in postoperative cognitive dysfunction. Western immunoblot analysis revealed 5′ adenosine monophosphate-activated protein kinase and nuclear factor-kappa B in the hippocampus of aged rats were increased 1–7 days after splenectomy. Moreover, interleukin-1β and tumor necrosis factor-α were upregulated and gradually decreased. Therefore, these inflammatory mediators may participate in the splenectomy model of postoperative cognitive dysfunction in aged rats. PMID:25206851

Pathogenesis of Cognitive Dysfunction in Patients with Obstructive Sleep Apnea: A Hypothesis with Emphasis on the Nucleus Tractus Solitarius

PubMed Central

Daulatzai, Mak Adam

2012-01-01

OSA is characterized by the quintessential triad of intermittent apnea, hypoxia, and hypoxemia due to pharyngeal collapse. This paper highlights the upstream mechanisms that may trigger cognitive decline in OSA. Three interrelated steps underpin cognitive dysfunction in OSA patients. First, several risk factors upregulate peripheral inflammation; these crucial factors promote neuroinflammation, cerebrovascular endothelial dysfunction, and oxidative stress in OSA. Secondly, the neuroinflammation exerts negative impact globally on the CNS, and thirdly, important foci in the neocortex and brainstem are rendered inflamed and dysfunctional. A strong link is known to exist between neuroinflammation and neurodegeneration. A unique perspective delineated here underscores the importance of dysfunctional brainstem nuclei in etiopathogenesis of cognitive decline in OSA patients. Nucleus tractus solitarius (NTS) is the central integration hub for afferents from upper airway (somatosensory/gustatory), respiratory, gastrointestinal, cardiovascular (baroreceptor and chemoreceptor) and other systems. The NTS has an essential role in sympathetic and parasympathetic systems also; it projects to most key brain regions and modulates numerous physiological functions. Inflamed and dysfunctional NTS and other key brainstem nuclei may play a pivotal role in triggering memory and cognitive dysfunction in OSA. Attenuation of upstream factors and amelioration of the NTS dysfunction remain important challenges. PMID:23470865

Cognitive dysfunction in patients with Systemic Lupus Erythematosus.

PubMed

Butt, Bilal Azeem; Farman, Sumaira; Khan, Saira Elaine Anwer; Saeed, Muhammad Ahmed; Ahmad, Nighat Mir

2017-01-01

To determine the frequency of cognitive dysfunction in patients with Systemic Lupus Erythematosus in a Pakistani population, presenting at a tertiary care Rheumatology setting. This cross-sectional study was conducted at the Division of Rheumatology, Fatima Memorial Hospital, Lahore, from March to June 2016. A total of 43 consecutive patients, who fulfilled the 2012 SLICC (Systemic Lupus International Collaborating Clinics) classification criteria for Systemic Lupus Erythematosus (SLE), were enrolled. Cognitive function was assessed using Montréal Cognitive Assessment (MoCA) questionnaire. Demographic data and disease dynamics were collected in a proforma. Cognitive dysfunction was defined as score < 26/30, adjusted for duration of formal education. SPSS version 16.0 for windows was used to analyse data and to calculate frequency of cognitive dysfunction. Out of 43 enrolled patients, 95.3% were females and 4.7% were males, with mean age of 28.72 ± 9.25 years and mean formal education duration of 10.98 ± 3.29 years. The mean disease duration was 24.21 ± 30.46 months. Anti-nuclear antibodies (ANA) were present in all patients and anti-ds DNA in 93% patients. Cognitive dysfunction according to MoCA score was found in 65.1% (n=28) patients. For patients with disease duration more than two years, cognitive dysfunction was found in 60% patients [p>0.05] and for duration of formal education less than 12 years in 74.1% patients [p>0.05]. In this study, two third of SLE patients had Cognitive dysfunction. Hence, there is an increasing need to recognise and initiate early therapy for this overlooked aspect of SLE with an aim to achieve better quality of life.

A cross-sectional study of functional disabilities and perceived cognitive dysfunction in patients with major depressive disorder in South Korea: The PERFORM-K study.

PubMed

Kim, Jae Min; Chalem, Ylana; di Nicola, Sylvia; Hong, Jin Pyo; Won, Seung Hee; Milea, Dominique

2016-05-30

PERFORM-K was a cross-sectional observational study that investigated functional disability, productivity and quality of life in MDD outpatients in South Korea, and the associations of these with depressive symptoms, perceived cognitive dysfunction and other factors. A total of 312 outpatients who started antidepressant monotherapy underwent a single study interview. Physicians and patients assessed depression severity. Patients also assessed: perceived cognitive dysfunction, functional disability, impaired productivity and quality of life. Patients had moderate to severe depression (MADRS mean total score: 28.9±7.3), and reported marked functional disability (SDS mean total score: 16.7±8.6), impaired productivity (WPAI mean overall work productivity loss: 52.4±31.8%), perceived cognitive dysfunction (PDQ-D mean total score: 29.9±18.6) and impaired quality of life (EQ-5D mean utility index score of 0.726±0.192). Greater functional disability and impairment in daily activities were associated with more severe depression and greater perceived cognitive dysfunction. Irrespective of depression severity, patients with more severe perceived cognitive dysfunction reported worse work-related productivity outcomes (higher presenteeism and greater overall work productivity loss). PERFORM-K confirms the impact of MDD on functional status and well-being in South Korean patients, and highlights the importance of recognising cognitive dysfunction in clinical practice. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Cognitive Rehabilitation for Executive Dysfunction in Parkinson's Disease: Application and Current Directions

PubMed Central

Calleo, Jessica; Burrows, Cristina; Levin, Harvey; Marsh, Laura; Lai, Eugene; York, Michele K.

2012-01-01

Cognitive dysfunction in Parkinson's disease contributes to disability, caregiver strain, and diminished quality of life. Cognitive rehabilitation, a behavioral approach to improve cognitive skills, has potential as a treatment option to improve and maintain cognitive skills and increase quality of life for those with Parkinson's disease-related cognitive dysfunction. Four cognitive rehabilitation programs in individuals with PD are identified from the literature. Characteristics of the programs and outcomes are reviewed and critiqued. Current studies on cognitive rehabilitation in PD demonstrate feasibility and acceptability of a cognitive rehabilitation program for patients with PD, but are limited by their small sample size and data regarding generalization of effects over the long term. Because PD involves progressive heterogeneous physical, neurological, and affective difficulties, future cognitive rehabilitation programs should aim for flexibility and individualization, according to each patient's strengths and deficits. PMID:22135762

Behavioral Effects of the Benzodiazepine-Positive Allosteric Modulator SH-053-2’F-S-CH3 in an Immune-Mediated Neurodevelopmental Disruption Model

PubMed Central

Richetto, Juliet; Labouesse, Marie A.; Poe, Michael M.; Cook, James M.; Grace, Anthony A.; Riva, Marco A.

2015-01-01

Background: Impaired γ-aminobutyric acid (GABA) signaling may contribute to the emergence of cognitive deficits and subcortical dopaminergic hyperactivity in patients with schizophrenia and related psychotic disorders. Against this background, it has been proposed that pharmacological interventions targeting GABAergic dysfunctions may prove useful in correcting such cognitive impairments and dopaminergic imbalances. Methods: Here, we explored possible beneficial effects of the benzodiazepine-positive allosteric modulator SH-053-2’F-S-CH3, with partial selectivity at the α2, α3, and α5 subunits of the GABAA receptor in an immune-mediated neurodevelopmental disruption model. The model is based on prenatal administration of the viral mimetic polyriboinosinic-polyribocytidilic acid [poly(I:C)] in mice, which is known to capture various GABAergic, dopamine-related, and cognitive abnormalities implicated in schizophrenia and related disorders. Results: Real-time polymerase chain reaction analyses confirmed the expected alterations in GABAA receptor α subunit gene expression in the medial prefrontal cortices and ventral hippocampi of adult poly(I:C) offspring relative to control offspring. Systemic administration of SH-053-2’F-S-CH3 failed to normalize the poly(I:C)-induced deficits in working memory and social interaction, but instead impaired performance in these cognitive and behavioral domains both in control and poly(I:C) offspring. In contrast, SH-053-2’F-S-CH3 was highly effective in mitigating the poly(I:C)-induced amphetamine hypersensitivity phenotype without causing side effects in control offspring. Conclusions: Our preclinical data suggest that benzodiazepine-like positive allosteric modulators with activity at the α2, α3, and α5 subunits of the GABAA receptor may be particularly useful in correcting pathological overactivity of the dopaminergic system, but they may be ineffective in targeting multiple pathological domains that involve the co-existence of psychotic, social, and cognitive dysfunctions. PMID:25636893

[Cognitive dysfunction in schizophrenic psychoses. Drug and psychological treatment choices].

PubMed

Sachs, G; Katschnig, H

2001-03-01

Primarily from the perspective of psychopharmacology, schizophrenic symptomatology has recently been dichotomized into "plus" and "minus" symptoms, although the role of cognitive dysfunctions has been regarded as particularly important for the diagnosis since the time of Eugen Bleuler. Many studies show that schizophrenic patients suffer consistently from cognitive dysfunction. Among these, are impairments of attention and memory functions as well as executive functions such as planning and problem solving. These impairments are stable or progressive and often continue into the remission phase of schizophrenia and impair both social integration as well as occupational performance. In this overview, research results on cognitive dysfunction in patients with schizophrenic illnesses and their relation to psychosocial disabilities are described first. The therapeutic value and possible clinical-practice implications of atypical anti-psychotics and various cognitive therapy methods are then presented. Methodological weaknesses and open questions, both pharmacological and with regard to cognitive interventions, are discussed.

Assessment and clinical implications of cognitive impairment in acutely ill geriatric patients using a revised simplified short-term memory recall test (STMT-R).

PubMed

Yamamoto, Hiroshi; Ogawa, Kenichi; Huaman Battifora, Henry; Yamamuro, Kaori; Ishitake, Tatsuya

2018-05-24

Cognitive dysfunction due to delirium or dementia is a common finding in acutely ill geriatric patients, but often remains undetected. A brief and sensitive clinical identification method could prevent errors or complications while evaluating the mental status of elderly patients. To evaluate the usefulness and clinical implications of the revised simplified short-term memory recall test (STMT-R) in geriatric patients admitted in the emergency department; with age, gender, dementia history, serum albumin, underlying diseases and clinical outcome used as comparative factors. Mini-mental state examination and STMT-R scores were initially compared and a positive correlation was observed (r = 0.66, p < 0.001). Subsequently, 885 inpatients aged over 50 years underwent STMT-R evaluation between October 2014 and September 2015. We considered as cognitive dysfunction STMT-R scores ≤ 4 of a maximum score of 8. Among enrolled patients, 52.2% were female and the mean age was 78.9 years. There were 159 patients who were unable to complete the test (incomplete testing group). We observed cognitive dysfunction in 460 patients, while 266 did not have cognitive dysfunction. There were significant differences between those with and without cognitive dysfunction in terms of age, dementia history, underlying respiratory diseases, and hospital outcome. Cognitive dysfunction at admission can have a negative effect on the hospital outcomes of elderly patients. Age, a history of dementia and underlying respiratory diseases may also influence cognitive functional decline.

Brain metabolite alterations and cognitive dysfunction in early Huntington’s Disease

PubMed Central

Unschuld, Paul G.; Edden, Richard A. E.; Carass, Aaron; Liu, Xinyang; Shanahan, Megan; Wang, Xin; Oishi, Kenichi; Brandt, Jason; Bassett, Susan S.; Redgrave, Graham W.; Margolis, Russell L.; van Zijl, Peter C. M.; Barker, Peter B.; Ross, Christopher A.

2012-01-01

Background Huntington’s Disease (HD) is a neurodegenerative disorder characterized by early cognitive decline, which progresses at later stages to dementia and severe movement disorder. HD is caused by a cytosine-adenine-guanine triplet-repeat expansion mutation in the Huntingtin gene, allowing early diagnosis by genetic testing. This study aims to identify the relationship of N-acetylaspartate and other brain metabolites to cognitive function in HD-mutation carriers by using high field strength magnetic-resonance-spectroscopy at 7-Tesla. Methods Twelve individuals with the HD-mutation in premanifest or early stage of disease versus twelve healthy controls underwent 1H magnetic-resonance-spectroscopy (7.2ml voxel in the posterior cingulate cortex) at 7-Tesla, and also T1-weighted structural magnetic-resonance-imaging. All participants received standardized tests of cognitive functioning including the Montreal Cognitive Assessment and standardized quantified neurological examination within an hour before scanning. Results Individuals with the HD mutation had significantly lower posterior cingulate cortex N-acetylaspartate (−9.6%, p=0.02) and glutamate levels (−10.1%, p=0.02) than controls. By contrast, in this small group, measures of brain morphology including striatal and ventricle volumes did not differ significantly. Linear regression with Montreal Cognitive Assessment scores revealed significant correlations with N-acetylaspartate (r2=0.50, p=0.01) and glutamate (r2=0.64, p=0.002) in HD subjects. Conclusions Our data suggest a relationship between reduced N-acetylaspartate and glutamate levels in the posterior cingulate cortex with cognitive decline in early stages of HD. N-acetylaspartate and glutamate magnetic-resonance-spectroscopy signals of the posterior cingulate cortex region may serve as potential biomarkers of disease progression or treatment outcome in HD and other neurodegenerative disorders with early cognitive dysfunction, when structural brain changes are still minor. PMID:22649062

Validation of the German version of the short form of the dysfunctional beliefs and attitudes about sleep scale (DBAS-16).

PubMed

Lang, Christin; Brand, Serge; Holsboer-Trachsler, Edith; Pühse, Uwe; Colledge, Flora; Gerber, Markus

2017-06-01

Research shows that dysfunctional sleep-related cognitions play an important role in the development, maintenance and exacerbation of insomnia. This study examines the factorial validity, psychometric properties and both concurrent and predictive validity of the German version of the 16-item DBAS (dysfunctional beliefs and attitudes about sleep) scale. Data was collected in 864 vocational students from the German-speaking part of Switzerland (43% females, M age  = 17.9 years). Data collection took place twice within a 10-month interval. The students completed a German translation of the DBAS-16, the Insomnia Severity Index (ISI), the Pittsburgh Sleep Quality Index (PSQI), and provided information about their psychological functioning. Descriptive statistics, factorial validity, internal consistency, gender differences, concurrent, and predictive validity were examined. Confirmatory factor analysis supported the 4-factor structure of the DBAS-16. All factors (consequences, worry/helplessness, expectations, medication) were positively correlated and had acceptable psychometric properties. Females reported higher scores across all DBAS measures. Weak-to-moderate correlations were found between dysfunctional sleep-related beliefs, insomnia and poor sleep quality. Dysfunctional sleep-related beliefs were also associated with decreased psychological functioning, and consistently predicted insomnia and poor psychological functioning at follow-up, even after controlling for socio-demographic background and baseline levels. The present study provides support for the validity and psychometric properties of the German version of the DBAS-16. Most importantly, it corroborates the relevance of cognitive-emotional factors in the onset and maintenance of insomnia and psychological symptoms among young people.

Early Maladaptive Schemas and Cognitive Distortions in Adults with Morbid Obesity: Relationships with Mental Health Status

PubMed Central

da Luz, Felipe Q.; Sainsbury, Amanda; Hay, Phillipa; Roekenes, Jessica A.; Swinbourne, Jessica; da Silva, Dhiordan C.; da S. Oliveira, Margareth

2017-01-01

Dysfunctional cognitions may be associated with unhealthy eating behaviors seen in individuals with obesity. However, dysfunctional cognitions commonly occur in individuals with poor mental health independently of weight. We examined whether individuals with morbid obesity differed with regard to dysfunctional cognitions when compared to individuals of normal weight, when mental health status was controlled for. 111 participants—53 with morbid obesity and 58 of normal weight—were assessed with the Mini-Mental State Examination, Young Schema Questionnaire, Cognitive Distortions Questionnaire, Depression, Anxiety and Stress Scale, and a Demographic and Clinical Questionnaire. Participants with morbid obesity showed higher scores in one (insufficient self-control/self-discipline) of 15 early maladaptive schemas and in one (labeling) of 15 cognitive distortions compared to participants of normal weight. The difference between groups for insufficient self-control/self-discipline was not significant when mental health status was controlled for. Participants with morbid obesity showed more severe anxiety than participants of normal weight. Our findings did not show clinically meaningful differences in dysfunctional cognitions between participants with morbid obesity or of normal weight. Dysfunctional cognitions presented by individuals with morbid obesity are likely related to their individual mental health and not to their weight. PMID:28264484

Curcumin attenuates surgery-induced cognitive dysfunction in aged mice.

PubMed

Wu, Xiang; Chen, Huixin; Huang, Chunhui; Gu, Xinmei; Wang, Jialing; Xu, Dilin; Yu, Xin; Shuai, Chu; Chen, Liping; Li, Shun; Xu, Yiguo; Gao, Tao; Ye, Mingrui; Su, Wei; Liu, Haixiong; Zhang, Jinrong; Wang, Chuang; Chen, Junping; Wang, Qinwen; Cui, Wei

2017-06-01

Post-operative cognitive dysfunction (POCD) is associated with elderly patients undergoing surgery. However, pharmacological treatments for POCD are limited. In this study, we found that curcumin, an active compound derived from Curcuma longa, ameliorated the cognitive dysfunction following abdominal surgery in aged mice. Further, curcumin prevented surgery-induced anti-oxidant enzyme activity. Curcumin also increased brain-derived neurotrophic factor (BDNF)-positive area and expression of pAkt in the brain, suggesting that curcumin activated BDNF signaling in aged mice. Furthermore, curcumin neutralized cholinergic dysfunction involving choline acetyltransferase expression induced by surgery. These results strongly suggested that curcumin prevented cognitive impairments via multiple targets, possibly by increasing the activity of anti-oxidant enzymes, activation of BDNF signaling, and neutralization of cholinergic dysfunction, concurrently. Based on these novel findings, curcumin might be a potential agent in POCD prophylaxis and treatment.

Cognitive computer training in children with attention deficit hyperactivity disorder (ADHD) versus no intervention: study protocol for a randomized controlled trial.

PubMed

Bikic, Aida; Leckman, James F; Lindschou, Jane; Christensen, Torben Ø; Dalsgaard, Søren

2015-10-24

Attention Deficit Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder characterized by symptoms of inattention and impulsivity and/or hyperactivity and a range of cognitive dysfunctions. Pharmacological treatment may be beneficial; however, many affected individuals continue to have difficulties with cognitive functions despite medical treatment, and up to 30 % do not respond to pharmacological treatment. Inadequate medical compliance and the long-term effects of treatment make it necessary to explore nonpharmacological and supplementary treatments for ADHD. Treatment of cognitive dysfunctions may prove particularly important because of the impact of these dysfunctions on the ability to cope with everyday life. Lately, several trials have shown promising results for cognitive computer training, often referred to as cognitive training, which focuses on particular parts of cognition, mostly on the working memory or attention but with poor generalization of training on other cognitive functions and functional outcome. Children with ADHD have a variety of cognitive dysfunctions, and it is important that cognitive training target multiple cognitive functions. This multicenter randomized clinical superiority trial aims to investigate the effect of "ACTIVATE™," a computer program designed to improve a range of cognitive skills and ADHD symptoms. A total of 122 children with ADHD, aged 6 to 13 years, will be randomized to an intervention or a control group. The intervention group will be asked to use ACTIVATE™ at home 40 minutes per day, 6 days per week for 8 weeks. Both intervention and control group will receive treatment as usual. Outcome measures will assess cognitive functions, symptoms, and behavioral and functional measures before and after the 8 weeks of training and in a 12- and 24-week follow-up. Results of this trial will provide useful information on the effectiveness of computer training focusing on several cognitive functions. Cognitive training has the potential to reduce cognitive dysfunctions and to become a new treatment option, which can promote a more normal neural development in young children with ADHD and thus reduce cognitive dysfunctions and symptoms. This could help children with ADHD to perform better in everyday life and school. ClinicalTrials.gov: NCT01752530 , date of registration: 10 December 2012.

Beneficial effects of dexmedetomidine on early postoperative cognitive dysfunction in pediatric patients with tonsillectomy.

PubMed

Han, Chuanlai; Fu, Rong; Lei, Weifu

2018-07-01

According to clinical investigations, early postoperative cognitive dysfunction is the most common adverse event in pediatric patients after tonsillectomy. A previous study has indicated that dexmedetomidine (DEX) is an efficient drug for the treatment of postoperative cognitive dysfunction. However, the efficacy of DEX in alleviating early postoperative cognitive dysfunction in pediatric patients following tonsillectomy has remained elusive, which was therefore assessed in the present study. A total of 186 children presenting with cognitive dysfunction subsequent to tonsillectomy were recruited to analyze the efficacy of DEX. Patients were randomly divided into two groups and received intravenous treatment with DEX (n=112) or placebo (n=74). Duration of treatment, dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) of DEX were evaluated in a preliminary experiment. The improvement of postoperative cognitive function in children with tonsillectomy was analyzed with a Mini-Mental State Examination (MMSE) following treatment with DEX. A 40-item quality of life (MONEX-40) questionnaire was used to assess the efficacy of DEX. The plasma levels of interleukin (IL)-6, IL-1, tumor necrosis factor (TNF)-α, superoxide dismutase (SOD), neuron-specific enolase (NSE), C-reactive protein (CRP), cortisol and melatonin were also analyzed. The preliminary experiment determined that the DLT was 10 mg/kg and the MTD was 15 mg/kg. In the major clinical trial, it was revealed that MMSE scores in the DEX treatment group were markedly improved, indicating that DEX had a beneficial effect in pediatric patients with early postoperative cognitive dysfunction after tonsillectomy. In addition, IL-1and TNF-α were downregulated, while IL-6 and SOD were upregulated in patients with cognitive dysfunction after treatment with DEX compared with those in the placebo group. Furthermore, DEX treatment markedly decreased the serum levels of CRP, NSE cortisol and melatonin, which are associated with the occurrence of postoperative cognitive dysfunction in pediatric patients following tonsillectomy. In conclusion, intravenous administration of DEX at a dose of 10 mg/kg improves postoperative cognitive function in pediatric patients with tonsillectomy by decreasing the serum levels of inflammatory factors and stress-associated signaling molecules. Trial registration no. QLSDHOS0200810102C (Qilu Hospital of Shandong University, Jinan, China).

Anti-N-methyl-D-aspartate receptor and anti-ribosomal-P autoantibodies contribute to cognitive dysfunction in systemic lupus erythematosus.

PubMed

Massardo, L; Bravo-Zehnder, M; Calderón, J; Flores, P; Padilla, O; Aguirre, J M; Scoriels, L; González, A

2015-05-01

Autoantibodies against N-methyl-D-aspartate receptor (anti-NMDAR) and ribosomal-P (anti-P) antigens are potential pathogenic factors in the frequently observed diffuse brain dysfunctions in patients with systemic lupus erythematosus (SLE). Although studies have been conducted in this area, the role of anti-NMDAR antibodies in SLE cognitive dysfunction remains elusive. Moreover, the specific contribution of anti-P antibodies has not been reported yet. The present study attempts to clarify the contribution of anti-NMDAR and anti-P antibodies to cognitive dysfunction in SLE. The Cambridge Neuropsychological Test Automated Battery (CANTAB) was used to assess a wide range of cognitive function areas in 133 Chilean women with SLE. ANCOVA models included autoantibodies, patient and disease features. Cognitive deficit was found in 20%. Higher SLEDAI-2K scores were associated with impairment in spatial memory and learning abilities, whereas both anti-NMDAR and anti-P antibodies contributed to deficits in attention and spatial planning abilities, which reflect fronto-parietal cortex dysfunctions. These results reveal an association of active disease together with specific circulating autoantibodies, such as anti-NMDAR and anti-P, with cognitive dysfunction in SLE patients. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Aphasia and unilateral spatial neglect due to acute thalamic hemorrhage: clinical correlations and outcomes.

PubMed

Osawa, Aiko; Maeshima, Shinichiro

2016-04-01

Thalamic hemorrhages are associated with a variety of cognitive dysfunctions, and it is well known that such cognitive changes constitute a limiting factor of recovery of the activities of daily living (ADL). The relationship between cognitive dysfunction and hematomas is unclear. In this study, we investigated the relationship between aphasia/neglect and hematoma volume, hematoma type, and the ADL. One hundred fifteen patients with thalamic hemorrhage (70 men and 45 women) were studied. Their mean age was 68.9 ± 10.3 years, and patients with both left and right lesions were included. We calculated hematoma volume and examined the presence or absence of aphasia/neglect and the relationships between these dysfunctions and hematoma volume, hematoma type, and the ADL. Fifty-nine patients were found to have aphasia and 35 were found to have neglect. Although there was no relationship between hematoma type and cognitive dysfunction, hematoma volume showed a correlation with the severity of cognitive dysfunction. The ADL score and ratio of patient discharge for patients with aphasia/neglect were lower than those for patients without aphasia/neglect. We observed a correlation between the hematoma volume in thalamic hemorrhage and cognitive dysfunction. Aphasia/neglect is found frequently in patients with acute thalamic hemorrhage and may influence the ADL.

Cognitive reactivity versus dysfunctional cognitions and the prediction of relapse in recurrent major depressive disorder.

PubMed

Figueroa, Caroline A; Ruhé, Henricus G; Koeter, Maarten W; Spinhoven, Philip; Van der Does, Willem; Bockting, Claudi L; Schene, Aart H

2015-10-01

Major depressive disorder (MDD) is a burdensome disease that has a high risk of relapse/recurrence. Cognitive reactivity appears to be a risk factor for relapse. It remains unclear, however, whether dysfunctional cognitions alone or the reactivity of such cognitions to mild states of sadness (ie, cognitive reactivity) is the crucial factor that increases relapse risk. We aimed to assess the long-term predictive value of cognitive reactivity versus dysfunctional cognitions and other risk factors for depressive relapse. In a prospective cohort of outpatients (N = 116; studied between 2000-2005) who had experienced ≥ 2 previous major depressive episodes (MDEs) and were in remission (DSM-IV) at the start of follow-up, we measured cognitive reactivity, with the Leiden Index of Depression Sensitivity (LEIDS), and dysfunctional cognitions, with the Dysfunctional Attitudes Scale, simultaneously. Course of illness (with the primary outcome of MDE assessed by the Structured Clinical Interview for DSM-IV Axis I Disorders Patient Edition) and time to relapse were monitored prospectively for 3.5 years. Cognitive reactivity scores were associated with time to relapse over the 3.5-year follow-up and also when corrected for the number of previous MDEs and concurrent depressive symptoms (hazard ratio for 1 standard deviation [(HR(SD)); 20 points of the LEIDS, measuring cognitive reactivity] = 1.47; 95% CI, 1.04-2.09; P = .031). Rumination appeared to be a particularly strong predictor of relapse (HR(SD) = 1.60; 95% CI, 1.13-2.26; P = .007). Dysfunctional cognitions did not predict relapse over 3.5 years (HR(SD) = 1.00; 95% CI, 0.74-1.37; P = .93). Every 20-point increase on the cognitive reactivity scale resulted in a 10% to 15% increase in risk of relapse (corrected for previous MDEs and concurrent depressive symptoms). Cognitive reactivity--and particularly rumination--is a long-term predictor of relapse. Future research should address whether psychological interventions can improve cognitive reactivity scores and thereby prevent depressive relapses. ISRCTN Identifier: 68246470. © Copyright 2015 Physicians Postgraduate Press, Inc.

Should general anaesthesia be avoided in the elderly?

PubMed Central

Strøm, C.; Rasmussen, L. S.; Sieber, F. E.

2016-01-01

Summary Surgery and anaesthesia exert comparatively greater adverse effects on the elderly than on the younger brain, manifest by the higher prevalence of postoperative delirium and cognitive dysfunction. Postoperative delirium and cognitive dysfunction delay rehabilitation, and are associated with increases in morbidity and mortality among elderly surgical patients. We review the aetiology of postoperative delirium and cognitive dysfunction in the elderly with a particular focus on anaesthesia and sedation, discuss methods of diagnosing and monitoring postoperative cognitive decline, and describe the treatment strategies by which such decline may be prevented. PMID:24303859

Mild Cognitive Dysfunction: An Epidemiological Perspective with an Emphasis on African Americans

PubMed Central

Unverzagt, Frederick W.; Gao, Sujuan; Lane, Kathleen A.; Callahan, Christopher; Ogunniyi, Adesola; Baiyewu, Olusegun; Gureje, Oye; Hall, Kathleen S.; Hendrie, Hugh C.

2009-01-01

In this review, we begin with a historical accounting of the evolution of the concept of mild cognitive dysfunction including nomenclature and criteria from Kral to Petersen. A critical analysis of the main elements relating to assessment and diagnosis of mild cognitive dysfunction are described. Methodological limitations in design, measurement, and characterization, especially as they relate to older African Americans, are identified. Data from a 15-year longitudinal study of community-dwelling, African Americans in Indianapolis indicate 23% prevalence of all-cause mild cognitive dysfunction with approximately 25% progressing to dementia in 2 years and another 25% reverting to normal in the same interval. Factors contributing to this longitudinal variability in outcome are reviewed including the role of medical health factors. We close with suggestions for next steps in the epidemiological research of mild cognitive impairment. PMID:18004008

Cognitive disorders in children's hydrocephalus.

PubMed

Zielińska, Dorota; Rajtar-Zembaty, Anna; Starowicz-Filip, Anna

Hydrocephalus is defined as an increase of volume of cerebrospinal fluid in the ventricular system of the brain. It develops as a result of cerebrospinal fluid flow disorder due to dysfunctions of absorption or, less frequently, as a result of the increase of its production. Hydrocephalus may lead to various cognitive dysfunctions in children. In order to determine cognitive functioning in children with hydrocephalus, the authors reviewed available literature while investigating this subject. The profile of cognitive disorders in children with hydrocephalus may include a wide spectrum of dysfunctions and the process of neuropsychological assessment may be very demanding. The most frequently described cognitive disorders within children's hydrocephalus include attention, executive, memory, visual, spatial or linguistic dysfunctions, as well as behavioral problems. Copyright © 2017 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Physiologic Dysfunction Scores and Cognitive Function Test Performance in United States Adults

PubMed Central

Kobrosly, Roni W; Seplaki, Christopher L; Jones, Courtney M; van Wijngaarden, Edwin

2013-01-01

Objective To investigate the relationship between a measure of cumulative physiologic dysfunction and specific domains of cognitive function. Methods We examined a summary score measuring physiological dysfunction, a multisystem measure of the body’s ability to effectively adapt to physical and psychological demands, in relation to cognitive function deficits in a population of 4511 adults aged 20 to 59 who participated in the third National Health and Nutrition Examination Survey (1988–1994). Measures of cognitive function comprised three domains: working memory, visuomotor speed, and perceptual-motor speed. ‘Physiologic dysfunction’ scores summarizing measures of cardiovascular, immunologic, kidney, and liver function were explored. We used multiple linear regression models to estimate associations between cognitive function measures and physiological dysfunction scores, adjusting for socioeconomic factors, test conditions, and self-reported health factors. Results We noted a dose-response relationship between physiologic dysfunction and working memory (coefficient = 0.207, 95% CI = (0.066, 0.348), p < 0.0001) that persisted after adjustment for all covariates (p = 0.03). We did not observe any significant relationships between dysfunction scores and visuomotor (p = 0.37) or perceptual-motor ability (p = 0.33). Conclusions Our findings suggest that multisystem physiologic dysfunction is associated with working memory. Future longitudinal studies are needed to clarify the underlying mechanisms and explore the persistency of this association into later life. We suggest that such studies should incorporate physiologic data, neuroendocrine parameters, and a wide range of specific cognitive domains. PMID:22155941

Cognitive functions, electroencephalographic and diffusion tensor imaging changes in children with active idiopathic epilepsy.

PubMed

A Yassine, Imane; M Eldeeb, Waleed; A Gad, Khaled; A Ashour, Yossri; A Yassine, Inas; O Hosny, Ahmed

2018-07-01

Neurocognitive impairment represents one of the most common comorbidities occurring in children with idiopathic epilepsy. Diagnosis of the idiopathic form of epilepsy requires the absence of any macrostructural abnormality in the conventional MRI. Though changes can be seen at the microstructural level imaged using advanced techniques such as the Diffusion Tensor Imaging (DTI). The aim of this work is to study the correlation between the microstructural white matter DTI findings, the electroencephalographic changes and the cognitive dysfunction in children with active idiopathic epilepsy. A comparative cross-sectional study, included 60 children with epilepsy based on the Stanford-Binet 5th Edition Scores was conducted. Patients were equally assigned to normal cognitive function or cognitive dysfunction groups. The history of the epileptic condition was gathered via personal interviews. All patients underwent brain Electroencephalography (EEG) and DTI, which was analyzed using FSL. The Fractional Anisotropy (FA) was significantly higher whereas the Mean Diffusivity (MD) was significantly lower in the normal cognitive function group than in the cognitive dysfunction group. This altered microstructure was related to the degree of the cognitive performance of the studied children with epilepsy. The microstructural alterations of the neural fibers in children with epilepsy and cognitive dysfunction were significantly related to the younger age of onset of epilepsy, the poor control of the clinical seizures, and the use of multiple antiepileptic medications. Children with epilepsy and normal cognitive functions differ in white matter integrity, measured using DTI, compared with children with cognitive dysfunction. These changes have important cognitive consequences. Copyright © 2018 Elsevier Inc. All rights reserved.

Association between academic performance and cognitive dysfunction in patients with juvenile systemic lupus erythematosus.

PubMed

Frittoli, Renan Bazuco; de Oliveira Peliçari, Karina; Bellini, Bruna Siqueira; Marini, Roberto; Fernandes, Paula Teixeira; Appenzeller, Simone

2016-01-01

To determine whether there is an association between the profile of cognitive dysfunction and academic outcomes in patients with juvenile systemic lupus erythematosus (JSLE). Patients aged ≤18 years at the onset of the disease and education level at or above the fifth grade of elementary school were selected. Cognitive evaluation was performed according to the American College of Rheumatology (ACR) recommendations. Symptoms of anxiety and depression were assessed by Beck scales; disease activity was assessed by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI); and cumulative damage was assessed by Systemic Lupus International Collaborating Clinics (SLICC). The presence of autoantibodies and medication use were also assessed. A significance level of 5% (p<0.05) was adopted. 41 patients with a mean age of 14.5±2.84 years were included. Cognitive dysfunction was noted in 17 (41.46%) patients. There was a significant worsening in mathematical performance in patients with cognitive dysfunction (p=0.039). Anxiety symptoms were observed in 8 patients (19.51%) and were associated with visual perception (p=0.037) and symptoms of depression were observed in 1 patient (2.43%). Patients with JSLE concomitantly with cognitive dysfunction showed worse academic performance in mathematics compared to patients without cognitive impairment. Copyright © 2016 Elsevier Editora Ltda. All rights reserved.

Heading in Soccer: Integral Skill or Grounds for Cognitive Dysfunction?

ERIC Educational Resources Information Center

Kirkendall, Donald T.; Garrett, William E., Jr.

2001-01-01

Discusses how purposeful heading of soccer balls and head injuries affect soccer players' cognitive dysfunction. Cognitive deficits may occur for many reasons. Heading cannot be blamed when details of the actual event and impact are unknown. Concussions are the most common head injury in soccer and a factor in cognitive deficits and are probably…

Change in Dysfunctional Beliefs About Sleep in Behavior Therapy, Cognitive Therapy, and Cognitive-Behavioral Therapy for Insomnia.

PubMed

Eidelman, Polina; Talbot, Lisa; Ivers, Hans; Bélanger, Lynda; Morin, Charles M; Harvey, Allison G

2016-01-01

As part of a larger randomized controlled trial, 188 participants were randomized to behavior therapy (BT), cognitive therapy (CT), or cognitive-behavioral therapy (CBT) for insomnia. The aims of this study were threefold: (a) to determine whether change in dysfunctional beliefs about sleep was related to change in sleep, insomnia symptoms, and impairment following treatment; (b) to determine whether BT, CT, and CBT differ in their effects on dysfunctional beliefs; and (c) to determine whether the treatments differ in their effects on particular kinds of dysfunctional beliefs. Beliefs, sleep, insomnia symptoms, and sleep-related psychosocial impairment were assessed at pretreatment, posttreatment, and 6- and 12-month follow-up. Greater change in dysfunctional beliefs occurring over the course of BT, CT, or CBT was associated with greater improvement in insomnia symptoms and impairment at posttreatment and both follow-ups. All groups experienced a significant decrease in dysfunctional beliefs during treatment, which were sustained through 6- and 12-month follow-up. Compared with the BT group, a greater proportion of participants in the CT and/or CBT groups endorsed dysfunctional beliefs below a level considered clinically significant at posttreatment and 12-month follow-up. The results demonstrate the importance of targeting dysfunctional beliefs in insomnia treatment, suggest that beliefs may be significantly modified with BT alone, and indicate that cognitive interventions may be particularly powerful in enhancing belief change. Copyright © 2016. Published by Elsevier Ltd.

Innate Immune Signalling Genetics of Pain, Cognitive Dysfunction and Sickness Symptoms in Cancer Pain Patients Treated with Transdermal Fentanyl

PubMed Central

Barratt, Daniel T.; Klepstad, Pål; Dale, Ola; Kaasa, Stein; Somogyi, Andrew A.

2015-01-01

Common adverse symptoms of cancer and chemotherapy are a major health burden; chief among these is pain, with opioids including transdermal fentanyl the mainstay of treatment. Innate immune activation has been implicated generally in pain, opioid analgesia, cognitive dysfunction, and sickness type symptoms reported by cancer patients. We aimed to determine if genetic polymorphisms in neuroimmune activation pathways alter the serum fentanyl concentration-response relationships for pain control, cognitive dysfunction, and other adverse symptoms, in cancer pain patients. Cancer pain patients (468) receiving transdermal fentanyl were genotyped for 31 single nucleotide polymorphisms in 19 genes: CASP1, BDNF, CRP, LY96, IL6, IL1B, TGFB1, TNF, IL10, IL2, TLR2, TLR4, MYD88, IL6R, OPRM1, ARRB2, COMT, STAT6 and ABCB1. Lasso and backward stepwise generalised linear regression were used to identify non-genetic and genetic predictors, respectively, of pain control (average Brief Pain Inventory < 4), cognitive dysfunction (Mini-Mental State Examination ≤ 23), sickness response and opioid adverse event complaint. Serum fentanyl concentrations did not predict between-patient variability in these outcomes, nor did genetic factors predict pain control, sickness response or opioid adverse event complaint. Carriers of the MYD88 rs6853 variant were half as likely to have cognitive dysfunction (11/111) than wild-type patients (69/325), with a relative risk of 0.45 (95% CI: 0.27 to 0.76) when accounting for major non-genetic predictors (age, Karnofsky functional score). This supports the involvement of innate immune signalling in cognitive dysfunction, and identifies MyD88 signalling pathways as a potential focus for predicting and reducing the burden of cognitive dysfunction in cancer pain patients. PMID:26332828

Are all models susceptible to dysfunctional cognitions about eating and body image? The moderating role of personality styles.

PubMed

Blasczyk-Schiep, Sybilla; Sokoła, Kaja; Fila-Witecka, Karolina; Kazén, Miguel

2016-06-01

We investigated dysfunctional cognitions about eating and body image in relation to personality styles in a group of professional models. Dysfunctional cognitions in professional models (n = 43) and a control group (n = 43) were assessed with the 'Eating Disorder Cognition Questionnaire' (EDCQ), eating attitudes with the 'Eating Attitudes Test' (EAT), and personality with the 'Personality Styles and Disorders Inventory' (PSDI-S). Models had higher scores than controls on the EDCQ and EAT and on nine scales of the PSDI-S. Moderation analyses showed significant interactions between groups and personality styles in predicting EDCQ scales: The ambitious/narcissistic style was related to "negative body and self-esteem", the conscientious/compulsive style to "dietary restraint", and the spontaneous/borderline style to "loss of control in eating". The results indicate that not all models are susceptible to dysfunctional cognitions about eating and body image. Models are at a higher risk of developing negative automatic thoughts and dysfunctional assumptions relating to body size, shape and weight, especially if they have high scores on the above personality styles.

Urtica dioica extract attenuates depressive like behavior and associative memory dysfunction in dexamethasone induced diabetic mice.

PubMed

Patel, Sita Sharan; Udayabanu, Malairaman

2014-03-01

Evidences suggest that glucocorticoids results in depression and is a risk factor for type 2 diabetes. Further diabetes induces oxidative stress and hippocampal dysfunction resulting in cognitive decline. Traditionally Urtica dioica has been used for diabetes mellitus and cognitive dysfunction. The present study investigated the effect of the hydroalcoholic extract of Urtica dioica leaves (50 and 100 mg/kg, p.o.) in dexamethasone (1 mg/kg, i.m.) induced diabetes and its associated complications such as depressive like behavior and cognitive dysfunction. We observed that mice administered with chronic dexamethasone resulted in hypercortisolemia, oxidative stress, depressive like behavior, cognitive impairment, hyperglycemia with reduced body weight, increased water intake and decreased hippocampal glucose transporter-4 (GLUT4) mRNA expression. Urtica dioica significantly reduced hyperglycemia, plasma corticosterone, oxidative stress and depressive like behavior as well as improved associative memory and hippocampal GLUT4 mRNA expression comparable to rosiglitazone (5 mg/kg, p.o.). Further, Urtica dioica insignificantly improved spatial memory and serum insulin. In conclusion, Urtica dioica reversed dexamethasone induced hyperglycemia and its associated complications such as depressive like behavior and cognitive dysfunction.

Neuroanatomical Substrates of Social Cognition Dysfunction in Autism

ERIC Educational Resources Information Center

Pelphrey, Kevin; Adolphs, Ralph; Morris, James P.

2004-01-01

In this review article, we summarize recent progress toward understanding the neural structures and circuitry underlying dysfunctional social cognition in autism. We review selected studies from the growing literature that has used the functional neuroimaging techniques of cognitive neuroscience to map out the neuroanatomical substrates of social…

Three screening methods for cognitive dysfunction using the Mini-Mental State Examination and Korean Dementia Screening Questionnaire.

PubMed

Choi, Seong Hye; Park, Moon Ho

2016-02-01

To screen for and determine cognitive dysfunction, cognitive tests and/or informant reports are commonly used. However, these cognitive tests and informant reports are not always available. The present study investigated three screening methods using the Mini-Mental State Examination (MMSE) as the cognitive test, and the Korean dementia screening questionnaire (KDSQ) as the informant report. Participants were recruited from the Korea Clinical Research Center for Dementia of South Korea, and included 2861 patients with Alzheimer's disease (dementia), 3519 patients with mild cognitive impairment and 1375 controls with no cognitive dysfunction. Three screening methods were tested: (i) MMSE alone (MMSE(cut-off) ); (ii) a conventional combination of MMSE and KDSQ (MMSE+KDSQ(cut-off) ); and (iii) a decision tree with MMSE and KDSQ (MMSE+KDSQ(decision tree) ). For discriminating any cognitive dysfunction from controls, MMSE+KDSQ(cut-off) had the highest area under the receiver operating characteristic curve (0.784). For discriminating dementia from controls, MMSE+KDSQ(cut-off) had the highest area under the receiver operating characteristic curve (0.899). For discriminating mild cognitive impairment from controls, MMSE(cut-off) had the highest area under the receiver operating characteristic curve (0.683). MMSE+KDSQ(decision tree) showed the highest sensitivity for all discriminations. For overall classification accuracy, MMSE+KDSQ(decision tree) had the highest value (70.0%). These three methods had different advantageous properties for screening and staging cognitive dysfunction. As there might be different availability across clinical settings, these three methods can be selected and used according to situational needs. © 2015 Japan Geriatrics Society.

Stability of Cognitive Vulnerabilities to Depression: A Short-Term Prospective Multiwave Study

PubMed Central

Hankin, Benjamin L.

2009-01-01

The stability of 3 cognitive vulnerabilities—a negative cognitive style, dysfunctional attitudes, and rumination—as well as depressive symptoms as a benchmark were examined to investigate whether cognitive vulnerabilities are stable, enduring risks for depression. A sample of adolescents (6th–10th graders) completed measures of these 3 cognitive vulnerabilities and depressive symptoms every 5 weeks for 4 waves of data across 5 months. Mean-level and differential stability were examined for the sample overall and by age subgroups. A negative cognitive style exhibited mean-level stability, whereas rumination and dysfunctional attitudes showed some mean-level change. Absolute magnitudes of test–retest reliabilities were strong for depressive symptoms (mean r = .70), moderately high for a negative cognitive style (mean r = .52), and more modest for rumination (mean r = .28) and dysfunctional attitudes (mean r = .26). Structural equation modeling showed that primarily enduring processes, but not contextual forces, contributed to the patterning of these test–retest reliabilities over time for a negative cognitive style and dysfunctional attitudes, whereas both enduring and contextual dynamics appeared to underlie the stability for rumination. Theoretical and clinical implications of these findings are discussed. PMID:18489208

4C.05: PWV IS AN INDEPENDENT DETERMINANT OF COGNITIVE DYSFUNCTION IN CKD PATIENTS.

PubMed

Karasavvidou, D; Pappas, K; Stagikas, D; Makridis, D; Katsinas, C; Kalaitzidis, R

2015-06-01

Cognitive dysfunction has long been recognized as a complication of chronic kidney disease (CKD), through several putative mechanisms, including high BP, large and small artery damage. Our study tests the hypothesis that large artery stiffness and microvascular damage are related to brain microcirculation changes as reflected by impaired cognitive function in CKD patients.(Figure is included in full-text article.) : Two hundred seventeen patients (50 with CKD stage 1; 67 stage 2; 53 stage 3; 47 stage 4), with mean age 58.4 years (64.5% males), were enrolled in a cross-sectional study. Cognitive function was assessed using Mini Mental State Examination (MMSE). Full score on the MMSE is 30; cognitive impairment was defined as <26 and cognitive dysfunction as <19. Educational level was categorized as lower versus higher education. Using the Sphygmocor system and an oscillometric device, we directly measured brachial SBP (bSBP) and pulse pressure (bPP), carotid SBP (cSBP) and pulse pressure (cPP) and estimated aortic SBP (aSBP) and pulse pressure (aPP) from the radial pressure waveform. Pulse Pressure Amplification (PPA), augmentation index (AIx) and carotid-femoral pulse wave velocity (cfPWV) were calculated. The risk of cognitive dysfunction increased significantly from CKD stage 3 to 4 (p < 0.01). Table. In univariate analysis, age (p < 0.001), education level (p < 0.001) stages of CKD (p < 0.004), cfPWV (p < 0.029), AIx (p < 0.03), bSBP (p < 0.002), aSBP (p < 0.012), cSBP (p < 0.015) and cPP (p < 0.002) were significantly and negatively associated with MMSE. In multivariate regression analysis, adjusted for CKD stages, the remaining independent factor significantly (p < 0.02) associated with cognitive dysfunction was cfPWV. Carotid-femoral PWV may be a more sensitive marker of cognitive dysfunction than other parameters of central blood pressure. Since high cfPWV is associated with high pressure pulsatility at the cerebrovascular level, these data suggest that the later could play a pathophysiological role in cognitive dysfunction. In clinical practice, measuring aortic stiffness may help predicting the cognitive decline. Whether, the reduction in aortic stiffness following treatment translates into improved cognitive outcomes remains to be determined.

Cognitive control dysfunction in emotion dysregulation and psychopathology of major depression (MD): Evidence from transcranial brain stimulation of the dorsolateral prefrontal cortex (DLPFC).

PubMed

Salehinejad, Mohammad Ali; Ghanavai, Elham; Rostami, Reza; Nejati, Vahid

2017-03-01

Previous studies showed that MD is associated with a variety of cognitive deficits and executive dysfunctions which can persist even in remitted states. However, the role of cognitive impairments in MD psychopathology and treatment is not fully understood. This article aims to discuss how executive functions central components (e.g., Working memory and attention) mediate MD psychopathology considering the role of dorsolateral prefrontal cortex (dLPFC) and present findings of a brain stimulation experiment to support this notion. The effect of transcranial direct current stimulation (tDCS) of the dLPFC on enhancing cognitive control functions was investigated. Twenty-four patients with MD (Experimental group=12, Control group=12) received 10 sessions of tDCS (2mA for 30min) over 10 consecutive days. The experimental group received active stimulation and the control group received sham stimulation. Participant's performance on cognitive functions (PAL, SRM, RVP and CRT from CANTAB) and their depression scores were assessed before and after tDCS. Results showed that brain stimulation of the dLPFC improved executive dysfunction in patients and a significant improvement on depression scores was also observed suggesting that cognitive control dysfunction may be a mediator in emotional dysregulation and psychopathology of MD. No follow-up investigation was done in this study which does not allow to infer long-term effect of tDCS. Low-focality of tDCS might have stimulated adjacent areas too. Cognitive components, namely cognitive control dysfunction, play role in MD psychopathology as they are involved in emotion dysregulation in MD. The amount of contribution of cognitive components in MD psychopathology is however, an open question. tDCS can be used as an intervention to improve cognitive dysfunction in MD. Copyright © 2017 Elsevier B.V. All rights reserved.

Correlation of Visuospatial Ability and EEG Slowing in Patients with Parkinson's Disease

PubMed Central

Meyer, Antonia; Chaturvedi, Menorca; Hatz, Florian; Gschwandtner, Ute

2017-01-01

Background. Visuospatial dysfunction is among the first cognitive symptoms in Parkinson's disease (PD) and is often predictive for PD-dementia. Furthermore, cognitive status in PD-patients correlates with quantitative EEG. This cross-sectional study aimed to investigate the correlation between EEG slowing and visuospatial ability in nondemented PD-patients. Methods. Fifty-seven nondemented PD-patients (17 females/40 males) were evaluated with a comprehensive neuropsychological test battery and a high-resolution 256-channel EEG was recorded. A median split was performed for each cognitive test dividing the patients sample into either a normal or lower performance group. The electrodes were split into five areas: frontal, central, temporal, parietal, and occipital. A linear mixed effects model (LME) was used for correlational analyses and to control for confounding factors. Results. Subsequently, for the lower performance, LME analysis showed a significant positive correlation between ROCF score and parietal alpha/theta ratio (b = .59, p = .012) and occipital alpha/theta ratio (b = 0.50, p = .030). No correlations were found in the group of patients with normal visuospatial abilities. Conclusion. We conclude that a reduction of the parietal alpha/theta ratio is related to visuospatial impairments in PD-patients. These findings indicate that visuospatial impairment in PD-patients could be influenced by parietal dysfunction. PMID:28348918

Late-onset multiple sclerosis presenting with cognitive dysfunction and severe cortical/infratentorial atrophy.

PubMed

Calabrese, Massimiliano; Gajofatto, Alberto; Gobbin, Francesca; Turri, Giulia; Richelli, Silvia; Matinella, Angela; Oliboni, Eugenio Simone; Benedetti, Maria Donata; Monaco, Salvatore

2015-04-01

Although cognitive dysfunction is a relevant aspect of multiple sclerosis (MS) from the earliest disease phase, cognitive onset is unusual thus jeopardizing early and accurate diagnosis. Here we describe 12 patients presenting with cognitive dysfunction as primary manifestation of MS with either mild or no impairment in non-cognitive neurological domains. Twelve patients with cognitive onset who were subsequently diagnosed with MS (CI-MS) were included in this retrospective study. Twelve cognitively normal MS patients (CN-MS), 12 healthy controls and four patients having progressive supranuclear palsy (PSP) served as the reference population. Ten CI-MS patients had progressive clinical course and all patients had late disease onset (median age = 49 years; range = 40-58 years). Among cognitive functions, frontal domains were the most involved. Compared to CN-MS and healthy controls, significant cortical and infratentorial atrophy characterized CI-MS patients. Selective atrophy of midbrain tegmentum with relative sparing of pons, known as "The Hummingbird sign," was observed in eight CI-MS and in three PSP patients. Our observation suggests that MS diagnosis should be taken into consideration in case of cognitive dysfunction, particularly when associated with slowly progressive disease course and severe cortical, cerebellar and brainstem atrophy even in the absence of other major neurological symptoms and signs. © The Author(s), 2014.

Anti-NR2A/B Antibodies and Other Major Molecular Mechanisms in the Pathogenesis of Cognitive Dysfunction in Systemic Lupus Erythematosus

PubMed Central

Tay, Sen Hee; Mak, Anselm

2015-01-01

Systemic lupus erythematosus (SLE) is an autoimmune disease that affects approximately 1–45.3 per 100,000 people worldwide. Although deaths as a result of active and renal diseases have been substantially declining amongst SLE patients, disease involving the central nervous system (CNS), collectively termed neuropsychiatric systemic lupus erythematosus (NPSLE), remains one of the important causes of death in these patients. Cognitive dysfunction is one of the most common manifestations of NPSLE, which comprises deficits in information-processing speed, attention and executive function, in conjunction with preservation of speech. Albeit a prevalent manifestation of NPSLE, the pathogenetic mechanisms of cognitive dysfunction remain unclear. Recent advances in genetic studies, molecular techniques, neuropathology, neuroimaging and cognitive science have gleaned valuable insights into the pathophysiology of lupus-related cognitive dysfunction. In recent years, a role for autoantibodies, molecular and cellular mechanisms in cognitive dysfunction, has been emerging, challenging our previous concept of the brain as an immune privileged site. This review will focus on the potential pathogenic factors involved in NPSLE, including anti-N-methyl-d-aspartate receptor subunit NR2A/B (anti-NR2A/B) antibodies, matrix metalloproteinase-9, neutrophil extracellular traps and pro-inflammatory mediators. Better understanding of these mechanistic processes will enhance identification of new therapeutic modalities to halt the progression of cognitive decline in SLE patients. PMID:25955648

Attachment, dysfunctional attitudes, self-esteem, and association to depressive symptoms in patients with mood disorders.

PubMed

Fuhr, Kristina; Reitenbach, Ivanina; Kraemer, Jan; Hautzinger, Martin; Meyer, Thomas D

2017-04-01

Cognitive factors might be the link between early attachment experiences and later depression. Similar cognitive vulnerability factors are discussed as relevant for both unipolar and bipolar disorders. The goals of the study were to test if there are any differences concerning attachment style and cognitive factors between remitted unipolar and bipolar patients compared to controls, and to test if the association between attachment style and depressive symptoms is mediated by cognitive factors. A path model was tested in 182 participants (61 with remitted unipolar and 61 with remitted bipolar disorder, and 60 healthy subjects) in which adult attachment insecurity was hypothesized to affect subsyndromal depressive symptoms through the partial mediation of dysfunctional attitudes and self-esteem. No differences between patients with remitted unipolar and bipolar disorders concerning attachment style, dysfunctional attitudes, self-esteem, and subsyndromal depressive symptoms were found, but both groups reported a more dysfunctional pattern than healthy controls. The path models confirmed that the relationship between attachment style and depressive symptoms was mediated by the cognitive variables 'dysfunctional attitudes' and 'self-esteem'. With the cross-sectional nature of the study, results cannot explain causal development over time. The results emphasize the relevance of a more elaborate understanding of cognitive and interpersonal factors in mood disorders. It is important to address cognitive biases and interpersonal experiences in treatment of mood disorders. Copyright © 2017 Elsevier B.V. All rights reserved.

Prefrontal cortical gamma-aminobutyric acid transmission and cognitive function: drawing links to schizophrenia from preclinical research.

PubMed

Tse, Maric T; Piantadosi, Patrick T; Floresco, Stan B

2015-06-01

Cognitive dysfunction in schizophrenia is one of the most pervasive and debilitating aspects of the disorder. Among the numerous neural abnormalities that may contribute to schizophrenia symptoms, perturbations in markers for the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), particularly within the frontal lobes, are some of the most reliable alterations observed at postmortem examination. However, how prefrontal GABA dysfunction contributes to cognitive impairment in schizophrenia remains unclear. We provide an overview of postmortem GABAergic perturbations in the brain affected by schizophrenia and describe circumstantial evidence linking these alterations to cognitive dysfunction. In addition, we conduct a survey of studies using neurodevelopmental, genetic, and pharmacologic rodent models that induce schizophrenia-like cognitive impairments, highlighting the convergence of these mechanistically distinct approaches to prefrontal GABAergic disruption. We review preclinical studies that have directly targeted prefrontal cortical GABAergic transmission using local application of GABAA receptor antagonists. These studies have provided an important link between GABA transmission and cognitive dysfunction in schizophrenia because they show that reducing prefrontal inhibitory transmission induces various cognitive, emotional, and dopaminergic abnormalities that resemble aspects of the disorder. These converging clinical and preclinical findings provide strong support for the idea that perturbations in GABA signaling drive certain forms of cognitive dysfunction in schizophrenia. Future studies using this approach will yield information to refine further a putative "GABA hypothesis" of schizophrenia. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

A milk-based wolfberry preparation prevents prenatal stress-induced cognitive impairment of offspring rats, and inhibits oxidative damage and mitochondrial dysfunction in vitro.

PubMed

Feng, Zhihui; Jia, Haiqun; Li, Xuesen; Bai, Zhuanli; Liu, Zhongbo; Sun, Lijuan; Zhu, Zhongliang; Bucheli, Peter; Ballèvre, Olivier; Wang, Junkuan; Liu, Jiankang

2010-05-01

Lycium barbarum (Fructus Lycii, Wolfberry, or Gouqi) belongs to the Solanaceae. The red-colored fruits of L. barbarum have been used for a long time as an ingredient in Chinese cuisine and brewing, and also in traditional Chinese herbal medicine for improving health. However, its effects on cognitive function have not been well studied. In the present study, prevention of a milk-based wolfberry preparation (WP) on cognitive dysfunction was tested in a prenatal stress model with rats and the antioxidant mechanism was tested by in vitro experiments. We found that prenatal stress caused a significant decrease in cognitive function (Morris water maze test) in female offspring. Pretreatment of the mother rats with WP significantly prevented the prenatal stress-induced cognitive dysfunction. In vitro studies showed that WP dose-dependently scavenged hydroxyl and superoxide radicals (determined by an electron spin resonance spectrometric assay), and inhibited FeCl(2)/ascorbic acid-induced dysfunction in brain tissue and tissue mitochondria, including increases in reactive oxygen species and lipid peroxidation and decreases in the activities of complex I, complex II, and glutamate cysteine ligase. These results suggest that dietary supplementation with WP may be an effective strategy for preventing the brain oxidative mitochondrial damage and cognitive dysfunction associated with prenatal stress.

Neurotransmitter-based strategies for the treatment of cognitive dysfunction in Down syndrome.

PubMed

Das, Devsmita; Phillips, Cristy; Hsieh, Wayne; Sumanth, Krithika; Dang, Van; Salehi, Ahmad

2014-10-03

Down syndrome (DS) is a multisystem disorder affecting the cardiovascular, respiratory, gastrointestinal, neurological, hematopoietic, and musculoskeletal systems and is characterized by significant cognitive disability and a possible common pathogenic mechanism with Alzheimer's disease. During the last decade, numerous studies have supported the notion that the triplication of specific genes on human chromosome 21 plays a significant role in cognitive dysfunction in DS. Here we reviewed studies in trisomic mouse models and humans, including children and adults with DS. In order to identify groups of genes that contribute to cognitive disability in DS, multiple mouse models of DS with segmental trisomy have been generated. Over-expression of these particular genes in DS can lead to dysfunction of several neurotransmitter systems. Therapeutic strategies for DS have either focused on normalizing the expression of triplicated genes with important roles in DS or restoring the function of these systems. Indeed, our extensive review of studies on the pathogenesis of DS suggests that one plausible strategy for the treatment of cognitive dysfunction is to target the cholinergic, serotonergic, GABA-ergic, glutamatergic, and norepinephrinergic system. However, a fundamental strategy for treatment of cognitive dysfunction in DS would include reducing to normal levels the expression of specific triplicated genes in affected systems before the onset of neurodegeneration. Published by Elsevier Inc.

The synergistic effect of acupuncture and computer-based cognitive training on post-stroke cognitive dysfunction: a study protocol for a randomized controlled trial of 2 × 2 factorial design.

PubMed

Yang, Shanli; Ye, Haicheng; Huang, Jia; Tao, Jing; Jiang, Cai; Lin, Zhicheng; Zheng, Guohua; Chen, Lidian

2014-08-07

Stroke is one of the most common causes of cognitive impairment. Up to 75% of stroke survivors may be considered to have cognitive impairment, which severely limit individual autonomy for successful reintegration into family, work and social life. The clinical efficacy of acupuncture with Baihui (DU20) and Shenting (DU24) in stroke and post-stroke cognitive impairment has been previously demonstrated. Computer-assisted cognitive training is part of conventional cognitive rehabilitation and has also shown to be effective in improvement of cognitive function of affected patients. However, the cognitive impairment after stroke is so complexity that one single treatment cannot resolve effectively. Besides, the effects of acupuncture and RehaCom cognitive training have not been systematically compared, nor has the possibility of a synergistic effect of combination of the two therapeutic modalities been evaluated. Our primary aim of this trial is to evaluate the synergistic effect of acupuncture and RehaCom cognitive training on cognitive dysfunction after stroke. A randomized controlled trial of 2 × 2 factorial design will be conducted in the Rehabilitation Hospital Affiliated to Fujian University of Traditional Chinese Medicine. A total of 240 patients with cognitive dysfunction after stroke who meet the eligibility criteria will be recruited and randomized into RehaCom training group, acupuncture group, a combination of both or control group in a 1:1:1:1 ratio. All patients will receive conventional treatment. The interventions will last for 12 weeks (30 min per day, Monday to Friday every week). Evaluations will be conducted by blinded assessors at baseline and again at 4, 8 and 12 weeks. Outcome measurements include mini-mental state examination (MMSE), Montreal cognitive assessments (MoCA), functional independence measure scale (FIM) and adverse events. The results of this trial are expected to clarify the synergistic effect of acupuncture and RehaCom cognitive training on cognitive dysfunction after stroke. Furthermore, to confirm whether combined or alone of acupuncture and RehaCom cognitive training, is more effective than conventional treatment in the management of post-stroke cognitive dysfunction. Chinese Clinical Trial Registry: ChiCTR-TRC-13003704.

Bipolar Disorder and Cognitive Dysfunction: A Complex Link.

PubMed

Cipriani, Gabriele; Danti, Sabrina; Carlesi, Cecilia; Cammisuli, Davide Maria; Di Fiorino, Mario

2017-10-01

The aim of this article was to describe the current evidence regarding phenomenon of cognitive functioning and dementia in bipolar disorder (BD). Cochrane Library and PubMed searches were conducted for relevant articles, chapters, and books published before 2016. Search terms used included "bipolar disorder," "cognitive dysfunction," and "dementia." At the end of the selection process, 159 studies were included in our qualitative synthesis. As result, cognitive impairments in BD have been previously considered as infrequent and limited to the affective episodes. Nowadays, there is evidence of stable and lasting cognitive dysfunctions in all phases of BD, including remission phase, particularly in the following domains: attention, memory, and executive functions. The cause of cognitive impairment in BD raises the question if it subtends a neurodevelopmental or a neurodegenerative process. Impaired cognitive functioning associated with BD may contribute significantly to functional disability, in addition to the distorted affective component usually emphasized.

"Don't Look Now": The Role of Self-Focus in Sexual Dysfunction.

ERIC Educational Resources Information Center

Wiederman, Michael W.

2001-01-01

Couples and family counselors may aid in the remedy of sexual dysfunction when it has a cognitive or psychological basis. One important source of sexual dysfunction is cognitive distraction that results from certain forms of self-focus during sexual activity with a partner, a phenomenon sex therapists have labeled spectatoring. Introduces sensate…

A comprehensive assessment of cognitive function in the common genetic generalized epilepsy syndromes.

PubMed

Loughman, A; Bowden, S C; D'Souza, W J

2017-03-01

Considered to be benign conditions, the common genetic generalized epilepsy (GGE) syndromes are now known to be frequently accompanied by cognitive dysfunction. However, unresolved issues impede clinical management of this common comorbidity, including which cognitive abilities are most affected, whether there are differences between syndromes and how seizure type and mood symptoms affect cognitive dysfunction. We provide a detailed description of cognitive ability and evaluate factors contributing to cognitive dysfunction. A total of 76 adults with GGE were assessed with the Woodcock Johnson III Tests of Cognitive Abilities. Scores on tests of overall cognitive ability, acquired knowledge, long-term retrieval and speed of information processing were significantly below the normative mean. Long-term retrieval was a pronounced weakness with a large reduction in scores (d = 0.84). GGE syndrome, seizure type and the presence of recent psychopathology symptoms were not significantly associated with cognitive function. This study confirms previous meta-analytic findings with a prospective study, offers new insights into the cognitive comorbidity of these common epilepsy syndromes and reinforces the need for cognitive interventions in people with GGE. © 2016 EAN.

Cognitive Developmental Therapy: Aiding Adult Children of Dysfunctional Families.

ERIC Educational Resources Information Center

Towers, David A.

The works of Kegan and Guidano have presented cognition and emotion as complementary modes of knowing that develop together. Cognition is conceived of as being concerned with the knowledge of reality, and emotions are conceptualized as people's system for knowing of their relationship to that reality. Adult children of dysfunctional families are a…

Diet and exercise orthogonally alter the gut microbiome and reveal independent associations with anxiety and cognition

PubMed Central

2014-01-01

Background The ingestion of a high-fat diet (HFD) and the resulting obese state can exert a multitude of stressors on the individual including anxiety and cognitive dysfunction. Though many studies have shown that exercise can alleviate the negative consequences of a HFD using metabolic readouts such as insulin and glucose, a paucity of well-controlled rodent studies have been published on HFD and exercise interactions with regard to behavioral outcomes. This is a critical issue since some individuals assume that HFD-induced behavioral problems such as anxiety and cognitive dysfunction can simply be exercised away. To investigate this, we analyzed mice fed a normal diet (ND), ND with exercise, HFD diet, or HFD with exercise. Results We found that mice on a HFD had robust anxiety phenotypes but this was not rescued by exercise. Conversely, exercise increased cognitive abilities but this was not impacted by the HFD. Given the importance of the gut microbiome in shaping the host state, we used 16S rRNA hypervariable tag sequencing to profile our cohorts and found that HFD massively reshaped the gut microbial community in agreement with numerous published studies. However, exercise alone also caused massive shifts in the gut microbiome at nearly the same magnitude as diet but these changes were surprisingly orthogonal. Additionally, specific bacterial abundances were directly proportional to measures of anxiety or cognition. Conclusions Thus, behavioral domains and the gut microbiome are both impacted by diet and exercise but in unrelated ways. These data have important implications for obesity research aimed at modifications of the gut microbiome and suggest that specific gut microbes could be used as a biomarker for anxiety or cognition or perhaps even targeted for therapy. PMID:25217888

Rational pharmacological approaches for cognitive dysfunction and depression in Parkinson's disease.

PubMed

Sandoval-Rincón, Maritza; Sáenz-Farret, Michel; Miguel-Puga, Adán; Micheli, Federico; Arias-Carrión, Oscar

2015-01-01

Parkinson's disease (PD) is not a single entity but rather a heterogeneous neurodegenerative disorder. The present study aims to conduct a critical systematic review of the literature to describe the main pharmacological strategies to treat cognitive dysfunction and major depressive disorder in PD patients. We performed a search of articles cited in PubMed from 2004 to 2014 using the following MeSH terms (Medical subject headings) "Parkinson disease"; "Delirium," "Dementia," "Amnestic," "Cognitive disorders," and "Parkinson disease"; "depression," "major depressive disorder," "drug therapy." We found a total of 71 studies related to pharmacological treatment in cognitive dysfunction and 279 studies for pharmacological treatment in major depressive disorder. After fulfillment of all the inclusion and exclusion criteria, 13 articles remained for cognitive dysfunction and 11 for major depressive disorder, which are presented and discussed in this study. Further research into non-motor symptoms of PD may provide insights into mechanisms of neurodegeneration, and provide better quality of life by using rational drugs.

Mood state dependency of dysfunctional attitudes in bipolar affective disorder.

PubMed

Babakhani, Anet; Startup, Mike

2012-01-01

Studies of cognitive styles among euthymic people with bipolar affective disorder (BAD) without use of mood induction techniques to access those cognitive styles give misleading impressions of normality of those cognitions. The aim of this study was to assess dysfunctional attitudes of participants with BAD, and control participants with no previous psychiatric histories, after mood inductions. Sad and happy moods were induced within 49 BAD and 37 controls. Dysfunctional attitudes were measured following mood inductions using the Dysfunctional Attitude Scale-short form (DAS-24), which has three subscales of achievement, interpersonal, and goal attainment. It was hypothesised that within BAD the sad mood induction would help in accessing dysfunctional attitudes in all three domains relative to the happy mood induction. This was supported. It was also hypothesised that the mood inductions would not affect dysfunctional attitudes within controls. This was supported. When diagnosis was entered as a between group variable, achievement dysfunctional attitudes were significantly higher in BAD compared to controls after a happy induction. Both sad and happy moods provoked higher levels of dysfunctional attitudes within BAD. Euphoria may be related to elevated achievement dysfunctional attitudes, raising risk for mania.

Dysfunctional Sensory Modalities, Locus Coeruleus, and Basal Forebrain: Early Determinants that Promote Neuropathogenesis of Cognitive and Memory Decline and Alzheimer's Disease.

PubMed

Daulatzai, Mak Adam

2016-10-01

Sporadic Alzheimer's disease (AD) is a devastating neurodegenerative disorder. It is essential to unravel its etiology and pathogenesis. This should enable us to study the presymptomatic stages of the disease and to analyze and reverse the antemortem behavioral, memory, and cognitive dysfunction. Prima facie, an ongoing chronic vulnerability involving neural insult may lead normal elderly to mild cognitive impairment (MCI) and then to AD. Development of effective preventive and therapeutic strategies to thwart the disease pathology obviously requires a thorough delineation of underlying disruptive neuropathological processes. Our sensory capacity for touch, smell, taste, hearing, and vision declines with advancing age. Declines in different sensory attributes are considered here to be the primary "first-tier pathologies." Olfactory loss is among the first clinical signs of neurodegenerative diseases including AD and Parkinson's disease (PD). Sensory dysfunction in the aged promotes pathological disturbances in the locus coeruleus, basal forebrain, entorhinal cortex, hippocampus, and several key areas of neocortex and brainstem. Hence, sensory dysfunction is the pivotal factor that may upregulate cognitive and memory dysfunction. The age-related constellation of comorbid pathological factors may include apolipoprotein E (APOE) genotype, obesity, diabetes, hypertension, alcohol abuse, head trauma, and obstructive sleep apnea. The concepts and trajectories delineated here are the dynamic pillars of the current hypothesis presented-it postulates that the sensory decline, in conjunction with the above pathologies, is crucial in triggering neurodegeneration and promoting cognitive/memory dysfunction in aging and AD. The application of this thesis can be important in formulating new multifactorial preventive and treatment strategies (suggested here) in order to attenuate cognitive and memory decline and ameliorate pathological dysfunction in aging, MCI, and AD.

[Discipline styles and co-morbid disorders of adolescents with attention deficit hyperactivity disorder: a longitudinal study].

PubMed

Colomer-Diago, Carla; Berenguer-Forner, Carmen; Tárraga-Mínguez, Raúl; Miranda-Casas, Ana

2014-02-24

Problems in cognitive functioning, social and educational development of children with attention deficit hyperactivity disorder (ADHD) continue to be present in adolescence and adulthood. Although the literature shows a significant relationship between the use of dysfunctional discipline methods and severity in the course of ADHD, follow-up studies have been rare. To analyze parenting style and ADHD symptomatology assessed in childhood (time 1) to predict the oppositional behavior and cognitive problems in early adolescence (time 2), and to study, depending on the use of dysfunctional parenting style, the course of oppositional behavior and cognitive problems. Forty-five children with ADHD-combined presentation were assessed in two different moments: time 1 (ages: 6-13) and time 2 (ages: 8-16). Oppositionism and cognitive problems in the follow-up were predicted by dysfunctional discipline styles and ADHD severity (assessed in time 1). Oppositional behavior increased between time 1 and time 2 in children with a dysfunctional parenting, whereas a decrease on oppositional symptoms was observed in the functional parenting group (time x discipline interaction effect). Dysfunctional parenting practices in childhood predicted cognitive and behavioral problems associated in adolescence. The findings have implications for the planning of interventions.

Efficiently Assessing Negative Cognition in Depression: An Item Response Theory Analysis of the Dysfunctional Attitude Scale

ERIC Educational Resources Information Center

Beevers, Christopher G.; Strong, David R.; Meyer, Bjorn; Pilkonis, Paul A.; Miller, Ivan R.

2007-01-01

Despite a central role for dysfunctional attitudes in cognitive theories of depression and the widespread use of the Dysfunctional Attitude Scale, form A (DAS-A; A. Weissman, 1979), the psychometric development of the DAS-A has been relatively limited. The authors used nonparametric item response theory methods to examine the DAS-A items and…

Early-Stage Visual Processing and Cortical Amplification Deficits in Schizophrenia

PubMed Central

Butler, Pamela D.; Zemon, Vance; Schechter, Isaac; Saperstein, Alice M.; Hoptman, Matthew J.; Lim, Kelvin O.; Revheim, Nadine; Silipo, Gail; Javitt, Daniel C.

2005-01-01

Background Patients with schizophrenia show deficits in early-stage visual processing, potentially reflecting dysfunction of the magnocellular visual pathway. The magnocellular system operates normally in a nonlinear amplification mode mediated by glutamatergic (N-methyl-d-aspartate) receptors. Investigating magnocellular dysfunction in schizophrenia therefore permits evaluation of underlying etiologic hypotheses. Objectives To evaluate magnocellular dysfunction in schizophrenia, relative to known neurochemical and neuroanatomical substrates, and to examine relationships between electrophysiological and behavioral measures of visual pathway dysfunction and relationships with higher cognitive deficits. Design, Setting, and Participants Between-group study at an inpatient state psychiatric hospital and out-patient county psychiatric facilities. Thirty-three patients met DSM-IV criteria for schizophrenia or schizoaffective disorder, and 21 nonpsychiatric volunteers of similar ages composed the control group. Main Outcome Measures (1) Magnocellular and parvocellular evoked potentials, analyzed using nonlinear (Michaelis-Menten) and linear contrast gain approaches; (2) behavioral contrast sensitivity measures; (3) white matter integrity; (4) visual and nonvisual neuropsychological measures, and (5) clinical symptom and community functioning measures. Results Patients generated evoked potentials that were significantly reduced in response to magnocellular-biased, but not parvocellular-biased, stimuli (P=.001). Michaelis-Menten analyses demonstrated reduced contrast gain of the magnocellular system (P=.001). Patients showed decreased contrast sensitivity to magnocellular-biased stimuli (P<.001). Evoked potential deficits were significantly related to decreased white matter integrity in the optic radiations (P<.03). Evoked potential deficits predicted impaired contrast sensitivity (P=.002), which was in turn related to deficits in complex visual processing (P≤.04). Both evoked potential (P≤.04) and contrast sensitivity (P=.01) measures significantly predicted community functioning. Conclusions These findings confirm the existence of early-stage visual processing dysfunction in schizophrenia and provide the first evidence that such deficits are due to decreased nonlinear signal amplification, consistent with glutamatergic theories. Neuroimaging studies support the hypothesis of dysfunction within low-level visual pathways involving thalamocortical radiations. Deficits in early-stage visual processing significantly predict higher cognitive deficits. PMID:15867102

Counterfactual Thinking Deficit in Huntington’s Disease

PubMed Central

Solca, Federica; Poletti, Barbara; Zago, Stefano; Crespi, Chiara; Sassone, Francesca; Lafronza, Annalisa; Maraschi, Anna Maria; Sassone, Jenny; Silani, Vincenzo; Ciammola, Andrea

2015-01-01

Background and Objective Counterfactual thinking (CFT) refers to the generation of mental simulations of alternatives to past events, actions and outcomes. CFT is a pervasive cognitive feature in every-day life and is closely related to decision-making, planning and problem-solving – all of which are cognitive processes linked to unimpaired frontal lobe functioning. Huntington’s Disease (HD) is a neurodegenerative disorder characterised by motor, behavioral and cognitive dysfunctions. Because an impairment in frontal and executive functions has been described in HD, we hypothesised that HD patients may have a CFT impairment. Methods Tests of spontaneous counterfactual thoughts and counterfactual-derived inferences were administered to 24 symptomatic HD patients and 24 age- and sex-matched healthy subjects. Results Our results show a significant impairment in the spontaneous generation of CFT and low performance on the Counterfactual Inference Test (CIT) in HD patients. Low performance on the spontaneous CFT test significantly correlates with impaired attention abilities, verbal fluency and frontal lobe efficiency, as measured by Trail Making Test – Part A, Phonemic Verbal Fluency Test and FAB. Conclusions Spontaneous CFT and the use of this type of reasoning are impaired in HD patients. This deficit may be related to frontal lobe dysfunction, which is a hallmark of HD. Because CFT has a pervasive role in patients’ daily lives regarding their planning, decision making and problem solving skills, cognitive rehabilitation may improve HD patients’ ability to analyse current behaviors and future actions. PMID:26070155

Acute transient cognitive dysfunction and acute brain injury induced by systemic inflammation occur by dissociable IL-1-dependent mechanisms.

PubMed

Skelly, Donal T; Griffin, Éadaoin W; Murray, Carol L; Harney, Sarah; O'Boyle, Conor; Hennessy, Edel; Dansereau, Marc-Andre; Nazmi, Arshed; Tortorelli, Lucas; Rawlins, J Nicholas; Bannerman, David M; Cunningham, Colm

2018-06-06

Systemic inflammation can impair cognition with relevance to dementia, delirium and post-operative cognitive dysfunction. Episodes of delirium also contribute to rates of long-term cognitive decline, implying that these acute events induce injury. Whether systemic inflammation-induced acute dysfunction and acute brain injury occur by overlapping or discrete mechanisms remains unexplored. Here we show that systemic inflammation, induced by bacterial LPS, produces both working-memory deficits and acute brain injury in the degenerating brain and that these occur by dissociable IL-1-dependent processes. In normal C57BL/6 mice, LPS (100 µg/kg) did not affect working memory but impaired long-term memory consoliodation. However prior hippocampal synaptic loss left mice selectively vulnerable to LPS-induced working memory deficits. Systemically administered IL-1 receptor antagonist (IL-1RA) was protective against, and systemic IL-1β replicated, these working memory deficits. Dexamethasone abolished systemic cytokine synthesis and was protective against working memory deficits, without blocking brain IL-1β synthesis. Direct application of IL-1β to ex vivo hippocampal slices induced non-synaptic depolarisation and irrevesible loss of membrane potential in CA1 neurons from diseased animals and systemic LPS increased apoptosis in the degenerating brain, in an IL-1RI -/- -dependent fashion. The data suggest that LPS induces working memory dysfunction via circulating IL-1β but direct hippocampal action of IL-1β causes neuronal dysfunction and may drive neuronal death. The data suggest that acute systemic inflammation produces both reversible cognitive deficits, resembling delirium, and acute brain injury contributing to long-term cognitive impairment but that these events are mechanistically dissociable. These data have significant implications for management of cognitive dysfunction during acute illness.

Dysfunctions of decision-making and cognitive control as transdiagnostic mechanisms of mental disorders: advances, gaps, and needs in current research.

PubMed

Goschke, Thomas

2014-01-01

Disadvantageous decision-making and impaired volitional control over actions, thoughts, and emotions are characteristics of a wide range of mental disorders such as addiction, eating disorders, depression, and anxiety disorders and may reflect transdiagnostic core mechanisms and possibly vulnerability factors. Elucidating the underlying neurocognitive mechanisms is a precondition for moving from symptom-based to mechanism-based disorder classifications and ultimately mechanism-targeted interventions. However, despite substantial advances in basic research on decision-making and cognitive control, there are still profound gaps in our current understanding of dysfunctions of these processes in mental disorders. Central unresolved questions are: (i) to which degree such dysfunctions reflect transdiagnostic mechanisms or disorder-specific patterns of impairment; (ii) how phenotypical features of mental disorders relate to dysfunctional control parameter settings and aberrant interactions between large-scale brain systems involved in habit and reward-based learning, performance monitoring, emotion regulation, and cognitive control; (iii) whether cognitive control impairments are consequences or antecedent vulnerability factors of mental disorders; (iv) whether they reflect generalized competence impairments or context-specific performance failures; (v) whether not only impaired but also chronic over-control contributes to mental disorders. In the light of these gaps, needs for future research are: (i) an increased focus on basic cognitive-affective mechanisms underlying decision and control dysfunctions across disorders; (ii) longitudinal-prospective studies systematically incorporating theory-driven behavioural tasks and neuroimaging protocols to assess decision-making and control dysfunctions and aberrant interactions between underlying large-scale brain systems; (iii) use of latent-variable models of cognitive control rather than single tasks; (iv) increased focus on the interplay of implicit and explicit cognitive-affective processes; (v) stronger focus on computational models specifying neurocognitive mechanisms underlying phenotypical expressions of mental disorders. Copyright © 2013 John Wiley & Sons, Ltd.

Maternal depressive symptoms, dysfunctional cognitions, and infant night waking: the role of maternal nighttime behavior.

PubMed

Teti, Douglas M; Crosby, Brian

2012-01-01

Mechanisms were examined to clarify relations between maternal depressive symptoms, dysfunctional cognitions, and infant night waking among 45 infants (1-24 months) and their mothers. A mother-driven mediational model was tested in which maternal depressive symptoms and dysfunctional cognitions about infant sleep predicted infant night waking via their impact on mothers' bedtime and nighttime behavior with infants (from video). Two infant-driven mediational models were also examined, in which infant night waking predicted maternal depressive symptoms, or dysfunctional cognitions, via their impact on nighttime maternal behavior. Stronger support for the mother-driven model was obtained, which was further supported by qualitative observations from video-recordings. This study provides important insights about maternal depression's effects on nighttime parenting, and how such parenting affects infant sleep. © 2012 The Authors. Child Development © 2012 Society for Research in Child Development, Inc.

Multi-Modal Hallucinations and Cognitive Function in Parkinson's Disease

PubMed Central

Katzen, Heather; Myerson, Connie; Papapetropoulos, Spiridon; Nahab, Fatta; Gallo, Bruno; Levin, Bonnie

2010-01-01

Background/Aims Hallucinations have been linked to a constellation of cognitive deficits in Parkinson's disease (PD), but it is not known whether multi-modal hallucinations are associated with greater neuropsychological dysfunction. Methods 152 idiopathic PD patients were categorized based on the presence or absence of hallucinations and then were further subdivided into visual-only (VHonly; n = 35) or multi-modal (VHplus; n = 12) hallucination groups. All participants underwent detailed neuropsychological assessment. Results Participants with hallucinations performed more poorly on select neuropsychological measures and exhibited more mood symptoms. There were no differences between VHonly and VHplus groups. Conclusions PD patients with multi-modal hallucinations are not at greater risk for neuropsychological impairment than those with single-modal hallucinations. PMID:20689283

Objective Cognitive Functioning in Self-reported Habitual Short Sleepers not Reporting Daytime Dysfunction: Examination of Impulsivity via Delay Discounting.

PubMed

Curtis, Brian J; Williams, Paula G; Anderson, Jeffrey S

2018-05-30

1) Examine performance on an objective measure of reward-related cognitive impulsivity (delay discounting) among self-reported habitual short sleepers and medium (i.e., recommended 7-9 hours) length sleepers either reporting or not reporting daytime dysfunction; 2) Inform the debate regarding what type and duration of short sleep (e.g., 21 to 24 hours of total sleep deprivation, self-reported habitual short sleep duration) meaningfully influences cognitive impulsivity; 3) Compare the predictive utility of sleep duration and perceived dysfunction to other factors previously shown to influence cognitive impulsivity via delay discounting performance (age, income, education, and fluid intelligence). We analyzed data from 1,190 adults from the Human Connectome Project database. Participants were grouped on whether they reported habitual short (≤ 6 hours) vs. medium length (7-9 hours) sleep duration and whether they perceived daytime dysfunction using the Pittsburgh Sleep Quality Index. All short sleepers exhibited increased delay discounting compared to all medium length sleepers, regardless of perceived dysfunction. Of the variables examined, self-reported sleep duration was the strongest predictor of delay discounting behavior between groups and across all 1,190 participants. Individuals who report habitual short sleep are likely to exhibit increased reward-related cognitive impulsivity regardless of perceived sleep-related daytime impairment. Therefore, there is reason to suspect that these individuals exhibit more daytime dysfunction, in the form of reward-related cognitive impulsivity, than they may assume. Current findings suggest that assessment of sleep duration over the prior month has meaningful predictive utility for human reward-related impulsivity.

Gap junctional intercellular communication dysfunction mediates the cognitive impairment induced by cerebral ischemia-reperfusion injury: PI3K/Akt pathway involved.

PubMed

Zhou, Shujun; Fang, Zheng; Wang, Gui; Wu, Song

2017-01-01

Cerebral ischemia/reperfusion (I/R) injury causes hippocampal apoptosis and cognitive impairment, and the dysfunction of gap junction intercellular communication (GJIC) may contribute to the cognitive impairment. We aim to examine the impact of cerebral I/R injury on cognitive impairment, the role of GJIC dysfunction in the rat hippocampus and the involvement of the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) pathway. Rats were subjected to a cerebral I/R procedure and underwent cognitive assessment with the novel object recognition and Morris Water Maze tasks. The distance of Lucifer Yellow dye transfer and the Cx43 protein were examined to measure GJIC. Neural apoptosis was assessed with the terminal deoxynucleotide-transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) method. After rats received inhibitors of the PI3K/Akt pathway, GJIC and cognitive ability were measured again. GJIC promotion by ZP123 significantly reversed cognitive impairment and hippocampal apoptosis induced by cerebral I/R, while the inhibition of GJIC by octanol significantly facilitated cognitive impairment and hippocampal apoptosis. The phosphorylation of Akt was enhanced by cerebral I/R and octanol but inhibited by ZP123. The inhibition of the PI3K/Akt pathway significantly suppressed GJIC and cognitive impairment. The PI3K/Akt pathway is involved in cognitive impairment caused by gap junctional communication dysfunction in the rat hippocampus after ischemia-reperfusion injury.

PTSD symptom severity relates to cognitive and psycho-social dysfunctioning – a study with Congolese refugees in Uganda

PubMed Central

Ainamani, Herbert E.; Elbert, Thomas; Olema, David K.; Hecker, Tobias

2017-01-01

ABSTRACT Background: In the ongoing conflict in the Democratic Republic of the Congo (DRC), civilians have been heavily exposed to traumatic stressors. Traumatizing experiences cumulatively heighten the risk for trauma-related disorders, and with it affect cognitive and psycho-social functioning. Objectives: We aimed at investigating the association between trauma-related disorders and cognitive and psycho-social functioning and hypothesized that PTSD symptom severity would negatively correlate with executive functioning, working memory and psycho-social functioning in everyday life. Method: In total, 323 Congolese refugees (mean age: 31.3 years) who arrived in the Ugandan Nakivale refugee settlement after January 2012 were assessed regarding their exposure to traumatic events, PTSD symptom severity (posttraumatic symptom scale interview), executive functioning (Tower of London), working memory performance (Corsi block tapping task) and psycho-social dysfunctioning (Luo functioning scale). Results: Hierarchical regression analyses indicated a significant negative association between PTSD symptom severity and working memory (β = –0.32, p < 0.001), as well as executive functions (β = –0.19, p = 0.003). Furthermore, the impairment of psycho-social functioning in everyday life was positively related with PTSD symptom severity (β = 0.70, p < 0.001), and negatively with executive functioning (β = –0.15, p = 0.003). However, working memory performance was not significantly related to psycho-social dysfunctioning (β = 0.09, p > 0.05). Conclusion: Trauma survivors not only suffer from the core PTSD symptoms but also from impaired cognitive functioning. PTSD symptom severity seems furthermore to be related to impaired psycho-social functioning. Our findings suggest that trauma-related mental health problems may heighten the risk for poverty and lack of prospect and further aggravate the consequences of war and conflict. PMID:28326164

Psychometric Properties of the German Version of the Child Post-Traumatic Cognitions Inventory (CPTCI-GER).

PubMed

de Haan, Anke; Petermann, Franz; Meiser-Stedman, Richard; Goldbeck, Lutz

2016-02-01

Dysfunctional trauma-related cognitions are associated with posttraumatic stress disorder (PTSD). The psychometric properties of the German version of the Child Post-Traumatic Cognitions Inventory (CPTCI-GER) were assessed in a sample of 223 children and adolescents (7-16 years) with a history of different traumatic events. Confirmatory factor analyses supported the original two-factor structure--permanent and disturbing change (CPTCI-PC) and fragile person in a scary world (CPTCI-SW). The total scale and both subscales showed good internal consistency. Participants with PTSD had significantly more dysfunctional trauma-related cognitions than those without PTSD. Dysfunctional posttraumatic cognitions correlated significantly with posttraumatic stress symptoms (PTSS; r = .62), depression (r = .71), and anxiety (r = .67). The CPTCI-GER has good psychometric properties and may facilitate evaluation of treatments and further research on the function of trauma-related cognitions in children and adolescents. (Partial) correlations provide empirical support for the combined DSM-5 symptom cluster negative alterations in cognitions and mood.

The influence of personality and dysfunctional sleep-related cognitions on the severity of insomnia.

PubMed

Park, Jang Ho; An, Hoyoung; Jang, Eun Sook; Chung, Seockhoon

2012-05-30

Previous findings suggest that personality traits and dysfunctional sleep-related cognitions may perpetuate insomnia, but findings concerning this have been scarce. Thus, we hypothesized that personality and sleep-related cognitions influence the severity of insomnia, and investigated the association personality and sleep-related cognitions had with various sleep-related parameters, including severity of insomnia. Forty-four patients with psychophysiological insomnia were assessed using The Temperament and Character Inventory, the Insomnia Severity Index, the Pittsburgh Sleep Quality Index, the Epworth Sleepiness Scale, the Dysfunctional Belief and Attitudes toward Sleep Scale, the Pre-Sleep Arousal Scale and the Hospital Anxiety and Depression Scale. Insomnia severity was significantly and positively correlated with harm avoidance, self-transcendence and sleep-related cognitions, and negatively correlated with novelty seeking, reward dependence, and cooperativeness. Dysfunctional sleep-related cognitions were positively correlated with insomnia severity and sleep quality. Stepwise multiple regression analysis showed that sleep-related cognitions, depression and reward dependence scores were significant determinants of insomnia severity, and that sleep-related cognitions and self-transcendence were significant positive determinants of sleep quality. Reward dependence, depression and sleep-related cognitions were associated with insomnia severity, and comparison with previous findings implied that 'internalizing behavior' and depression may be more plausible candidates for the link between personality and insomnia than anxiety. Considering the major role of cognitive-behavioral treatment (CBT) in the treatment of insomnia, assessment of these factors and management of sleep-related cognitions may help alleviate symptoms in patients with insomnia. Copyright © 2011 Elsevier Ltd. All rights reserved.

Age Effects on Cognitive and Physiological Parameters in Familial Caregivers of Alzheimer's Disease Patients

PubMed Central

Corrêa, Márcio Silveira; Giacobbo, Bruno Lima; Vedovelli, Kelem; de Lima, Daiane Borba; Ferrari, Pamela; Argimon, Irani Iracema de Lima; Walz, Julio Cesar

2016-01-01

Objectives Older familial caregivers of Alzheimer’s disease patients are subjected to stress-related cognitive and psychophysiological dysfunctions that may affect their quality of life and ability to provide care. Younger caregivers have never been properly evaluated. We hypothesized that they would show qualitatively similar cognitive and psychophysiological alterations to those of older caregivers. Method The cognitive measures of 17 young (31–58 years) and 18 old (63–84 years) caregivers and of 17 young (37–57 years) and 18 old (62–84 years) non-caregiver controls were evaluated together with their salivary cortisol and dehydroepiandrosterone (DHEA) levels, as measured by radioimmunoassays and ELISA assays of brain-derived neurotrophic factor (BDNF) in serum. Results Although younger caregivers had milder impairments in memory and executive functions than older caregivers, their performances fell to the same or lower levels as those of the healthy older controls. Decreases in DHEA and BDNF levels were correlated with the cognitive dysfunctions observed in the older and younger caregivers, respectively. Cortisol at 10PM increased in both caregiver groups. Discussion Younger caregivers were prone to cognitive impairments similar to older caregivers, although the degree and the neuropsychological correlates of the cognitive dysfunctions were somewhat different between the two groups. This work has implications for caregiver and care-recipient health and for research on the neurobiology of stress-related cognitive dysfunctions. PMID:27706235

Dependent, but not Perfectionistic, Dysfunctional Attitudes Predict Worsened Mood and Appraisals after Emotional Support from a Romantic Partner

PubMed Central

Felix, Steven A. M.; Hooker, Christine I.

2016-01-01

Background: Receiving emotional support from a romantic partner often leads to emotional costs via negative appraisals about the self and one's relationship, but it is unclear whether certain individuals are more susceptible to these costs. We evaluate whether the presence of perfectionistic and dependent dysfunctional attitudes leads to more negative effects of receiving emotional support from a romantic partner. Methods: Twenty-nine couples (27 men, 31 women; mean age 24.5) completed the Dysfunctional Attitudes Scale and then a daily online questionnaire by recording their mood, appraisals, and received emotional support. Mixed-effects regressions were used to evaluate whether perfectionistic and dependent dysfunctional attitudes moderated the relationship between emotional support receipt and subsequent mood and appraisals. Results: Perfectionism did not interact with emotional support but exerted a main effect of increasing negative moods and appraisals. Dependency interacted with emotional support such that those with more dependent attitudes reported greater negative next-day moods and appraisals as a function of emotional support. Conclusions: Individuals with dependent, but not perfectionistic, dysfunctional attitudes are more likely to experience emotional and cognitive costs after receiving emotional support. These costs may stem from activation or exacerbation of the attitudes specific to dependency, including need for acceptance, support, and approval of others. PMID:27790161

Rational Pharmacological Approaches for Cognitive Dysfunction and Depression in Parkinson’s Disease

PubMed Central

Sandoval-Rincón, Maritza; Sáenz-Farret, Michel; Miguel-Puga, Adán; Micheli, Federico; Arias-Carrión, Oscar

2015-01-01

Parkinson’s disease (PD) is not a single entity but rather a heterogeneous neurodegenerative disorder. The present study aims to conduct a critical systematic review of the literature to describe the main pharmacological strategies to treat cognitive dysfunction and major depressive disorder in PD patients. We performed a search of articles cited in PubMed from 2004 to 2014 using the following MeSH terms (Medical subject headings) “Parkinson disease”; “Delirium,” “Dementia,” “Amnestic,” “Cognitive disorders,” and “Parkinson disease”; “depression,” “major depressive disorder,” “drug therapy.” We found a total of 71 studies related to pharmacological treatment in cognitive dysfunction and 279 studies for pharmacological treatment in major depressive disorder. After fulfillment of all the inclusion and exclusion criteria, 13 articles remained for cognitive dysfunction and 11 for major depressive disorder, which are presented and discussed in this study. Further research into non-motor symptoms of PD may provide insights into mechanisms of neurodegeneration, and provide better quality of life by using rational drugs. PMID:25873910

Applying a cognitive neuroscience perspective to the disorder of psychopathy.

PubMed

Blair, R J R

2005-01-01

Four models of psychopathy (frontal lobe dysfunction, response set modulation, fear dysfunction, and violence inhibition mechanism hypotheses) are reviewed from the perspective of cognitive neuroscience. Each model is considered both with respect to the psychopathy data and, more importantly, for the present purposes, with respect to the broader cognitive neuroscience fields to which the model refers (e.g., models of attention with respect to the response set modulation account and models of emotion with respect to the fear dysfunction and violence inhibition mechanism models). The paper concludes with an articulation of the more recent integrated emotion systems model, an account inspired both by recent findings in affective cognitive neuroscience as well as in the study of psychopathy. Some directions for future work are considered.

Cognitive Dysfunction in Major Depressive Disorder. A Translational Review in Animal Models of the Disease

PubMed Central

Darcet, Flavie; Gardier, Alain M.; Gaillard, Raphael; David, Denis J.; Guilloux, Jean-Philippe

2016-01-01

Major Depressive Disorder (MDD) is the most common psychiatric disease, affecting millions of people worldwide. In addition to the well-defined depressive symptoms, patients suffering from MDD consistently complain about cognitive disturbances, significantly exacerbating the burden of this illness. Among cognitive symptoms, impairments in attention, working memory, learning and memory or executive functions are often reported. However, available data about the heterogeneity of MDD patients and magnitude of cognitive symptoms through the different phases of MDD remain difficult to summarize. Thus, the first part of this review briefly overviewed clinical studies, focusing on the cognitive dysfunctions depending on the MDD type. As animal models are essential translational tools for underpinning the mechanisms of cognitive deficits in MDD, the second part of this review synthetized preclinical studies observing cognitive deficits in different rodent models of anxiety/depression. For each cognitive domain, we determined whether deficits could be shared across models. Particularly, we established whether specific stress-related procedures or unspecific criteria (such as species, sex or age) could segregate common cognitive alteration across models. Finally, the role of adult hippocampal neurogenesis in rodents in cognitive dysfunctions during MDD state was also discussed. PMID:26901205

Cognitive performance of people with traumatic spinal cord injury: a cross-sectional study comparing people with subacute and chronic injuries.

PubMed

Molina, B; Segura, A; Serrano, J P; Alonso, F J; Molina, L; Pérez-Borrego, Y A; Ugarte, M I; Oliviero, A

2018-02-22

Cross-sectional study. To assess the impact of spinal cord injury (SCI) on cognitive function in individuals with subacute and chronic SCI. National Hospital for SCI patients (Spain). The present investigation was designed to determine the nature, pattern, and extent of cognitive deficits in a group of participants with subacute (n = 32) and chronic (n = 34) SCI, using a comprehensive battery of reliable and validated neuropsychological assessments to study a broad range of cognitive functions. Twenty-seven able-bodied subjects matched to the groups with SCI for age and educational level formed the control group. The neuropsychological assessment showed alterations in the domain of attention, processing speed, memory and learning, executive functions, and in recognition in participants with SCI. The prevalence of cognitive dysfunction in the chronic stage was also confirmed at the individual level. The comparison of the neuropsychological assessment between the groups with subacute and chronic SCI showed a worsening of cognitive functions in those with chronic SCI compared to the group with subacute SCI. In participants with SCI, cognitive dysfunctions are present in the subacute stage and worsen over time. From a clinical point of view, we confirmed the presence of cognitive dysfunction that may interfere with the first stage of rehabilitation which is the most intense and important. Moreover, cognitive dysfunction may be important beyond the end of the first stage of rehabilitation as it can affect an individual's quality of life and possible integration to society.

Maintaining a balance: a focus group study on living and coping with chronic whiplash-associated disorder

PubMed Central

2010-01-01

Background There is little qualitative insight into how persons with chronic Whiplash-Associated Disorder cope on a day to day basis. This study seeks to identify the symptoms persons with Whiplash-Associated Disorder describe as dominating and explore their self-initiated coping strategies. Methods Qualitative study using focus groups interviews. Fourteen Norwegian men and women with Whiplash-Associated Disorder (I or II) were recruited to participate in two focus groups. Data were analyzed according to a phenomenological approach, and discussed within the model of Cognitive Activation Theory of Stress (CATS). Results Participants reported neck and head pain, sensory hypersensitivity, and cognitive dysfunction following their whiplash injury. Based on the intensity of symptoms, participants divided everyday life into good and bad periods. In good periods the symptoms were perceived as manageable. In bad periods the symptoms intensified and took control of the individual. Participants expressed a constant notion of trying to balance their three main coping strategies; rest, exercise, and social withdrawal. In good periods participants experienced coping by expecting good results from the strategies they used. In bad periods they experienced no or negative relationships between their behavioral strategies and their complaints. Conclusions Neck and head pain, sensory hypersensitivity, and cognitive dysfunction were reported as participants' main complaints. A constant notion of balancing between their three main coping strategies; rest, exercise, and social withdrawal, was described. PMID:20626855

Malva Sylvestris Attenuates Cognitive Deficits in a Repetitive Mild Traumatic Brain Injury Rat Model by Reducing Neuronal Degeneration and Astrocytosis in the Hippocampus

PubMed Central

Qin, Hailin; Qin, Jie; Hu, Junmin; Huang, He; Ma, Lianting

2017-01-01

Background The aim of our study was to evaluate the effect of Malva sylvestris (MS) on cognitive dysfunction in a repetitive mild traumatic brain injury (MTBI). Material/Methods MTBI was induced in all the study animals by hitting a metallic pendulum near the parietal-occipital area of the skull three times a day for ten days. Animals were treated with MS (250 mg/kg and 500 mg/kg) intragastrically per day for seven consecutive days. Cognitive function was estimated by the Morris water maze (MWM) method. Histopathology studies were performed on the hippocampal region by Nissl staining and anti GFAP staining. Concentrations of reactive oxygen species (ROS), and oxidative parameters including superoxide dismutase (SOD), catalase (CAT), and lipid peroxidation (LPO), and inflammatory cytokines in the brain tissues were measured. Result Treatment with MS significantly improved cognitive function compared to the negative control. Histopathology studies suggested that treatment with MS significantly decreased (p<0.01) the count of neurodegenerative cells and induction of astrocytosis in the MTBI treated group compared to the negative control group. However, the concentrations of ROS and LPO, and the activities of SOD and CAT were significantly decreased in the MS treated groups of MTBI rats compared to the negative control group. Inflammatory cytokines, such as IL-1β, IL6, and TNF-α were significantly decreased (p<0.01) in the brain tissues of the MTBI treated group compared to the control group of rats. Conclusions This study concluded that treatment with MS significantly improved cognitive dysfunction by reducing neurodegeneration and astrocytosis in brain tissues via decreasing oxidative stress and inflammation in neuronal cells. PMID:29276216

Butyrylcholinesterase inhibitors ameliorate cognitive dysfunction induced by amyloid-β peptide in mice

PubMed Central

Furukawa-Hibi, Yoko; Alkam, Tursun; Nitta, Atsumi; Matsuyama, Akihiro; Mizoguchi, Hiroyuki; Suzuki, Kazuhiko; Moussaoui, Saliha; Yu, Qian-Sheng; Greig, Nigel H.; Nagai, Taku; Yamada, Kiyofumi

2016-01-01

The cholinesterase inhibitor, rivastigmine, ameliorates cognitive dysfunction and is approved for the treatment of Alzheimer's disease (AD). Rivastigmine is a dual inhibitor of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE); however, the impact of BuChE inhibition on cognitive dysfunction remains to be determined. We compared the effects of a selective BuChE inhibitor, N1-phenethylnorcymserine (PEC), rivastigmine and donepezil (an AChE-selective inhibitor) on cognitive dysfunction induced by amyloid-β peptide (Aβ1–40) in mice. Five-week-old imprinting control region (ICR) mice were injected intracerebroventricularly (i.c.v.) with either Aβ1–40 or the control peptide Aβ40–1 on Day 0, and their recognition memory was analyzed by a novel object recognition test. Treatment with donepezil (1.0 mg/kg), rivastigmine (0.03, 0.1, 0.3 mg/kg) or PEC (1.0, 3.0 mg/kg) 20 min prior to, or immediately after the acquisition session (Day 4) ameliorated the Aβ1–40 induced memory impairment, indicating a beneficial effect on memory acquisition and consolidation. In contrast, none of the investigated drugs proved effective when administrated before the retention session (Day 5). Repeated daily administration of donepezil, rivastigmine or PEC, on Days 0–3 inclusively, ameliorated the cognitive dysfunction in Aβ1–40 challenged mice. Consistent with the reversal of memory impairments, donepezil, rivastigmine or PEC treatment significantly reduced Aβ1–40 induced tyrosine nitration of hippocampal proteins, a marker of oxidative damage. These results indicate that BuChE inhibition, as well as AChE inhibition, is a viable therapeutic strategy for cognitive dysfunction in AD. PMID:21820013

Development and initial validation of a brief self-report measure of cognitive dysfunction in fibromyalgia.

PubMed

Kratz, Anna L; Schilling, Stephen G; Goesling, Jenna; Williams, David A

2015-06-01

Pain is often the focus of research and clinical care in fibromyalgia (FM); however, cognitive dysfunction is also a common, distressing, and disabling symptom in FM. Current efforts to address this problem are limited by the lack of a comprehensive, valid measure of subjective cognitive dysfunction in FM that is easily interpretable, accessible, and brief. The purpose of this study was to leverage cognitive functioning item banks that were developed as part of the Patient Reported Outcomes Measurement Information System (PROMIS) to devise a 10-item short form measure of cognitive functioning for use in FM. In study 1, a nationwide (U.S.) sample of 1,035 adults with FM (age range = 18-82, 95.2% female) completed 2 cognitive item pools. Factor analyses and item response theory analyses were used to identify dimensionality and optimally performing items. A recommended 10-item measure, called the Multidimensional Inventory of Subjective Cognitive Impairment (MISCI) was created. In study 2, 232 adults with FM completed the MISCI and a legacy measure of cognitive functioning that is used in FM clinical trials, the Multiple Ability Self-Report Questionnaire (MASQ). The MISCI showed excellent internal reliability, low ceiling/floor effects, and good convergent validity with the MASQ (r = -.82). This paper presents the MISCI, a 10-item measure of cognitive dysfunction in FM, developed through classical test theory and item response theory. This brief but comprehensive measure shows evidence of excellent construct validity through large correlations with a lengthy legacy measure of cognitive functioning. Copyright © 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.

The role of nonverbal cognitive ability in the association of adverse life events with dysfunctional attitudes and hopelessness in adolescence.

PubMed

Flouri, Eirini; Panourgia, Constantina

2012-10-01

The aim of this study was to test whether nonverbal cognitive ability buffers the effect of life stress (number of adverse life events in the last year) on diatheses for depression. It was expected that, as problem-solving aptitude, nonverbal cognitive ability would moderate the effect of life stress on those diatheses (such as dysfunctional attitudes) that are depressogenic because they represent deficits in information-processing or problem-solving skills, but not on diatheses (such as hopelessness) that are depressogenic because they represent deficits in motivation or effort to apply problem-solving skills. The sample included 558 10- to 19-year-olds from a state secondary school in London. Nonverbal cognitive ability was negatively associated with both dysfunctional attitudes and hopelessness. As expected, nonverbal cognitive ability moderated the association between life adversity and dysfunctional attitudes. However, hopelessness was not related to life stress, and therefore, there was no life stress effect for nonverbal cognitive ability to moderate. This study adds to knowledge about the association between problem-solving ability and depressogenic diatheses. By identifying life stress as a risk factor for dysfunctional attitudes but not hopelessness, it highlights the importance of considering outcome specificity in models predicting adolescent outcomes from adverse life events. Importantly for practice, it suggests that an emphasis on recent life adversity will likely underestimate the true level of hopelessness among adolescents. Copyright © 2012 Elsevier Inc. All rights reserved.

Executive Dysfunction and Depressive Symptoms Associated With Reduced Participation of People With Severe Congestive Heart Failure

PubMed Central

Foster, Erin R.; Cunnane, Kathleen B.; Edwards, Dorothy F.; Morrison, M. Tracy; Ewald, Gregory A.; Geltman, Edward M.; Zazulia, Allyson R.

2011-01-01

OBJECTIVE We investigated participation levels and relationships among cognition, depression, and participation for people with severe congestive heart failure (CHF). METHOD People with severe CHF (New York Heart Association Class III or IV) awaiting heart transplantation (N = 27) completed standardized tests of cognition and self-report measures of executive dysfunction, depressive symptoms, and participation. RESULTS Possible depression (64%) and cognitive impairment (15%–59%) were prevalent. Participants reported significant reductions in participation across all activity domains since CHF diagnosis (ps < .001). Worse executive dysfunction and depressive symptoms were associated with reduced participation and together accounted for 35%–46% of the variance in participation (ps < .01). CONCLUSION Participation restrictions associated with CHF are not limited to physically demanding activities and are significantly associated with executive dysfunction and depression. Cardiac rehabilitation should address cognitive and psychological functioning in the context of all life situations instead of focusing solely on physical function and disability. PMID:21675336

SU33. Load-Sensitive Impairment of Working Memory for Biological Motion in Schizophrenia

PubMed Central

Lee, Hannah; Kim, Jejoong

2017-01-01

Abstract Background: Patients with schizophrenia (SZ) exhibit various deficits that may affect social functioning. The impairments in perceptual processing (eg, motion perception) and in higher cognitive processing such as working memory (WM), as well as deficits in social cognition, need to be closely examined in order to understand dysfunctions in social environments. However, comprehensive research conducted to date that takes these aspects into consideration all together is limited. Biological motion (BM) is a unique motion stimulus containing rich social information. Therefore, BM is optimal for our aim in this study to scrutinize how the dysfunctions in the cognitive processing of aforementioned 3 aspects (motion perception, WM, and social cognition) would be manifested in SZ, in a single experimental design. Methods: In the present study, we used BM in a delayed-response task for measuring WM. Non-BM motion stimulus (pairwise-shuffled motion or PSM) and polygons were also used for comparisons. One of the 3 types of stimuli was presented in each trial. After 12-second delays, 2 probes were shown, and the participants were asked to indicate whether one of them was identical to the memory item or whether both were novel. The number of memory items was either one (low load) or 2 (high load). Results: Overall, SZ performed worse than healthy controls (CO) regardless of the type of stimuli and memory loads, which is consistent with previous WM research. Across the low and high load conditions, CO were more accurate in recognizing BM than PSM, indicating that BM may have a facilitating effect for the encoding process involved in WM. Interestingly, SZ had similar accuracy patterns to that of CO in the low load condition. The BM facilitation effect, however, disappeared in the high load condition, yielding a significant interaction among group, stimulus type, and memory loads. These results suggest that BM, as a socially relevant stimulus, can facilitate encoding and/or maintenance to benefit WM performance in CO and that his effect is also partially valid among SZ. That is, SZ seem to successfully process the meaning of the stimulus when memory load is low. However, the ability is vulnerable to the increase of cognitive load in SZ, implying the presence of inefficiencies in the connections between perceptual and cognitive processes and/or limits in the capacity to process social information. Conclusion: The present study suggests that the intricate interaction among perceptual, cognitive, and social processes needs to be considered to explain cognitive deficits related with social dysfunction in schizophrenia. This study was supported by National Research Foundation of Korea.

Evidence of Cognitive Dysfunction after Soccer Playing with Ball Heading Using a Novel Tablet-Based Approach

PubMed Central

Lin, Angela H.; Patel, Saumil S.; Sereno, Anne B.

2013-01-01

Does frequent head-to-ball contact cause cognitive dysfunctions and brain injury to soccer players? An iPad-based experiment was designed to examine the impact of ball-heading among high school female soccer players. We examined both direct, stimulus-driven, or reflexive point responses (Pro-Point) as well as indirect, goal-driven, or voluntary point responses (Anti-Point), thought to require cognitive functions in the frontal lobe. The results show that soccer players were significantly slower than controls in the Anti-Point task but displayed no difference in Pro-Point latencies, indicating a disruption specific to voluntary responses. These findings suggest that even subconcussive blows in soccer can result in cognitive function changes that are consistent with mild traumatic brain injury of the frontal lobes. There is great clinical and practical potential of a tablet-based application for quick detection and monitoring of cognitive dysfunction. PMID:23460843

Cannabis and cognitive dysfunction: parallels with endophenotypes of schizophrenia?

PubMed

Solowij, Nadia; Michie, Patricia T

2007-01-01

Currently, there is a lot of interest in cannabis use as a risk factor for the development of schizophrenia. Cognitive dysfunction associated with long-term or heavy cannabis use is similar in many respects to the cognitive endophenotypes that have been proposed as vulnerability markers of schizophrenia. In this overview, we examine the similarities between these in the context of the neurobiology underlying cognitive dysfunction, particularly implicating the endogenous cannabinoid system, which plays a significant role in attention, learning and memory, and in general, inhibitory regulatory mechanisms in the brain. Closer examination of the cognitive deficits associated with specific parameters of cannabis use and interactions with neurodevelopmental stages and neural substrates will better inform our understanding of the nature of the association between cannabis use and psychosis. The theoretical and clinical significance of further research in this field is in enhancing our understanding of underlying pathophysiology and improving the provision of treatments for substance use and mental illness.

Counterfactual cognitive deficit in persons with Parkinson's disease

PubMed Central

McNamara, P; Durso, R; Brown, A; Lynch, A

2003-01-01

Background: Counterfactuals are mental representations of alternatives to past events. Recent research has shown them to be important for other cognitive processes, such as planning, causal reasoning, problem solving, and decision making—all processes independently linked to the frontal lobes. Objective: To test the hypothesis that counterfactual thinking is impaired in some patients with Parkinson's disease and is linked to frontal dysfunction in these patients. Methods. Measures of counterfactual processing and frontal lobe functioning were administered to 24 persons with Parkinson's disease and 15 age matched healthy controls. Results. Patients with Parkinson's disease spontaneously generated significantly fewer counterfactuals than controls despite showing no differences from controls on a semantic fluency test; they also performed at chance levels on a counterfactual inference test, while age matched controls performed above chance levels on this test. Performance on both the counterfactual generation and inference tests correlated significantly with performance on two tests traditionally linked to frontal lobe functioning (Stroop colour–word interference and Tower of London planning tasks) and one test of pragmatic social communication skills. Conclusions: Counterfactual thinking is impaired in Parkinson's disease. This impairment may be related to frontal lobe dysfunction. PMID:12876235

Executive dysfunction predicts social cognition impairment in amyotrophic lateral sclerosis.

PubMed

Watermeyer, Tamlyn J; Brown, Richard G; Sidle, Katie C L; Oliver, David J; Allen, Christopher; Karlsson, Joanna; Ellis, Catherine M; Shaw, Christopher E; Al-Chalabi, Ammar; Goldstein, Laura H

2015-07-01

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder of the motor system with recognised extra-motor and cognitive involvement. This cross-sectional study examined ALS patients' performance on measures requiring social inference, and determined the relationship between such changes and variations in mood, behaviour, personality, empathy and executive function. Fifty-five ALS patients and 49 healthy controls were compared on tasks measuring social cognition and executive function. ALS patients also completed measures examining mood, behaviour and personality. Regression analyses explored the contribution of executive function, mood, behaviour and personality to social cognition scores within the ALS sample. A between-group MANOVA revealed that, the ALS group was impaired relative to controls on two composite scores for social cognition and executive function. Patients also performed worse on individual tests of executive function measuring cognitive flexibility, response inhibition and concept formation, and on individual aspects of social cognition assessing the attribution of emotional and mental states. Regression analyses indicated that ALS-related executive dysfunction was the main predictor of social cognition performance, above and beyond demographic variables, behaviour, mood and personality. On at least some aspects of social cognition, impaired performance in ALS appears to be secondary to executive dysfunction. The profile of cognitive impairment in ALS supports a cognitive continuum between ALS and frontotemporal dementia.

Alpha-7 nicotinic agonists for cognitive deficits in neuropsychiatric disorders: A translational meta-analysis of rodent and human studies

PubMed Central

Lewis, Alan S.; van Schalkwyk, Gerrit I.; Bloch, Michael H.

2017-01-01

Cognitive dysfunction in schizophrenia (SCZ) and Alzheimer’s disease (AD) is a major driver of functional disability but is largely unresponsive to current therapeutics. Animal models of cognitive dysfunction relevant to both disorders suggest the α7 nicotinic acetylcholine receptor (nAChR) may be a promising drug development target, with multiple clinical trials subsequently testing this hypothesis in individuals with SCZ and AD. However, the translational value of rodent cognitive tasks for predicting the overall efficacy of this therapeutic target in clinical trials is unknown. To compare effect sizes between rodent and human studies, we searched PubMed and the Cochrane Library for all randomized, placebo-controlled trials of compounds with pharmacological activity at the α7 nAChR for treatment of cognitive dysfunction in SCZ and AD and identified 18 studies comprising 2670 subjects treated with eight different compounds acting as full or partial agonists. Cognitive outcomes were standardized, and random-effects meta-analyses revealed no statistically significant effects of α7 nAChR agonists on overall cognition or any of eight cognitive subdomains when all doses were included (Range of all cognitive outcomes: Cohen’s d = −0.077 to 0.12, negative favoring drug). In contrast, analysis of 29 rodent studies testing the same α7 agonists revealed large effect sizes in multiple commonly used preclinical behavioral tests of cognition (Range: d = −1.18 to −0.73). Our results suggest that targeting the α7 nAChR with agonists is not a robust treatment for cognitive dysfunction in SCZ or AD and necessitate a better understanding of the translational gap for therapeutics targeting the α7 nAChR. PMID:28065843

Comparison of a gratitude-based and cognitive restructuring intervention for body dissatisfaction and dysfunctional eating behavior in college women.

PubMed

Wolfe, Wendy L; Patterson, Kaitlyn

2017-01-01

Researchers have investigated the efficacy of a gratitude intervention for decreasing body dissatisfaction (BD) in an internet treatment-seeking sample and demonstrated it worked equally well to decrease BD as cognitive restructuring. We extend this research by testing the efficacy of a gratitude intervention on BD, along with common sequelae of BD: dysfunctional eating, negative mood, and depressive symptoms. Females were randomly assigned to Gratitude, Cognitive Restructuring, or Control conditions. Pre- to post-intervention period comparisons found the gratitude intervention to perform better than the other conditions at increasing body esteem, decreasing BD, reducing dysfunctional eating, and reducing depressive symptoms.

Adolescent Executive Dysfunction in Daily Life: Relationships to Risks, Brain Structure and Substance Use

PubMed Central

Clark, Duncan B.; Chung, Tammy; Martin, Christopher S.; Hasler, Brant P.; Fitzgerald, Douglas H.; Luna, Beatriz; Brown, Sandra A.; Tapert, Susan F.; Brumback, Ty; Cummins, Kevin; Pfefferbaum, Adolf; Sullivan, Edith V.; Pohl, Kilian M.; Colrain, Ian M.; Baker, Fiona C.; De Bellis, Michael D.; Nooner, Kate B.; Nagel, Bonnie J.

2017-01-01

During adolescence, problems reflecting cognitive, behavioral and affective dysregulation, such as inattention and emotional dyscontrol, have been observed to be associated with substance use disorder (SUD) risks and outcomes. Prior studies have typically been with small samples, and have typically not included comprehensive measurement of executive dysfunction domains. The relationships of executive dysfunction in daily life with performance based testing of cognitive skills and structural brain characteristics, thought to be the basis for executive functioning, have not been definitively determined. The aims of this study were to determine the relationships between executive dysfunction in daily life, measured by the Behavior Rating Inventory of Executive Function (BRIEF), cognitive skills and structural brain characteristics, and SUD risks, including a global SUD risk indicator, sleep quality, and risky alcohol and cannabis use. In addition to bivariate relationships, multivariate models were tested. The subjects (n = 817; ages 12 through 21) were participants in the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) study. The results indicated that executive dysfunction was significantly related to SUD risks, poor sleep quality, risky alcohol use and cannabis use, and was not significantly related to cognitive skills or structural brain characteristics. In multivariate models, the relationship between poor sleep quality and risky substance use was mediated by executive dysfunction. While these cross-sectional relationships need to be further examined in longitudinal analyses, the results suggest that poor sleep quality and executive dysfunction may be viable preventive intervention targets to reduce adolescent substance use. PMID:29180956

Post‐surgical changes in brain metabolism detected by magnetic resonance spectroscopy in normal pressure hydrocephalus: results of a pilot study

PubMed Central

del Mar Matarín, María; Pueyo, Roser; Poca, María Antonia; Falcón, Carles; Mataró, María; Bargalló, Núria; Sahuquillo, Juan; Junqué, Carme

2007-01-01

Background Adult normal pressure hydrocephalus (NPH) is one of the few potentially treatable causes of dementia. Some morphological and functional abnormalities attributed to hydrocephalus improve following treatment. Objectives We focused on analysis of changes in cerebral metabolites using proton magnetic resonance spectroscopy (1H‐MRS) after NPH treatment, and its clinical and cognitive correlation. Methods 1H‐MRS, neuropsychological and clinical status examinations were performed before and 6 months after shunting in 12 adults with idiopathic NPH. We obtained N‐acetyl‐aspartate (NAA), choline (Cho), myoinositol (MI) and creatine (Cr) values. Results After surgery, NAA/Cr was significantly increased. Moreover, NAA/Cr values were related to cognitive deterioration. Conclusion MRS could be a marker of neuronal dysfunction in NPH. PMID:17299021

Abnormal gut microbiota composition contributes to cognitive dysfunction in SAMP8 mice.

PubMed

Zhan, Gaofeng; Yang, Ning; Li, Shan; Huang, Niannian; Fang, Xi; Zhang, Jie; Zhu, Bin; Yang, Ling; Yang, Chun; Luo, Ailin

2018-06-10

Alzheimer's disease is characterized by cognitive dysfunction and aging is an important predisposing factor; however, the pathological and therapeutic mechanisms are not fully understood. Recently, the role of gut microbiota in Alzheimer's disease has received increasing attention. The cognitive function in senescence-accelerated mouse prone 8 (SAMP8) mice was significantly decreased and the Chao 1 and Shannon indices, principal coordinates analysis, and principal component analysis results were notably abnormal compared with that of those in senescence-accelerated mouse resistant 1 (SAMR1) mice. Moreover, 27 gut bacteria at six phylogenetic levels differed between SAMP8 and SAMR1 mice. In a separate study, we transplanted fecal bacteria from SAMP8 or SAMR1 mice into pseudo germ-free mice. Interestingly, the pseudo germ-free mice had significantly lower cognitive function prior to transplant. Pseudo germ-free mice that received fecal bacteria transplants from SAMR1 mice but not from SAMP8 mice showed improvements in behavior and in α-diversity and β-diversity indices. In total, 14 bacteria at six phylogenetic levels were significantly altered by the gut microbiota transplant. These results suggest that cognitive dysfunction in SAMP8 mice is associated with abnormal composition of the gut microbiota. Thus, improving abnormal gut microbiota may provide an alternative treatment for cognitive dysfunction and Alzheimer's disease.

Persistent activation of microglia and NADPH drive hippocampal dysfunction in experimental multiple sclerosis

PubMed Central

Di Filippo, Massimiliano; de Iure, Antonio; Giampà, Carmela; Chiasserini, Davide; Tozzi, Alessandro; Orvietani, Pier Luigi; Ghiglieri, Veronica; Tantucci, Michela; Durante, Valentina; Quiroga-Varela, Ana; Mancini, Andrea; Costa, Cinzia; Sarchielli, Paola; Fusco, Francesca Romana; Calabresi, Paolo

2016-01-01

Cognitive impairment is common in multiple sclerosis (MS). Unfortunately, the synaptic and molecular mechanisms underlying MS-associated cognitive dysfunction are largely unknown. We explored the presence and the underlying mechanism of cognitive and synaptic hippocampal dysfunction during the remission phase of experimental MS. Experiments were performed in a chronic-relapsing experimental autoimmune encephalomyelitis (EAE) model of MS, after the resolution of motor deficits. Immunohistochemistry and patch-clamp recordings were performed in the CA1 hippocampal area. The hole-board was utilized as cognitive/behavioural test. In the remission phase of experimental MS, hippocampal microglial cells showed signs of activation, CA1 hippocampal synapses presented an impaired long-term potentiation (LTP) and an alteration of spatial tests became evident. The activation of hippocampal microglia mediated synaptic and cognitive/behavioural alterations during EAE. Specifically, LTP blockade was found to be caused by the reactive oxygen species (ROS)-producing enzyme nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. We suggest that in the remission phase of experimental MS microglia remains activated, causing synaptic dysfunctions mediated by NADPH oxidase. Inhibition of microglial activation and NADPH oxidase may represent a promising strategy to prevent neuroplasticity impairment associated with active neuro-inflammation, with the aim to improve cognition and counteract MS disease progression. PMID:26887636

Relationship between maladaptive cognitions about sleep and recovery in patients with borderline personality disorder

PubMed Central

Plante, David T.; Frankenburg, Frances R.; Fitzmaurice, Garrett M.; Zanarini, Mary C.

2013-01-01

Borderline personality disorder (BPD) has been associated with maladaptive cognitive processes including dysfunctional attitudes and a negative attribution style. Comorbid insomnia affects the course of multiple psychiatric disorders, and has been associated with absence of recovery from BPD. Because dysfunctional beliefs and attitudes are common among patients with insomnia, the purpose of this study was to evaluate the association between maladaptive sleep-related cognitions and recovery status (symptomatic remission plus good concurrent psychosocial functioning) in patients with BPD. 223 BPD patients participating in the McLean Study of Adult Development (MSAD) were administered the Dysfunctional Beliefs and Attitudes about Sleep questionnaire (DBAS-16) as part of the 16-year follow-up wave. Maladaptive sleep cognitions were compared between recovered (n=105) and non-recovered (n=118) BPD participants, in analyses that adjusted for age, sex, depression, anxiety, and primary sleep disorders. Results demonstrated non-recovered BPD patients had significantly more severe maladaptive sleep-related cognitions as measured by the overall DBAS-16 score. These results demonstrate an association between dysfunctional beliefs and attitudes about sleep and recovery status among BPD patients. Further research is warranted to evaluate treatments targeted towards maladaptive sleep-related cognitions, and their subsequent effects on the course of BPD. PMID:23972789

Cognitive predictors and moderators of winter depression treatment outcomes in cognitive-behavioral therapy vs. light therapy.

PubMed

Sitnikov, Lilya; Rohan, Kelly J; Evans, Maggie; Mahon, Jennifer N; Nillni, Yael I

2013-12-01

There is no empirical basis for determining which seasonal affective disorder (SAD) patients are best suited for what type of treatment. Using data from a parent clinical trial comparing light therapy (LT), cognitive-behavioral therapy (CBT), and their combination (CBT + LT) for SAD, we constructed hierarchical linear regression models to explore baseline cognitive vulnerability constructs (i.e., dysfunctional attitudes, negative automatic thoughts, response styles) as prognostic and prescriptive factors of acute and next winter depression outcomes. Cognitive constructs did not predict or moderate acute treatment outcomes. Baseline dysfunctional attitudes and negative automatic thoughts were prescriptive of next winter treatment outcomes. Participants with higher baseline levels of dysfunctional attitudes and negative automatic thoughts had less severe depression the next winter if treated with CBT than if treated with LT. In addition, participants randomized to solo LT who scored at or above the sample mean on these cognitive measures at baseline had more severe depressive symptoms the next winter relative to those who scored below the mean. Baseline dysfunctional attitudes and negative automatic thoughts did not predict treatment outcomes in participants assigned to solo CBT or CBT + LT. Therefore, SAD patients with extremely rigid cognitions did not fare as well in the subsequent winter if treated initially with solo LT. Such patients may be better suited for initial treatment with CBT, which directly targets cognitive vulnerability processes. Copyright © 2013 Elsevier Ltd. All rights reserved.

Reduced Cardiac Vagal Modulation Impacts on Cognitive Performance in Chronic Fatigue Syndrome

PubMed Central

Beaumont, Alison; Burton, Alexander R.; Lemon, Jim; Bennett, Barbara K.; Lloyd, Andrew; Vollmer-Conna, Uté

2012-01-01

Background Cognitive difficulties and autonomic dysfunction have been reported separately in patients with chronic fatigue syndrome (CFS). A role for heart rate variability (HRV) in cognitive flexibility has been demonstrated in healthy individuals, but this relationship has not as yet been examined in CFS. The objective of this study was to examine the relationship between HRV and cognitive performance in patients with CFS. Methods Participants were 30 patients with CFS and 40 healthy controls; the groups were matched for age, sex, education, body mass index, and hours of moderate exercise/week. Questionnaires were used to obtain relevant medical and demographic information, and assess current symptoms and functional impairment. Electrocardiograms, perceived fatigue/effort and performance data were recorded during cognitive tasks. Between–group differences in autonomic reactivity and associations with cognitive performance were analysed. Results Patients with CFS showed no deficits in performance accuracy, but were significantly slower than healthy controls. CFS was further characterized by low and unresponsive HRV; greater heart rate (HR) reactivity and prolonged HR-recovery after cognitive challenge. Fatigue levels, perceived effort and distress did not affect cognitive performance. HRV was consistently associated with performance indices and significantly predicted variance in cognitive outcomes. Conclusions These findings reveal for the first time an association between reduced cardiac vagal tone and cognitive impairment in CFS and confirm previous reports of diminished vagal activity. PMID:23166694

[Postoperative cognitive deficits].

PubMed

Kalezić, Nevena; Dimitrijević, Ivan; Leposavić, Ljubica; Kocica, Mladen; Bumbasirević, Vesna; Vucetić, Cedomir; Paunović, Ivan; Slavković, Nemanja; Filimonović, Jelena

2006-01-01

Cognitive dysfunctions are relatively common in postoperative and critically ill patients. This complication not only compromises recovery after surgery, but, if persistent, it minimizes and compromises surgery itself. Risk factors of postoperative cognitive disorders can be divided into age and comorbidity dependent, and those related to anesthesia and surgery. Cardiovascular, orthopedic and urologic surgery carries high risk of postoperative cognitive dysfunction. It can also occur in other types of surgical treatment, especially in elderly. Among risk factors of cognitive disorders, associated with comorbidity, underlying psychiatric and neurological disorders, substance abuse and conditions with elevation of intracranial pressure are in the first place in postoperative patients. Preoperative and perioperative predisposing conditions for cognitive dysfunction and their incidence were described in our paper. These are: geriatric patients, patients with substance abuse, preexisting psychiatric or cognitive disorders, neurologic disease with high intracranial pressure, cerebrovascular insufficiency, epilepsia, preeclampsia, acute intermittent porphyria, operation type, brain hypoxia, changes in blood glucose level, electrolyte imbalance, anesthetic agents, adjuvant medication and intraoperative awareness. For each of these factors, evaluation, prevention and treatment strategies were suggested, with special regard on anesthetic technique.

Brain aging in the canine: a diet enriched in antioxidants reduces cognitive dysfunction.

PubMed

Cotman, Carl W; Head, Elizabeth; Muggenburg, Bruce A; Zicker, S; Milgram, Norton W

2002-01-01

Animal models that simulate various aspects of human brain aging are an essential step in the development of interventions to manage cognitive dysfunction in the elderly. Over the past several years we have been studying cognition and neuropathology in the aged-canine (dog). Like humans, canines naturally accumulate deposits of beta-amyloid (Abeta) in the brain with age. Further, canines and humans share the same Abeta sequence and also first show deposits of the longer Abeta1-42 species followed by the deposition of Abeta1-40. Aged canines like humans also show increased oxidative damage. As a function of age, canines show impaired learning and memory on tasks similar to those used in aged primates and humans. The extent of Abeta deposition correlates with the severity of cognitive dysfunction in canines. To test the hypothesis that a cascade of mechanisms centered on oxidative damage and Abeta results in cognitive dysfunction we have evaluated the cognitive effects of an antioxidant diet in aged canines. The diet resulted in a significant improvement in the ability of aged but not young animals to acquire progressively more difficult learning tasks (e.g. oddity discrimination learning). The canine represent a higher animal model to study the earliest declines in the cognitive continuum that includes age associated memory impairments (AAMI) and mild cognitive impairment (MCI) observed in human aging. Thus, studies in the canine model suggest that oxidative damage impairs cognitive function and that antioxidant treatment can result in significant improvements, supporting the need for further human studies. Copyright 2002 Elsevier Science Inc.

Neurocognitive function in obstructive sleep apnoea: a meta-review.

PubMed

Bucks, Romola S; Olaithe, Michelle; Eastwood, Peter

2013-01-01

Adult obstructive sleep apnoea (OSA) is associated with cognitive dysfunction. While many review articles have attempted to summarize the evidence for this association, it remains difficult to determine which domains of cognition are affected by OSA. This is because of marked differences in the nature of these reviews (e.g. many are unsystematic) and the many different tasks and domains assessed. This paper addresses this issue by comparing the results of only systematic reviews or meta-analyses assessing the effects of OSA on cognition, the relationship between OSA severity and cognition, and/or the effects of treatment on cognition in OSA. Electronic databases and hand-searching were undertaken to select reviews that reported on these areas. We found 33 reviews; five reviews met predetermined, stringent selection criteria. The majority of reviews supported deficits in attention/vigilance, delayed long-term visual and verbal memory, visuospatial/constructional abilities, and executive function in individuals with OSA. There is also general agreement that language ability and psychomotor function are unaffected by OSA. Data are equivocal for the effects of OSA on working memory, short-term memory and global cognitive functioning. Attention/vigilance dysfunction appears to be associated with sleep fragmentation and global cognitive function with hypoxaemia. Continuous positive airway pressure treatment of OSA appears to improve executive dysfunction, delayed long-term verbal and visual memory, attention/vigilance and global cognitive functioning. In order to improve our understanding of cognitive dysfunction in OSA, future research should pay particular attention to participant characteristics, measures of disease severity and choice of neuropsychological tests. © 2012 The Authors. Respirology © 2012 Asian Pacific Society of Respirology.

Executive Functioning in Alcoholics Following an mHealth Cognitive Stimulation Program: Randomized Controlled Trial

PubMed Central

Oliveira, Jorge; Lopes, Paulo; Brito, Rodrigo; Morais, Diogo; Silva, Diana; Silva, Ana; Rebelo, Sara; Bastos, Marta; Deus, Alberto

2014-01-01

Background The consequences of alcohol dependence are severe and may range from physical disease to neuropsychological deficits in several cognitive domains. Alcohol abuse has also been related to brain dysfunction specifically in the prefrontal cortex. Conventional neuropsychological interventions (paper-and-pencil cognitive stimulation training) have a positive effect but are time-consuming, costly, and not motivating for patients. Objective Our goal was to test the cognitive effects of a novel approach to neuropsychological intervention, using mobile technology and serious games, on patients with alcohol dependence. Methods The trial design consisted of a two-arm study assessing the cognitive outcomes of neuropsychological intervention with mobile serious games (mHealth) versus control (treatment-as-usual with no neuropsychological intervention) in patients undergoing treatment for alcohol dependence syndrome. Sixty-eight patients were recruited from an alcohol-rehab clinic and randomly assigned to the mHealth (n=33) or control condition (n=35). The intervention on the experimental group consisted of a therapist-assisted cognitive stimulation therapy for 4 weeks on a 2-3 days/week basis. Results Fourteen patients dropped out of the study. The results of the neuropsychological assessments with the remaining 54 patients showed an overall increase (P<.05) of general cognitive abilities, mental flexibility, psychomotor processing speed, and attentional ability in both experimental (n=26) and control groups (n=28). However, there was a more pronounced improvement (P=.01) specifically in frontal lobe functions from baseline (mean 13.89, SE 0.58) to follow-up (mean 15.50, SE 0.46) in the experimental group but not in the control group. Conclusions The overall increase in general cognitive function for both experimental and control groups supports the beneficial role of existing alcohol treatment protocols aimed at minimizing withdrawal symptoms, but the differential improvements observed in frontal lobe functioning supports the use of mobile serious games for neuropsychological stimulation to overcome executive dysfunction in patients with alcohol dependence. This trial was negative on two neuropsychological/cognitive tests, and positive on one. Trial Registration ClinicalTrials.gov NCT01942954; http://www.clinicaltrials.gov/ct2/show/NCT01942954 (Archived by WebCite at http://www.webcitation.org/6OYDqHLwB). PMID:24742381

Nrf2 Deficiency Exacerbates Obesity-Induced Oxidative Stress, Neurovascular Dysfunction, Blood-Brain Barrier Disruption, Neuroinflammation, Amyloidogenic Gene Expression, and Cognitive Decline in Mice, Mimicking the Aging Phenotype.

PubMed

Tarantini, Stefano; Valcarcel-Ares, M Noa; Yabluchanskiy, Andriy; Tucsek, Zsuzsanna; Hertelendy, Peter; Kiss, Tamas; Gautam, Tripti; Zhang, Xin A; Sonntag, William E; de Cabo, Rafael; Farkas, Eszter; Elliott, Michael H; Kinter, Michael T; Deak, Ferenc; Ungvari, Zoltan; Csiszar, Anna

2018-06-14

Obesity has deleterious effects on cognitive function in the elderly adults. In mice, aging exacerbates obesity-induced oxidative stress, microvascular dysfunction, blood-brain barrier (BBB) disruption, and neuroinflammation, which compromise cognitive health. However, the specific mechanisms through which aging and obesity interact to remain elusive. Previously, we have shown that Nrf2 signaling plays a critical role in microvascular resilience to obesity and that aging is associated with progressive Nrf2 dysfunction, promoting microvascular impairment. To test the hypothesis that Nrf2 deficiency exacerbates cerebromicrovascular dysfunction induced by obesity Nrf2+/+ and Nrf2-/-, mice were fed an adipogenic high-fat diet (HFD). Nrf2 deficiency significantly exacerbated HFD-induced oxidative stress and cellular senescence, impairment of neurovascular coupling responses, BBB disruption, and microglia activation, mimicking the aging phenotype. Obesity in Nrf2-/- mice elicited complex alterations in the amyloidogenic gene expression profile, including upregulation of amyloid precursor protein. Nrf2 deficiency and obesity additively reduced long-term potentiation in the CA1 area of the hippocampus. Collectively, Nrf2 dysfunction exacerbates the deleterious effects of obesity, compromising cerebromicrovascular and brain health by impairing neurovascular coupling mechanisms, BBB integrity and synaptic function and promoting neuroinflammation. These results support a possible role for age-related Nrf2 dysfunction in the pathogenesis of vascular cognitive impairment and Alzheimer's disease.

BEHAVIORAL AND LEARNING DISABILITIES ASSOCIATED WITH COGNITIVE-MOTOR DYSFUNCTION. INTERIM REPORT.

ERIC Educational Resources Information Center

BRAUN, JEAN S.; RUBIN, ELI Z.

THIS REPORT EXAMINES THE RELATIONSHIP BETWEEN BEHAVIORAL AND ACADEMIC DISABILITIES AND COGNITIVE-MOTOR DYSFUNCTION AS REVEALED BY DATA ON 400 ELEMENTARY SCHOOL CHILDREN. THE BEHAVIOR CHECKLIST WAS USED AS A BASIS FOR SAMPLE SELECTION. BEHAVIOR CLUSTERS REFLECTING BOTH ANTI-SOCIAL TENDENCIES AND UNASSERTIVE, WITHDRAWN BEHAVIOR WERE IDENTIFIED. A…

The evolution of the cognitive model of depression and its neurobiological correlates.

PubMed

Beck, Aaron T

2008-08-01

Although the cognitive model of depression has evolved appreciably since its first formulation over 40 years ago, the potential interaction of genetic, neurochemical, and cognitive factors has only recently been demonstrated. Combining findings from behavioral genetics and cognitive neuroscience with the accumulated research on the cognitive model opens new opportunities for integrated research. Drawing on advances in cognitive, personality, and social psychology as well as clinical observations, expansions of the original cognitive model have incorporated in successive stages automatic thoughts, cognitive distortions, dysfunctional beliefs, and information-processing biases. The developmental model identified early traumatic experiences and the formation of dysfunctional beliefs as predisposing events and congruent stressors in later life as precipitating factors. It is now possible to sketch out possible genetic and neurochemical pathways that interact with or are parallel to cognitive variables. A hypersensitive amygdala is associated with both a genetic polymorphism and a pattern of negative cognitive biases and dysfunctional beliefs, all of which constitute risk factors for depression. Further, the combination of a hyperactive amygdala and hypoactive prefrontal regions is associated with diminished cognitive appraisal and the occurrence of depression. Genetic polymorphisms also are involved in the overreaction to the stress and the hypercortisolemia in the development of depression--probably mediated by cognitive distortions. I suggest that comprehensive study of the psychological as well as biological correlates of depression can provide a new understanding of this debilitating disorder.

Multifactorial determinants of cognition — Thyroid function is not the only one

PubMed Central

Moncayo, Roy; Ortner, Karina

2015-01-01

Background Since the 1960s hypothyroidism together with iodine deficiency have been considered to be a principal determinant of cognition development. Following iodine supplementation programs and improved treatment options for hypothyroidism this relation might not be valid in 2015. On the other hand neurosciences have added different inputs also related to cognition. Scope of review We will examine the characteristics of the original and current publications on thyroid function and cognition and also add some general determinants of intelligence and cognition. One central issue for us is the relation of stress to cognition knowing that both physical and psychological stress, are frequent elements in subjects with thyroid dysfunction. We have considered a special type of stress called pre-natal stress which can influence cognitive functions. Fear and anxiety can be intermingled requiring mechanisms of fear extinction. Major conclusions Recent studies have failed to show an influence of thyroid medication during pregnancy on intellectual development. Neuroscience offers a better explanation of cognition than hypothyroidism and iodine deficiency. Additional factors relevant to cognition are nutrition, infection, prenatal stress, and early life stress. In turn stress is related to low magnesium levels. Magnesium supplementation can correct both latent hypothyroidism and acquired mild cognitive deficits. General significance Cognition is a complex process that depends on many determinants and not only on thyroid function. Magnesium deficiency appears to be a basic mechanism for changes in thyroid function as well as of cognition. PMID:26672993

The Activation of Incompetence Schemas in Response to Negative Sexual Events in Heterosexual and Lesbian Women: The Moderator Role of Personality Traits and Dysfunctional Sexual Beliefs.

PubMed

Peixoto, Maria Manuela; Nobre, Pedro

2017-01-01

Personality traits and dysfunctional sexual beliefs have been described as vulnerability factors for sexual dysfunction in women, and have also been proposed as dispositional variables for the activation of incompetence schemas in response to negative sexual events. However, no study has tested the role of personality traits and dysfunctional sexual beliefs in the activation of incompetence schemas. The current study aimed to assess the moderator role of neuroticism, extraversion, and dysfunctional sexual beliefs in the association between frequency of unsuccessful sexual episodes and activation of incompetence schemas in heterosexual and lesbian women. An online survey was completed by 1,121 women (831 heterosexual; 290 lesbian). Participants completed the NEO Five-Factor Inventory (NEO-FFI), the Sexual Dysfunctional Beliefs Questionnaire-Female Version (SDBQ), and the Questionnaire of Cognitive Schemas Activated in Sexual Context (QCSASC). Findings indicate that neuroticism moderates the association between frequency of negative sexual events and activation of incompetence schemas in heterosexual women. Moreover, several sexual beliefs also act as moderators of the relationship between negative sexual episodes and the activation of cognitive schemas in both heterosexual and lesbian women. Overall, findings support the cognitive-emotional model of sexual dysfunctions, emphasizing the role of personality traits and dysfunctional sexual beliefs as facilitators of the activation of incompetence schemas in response to negative events in women.

Cognitive dysfunction in antiphospholipid antibody (aPL)-negative systemic lupus erythematosus (SLE) versus aPL-positive non-SLE patients.

PubMed

Kozora, Elizabeth; Erkan, Doruk; Zhang, Lening; Zimmerman, Robert; Ramon, Glendalee; Ulug, Aziz M; Lockshin, Michael D

2014-01-01

The aim of this study was to compare the cognitive function of antiphospholipid antibody (aPL)-negative systemic lupus erythematosus (SLE) and aPL-positive non-SLE patients. Twenty aPL-negative SLE and 20 aPL-positive non-SLE female patients with no history of overt neuropsychiatric manifestations took standardised cognitive tests of learning and memory, attention and working memory, executive functions, verbal fluency, visuoconstruction, and motor function. The primary outcome measure was an established global cognitive impairment index (CII). Cranial magnetic resonance imaging (MRI) was also obtained on all patients. Twelve of 20 (60%) of the SLE and 8/20 (40%) of the aPL-positive patients had global cognitive impairment on CII; there were no group differences on CII or on individual measures. Cognitive impairment was not associated with duration of disease, level of disease activity, or prednisone use. No correlations were found between clinical disease factors and cognitive impairment, and neither group showed an association between incidental or major MRI abnormalities and cognitive dysfunction. Both aPL-negative SLE and aPL-positive non-SLE patients, without other overt neuropsychiatric disease, demonstrated high levels of cognitive impairment. No clinical, serologic, or radiologic characteristics were associated with cognitive impairment. Cognitive dysfunction is common in APS and in SLE, but its mechanisms remain unknown.

Chronic methamphetamine self-administration disrupts cortical control of cognition.

PubMed

Bernheim, Aurelien; See, Ronald E; Reichel, Carmela M

2016-10-01

Methamphetamine (meth) is one of the most abused substances worldwide. Chronic use has been associated with repeated relapse episodes that may be exacerbated by cognitive impairments during drug abstinence. Growing evidence demonstrates that meth compromises prefrontal cortex activity, resulting in persisting attentional and memory impairments. After summarizing recent studies of meth-induced cognitive dysfunction using a translationally relevant model of self-administered meth, this review emphasizes the cortical brain changes contributing to cognitive dysregulation during abstinence. Finally, we propose the use of cognitive enhancers during abstinence that may promote a drug-free state by reversing cortical dysfunction linked with prolonged meth abuse. Copyright © 2016 Elsevier Ltd. All rights reserved.

Thinking through postoperative cognitive dysfunction: How to bridge the gap between clinical and pre-clinical perspectives.

PubMed

Hovens, Iris B; Schoemaker, Regien G; van der Zee, Eddy A; Heineman, Erik; Izaks, Gerbrand J; van Leeuwen, Barbara L

2012-10-01

Following surgery, patients may experience cognitive decline, which can seriously reduce quality of life. This postoperative cognitive dysfunction (POCD) is mainly seen in the elderly and is thought to be mediated by surgery-induced inflammatory reactions. Clinical studies tend to define POCD as a persisting, generalised decline in cognition, without specifying which cognitive functions are impaired. Pre-clinical research mainly describes early hippocampal dysfunction as a consequence of surgery-induced neuroinflammation. These different approaches to study POCD impede translation between clinical and pre-clinical research outcomes and may hamper the development of appropriate interventions. This article analyses which cognitive domains deteriorate after surgery and which brain areas might be involved. The most important outcomes are: (1) POCD encompasses a wide range of cognitive impairments; (2) POCD affects larger areas of the brain; and (3) individual variation in the vulnerability of neuronal networks to neuroinflammatory mechanisms may determine if and how POCD manifests itself. We argue that, for pre-clinical and clinical research of POCD to advance, the effects of surgery on various cognitive functions and brain areas should be studied. Moreover, in addition to general characteristics, research should take inter-relationships between cognitive complaints and physical and mental characteristics into account. Copyright © 2012 Elsevier Inc. All rights reserved.

Cognitive Visual Dysfunctions in Preterm Children with Periventricular Leukomalacia

ERIC Educational Resources Information Center

Fazzi, Elisa; Bova, Stefania; Giovenzana, Alessia; Signorini, Sabrina; Uggetti, Carla; Bianchi, Paolo

2009-01-01

Aim: Cognitive visual dysfunctions (CVDs) reflect an impairment of the capacity to process visual information. The question of whether CVDs might be classifiable according to the nature and distribution of the underlying brain damage is an intriguing one in child neuropsychology. Method: We studied 22 children born preterm (12 males, 10 females;…

Cerebellar Dysfunction, Cognitive Flexibility and Autistic Traits in a Non-Clinical Sample

ERIC Educational Resources Information Center

Ridley, Nicole J.; Homewood, Judi; Walters, Jenny

2011-01-01

Cerebellar dysfunction and impaired cognitive flexibility are key features of autism spectrum disorders (ASD). However, despite the increasing interest in subclinical autism, no research has yet examined the relationship between these signs and autistic traits in the wider population. This study used the Autism-Spectrum Quotient (AQ) questionnaire…

Specificity of spontaneous EEG associated with different levels of cognitive and communicative dysfunctions in children.

PubMed

Kozhushko, Nadezhda Ju; Nagornova, Zhanna V; Evdokimov, Sergey A; Shemyakina, Natalia V; Ponomarev, Valery A; Tereshchenko, Ekaterina P; Kropotov, Jury D

2018-06-01

This study aimed to reveal electrophysiological markers of communicative and cognitive dysfunctions of different severity in children with autism spectrum disorder (ASD). Eyes-opened electroencephalograms (EEGs) of 42 children with ASD, divided into two groups according to the severity of their communicative and cognitive dysfunctions (24 with severe and 18 children with less severe ASD), and 70 age-matched controls aged 4-9 years were examined by means of spectral and group independent component (gIC) analyses. A predominance of theta and beta EEG activity in both groups of children with ASD compared to the activity in the control group was found in the global gIC together with a predominance of beta EEG activity in the right occipital region. The quantity of local gICs with enhanced slow and high-frequency EEG activity (within the frontal, temporal, and parietal cortex areas) in children 4-9 years of age might be considered a marker of cognitive and communicative dysfunction severity. Copyright © 2018 Elsevier B.V. All rights reserved.

Neuroprotective effects of voluntary running on cognitive dysfunction in an α-synuclein rat model of Parkinson's disease.

PubMed

Crowley, Erin K; Nolan, Yvonne M; Sullivan, Aideen M

2018-05-01

Parkinson's disease (PD) is no longer primarily classified as a motor disorder due to increasing recognition of the impact on patients of several nonmotor PD symptoms, including cognitive dysfunction. These nonmotor symptoms are highly prevalent and greatly affect the quality of life of patients with PD, and so, therapeutic interventions to alleviate these symptoms are urgently needed. The aim of this study was to investigate the potential neuroprotective effects of voluntary running on cognitive dysfunction in an adeno-associated virus-α-synuclein rat model of PD. Bilateral intranigral administration of adeno-associated virus-α-synuclein was found to induce motor dysfunction and a significant loss of nigral dopaminergic neurons, neither of which were rescued by voluntary running. Overexpression of α-synuclein also resulted in significant impairment on hippocampal neurogenesis-dependent pattern separation, a cognitive task; this was rescued by voluntary running. This was substantiated by an effect of running on neurogenesis levels in the dorsal dentate gyrus, suggesting that the functional effects of running on pattern separation were mediated via increased neurogenesis. Copyright © 2018 Elsevier Inc. All rights reserved.

Neuroprotective effects of oleuropein against cognitive dysfunction induced by colchicine in hippocampal CA1 area in rats.

PubMed

Pourkhodadad, Soheila; Alirezaei, Masoud; Moghaddasi, Mehrnoush; Ahmadvand, Hassan; Karami, Manizheh; Delfan, Bahram; Khanipour, Zahra

2016-09-01

Alzheimer's disease is a progressive neurodegenerative disorder with decline in memory. The role of oxidative stress is well known in the pathogenesis of the disease. The purpose of this study was to evaluate pretreatment effects of oleuropein on oxidative status and cognitive dysfunction induced by colchicine in the hippocampal CA1 area. Male Wistar rats were pretreated orally once daily for 10 days with oleuropein at doses of 10, 15 and 20 mg/kg. Thereafter, colchicine (15 μg/rat) was administered into the CA1 area of the hippocampus to induce cognitive dysfunction. The Morris water maze was used to assess learning and memory. Biochemical parameters such as glutathione peroxidase and catalase activities, nitric oxide and malondialdehyde concentrations were measured to evaluate the antioxidant status in the rat hippocampus. Our results indicated that colchicine significantly impaired spatial memory and induced oxidative stress; in contrast, oleuropein pretreatment significantly improved learning and memory retention, and attenuated the oxidative damage. The results clearly indicate that oleuropein has neuroprotective effects against colchicine-induced cognitive dysfunction and oxidative damage in rats.

Modification of dysfunctional thoughts about caregiving in dementia family caregivers: description and outcomes of an intervention programme.

PubMed

Márquez-González, M; Losada, A; Izal, M; Pérez-Rojo, G; Montorio, I

2007-11-01

Among the diverse group of interventions developed to help dementia family caregivers cognitive-behavioural approaches show especially promising results. This study describes a cognitive-behavioural group intervention aimed principally at the modification of dysfunctional thoughts associated with caregiving (MDTC). The efficacy of the MDTC intervention in reducing caregivers' depressive symptomatology, together with the frequency and appraisal of problem behaviours, is compared to that of a waiting-list control group (WL). Furthermore, the potential mediating role of the dysfunctional thoughts in the relationship between this intervention and caregivers' depressive symptomatology is analyzed. Of the 74 dementia caregivers who were randomized to one of two conditions (MDTC and WL), 39 completed the post-intervention assessment. Statistical analyses were performed on an intention-to-treat basis, using last observation carried forward. The results reveal that the MDTC intervention is successful in reducing caregivers' level of depressive symptomatology and dysfunctional thoughts about caregiving, as well as in modifying their appraisal of their relative's problem behaviours. Furthermore, a mediating role for dysfunctional thoughts was found in the relationship between the MDTC intervention and levels of depressive symptomatology. The relevance of addressing dysfunctional thoughts and cognitive distortions in group interventions with caregivers is highlighted.

Schizophrenia.

PubMed

Kahn, René S; Sommer, Iris E; Murray, Robin M; Meyer-Lindenberg, Andreas; Weinberger, Daniel R; Cannon, Tyrone D; O'Donovan, Michael; Correll, Christoph U; Kane, John M; van Os, Jim; Insel, Thomas R

2015-11-12

Schizophrenia is a chronic psychiatric disorder with a heterogeneous genetic and neurobiological background that influences early brain development, and is expressed as a combination of psychotic symptoms - such as hallucinations, delusions and disorganization - and motivational and cognitive dysfunctions. The mean lifetime prevalence of the disorder is just below 1%, but large regional differences in prevalence rates are evident owing to disparities in urbanicity and patterns of immigration. Although gross brain pathology is not a characteristic of schizophrenia, the disorder involves subtle pathological changes in specific neural cell populations and in cell-cell communication. Schizophrenia, as a cognitive and behavioural disorder, is ultimately about how the brain processes information. Indeed, neuroimaging studies have shown that information processing is functionally abnormal in patients with first-episode and chronic schizophrenia. Although pharmacological treatments for schizophrenia can relieve psychotic symptoms, such drugs generally do not lead to substantial improvements in social, cognitive and occupational functioning. Psychosocial interventions such as cognitive-behavioural therapy, cognitive remediation and supported education and employment have added treatment value, but are inconsistently applied. Given that schizophrenia starts many years before a diagnosis is typically made, the identification of individuals at risk and those in the early phases of the disorder, and the exploration of preventive approaches are crucial.

Diagnosing Contributions of Sensory and Cognitive Deficits to Hearing Dysfunction in Blast Exposed/TBI Service Members

DTIC Science & Technology

2016-10-01

1 AWARD NUMBER: W81XWH-15-1-0490 TITLE: Diagnosing Contributions of Sensory and Cognitive Deficits to Hearing Dysfunction in Blast-Exposed/ TBI...3. DATES COVERED 15 Sep 2015 - 14 Sep 2016 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Diagnosing Contributions of Sensory and Cognitive Deficits to...installed at WRNMMC, and is running finalized versions of both the auditory and visual selective attention tasks. Subject recruitment has started, and

mTOR drives cerebral blood flow and memory deficits in LDLR-/- mice modeling atherosclerosis and vascular cognitive impairment.

PubMed

Jahrling, Jordan B; Lin, Ai-Ling; DeRosa, Nicholas; Hussong, Stacy A; Van Skike, Candice E; Girotti, Milena; Javors, Martin; Zhao, Qingwei; Maslin, Leigh Ann; Asmis, Reto; Galvan, Veronica

2018-01-01

We recently showed that mTOR attenuation blocks progression and abrogates established cognitive deficits in Alzheimer's disease (AD) mouse models. These outcomes were associated with the restoration of cerebral blood flow (CBF) and brain vascular density (BVD) resulting from relief of mTOR inhibition of NO release. Recent reports suggested a role of mTOR in atherosclerosis. Because mTOR drives aging and vascular dysfunction is a universal feature of aging, we hypothesized that mTOR may contribute to brain vascular and cognitive dysfunction associated with atherosclerosis. We measured CBF, BVD, cognitive function, markers of inflammation, and parameters of cardiovascular disease in LDLR -/- mice fed maintenance or high-fat diet ± rapamycin. Cardiovascular pathologies were proportional to severity of brain vascular dysfunction. Aortic atheromas were reduced, CBF and BVD were restored, and cognitive dysfunction was attenuated potentially through reduction in systemic and brain inflammation following chronic mTOR attenuation. Our studies suggest that mTOR regulates vascular integrity and function and that mTOR attenuation may restore neurovascular function and cardiovascular health. Together with our previous studies in AD models, our data suggest mTOR-driven vascular damage may be a mechanism shared by age-associated neurological diseases. Therefore, mTOR attenuation may have promise for treatment of cognitive impairment in atherosclerosis.

Cardiovascular disease and cognitive dysfunction in systemic lupus erythematosus.

PubMed

Murray, Sara G; Yazdany, Jinoos; Kaiser, Rachel; Criswell, Lindsey A; Trupin, Laura; Yelin, Edward H; Katz, Patricia P; Julian, Laura J

2012-09-01

Cognitive dysfunction and cardiovascular disease are common and debilitating manifestations of systemic lupus erythematosus (SLE). In this study, we evaluated the relationship between cardiovascular events, traditional cardiovascular risk factors, and SLE-specific risk factors as predictors of cognitive dysfunction in a large cohort of participants with SLE. Subjects included 694 participants from the Lupus Outcomes Study (LOS), a longitudinal study of SLE outcomes based on an annual telephone survey querying demographic and clinical variables. The Hopkins Verbal Learning Test-Revised and the Controlled Oral Word Association Test were administered to assess cognitive function. Multiple logistic regression was used to identify cardiovascular events (myocardial infarction, stroke), traditional cardiovascular risk factors (hypertension, hyperlipidemia, diabetes mellitus, obesity, smoking), and SLE-specific risk factors (antiphospholipid antibodies [aPL], disease activity, disease duration) associated with cognitive impairment in year 7 of the LOS. The prevalence of cognitive impairment as measured by verbal memory and verbal fluency metrics was 15%. In adjusted multiple logistic regression analyses, aPL (odds ratio [OR] 2.10, 95% confidence interval [95% CI] 1.3-3.41), hypertension (OR 2.06, 95% CI 1.19-3.56), and a history of stroke (OR 2.27, 95% CI 1.16-4.43) were significantly associated with cognitive dysfunction. In additional analyses evaluating the association between these predictors and severity of cognitive impairment, stroke was significantly more prevalent in participants with severe impairment when compared to those with mild or moderate impairment (P = 0.036). These results suggest that the presence of aPL, hypertension, and stroke are key variables associated with cognitive impairment, which may aid in identification of patients at greatest risk. Copyright © 2012 by the American College of Rheumatology.

Cognitive dysfunction in naturally occurring canine idiopathic epilepsy.

PubMed

Packer, Rowena M A; McGreevy, Paul D; Salvin, Hannah E; Valenzuela, Michael J; Chaplin, Chloe M; Volk, Holger A

2018-01-01

Globally, epilepsy is a common serious brain disorder. In addition to seizure activity, epilepsy is associated with cognitive impairments including static cognitive impairments present at onset, progressive seizure-induced impairments and co-morbid dementia. Epilepsy occurs naturally in domestic dogs but its impact on canine cognition has yet to be studied, despite canine cognitive dysfunction (CCD) recognised as a spontaneous model of dementia. Here we use data from a psychometrically validated tool, the canine cognitive dysfunction rating (CCDR) scale, to compare cognitive dysfunction in dogs diagnosed with idiopathic epilepsy (IE) with controls while accounting for age. An online cross-sectional study resulted in a sample of 4051 dogs, of which n = 286 had been diagnosed with IE. Four factors were significantly associated with a diagnosis of CCD (above the diagnostic cut-off of CCDR ≥50): (i) epilepsy diagnosis: dogs with epilepsy were at higher risk; (ii) age: older dogs were at higher risk; (iii) weight: lighter dogs (kg) were at higher risk; (iv) training history: dogs with more exposure to training activities were at lower risk. Impairments in memory were most common in dogs with IE, but progression of impairments was not observed compared to controls. A significant interaction between epilepsy and age was identified, with IE dogs exhibiting a higher risk of CCD at a young age, while control dogs followed the expected pattern of low-risk throughout middle age, with risk increasing exponentially in geriatric years. Within the IE sub-population, dogs with a history of cluster seizures and high seizure frequency had higher CCDR scores. The age of onset, nature and progression of cognitive impairment in the current IE dogs appear divergent from those classically seen in CCD. Longitudinal monitoring of cognitive function from seizure onset is required to further characterise these impairments.

Cognitive dysfunction in naturally occurring canine idiopathic epilepsy

PubMed Central

McGreevy, Paul D.; Salvin, Hannah E.; Valenzuela, Michael J.; Chaplin, Chloe M.; Volk, Holger A.

2018-01-01

Globally, epilepsy is a common serious brain disorder. In addition to seizure activity, epilepsy is associated with cognitive impairments including static cognitive impairments present at onset, progressive seizure-induced impairments and co-morbid dementia. Epilepsy occurs naturally in domestic dogs but its impact on canine cognition has yet to be studied, despite canine cognitive dysfunction (CCD) recognised as a spontaneous model of dementia. Here we use data from a psychometrically validated tool, the canine cognitive dysfunction rating (CCDR) scale, to compare cognitive dysfunction in dogs diagnosed with idiopathic epilepsy (IE) with controls while accounting for age. An online cross-sectional study resulted in a sample of 4051 dogs, of which n = 286 had been diagnosed with IE. Four factors were significantly associated with a diagnosis of CCD (above the diagnostic cut-off of CCDR ≥50): (i) epilepsy diagnosis: dogs with epilepsy were at higher risk; (ii) age: older dogs were at higher risk; (iii) weight: lighter dogs (kg) were at higher risk; (iv) training history: dogs with more exposure to training activities were at lower risk. Impairments in memory were most common in dogs with IE, but progression of impairments was not observed compared to controls. A significant interaction between epilepsy and age was identified, with IE dogs exhibiting a higher risk of CCD at a young age, while control dogs followed the expected pattern of low-risk throughout middle age, with risk increasing exponentially in geriatric years. Within the IE sub-population, dogs with a history of cluster seizures and high seizure frequency had higher CCDR scores. The age of onset, nature and progression of cognitive impairment in the current IE dogs appear divergent from those classically seen in CCD. Longitudinal monitoring of cognitive function from seizure onset is required to further characterise these impairments. PMID:29420639

White matter structural network abnormalities underlie executive dysfunction in amyotrophic lateral sclerosis.

PubMed

Dimond, Dennis; Ishaque, Abdullah; Chenji, Sneha; Mah, Dennell; Chen, Zhang; Seres, Peter; Beaulieu, Christian; Kalra, Sanjay

2017-03-01

Research in amyotrophic lateral sclerosis (ALS) suggests that executive dysfunction, a prevalent cognitive feature of the disease, is associated with abnormal structural connectivity and white matter integrity. In this exploratory study, we investigated the white matter constructs of executive dysfunction, and attempted to detect structural abnormalities specific to cognitively impaired ALS patients. Eighteen ALS patients and 22 age and education matched healthy controls underwent magnetic resonance imaging on a 4.7 Tesla scanner and completed neuropsychometric testing. ALS patients were categorized into ALS cognitively impaired (ALSci, n = 9) and ALS cognitively competent (ALScc, n = 5) groups. Tract-based spatial statistics and connectomics were used to compare white matter integrity and structural connectivity of ALSci and ALScc patients. Executive function performance was correlated with white matter FA and network metrics within the ALS group. Executive function performance in the ALS group correlated with global and local network properties, as well as FA, in regions throughout the brain, with a high predilection for the frontal lobe. ALSci patients displayed altered local connectivity and structural integrity in these same frontal regions that correlated with executive dysfunction. Our results suggest that executive dysfunction in ALS is related to frontal network disconnectivity, which potentially mediates domain-specific, or generalized cognitive impairment, depending on the degree of global network disruption. Furthermore, reported co-localization of decreased network connectivity and diminished white matter integrity suggests white matter pathology underlies this topological disruption. We conclude that executive dysfunction in ALSci is associated with frontal and global network disconnectivity, underlined by diminished white matter integrity. Hum Brain Mapp 38:1249-1268, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Cognitive structures in women with sexual dysfunction: the role of early maladaptive schemas.

PubMed

Oliveira, Cátia; Nobre, Pedro J

2013-07-01

Cognitive schemas are often related to psychological problems. However, the role of these structures within sexual problems is not yet well established. The aim of this study was to evaluate the presence and importance of early maladaptive schemas on women's sexual functioning and cognitive schemas activated in response to negative sexual events. A total of 228 women participated in the study: a control sample of 167 women without sexual problems, a subclinical sample of 37 women with low sexual functioning, and a clinical sample of 24 women with sexual dysfunction. Participants completed several self-reported measures: the Schema Questionnaire, the Questionnaire of Cognitive Schema Activation in Sexual Context, the Brief Symptom Inventory, the Beck Depression Inventory, and the Female Sexual Function Index. Findings indicated that women with sexual dysfunction presented significantly more early maladaptive schemas from the Impaired Autonomy and Performance domain, particularly failure (P < 0.001, η(2) = 0.08), dependence/incompetence (P < 0.05, η(2) = 0.03), and vulnerability to danger (P < 0.05, η(2) = 0.04). Additionally, in response to negative sexual events, women with sexual dysfunction presented significantly higher scores on incompetence (P < 0.001, η(2) = 0.16), self-depreciation (P < 0.01, η(2) = 0.05), and difference/loneliness (P < 0.01, η(2) = 0.05) schemas. Results supported differences between women with and without sexual problems regarding cognitive factors. This may have implications for the knowledge, assessment, and treatment of sexual dysfunction in women. © 2012 International Society for Sexual Medicine.

Thyroid function abnormalities and cognitive impairment in elderly people: results of the Invecchiare in Chianti study.

PubMed

Ceresini, Graziano; Lauretani, Fulvio; Maggio, Marcello; Ceda, Gian Paolo; Morganti, Simonetta; Usberti, Elisa; Chezzi, Carlo; Valcavi, Rita; Bandinelli, Stefania; Guralnik, Jack M; Cappola, Anne R; Valenti, Giorgio; Ferrucci, Luigi

2009-01-01

To investigate thyroid function testing abnormalities in older persons and to explore the relationship between thyroid dysfunction and cognition. Cross-sectional. Community-based. One thousand one hundred seventy-one men and women aged 23 to 102. Thyroid function was evaluated by measuring plasma concentrations of thyrotropin (TSH), free thyroxine (FT4), and free triiodothyronine (FT3). Cognition was evaluated using the Mini-Mental State Examination (MMSE). Prevalence of overt and subclinical thyroid dysfunction was evaluated in different age groups (<65 vs > or =65). Age trends in TSH, FT4, and FT3 were examined in euthyroid participants. The cross-sectional association between thyroid dysfunction and MMSE score was evaluated adjusting for confounders. Subclinical hypothyroidism and subclinical hyperthyroidism were more prevalent in older than in younger participants (subclinical hypothyroidism, 3.5% vs 0.4%, P<.03; subclinical hyperthyroidism, 7.8% vs 1.9%, P<.002). In euthyroid participants, TSH and FT3 declined with age, whereas FT4 increased. Older participants with subclinical hyperthyroidism had lower MMSE scores than euthyroid subjects (22.61+/-6.88 vs 24.72+/-4.52, P<.03). In adjusted analyses, participants with subclinical hyperthyroidism were significantly more likely to have cognitive dysfunction (hazard rate=2.26, P=.003). Subtle age-related changes in FT3, FT4, and TSH occur in individuals who remain euthyroid. Subclinical hyperthyroidism is the most prevalent thyroid dysfunction in Italian older persons and is associated with cognitive impairment.

No strong evidence for abnormal levels of dysfunctional attitudes, automatic thoughts, and emotional information-processing biases in remitted bipolar I affective disorder.

PubMed

Lex, Claudia; Meyer, Thomas D; Marquart, Barbara; Thau, Kenneth

2008-03-01

Beck extended his original cognitive theory of depression by suggesting that mania was a mirror image of depression characterized by extreme positive cognition about the self, the world, and the future. However, there were no suggestions what might be special regarding cognitive features in bipolar patients (Mansell & Scott, 2006). We therefore used different indicators to evaluate cognitive processes in bipolar patients and healthy controls. We compared 19 remitted bipolar I patients (BPs) without any Axis I comorbidity with 19 healthy individuals (CG). All participants completed the Beck Depression Inventory, the Dysfunctional Attitude Scale, the Automatic Thoughts Questionnaire, the Emotional Stroop Test, and an incidental recall task. No significant group differences were found in automatic thinking and the information-processing styles (Emotional Stroop Test, incidental recall task). Regarding dysfunctional attitudes, we obtained ambiguous results. It appears that individuals with remitted bipolar affective disorder do not show cognitive vulnerability as proposed in Beck's theory of depression if they only report subthreshold levels of depressive symptoms. Perhaps, the cognitive vulnerability might only be observable if mood induction procedures are used.

Sleeping with technology: cognitive, affective, and technology usage predictors of sleep problems among college students.

PubMed

Rosen, Larry; Carrier, Louis M; Miller, Aimee; Rokkum, Jeffrey; Ruiz, Abraham

2016-03-01

Sleep problems related to technology affect college students through several potential mechanisms including displacement of sleep due to technology use, executive functioning abilities, and the impact of emotional states related to stress and anxiety about technology availability. In the present study, cognitive and affective factors that influence technology usage were examined for their impact upon sleep problems. More than 700 US college students completed an online questionnaire addressing technology usage, anxiety/dependence, executive functioning, nighttime phone usage, bedtime phone location, and sleep problems. A path model controlling for background variables was tested using the data. The results showed that executive dysfunction directly predicted sleep problems as well as affected sleep problems through nighttime awakenings. In addition, anxiety/dependence increased daily smartphone usage and also increased nighttime awakenings, which, in turn, affected sleep problems. Thus, both the affective and cognitive factors that influence technology usage affected sleep problems. Copyright © 2016 National Sleep Foundation. Published by Elsevier Inc. All rights reserved.

Vascular cognitive impairment, a cardiovascular complication.

PubMed

Frances, Adiukwu; Sandra, Ofori; Lucy, Ugbomah

2016-06-22

Over the past two decades, the term vascular cognitive impairment (VCI) has been used to refer to a spectrum of cognitive decline characterized by executive dysfunction, associated with vascular pathology. With 30% of stroke survivors showing cognitive impairments, it is regarded as the most common cause of cognitive impairment. This is a narrative review of available literature citing sources from PubMed, MEDLINE and Google Scholar. VCI has a high prevalence both before and after a stroke and is associated with great economic and caregiver burden. Despite this, there is no standardized diagnostic criteria for VCI. Hypertension has been identified as a risk factor for VCI and causes changes in cerebral vessel structure and function predisposing to lacuna infarcts and small vessel haemorrhages in the frontostriatal loop leading to executive dysfunction and other cognitive impairments. Current trials have shown promising results in the use of antihypertensive medications in the management of VCI and prevention of disease progression to vascular dementia. Prevention of VCI is necessary in light of the looming dementia pandemic. All patients with cardiovascular risk factors would therefore benefit from cognitive screening with screening instruments sensitive to executive dysfunction as well as prompt and adequate control of hypertension.

Vascular cognitive impairment, a cardiovascular complication

PubMed Central

Frances, Adiukwu; Sandra, Ofori; Lucy, Ugbomah

2016-01-01

Over the past two decades, the term vascular cognitive impairment (VCI) has been used to refer to a spectrum of cognitive decline characterized by executive dysfunction, associated with vascular pathology. With 30% of stroke survivors showing cognitive impairments, it is regarded as the most common cause of cognitive impairment. This is a narrative review of available literature citing sources from PubMed, MEDLINE and Google Scholar. VCI has a high prevalence both before and after a stroke and is associated with great economic and caregiver burden. Despite this, there is no standardized diagnostic criteria for VCI. Hypertension has been identified as a risk factor for VCI and causes changes in cerebral vessel structure and function predisposing to lacuna infarcts and small vessel haemorrhages in the frontostriatal loop leading to executive dysfunction and other cognitive impairments. Current trials have shown promising results in the use of antihypertensive medications in the management of VCI and prevention of disease progression to vascular dementia. Prevention of VCI is necessary in light of the looming dementia pandemic. All patients with cardiovascular risk factors would therefore benefit from cognitive screening with screening instruments sensitive to executive dysfunction as well as prompt and adequate control of hypertension. PMID:27354961

COGNITION AS A THERAPEUTIC TARGET IN LATE-LIFE DEPRESSION: POTENTIAL FOR NICOTINIC THERAPEUTICS

PubMed Central

Zurkovsky, Lilia; Taylor, Warren D.; Newhouse, Paul A.

2013-01-01

Depression is associated with impairments to cognition and brain function at any age, but such impairments in the elderly are particularly problematic because of the additional burden of normal cognitive aging and in some cases, structural brain pathology. Individuals with late-life depression exhibit impairments in cognition and brain structural integrity, alongside mood dysfunction. Antidepressant treatment improves symptoms in some but not all patients, and those who benefit may not return to the cognitive and functional level of nondepressed elderly. Thus, for comprehensive treatment of late-life depression, it may be necessary to address both the affective and cognitive deficits. In this review, we propose a model for the treatment of late-life depression in which nicotinic stimulation is used to improve cognitive performance and improve the efficacy of an antidepressant treatment of the syndrome of late-life depression. The cholinergic system is well-established as important to cognition. Although muscarinic stimulation may exacerbate depressive symptoms, nicotinic stimulation may improve cognition and neural functioning without a detriment to mood. While some studies of nicotinic subtype specific receptor agonists have shown promise in improving cognitive performance, less is known regarding how nicotinic receptor stimulation affects cognition in depressed elderly patients. Late-life depression thus represents a new therapeutic target for the development of nicotinic agonist drugs and parallel treatment of cognitive dysfunction along with medical and psychological approaches to treating mood dysfunction may be necessary to ensure full resolution of depressive illness in aging. PMID:23933385

Obesity Reduces Cognitive and Motor Functions across the Lifespan

PubMed Central

Wang, Chuanming; Chan, John S. Y.; Ren, Lijie; Yan, Jin H.

2016-01-01

Due to a sedentary lifestyle, more and more people are becoming obese nowadays. In addition to health-related problems, obesity can also impair cognition and motor performance. Previous results have shown that obesity mainly affects cognition and motor behaviors through altering brain functions and musculoskeletal system, respectively. Many factors, such as insulin/leptin dysregulation and inflammation, mediate the effect of obesity and cognition and motor behaviors. Substantial evidence has suggested exercise to be an effective way to improve obesity and related cognitive and motor dysfunctions. This paper aims to discuss the association of obesity with cognition and motor behaviors and its underlying mechanisms. Following this, mechanisms of exercise to improve obesity-related dysfunctions are described. Finally, implications and future research direction are raised. PMID:26881095

Obesity Reduces Cognitive and Motor Functions across the Lifespan.

PubMed

Wang, Chuanming; Chan, John S Y; Ren, Lijie; Yan, Jin H

2016-01-01

Due to a sedentary lifestyle, more and more people are becoming obese nowadays. In addition to health-related problems, obesity can also impair cognition and motor performance. Previous results have shown that obesity mainly affects cognition and motor behaviors through altering brain functions and musculoskeletal system, respectively. Many factors, such as insulin/leptin dysregulation and inflammation, mediate the effect of obesity and cognition and motor behaviors. Substantial evidence has suggested exercise to be an effective way to improve obesity and related cognitive and motor dysfunctions. This paper aims to discuss the association of obesity with cognition and motor behaviors and its underlying mechanisms. Following this, mechanisms of exercise to improve obesity-related dysfunctions are described. Finally, implications and future research direction are raised.

Spatial Working Memory Impairment in Patients with Non-neuropsychiatric Systemic Lupus Erythematosus: A Blood-oxygen-level Dependent Functional Magnetic Resonance Imaging Study.

PubMed

Zhu, Chun-Min; Ma, Ye; Xie, Lei; Huang, Jin-Zhuang; Sun, Zong-Bo; Duan, Shou-Xing; Lin, Zhi-Rong; Yin, Jing-Jing; Le, Hong-Bo; Sun, Dan-Miao; Xu, Wen-Can; Ma, Shu-Hua

2017-02-01

Using ethology and functional magnetic resonance imaging (fMRI) to explore mild cognitive dysfunction and spatial working memory (WM) impairment in patients with systemic lupus erythematosus (SLE) without overt neuropsychiatric symptoms (non-NPSLE) and to study whether any clinical biomarkers could serve as predictors of brain dysfunction in this disease. Eighteen non-NPSLE patients and 18 matched subjects were all tested using the Montreal cognitive assessment scale test and scanned using blood-oxygen-level dependent fMRI while performing the n-back task to investigate the activation intensity of some cognition-related areas. Ethology results showed that non-NPSLE patients had mild cognitive dysfunction and memory dysfunction (p < 0.05). The fMRI scan confirmed a neural network consisting of bilateral dorsolateral prefrontal cortex (DLPFC), premotor area, parietal lobe, and supplementary motor area (SMA)/anterior cingulate cortex (ACC) that was activated during the n-back task, with right hemisphere dominance. However, only the right SMA/ACC showed a load effect in the non-NPSLE group; the activation intensity of most WM-related brain areas for the non-NPSLE group was lower than for the control group under 3 memory loads. Further, we found that the activation intensity of some cognition-related areas, including the bilateral caudate nucleus/insula and hippocampus/parahippocampal gyrus were lower than the control group under the memory loads. An inverse correlation existed between individual activation intensity and disease duration. Non-NPSLE-related brain damage with right DLPFC-posterior parietal lobe and parahippocampal gyrus default network causes impairment of spatial WM and mild cognitive dysfunction. Patients with longer disease duration would be expected to exhibit increased central nervous system damage.

Suicidal Ideation and Schizophrenia: Contribution of Appraisal, Stigmatization, and Cognition.

PubMed

Stip, Emmanuel; Caron, Jean; Tousignant, Michel; Lecomte, Yves

2017-10-01

To predict suicidal ideation in people with schizophrenia, certain studies have measured its relationship with the variables of defeat and entrapment. The relationships are positive, but their interactions remain undefined. To further their understanding, this research sought to measure the relationship between suicidal ideation with the variables of loss, entrapment, and humiliation. The convenience sample included 30 patients with schizophrenia spectrum disorders. The study was prospective (3 measurement times) during a 6-month period. Results were analyzed by stepwise multiple regression. The contribution of the 3 variables to the variance of suicidal ideation was not significant at any of the 3 times (T1: 16.2%, P = 0.056; T2: 19.9%, P = 0.117; T3: 11.2%, P = 0.109). Further analyses measured the relationship between the variables of stigmatization, perceived cognitive dysfunction, symptoms, depression, self-esteem, reason to live, spirituality, social provision, and suicidal ideation. Stepwise multiple regression demonstrated that the contribution of the variables of stigmatization and perceived cognitive dysfunction to the variance of suicidal ideation was significant at all 3 times (T1: 41.7.5%, P = 0.000; T2: 35.2%, P = 0.001; T3: 21.5%, P = 0.012). Yet, over time, the individual contribution of the variables changed: T1, stigmatization (β = 0.518; P = 0.002); T2, stigmatization (β = 0.394; P = 0.025) and perceived cognitive dysfunction (β = 0.349; P = 0.046). Then, at T3, only perceived cognitive dysfunction contributed significantly to suicidal ideation (β = 0.438; P = 0.016). The results highlight the importance of the contribution of the variables of perceived cognitive dysfunction and stigmatization in the onset of suicidal ideation in people with schizophrenia spectrum disorders.

Ursolic acid improves domoic acid-induced cognitive deficits in mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Dong-mei; Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Xuzhou Normal University, Xuzhou 221116, Jiangsu Province; Lu, Jun, E-mail: lu-jun75@163.com

Our previous findings suggest that mitochondrial dysfunction is the mechanism underlying cognitive deficits induced by domoic acid (DA). Ursolic acid (UA), a natural triterpenoid compound, possesses many important biological functions. Evidence shows that UA can activate PI3K/Akt signaling and suppress Forkhead box protein O1 (FoxO1) activity. FoxO1 is an important regulator of mitochondrial function. Here we investigate whether FoxO1 is involved in the oxidative stress-induced mitochondrial dysfunction in DA-treated mice and whether UA inhibits DA-induced mitochondrial dysfunction and cognitive deficits through regulating the PI3K/Akt and FoxO1 signaling pathways. Our results showed that FoxO1 knockdown reversed the mitochondrial abnormalities and cognitivemore » deficits induced by DA in mice through decreasing HO-1 expression. Mechanistically, FoxO1 activation was associated with oxidative stress-induced JNK activation and decrease of Akt phosphorylation. Moreover, UA attenuated the mitochondrial dysfunction and cognitive deficits through promoting Akt phosphorylation and FoxO1 nuclear exclusion in the hippocampus of DA-treated mice. LY294002, an inhibitor of PI3K/Akt signaling, significantly decreased Akt phosphorylation in the hippocampus of DA/UA mice, which weakened UA actions. These results suggest that UA could be recommended as a possible candidate for the prevention and therapy of cognitive deficits in excitotoxic brain disorders. - Highlights: • Ursolic acid (UA) is a naturally triterpenoid compound. • UA attenuated the mitochondrial dysfunction and cognitive deficits. • Mechanistically, UA activates PI3K/Akt signaling and suppresses FoxO1 activity. • UA could be recommended as a possible candidate for anti-excitotoxic brain disorders.« less

Suicidal Ideation and Schizophrenia: Contribution of Appraisal, Stigmatization, and Cognition

PubMed Central

Stip, Emmanuel; Caron, Jean; Tousignant, Michel

2017-01-01

Objective: To predict suicidal ideation in people with schizophrenia, certain studies have measured its relationship with the variables of defeat and entrapment. The relationships are positive, but their interactions remain undefined. To further their understanding, this research sought to measure the relationship between suicidal ideation with the variables of loss, entrapment, and humiliation. Method: The convenience sample included 30 patients with schizophrenia spectrum disorders. The study was prospective (3 measurement times) during a 6-month period. Results were analyzed by stepwise multiple regression. Results: The contribution of the 3 variables to the variance of suicidal ideation was not significant at any of the 3 times (T1: 16.2%, P = 0.056; T2: 19.9%, P = 0.117; T3: 11.2%, P = 0.109). Further analyses measured the relationship between the variables of stigmatization, perceived cognitive dysfunction, symptoms, depression, self-esteem, reason to live, spirituality, social provision, and suicidal ideation. Stepwise multiple regression demonstrated that the contribution of the variables of stigmatization and perceived cognitive dysfunction to the variance of suicidal ideation was significant at all 3 times (T1: 41.7.5%, P = 0.000; T2: 35.2%, P = 0.001; T3: 21.5%, P = 0.012). Yet, over time, the individual contribution of the variables changed: T1, stigmatization (β = 0.518; P = 0.002); T2, stigmatization (β = 0.394; P = 0.025) and perceived cognitive dysfunction (β = 0.349; P = 0.046). Then, at T3, only perceived cognitive dysfunction contributed significantly to suicidal ideation (β = 0.438; P = 0.016). Conclusion: The results highlight the importance of the contribution of the variables of perceived cognitive dysfunction and stigmatization in the onset of suicidal ideation in people with schizophrenia spectrum disorders. PMID:28673099

Post-operative cognitive dysfunction after knee arthroplasty: a diagnostic dilemma

PubMed Central

Yap, Kiryu K.; Joyner, Peter

2014-01-01

Post-operative cognitive dysfunction (POCD) is common in the elderly, and significantly impacts their recovery. We present an unusual diagnostic challenge where a 65-year-old male presented 4-week post-total knee arthroplasty with acute cognitive dysfunction lasting 19 days. Curiously, there were no findings uncovering a specific cause, but during investigation underlying predisposing factors such as depression, mild memory deficits and generalized brain volume loss were identified. The impression after psychogeriatric review was that of an organic brain syndrome with overlay of depression, with a complex presentation as POCD. After escalation of behavioural disturbance, he was commenced on anti-psychotic/depressant, with immediate response. We emphasize the importance of pre-operative evaluation of cognitive function and risk factors in all geriatric patients undergoing elective surgery, and the need for further characterization of POCD, as well as experimental research elucidating the underlying mechanisms to better identify and treat this important post-surgical phenomenon. PMID:25988029

Impact of Rivastigmine on Cognitive Dysfunction and Falling in Parkinson's Disease Patients.

PubMed

Li, Zhenguang; Yu, Zhancai; Zhang, Jinbiao; Wang, Jing; Sun, Chao; Wang, Pengfei; Zhang, Jiangshan

2015-01-01

The purpose of this study was to observe the incidence of falls in Parkinson's disease (PD) patients with different cognitive levels and to investigate the effect of the cholinesterase inhibitor Rivastigmine on cognitive dysfunction and falling in PD patients. Data from 176 PD patients participating in the collaborative PD study between June 2010 and June 2014 were collected; the Chinese edition of the Montreal Cognitive Assessment (MoCA) score was used to evaluate the cognitive function of patients, and falls were recorded. PD patients with cognitive dysfunction were randomly administered either a placebo or Rivastigmine. The cognitive function changes and difference in fall incidence were compared between the 2 groups. The average number of falls per person in PD patients without cognitive impairment dysfunction was significantly lower than that in patients in the PD mild cognitive impairment (PD-MCI) group and that in the PD dementia (PDD) group (p < 0.01, p < 0.001, respectively), and the incidence of falls was significantly lower than that in patients in the PD-MCI and PDD groups (p < 0.01, p < 0.01, respectively). Compared to the PD-MCI group, the incidence of falls of patients in the PDD group (OR 2.45, 95% CI 0.97-6.20, p < 0.01) and the number of falls per person were significantly increased (p < 0.01). After taking the placebo or Rivastigmine for 12 months, the MoCA scores of patients in the Rivastigmine treatment group were significantly higher than those of the control group (p = 0.002). The number of falls per person and the incidence of falls of patients in Rivastigmine treatment group were significantly lower than those in the placebo group (p < 0.01). This study suggests that the degree of cognitive impairment is closely associated with the incidence of falls, and the cholinesterase inhibitor Rivastigmine can delay the deterioration of cognitive function and lower the incidence of falls in PD patients. © 2015 S. Karger AG, Basel.

A multilevel analysis of cognitive dysfunction and psychopathology associated with chromosome 22q11.2 deletion syndrome in children

PubMed Central

SIMON, TONY J.; BISH, JOEL P.; BEARDEN, CARRIE E.; DING, LIJUN; FERRANTE, SAMANTHA; NGUYEN, VY; GEE, JAMES C.; McDONALD–McGINN, DONNA M.; ZACKAI, ELAINE H.; EMANUEL, BEVERLY S.

2006-01-01

We present a multilevel approach to developing potential explanations of cognitive impairments and psychopathologies common to individuals with chromosome 22q11.2 deletion syndrome. Results presented support our hypothesis of posterior parietal dysfunction as a central determinant of characteristic visuospatial and numerical cognitive impairments. Converging data suggest that brain development anomalies, primarily tissue reductions in the posterior brain and changes to the corpus callosum, may affect parietal connectivity. Further findings indicate that dysfunction in “frontal” attention systems may explain some executive cognition impairments observed in affected children, and that there may be links between these domains of cognitive function and some of the serious psychiatric conditions, such as attention-deficit/hyperactivity disorder, autism, and schizophrenia, that have elevated incidence rates in the syndrome. Linking the neural structure and the cognitive processing levels in this way enabled us to develop an elaborate structure/function mapping hypothesis for the impairments that are observed. We show also, that in the case of the catechol-O-methyltransferase gene, a fairly direct relationship between gene expression, cognitive function, and psychopathology exists in the affected population. Beyond that, we introduce the idea that variation in other genes may further explain the phenotypic variation in cognitive function and possibly the anomalies in brain development. PMID:16262991

Cognitive Dysfunction, Locus of Control and Treatment Outcome among Chronic Alcoholics.

ERIC Educational Resources Information Center

Abbott, Max W.

While alcoholism is no longer regarded as a unitary disorder, conventional measures of congition and personality have yet to be shown capable of consistently predicting clinical outcomes. To investigate cognitive dysfunction and locus of control as predictors of post treatment outcome in a large sample of alcoholics, 106 alcoholics (74 men, 32…

[Social dysfunction in schizotypy].

PubMed

de Wachter, O; De La Asuncion, J; Sabbe, B; Morrens, M

2016-01-01

Schizotypy is a personality organisation that is closely related to schizotypal personality disorder and schizophrenia and is characterised by deficits in social functioning. Although the dimensions of social dysfunction have not yet been fully explored certain aspects of social dysfunction are promising predictive markers for schizophrenia. To describe schizotypy and its influence on social functioning. We reviewed the literature systematically using the online databases PubMed and PsycINFO. The disorder known as schizotypy lies at the basis of schizotypal personality disorder. Both disorders are characterised by an increased risk for schizophrenia. The social dysfunctioning seen in schizotypy corresponds to the social dysfunction seen in schizophrenia. Impairments in social cognition are causal factors of this social dysfunction. Both the negative and the positive dimension of schizotypy influence social cognition. More focused, objective and interactive research to the various aspects of social functioning in schizotypy is needed in order to discover potential premorbid markers for schizophrenia.

Temporal Cerebral Microbleeds Are Associated With Radiation Necrosis and Cognitive Dysfunction in Patients Treated for Nasopharyngeal Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shen, Qingyu; Department of Neurology, Zengcheng People's Hospital, Guangzhou; Lin, Focai

Purpose: Radiation therapy for patients with nasopharyngeal carcinoma (NPC) may be complicated with radiation-induced brain necrosis (RN), resulting in deteriorated cognitive function. However, the underlying mechanism of this phenomenon remains unclear. This study attempts to elucidate the association between cerebral microbleeds (CMBs) and radiation necrosis and cognitive dysfunction in NPC patients treated with radiation therapy. Methods and Materials: This cross-sectional study included 106 NPC patients who were exposed to radiation therapy (78 patients with RN and 28 without RN). Sixty-six patients without discernable intracranial pathology were included as the control group. CMBs were confirmed using susceptibility-weighted magnetic resonance imaging. Cognitivemore » function was accessed using Montreal Cognitive Assessment. Patients with a total score below 26 were defined as cognitively dysfunction. Results: Seventy-seven patients (98.7%) in the RN group and 12 patients (42.9%) in the non-RN group had at least 1 CMB. In contrast, only 14 patients (21.2%) in the control group had CMBs. In patients with a history of radiation therapy, CMBs most commonly presented in temporal lobes (76.4%) followed by cerebellum (23.7%). Patients with RN had more temporal CMBs than those in the non-RN group (37.7 ± 51.9 vs 3.8 ± 12.6, respectively; P<.001). The number of temporal lobe CMBs was predictive for larger volume of brain necrosis (P<.001) in multivariate linear regression analysis. Although cognitive impairment was diagnosed in 55.1% of RN patients, only 7.1% of non-RN patients sustained cognitive impairment (P<.001). After adjusting for age, sex, education, period after radiation therapy, CMBs in other lobes, and RN volume, the number of temporal CMBs remained an independent risk factor for cognitive dysfunction (odds ratio [OR]: 1.03; 95% confidence interval [CI]: 1.01-1.04; P=.003). Conclusions: CMBs is a common radiological manifestation in NPC patients with RN. The number of temporal CMBs is independently associated with increased likelihood of cognitive dysfunction in patients with RN.« less

G protein-gated K+ channel ablation in forebrain pyramidal neurons selectively impairs fear learning

PubMed Central

Victoria, Nicole C.; de Velasco, Ezequiel Marron Fernandez; Ostrovskaya, Olga; Metzger, Stefania; Xia, Zhilian; Kotecki, Lydia; Benneyworth, Michael A.; Zink, Anastasia N.; Martemyanov, Kirill A.; Wickman, Kevin

2015-01-01

Background Cognitive dysfunction occurs in many debilitating conditions including Alzheimer’s disease, Down syndrome, schizophrenia, and mood disorders. The dorsal hippocampus is a critical locus of cognitive processes linked to spatial and contextual learning. G protein-gated inwardly rectifying K+ (GIRK/Kir3) channels, which mediate the postsynaptic inhibitory effect of many neurotransmitters, have been implicated in hippocampal-dependent cognition. Available evidence, however, derives primarily from constitutive gain-of-function models that lack cellular specificity. Methods We used constitutive and neuron-specific gene ablation models targeting an integral subunit of neuronal GIRK channels (GIRK2) to probe the impact of GIRK channels on associative learning and memory. Results Constitutive Girk2−/− mice exhibited a striking deficit in hippocampal-dependent (contextual) and hippocampal-independent (cue) fear conditioning. Mice lacking GIRK2 in GABA neurons (GAD-Cre:Girk2flox/flox mice) exhibited a clear deficit in GIRK-dependent signaling in dorsal hippocampal GABA neurons, but no evident behavioral phenotype. Mice lacking GIRK2 in forebrain pyramidal neurons (CaMKII-Cre(+):Girk2flox/flox mice) exhibited diminished GIRK-dependent signaling in dorsal, but not ventral, hippocampal pyramidal neurons. CaMKII-Cre(+):Girk2flox/flox mice also displayed a selective impairment in contextual fear conditioning, as both cue-fear and spatial learning were intact in these mice. Finally, loss of GIRK2 in forebrain pyramidal neurons correlated with enhanced long-term depression and blunted depotentiation of long-term potentiation at the Schaffer collateral/CA1 synapse in the dorsal hippocampus. Conclusions Our data suggest that GIRK channels in dorsal hippocampal pyramidal neurons are necessary for normal learning involving aversive stimuli, and support the contention that dysregulation of GIRK-dependent signaling may underlie cognitive dysfunction in some disorders. PMID:26612516

Beyond Emotional and Spatial Processes: Cognitive Dysfunction in a Depressive Phenotype Produced by Long Photoperiod Exposure.

PubMed

Barnes, Abigail K; Smith, Summer B; Datta, Subimal

2017-01-01

Cognitive dysfunction in depression has recently been given more attention and legitimacy as a core symptom of the disorder. However, animal investigations of depression-related cognitive deficits have generally focused on emotional or spatial memory processing. Additionally, the relationship between the cognitive and affective disturbances that are present in depression remains obscure. Interestingly, sleep disruption is one aspect of depression that can be related both to cognition and affect, and may serve as a link between the two. Previous studies have correlated sleep disruption with negative mood and impaired cognition. The present study investigated whether a long photoperiod-induced depressive phenotype showed cognitive deficits, as measured by novel object recognition, and displayed a cognitive vulnerability to an acute period of total sleep deprivation. Adult male Wistar rats were subjected to a long photoperiod (21L:3D) or a normal photoperiod (12L:12D) condition. Our results indicate that our long photoperiod exposed animals showed behaviors in the forced swim test consistent with a depressive phenotype, and showed significant deficits in novel object recognition. Three hours of total sleep deprivation, however, did not significantly change novel object recognition in either group, but the trends suggest that the long photoperiod and normal photoperiod groups had different cognitive responses to total sleep deprivation. Collectively, these results underline the extent of cognitive dysfunction present in depression, and suggest that altered sleep plays a role in generating both the affective and cognitive symptoms of depression.

Brain imaging and cognitive dysfunctions in Huntington's disease

PubMed Central

Montoya, Alonso; Price, Bruce H.; Menear, Matthew; Lepage, Martin

2006-01-01

Recent decades have seen tremendous growth in our understanding of the cognitive dysfunctions observed in Huntington's disease (HD). Advances in neuroimaging have contributed greatly to this growth. We reviewed the role that structural and functional neuroimaging techniques have played in elucidating the cerebral bases of the cognitive deficits associated with HD. We conducted a computer-based search using PubMed and PsycINFO databases to retrieve studies of patients with HD published between 1965 and December 2004 that reported measures on cognitive tasks and used neuroimaging techniques. Structural neuroimaging has provided important evidence of morphological brain changes in HD. Striatal and cortical atrophy are the most common findings, and they correlate with cognitive deficits in attention, working memory and executive functions. Functional studies have also demonstrated correlations between striatal dysfunction and cognitive performance. Striatal hypoperfusion and decreased glucose utilization correlate with executive dysfunction. Hypometabolism also occurs throughout the cerebral cortex and correlates with performance on recognition memory, language and perceptual tests. Measures of presynaptic and postsynaptic dopamine biochemistry have also correlated with measurements of episodic memory, speed of processing and executive functioning. Aided by the results of numerous neuroimaging studies, it is becoming increasingly clear that cognitive deficits in HD involve abnormal connectivity between the basal ganglia and cortical areas. In the future, neuroimaging techniques may shed the most light on the pathophysiology of HD by defining neurodegenerative disease phenotypes as a valuable tool for knowing when patients become “symptomatic,” having been in a gene-positive presymptomatic state, and as a biomarker in following the disease, thereby providing a prospect for improved patient care. PMID:16496032

Post-treatment cognitive dysfunction in women treated with thyroidectomy for papillary thyroid carcinoma.

PubMed

Jung, Mi Sook; Visovatti, Moira

2017-03-01

The purpose of the study is to assess cognitive function in papillary thyroid cancer, one type of differentiated thyroid cancer, and to identify factors associated with cognitive dysfunction. Korean women treated with papillary thyroid cancer post thyroidectomy (n = 90) and healthy women similar in age and educational level (n = 90) performed attention and working memory tests and completed self-report questionnaires on cognitive complaints, psychological distress, symptom distress, and cultural characteristics. Comparative and multivariable regression analyses were performed to determine differences in cognitive function and possible predictors of neurocognitive performance and cognitive complaints. Thyroid cancer survivors performed and perceived their function to be significantly worse on tests of attention and working memory compared to individuals without thyroid cancer. Regression analyses found that having thyroid cancer, older age, and lower educational level were associated with worse neurocognitive performance, while greater fatigue, more sleep problems, and higher levels of childrearing burden but not having thyroid cancer were associated with lower perceived effectiveness in cognitive functioning. Findings suggest that women receiving thyroid hormone replacement therapy after thyroidectomy for papillary thyroid cancer are at risk for attention and working memory problems. Coexisting symptoms and culture-related women's burden affected perceived cognitive dysfunction. Health care providers should assess for cognitive problems in women with thyroid cancer and intervene to reduce distress and improve quality of life.

Can Valeriana officinalis root extract prevent early postoperative cognitive dysfunction after CABG surgery? A randomized, double-blind, placebo-controlled trial.

PubMed

Hassani, Soghra; Alipour, Abbas; Darvishi Khezri, Hadi; Firouzian, Abolfazl; Emami Zeydi, Amir; Gholipour Baradari, Afshin; Ghafari, Rahman; Habibi, Wali-Allah; Tahmasebi, Homeyra; Alipour, Fatemeh; Ebrahim Zadeh, Pooneh

2015-03-01

We hypothesized that valerian root might prevent cognitive dysfunction in coronary artery bypass graft (CABG) surgery patients through stimulating serotonin receptors and anti-inflammatory activity. The aim of this study was to evaluate the effect of Valeriana officinalis root extract on prevention of early postoperative cognitive dysfunction after on-pump CABG surgery. In a randomized, double-blind, placebo-controlled trial, 61 patients, aged between 30 and 70 years, scheduled for elective CABG surgery using cardiopulmonary bypass (CPB), were recruited into the study. Patients were randomly divided into two groups who received either one valerian capsule containing 530 mg of valerian root extract (1,060 mg/daily) or placebo capsule each 12 h for 8 weeks, respectively. For all patients, cognitive brain function was evaluated before the surgery and at 10-day and 2-month follow-up by Mini Mental State Examination (MMSE) test. Mean MMSE score decreased from 27.03 ± 2.02 in the preoperative period to 26.52 ± 1.82 at the 10th day and then increased to 27.45 ± 1.36 at the 60th day in the valerian group. Conversely, its variation was reduced significantly after 60 days in the placebo group, 27.37 ± 1.87 at the baseline to 24 ± 1.91 at the 10th day, and consequently slightly increased to 24.83 ± 1.66 at the 60th day. Valerian prophylaxis reduced odds of cognitive dysfunction compared to placebo group (OR = 0.108, 95 % CI 0.022-0.545). We concluded that, based on this study, the cognitive state of patients in the valerian group was better than that in the placebo group after CABG; therefore, it seems that the use of V. officinalis root extract may prevent early postoperative cognitive dysfunction after on-pump CABG surgery.

Fetal alcohol spectrum disorders: gene-environment interactions, predictive biomarkers, and the relationship between structural alterations in the brain and functional outcomes.

PubMed

Reynolds, James N; Weinberg, Joanne; Clarren, Sterling; Beaulieu, Christian; Rasmussen, Carmen; Kobor, Michael; Dube, Marie-Pierre; Goldowitz, Daniel

2011-03-01

Prenatal alcohol exposure is a major, preventable cause of behavioral and cognitive deficits in children. Despite extensive research, a unique neurobehavioral profile for children affected by prenatal alcohol exposure remains elusive. A fundamental question that must be addressed is how genetic and environmental factors interact with gestational alcohol exposure to produce neurobehavioral and neurobiological deficits in children. The core objectives of the NeuroDevNet team in fetal alcohol spectrum disorders is to create an integrated research program of basic and clinical investigations that will (1) identify genetic and epigenetic modifications that may be predictive of the neurobehavioral and neurobiological dysfunctions in offspring induced by gestational alcohol exposure and (2) determine the relationship between structural alterations in the brain induced by gestational alcohol exposure and functional outcomes in offspring. The overarching hypothesis to be tested is that neurobehavioral and neurobiological dysfunctions induced by gestational alcohol exposure are correlated with the genetic background of the affected child and/or epigenetic modifications in gene expression. The identification of genetic and/or epigenetic markers that are predictive of the severity of behavioral and cognitive deficits in children affected by gestational alcohol exposure will have a profound impact on our ability to identify children at risk. Copyright © 2011 Elsevier Inc. All rights reserved.

Fetal Alcohol Spectrum Disorders: Gene-Environment Interactions, Predictive Biomarkers, and the Relationship Between Structural Alterations in the Brain and Functional Outcomes

PubMed Central

Reynolds, James N.; Weinberg, Joanne; Clarren, Sterling; Beaulieu, Christian; Rasmussen, Carmen; Kobor, Michael; Dube, Marie-Pierre; Goldowitz, Daniel

2016-01-01

Prenatal alcohol exposure is a major, preventable cause of behavioral and cognitive deficits in children. Despite extensive research, a unique neurobehavioral profile for children affected by prenatal alcohol exposure remains elusive. A fundamental question that must be addressed is how genetic and environmental factors interact with gestational alcohol exposure to produce neurobehavioral and neurobiological deficits in children. The core objectives of the NeuroDevNet team in fetal alcohol spectrum disorders is to create an integrated research program of basic and clinical investigations that will (1) identify genetic and epigenetic modifications that may be predictive of the neurobehavioral and neurobiological dysfunctions in offspring induced by gestational alcohol exposure and (2) determine the relationship between structural alterations in the brain induced by gestational alcohol exposure and functional outcomes in offspring. The overarching hypothesis to be tested is that neurobehavioral and neurobiological dysfunctions induced by gestational alcohol exposure are correlated with the genetic background of the affected child and/or epigenetic modifications in gene expression. The identification of genetic and/or epigenetic markers that are predictive of the severity of behavioral and cognitive deficits in children affected by gestational alcohol exposure will have a profound impact on our ability to identify children at risk. PMID:21575841

Executive Functions Profile in Extreme Eating/Weight Conditions: From Anorexia Nervosa to Obesity

PubMed Central

Fagundo, Ana B.; de la Torre, Rafael; Jiménez-Murcia, Susana; Agüera, Zaida; Granero, Roser; Tárrega, Salomé; Botella, Cristina; Baños, Rosa; Fernández-Real, Jose M.; Rodríguez, Roser; Forcano, Laura; Frühbeck, Gema; Gómez-Ambrosi, Javier; Tinahones, Francisco J.; Fernández-García, Jose C.; Casanueva, Felipe F.; Fernández-Aranda, Fernando

2012-01-01

Background Extreme weight conditions (EWC) groups along a continuum may share some biological risk factors and intermediate neurocognitive phenotypes. A core cognitive trait in EWC appears to be executive dysfunction, with a focus on decision making, response inhibition and cognitive flexibility. Differences between individuals in these areas are likely to contribute to the differences in vulnerability to EWC. The aim of the study was to investigate whether there is a common pattern of executive dysfunction in EWC while comparing anorexia nervosa patients (AN), obese subjects (OB) and healthy eating/weight controls (HC). Methods Thirty five AN patients, fifty two OB and one hundred thirty seven HC were compared using the Wisconsin Card Sorting Test (WCST); Stroop Color and Word Test (SCWT); and Iowa Gambling Task (IGT). All participants were female, aged between 18 and 60 years. Results There was a significant difference in IGT score (F(1.79); p<.001), with AN and OB groups showing the poorest performance compared to HC. On the WCST, AN and OB made significantly more errors than controls (F(25.73); p<.001), and had significantly fewer correct responses (F(2.71); p<.001). Post hoc analysis revealed that the two clinical groups were not significantly different from each other. Finally, OB showed a significant reduced performance in the inhibition response measured with the Stroop test (F(5.11); p<.001) compared with both AN and HC. Conclusions These findings suggest that EWC subjects (namely AN and OB) have similar dysfunctional executive profile that may play a role in the development and maintenance of such disorders. PMID:22927962

Benign childhood epilepsy with occipital paroxysms: neuropsychological findings.

PubMed

Germanò, Eva; Gagliano, Antonella; Magazù, Angela; Sferro, Caterina; Calarese, Tiziana; Mannarino, Erminia; Calamoneri, Filippo

2005-05-01

Benign childhood epilepsy with occipital paroxysms is classified among childhood benign partial epilepsies. The absence of neurological and neuropsychological deficits has long been considered as a prerequisite for a diagnosis of benign childhood partial epilepsy. Much evidence has been reported in literature in the latest years suggesting a neuropsychological impairment in this type of epilepsy, particularly in the type with Rolandic paroxysms. The present work examines the neuropsychological profiles of a sample of subjects affected by the early-onset benign childhood occipital seizures (EBOS) described by Panayotopulos. The patient group included 22 children (14 males and 8 females; mean age 10.1+/-3.3 years) diagnosed as having EBOS. The patients were examined with a set of tests investigating neuropsychological functions: memory, attention, perceptive, motor, linguistic and academic (reading, writing, arithmetic) abilities. The same instruments have been given to a homogeneous control group as regards sex, age, level of education and socio-economic background. None of the subjects affected by EBOS showed intellectual deficit (mean IQ in Wechsler Full Scale 91.7; S.D. 8.9). Results show a widespread cognitive dysfunction in the context of a focal epileptogenic process in EBOS. In particular, children with EBOS show a significant occurrence of specific learning disabilities (SLD) and other subtle neuropsychological deficits. We found selective dysfunctions relating to perceptive-visual attentional ability (p<0.05), verbal and visual-spatial memory abilities (p<0.01), visual perception and visual-motor integration global abilities (p<0.01), manual dexterity tasks (p<0.05), some language tasks (p<0.05), reading and writing abilities (p<0.01) and arithmetic ability (p<0.01). The presence of cognitive dysfunctions in subjects with EBOS supports the hypothesis that epilepsy itself plays a role in the development of neuropsychological impairment. Supported by other studies that have documented subtle neuropsychological deficits in benign partial epilepsy, we stress the importance of reconsidering its supposed "cognitive benignity", particularly in occipital types.

Thyroid Function Abnormalities and Cognitive Impairment in the Elderly. Results of the InCHIANTI Study

PubMed Central

Ceresini, Graziano; Lauretani, Fulvio; Maggio, Marcello; Ceda, Gian Paolo; Morganti, Simonetta; Usberti, Elisa; Chezzi, Carlo; Valcavi, Rita; Bandinelli, Stefania; Guralnik, Jack M.; Cappola, Anne R.; Valenti, Giorgio; Ferrucci, Luigi

2008-01-01

Objectives To investigate thyroid function testing abnormalities in older persons and to explore the relationship between thyroid dysfunction and cognition. Design Cross-sectional study Setting Community-based Participants 1171 men and women aged 23-102 yrs Measurements Thyroid function was evaluated by measuring plasma concentrations of thyrotropin (TSH), free thyroxine (FT4), and free triiodothyronine (FT3). Cognition was evaluated by the Mini Mental State Examination (MMSE). Prevalence of overt and subclinical thyroid dysfunction was evaluated in different age groups (<65 versus ≥65 years). Age trends in TSH, FT4, and FT3 were examined in euthyroid participants. The cross-sectional association of thyroid dysfunction with MMSE score was evaluated adjusting for confounders. Results Both subclinical hypothyroidism and subclinical hyperthyroidism were more prevalent in older than in younger participants (Subclinical hypothyroidism, 0.4 % vs 3.5 % in younger vs older participants, respectively, P<.03 Subclinical hyperthyroidism, 1.9 % vs 7.8 % in younger vs older participants, respectively, P<.002). In euthyroid participants TSH and FT3 declined with age while FT4 increased. Old participants with subclinical hyperthyroidism had a lower MMSE score than euthyroid subjects (22.61 ± 6.88 vs 24.72 ± 4.52, P<.03). In adjusted analyses, participants with subclinical hyperthyroidism were significantly more likely to have cognitive dysfunction (HR: 2.26, P= .003). Conclusion Subtle age-related changes in FT3, FT4 and TSH occur in individuals who remain euthyroid. Subclinical hyperthyroidism is the most prevalent thyroid dysfunction in Italian older persons and is associated with cognitive impairment. PMID:19054181

Histone Deacetylase Inhibitor Trichostatin A Ameliorated Endotoxin-Induced Neuroinflammation and Cognitive Dysfunction

PubMed Central

Chen, Yeong-Chang; Wei, Tsui-Shan; Sun, Ding-Ping; Wang, Jhi-Joung; Yeh, Ching-Hua

2015-01-01

Excessive production of cytokines by microglia may cause cognitive dysfunction and long-lasting behavioral changes. Activating the peripheral innate immune system stimulates cytokine secretion in the central nervous system, which modulates cognitive function. Histone deacetylases (HDACs) modulate cytokine synthesis and release. Trichostatin A (TSA), an HDAC inhibitor, is documented to be anti-inflammatory and neuroprotective. We investigated whether TSA reduces lipopolysaccharide- (LPS-) induced neuroinflammation and cognitive dysfunction. ICR mice were first intraperitoneally (i.p.) injected with vehicle or TSA (0.3 mg/kg). One hour later, they were injected (i.p.) with saline or Escherichia coli LPS (1 mg/kg). We analyzed the food and water intake, body weight loss, and sucrose preference of the injected mice and then determined the microglia activation and inflammatory cytokine expression in the brains of LPS-treated mice and LPS-treated BV-2 microglial cells. In the TSA-pretreated mice, microglial activation was lower, anhedonia did not occur, and LPS-induced cognitive dysfunction (anorexia, weight loss, and social withdrawal) was attenuated. Moreover, mRNA expression of HDAC2, HDAC5, indoleamine 2,3-dioxygenase (IDO), TNF-α, MCP-1, and IL-1β in the brain of LPS-challenged mice and in the LPS-treated BV-2 microglial cells was lower. TSA diminished LPS-induced inflammatory responses in the mouse brain and modulated the cytokine-associated changes in cognitive function, which might be specifically related to reducing HDAC2 and HDAC5 expression. PMID:26273133

Hemodynamic Profiles of Functional and Dysfunctional Forms of Repetitive Thinking.

PubMed

Ottaviani, Cristina; Brosschot, Jos F; Lonigro, Antonia; Medea, Barbara; Van Diest, Ilse; Thayer, Julian F

2017-04-01

The ability of the human brain to escape the here and now (mind wandering) can take functional (problem solving) and dysfunctional (perseverative cognition) routes. Although it has been proposed that only the latter may act as a mediator of the relationship between stress and cardiovascular disease, both functional and dysfunctional forms of repetitive thinking have been associated with blood pressure (BP) reactivity of the same magnitude. However, a similar BP reactivity may be caused by different physiological determinants, which may differ in their risk for cardiovascular pathology. To examine the way (hemodynamic profile) and the extent (compensation deficit) to which total peripheral resistance and cardiac output compensate for each other in determining BP reactivity during functional and dysfunctional types of repetitive thinking. Fifty-six healthy participants randomly underwent a perseverative cognition, a mind wandering, and a problem solving induction, each followed by a 5-min recovery period while their cardiovascular parameters were continuously monitored. Perseverative cognition and problem solving (but not mind wandering) elicited BP increases of similar magnitude. However, perseverative cognition was characterized by a more vascular (versus myocardial) profile compared to mind wandering and problem solving. As a consequence, BP recovery was impaired after perseverative cognition compared to the other two conditions. Given that high vascular resistance and delayed recovery are the hallmarks of hypertension the results suggest a potential mechanism through which perseverative cognition may act as a mediator in the relationship between stress and risk for developing precursors to cardiovascular disease.

A Network Meta-Analysis Comparing Effects of Various Antidepressant Classes on the Digit Symbol Substitution Test (DSST) as a Measure of Cognitive Dysfunction in Patients with Major Depressive Disorder.

PubMed

Baune, Bernhard T; Brignone, Mélanie; Larsen, Klaus Groes

2018-02-01

Major depressive disorder is a common condition that often includes cognitive dysfunction. A systematic literature review of studies and a network meta-analysis were carried out to assess the relative effect of antidepressants on cognitive dysfunction in major depressive disorder. MEDLINE, Embase, Cochrane, CDSR, and PsychINFO databases; clinical trial registries; and relevant conference abstracts were searched for randomized controlled trials assessing the effects of antidepressants/placebo on cognition. A network meta-analysis comparing antidepressants was conducted using a random effects model. The database search retrieved 11337 citations, of which 72 randomized controlled trials from 103 publications met the inclusion criteria. The review identified 86 cognitive tests assessing the effect of antidepressants on cognitive functioning. However, the Digit Symbol Substitution Test, which targets multiple domains of cognition and is recognized as being sensitive to change, was the only test that was used across 12 of the included randomized controlled trials and that allowed the construction of a stable network suitable for the network meta-analysis. The interventions assessed included selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and other non-selective serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitors. The network meta-analysis using the Digit Symbol Substitution Test showed that vortioxetine was the only antidepressant that improved cognitive dysfunction on the Digit Symbol Substitution Test vs placebo {standardized mean difference: 0.325 (95% CI = 0.120; 0.529, P=.009}. Compared with other antidepressants, vortioxetine was statistically more efficacious on the Digit Symbol Substitution Test vs escitalopram, nortriptyline, and the selective serotonin reuptake inhibitor and tricyclic antidepressant classes. This study highlighted the large variability in measures used to assess cognitive functioning. The findings on the Digit Symbol Substitution Test indicate differential effects of various antidepressants on improving cognitive function in patients with major depressive disorder. © The Author 2017. Published by Oxford University Press on behalf of CINP.

Role of fruits, nuts, and vegetables in maintaining cognitive health.

PubMed

Miller, Marshall G; Thangthaeng, Nopporn; Poulose, Shibu M; Shukitt-Hale, Barbara

2017-08-01

Population aging is leading to an increase in the incidence of age-related cognitive dysfunction and, with it, the health care burden of caring for older adults. Epidemiological studies have shown that consumption of fruits, nuts, and vegetables is positively associated with cognitive ability; however, these foods, which contain a variety of neuroprotective phytochemicals, are widely under-consumed. Surprisingly few studies have investigated the effects of individual plant foods on cognitive health but recent clinical trials have shown that dietary supplementation with individual foods, or switching to a diet rich in several of these foods, can improve cognitive ability. While additional research is needed, increasing fruit, nut, and vegetable intake may be an effective strategy to prevent or delay the onset of cognitive dysfunction during aging. Published by Elsevier Inc.

Awareness of financial skills in dementia.

PubMed

Van Wielingen, L E; Tuokko, H A; Cramer, K; Mateer, C A; Hultsch, D F

2004-07-01

The present study examined the relations among levels of cognitive functioning, executive dysfunction, and awareness of financial management capabilities among a sample of 42 community-dwelling persons with dementia. Financial tasks on the Measure of Awareness of Financial Skills (MAFS) were dichotomized as simple or complex based on Piaget's operational levels of childhood cognitive development. Severity of global cognitive impairment and executive dysfunction were significantly related to awareness of financial abilities as measured by informant-participant discrepancy scores on the MAFS. For persons with mild and moderate/severe dementia, and persons with and without executive dysfunction, proportions of awareness within simple and complex financial task categories were tabulated. Significantly less awareness of financial abilities occurred on complex compared with simple tasks. Individuals with mild dementia were significantly less aware of abilities on complex items, whereas persons with moderate/severe dementia were less aware of abilities, regardless of task complexity. Similar patterns of awareness were observed for individuals with and without executive dysfunction. These findings support literature suggesting that deficits associated with dementia first occur for complex cognitive tasks involving inductive reasoning or decision-making in novel situations, and identify where loss of function in the financial domain may first be expected. Copyright Taylor & Francis Ltd

Dopamine and the Development of Executive Dysfunction in Autism Spectrum Disorders

PubMed Central

Kriete, Trenton; Noelle, David C.

2015-01-01

Persons with autism regularly exhibit executive dysfunction (ED), including problems with deliberate goal-directed behavior, planning, and flexible responding in changing environments. Indeed, this array of deficits is sufficiently prominent to have prompted a theory that executive dysfunction is at the heart of these disorders. A more detailed examination of these behaviors reveals, however, that some aspects of executive function remain developmentaly appropriate. In particular, while people with autism often have difficulty with tasks requiring cognitive flexibility, their fundamental cognitive control capabilities, such as those involved in inhibiting an inappropriate but relatively automatic response, show no significant impairment on many tasks. In this article, an existing computational model of the prefrontal cortex and its role in executive control is shown to explain this dichotomous pattern of behavior by positing abnormalities in the dopamine-based modulation of frontal systems in individuals with autism. This model offers excellent qualitative and quantitative fits to performance on standard tests of cognitive control and cognitive flexibility in this clinical population. By simulating the development of the prefrontal cortex, the computational model also offers a potential explanation for an observed lack of executive dysfunction early in life. PMID:25811610

Dopamine and the development of executive dysfunction in autism spectrum disorders.

PubMed

Kriete, Trenton; Noelle, David C

2015-01-01

Persons with autism regularly exhibit executive dysfunction (ED), including problems with deliberate goal-directed behavior, planning, and flexible responding in changing environments. Indeed, this array of deficits is sufficiently prominent to have prompted a theory that executive dysfunction is at the heart of these disorders. A more detailed examination of these behaviors reveals, however, that some aspects of executive function remain developmentaly appropriate. In particular, while people with autism often have difficulty with tasks requiring cognitive flexibility, their fundamental cognitive control capabilities, such as those involved in inhibiting an inappropriate but relatively automatic response, show no significant impairment on many tasks. In this article, an existing computational model of the prefrontal cortex and its role in executive control is shown to explain this dichotomous pattern of behavior by positing abnormalities in the dopamine-based modulation of frontal systems in individuals with autism. This model offers excellent qualitative and quantitative fits to performance on standard tests of cognitive control and cognitive flexibility in this clinical population. By simulating the development of the prefrontal cortex, the computational model also offers a potential explanation for an observed lack of executive dysfunction early in life.

Predictors of Smoking Cessation in Old–Old Age

PubMed Central

2016-01-01

Introduction: There is a dearth of knowledge on smoking cessation in older adults. This study examined predictors of smoking cessation in persons over age 75. Methods: This study is a secondary analysis of a prospective longitudinal study. A sample of 619 older persons aged 75–94 was drawn from a representative cohort of older persons in Israel and was examined longitudinally. By means of interviews, we assessed smoking, health, Activities of Daily Living (ADL), Instrumental ADL, cognitive dysfunction, and well-being. Results: Continuing smokers tended to be lonelier. Participants who quit smoking took more medications and had greater cognitive dysfunction compared to those who continued smoking. Conclusions: Greater cognitive dysfunction and high medication use or the physical causes for high medication use may precipitate smoking cessation in persons aged 75–94, potentially through a greater influence of caregivers on one’s lifestyle. Implications: Cognitive dysfunction and high medication use predicted smoking cessation. Smoking cessation for long time smokers may be influenced by greater ill health. Influence of caregivers may augment smoking cessation. Given these findings, for persistent smokers into old age, smoking cessation may occur at the time of physical and functional decline during the end of life period. PMID:26783294

The effect of a negative mood priming challenge on dysfunctional attitudes, explanatory style, and explanatory flexibility.

PubMed

Fresco, David M; Heimberg, Richard G; Abramowitz, Adrienne; Bertram, Tara L

2006-06-01

Ninety-seven undergraduates, 48 of whom had a history of self-reported major depression, completed measures of mood and cognitive style (e.g. explanatory style, explanatory flexibility, dysfunctional attitudes) prior to and directly after a negative mood priming challenge that consisted of listening to sad music and thinking about an upsetting past event. Eighteen of the previously depressed participants endorsed baseline levels of depression, explanatory style for negative events, and dysfunctional attitudes higher than levels reported by never depressed participants or euthymic participants with a history of depression. All three groups (never depressed participants, dysphoric participants with a history of depression, euthymic participants with a history of depression) demonstrated increases in dysphoria and dysfunctional attitudes in response to the negative mood priming challenge. Dysphoric participants with a history of depression, but not the other two groups, evidenced modest increases in explanatory style following the negative mood priming challenge. Finally, euthymic participants with a history of depression, but not the other two groups, evidenced drops in explanatory flexibility. Findings from the present study suggest that the cognitive theories of depression may benefit from examining both cognitive content and cognitive flexibility when assessing risk for depression.

Blood Biomarkers Predict the Cognitive Effects of Aripiprazole in Patients with Acute Schizophrenia.

PubMed

Hori, Hikaru; Yoshimura, Reiji; Katsuki, Asuka; Atake, Kiyokazu; Igata, Ryohei; Konishi, Yuki; Beppu, Hiroki; Tominaga, Hirotaka

2017-03-06

Aripiprazole has been reported to exert variable effects on cognitive function in patients with schizophrenia. Therefore, in the present study, we evaluated biological markers, clinical data, and psychiatric symptoms in order to identify factors that influence cognitive function in patients with schizophrenia undergoing aripiprazole treatment. We evaluated cognitive function in 51 patients with schizophrenia using Brief Assessment of Cognition in Schizophrenia (BACS), as well as background information, psychiatric symptoms, plasma catecholamine metabolites-homovanillic acid (HVA), 3-methoxy-4-hydroxyphenylglycol (MHPG)-, and serum brain-derived neurotrophic factor (BDNF). Multivariate analyses were performed in order to identify factors independently associated with cognitive function. Brain-derived neurotrophic factor levels, number of hospitalizations, and MHPG levels were associated with verbal memory and learning. Total hospitalization period and MHPG levels were associated with working memory. Age at first hospitalization and education were associated with motor speed. The number of hospital admissions, Positive and Negative Syndrome Scale negative subscale scores (PANSS-N), MHPG levels, BDNF levels, and Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) scores were associated with verbal fluency. Homovanillic acid and MHPG levels, duration of illness, and PANSS-N scores were associated with attention and processing speed. Brain-derived neurotrophic factor and MHPG levels were associated with executive function. These results suggest that treatment of psychiatric symptoms and cognitive dysfunction may be improved in patients treated with aripiprazole by controlling for these contributing factors.

The relationship between cognitive dysfunction and coping abilities in schizophrenia.

PubMed

Wilder-Willis, Kelly E; Shear, Paula K; Steffen, John J; Borkin, Joyce

2002-06-01

Cognitive dysfunction is a core feature of schizophrenia [Psychiatr. Clin. North Am., 16 (1993) 295; Psychopharmacology: The fourth generation of progress, Raven Press, New York (1995) 1171; Clinical Neuropsychology, Oxford University Press, New York (1993) 449] and is related to psychosocial functioning in this population [Am. J. Psychiatry, 153 (1996) 321]. It is unclear whether cognitive dysfunction is related to specific areas of functioning in schizophrenia, such as coping abilities. Individuals with schizophrenia have deficient coping skills, which may contribute to their difficulties dealing with stressors [Am. J. Orthopsychiatry, 62 (1992) 117; J. Abnorm. Psychol., 82 (1986) 189]. The current study examined the relationship between coping abilities and cognitive dysfunction in a community sample of individuals with schizophrenia. It was hypothesized that executive dysfunction and mnemonic impairments would be positively related to deficiencies in active coping efforts involving problem solving and self-initiation (e.g. advocating for oneself and others with mental illness and becoming involved in meaningful activities, such as work), independent of the contributions of the general intellectual deficits associated with the disorder and psychiatric symptoms. The results indicated that both executive dysfunction and mnemonic impairments were related to decreased usage of active coping mechanisms after controlling for general intellectual deficits. Further, recognition memory made independent contributions to the prediction of coping involving action and help seeking after controlling for the effects of negative symptoms. These findings suggest that individuals with schizophrenia may be less flexible in their use of coping strategies, which may in turn contribute to their difficulties in coping with mental illness and its consequences.

Vascular impairment as a pathological mechanism underlying long-lasting cognitive dysfunction after pediatric traumatic brain injury.

PubMed

Ichkova, Aleksandra; Rodriguez-Grande, Beatriz; Bar, Claire; Villega, Frederic; Konsman, Jan Pieter; Badaut, Jerome

2017-12-01

Traumatic brain injury (TBI) is the leading cause of death and disability in children. Indeed, the acute mechanical injury often evolves to a chronic brain disorder with long-term cognitive, emotional and social dysfunction even in the case of mild TBI. Contrary to the commonly held idea that children show better recovery from injuries than adults, pediatric TBI patients actually have worse outcome than adults for the same injury severity. Acute trauma to the young brain likely interferes with the fine-tuned developmental processes and may give rise to long-lasting consequences on brain's function. This review will focus on cerebrovascular dysfunction as an important early event that may lead to long-term phenotypic changes in the brain after pediatric TBI. These, in turn may be associated with accelerated brain aging and cognitive dysfunction. Finally, since no effective treatments are currently available, understanding the unique pathophysiological mechanisms of pediatric TBI is crucial for the development of new therapeutic options. Copyright © 2017 Elsevier Ltd. All rights reserved.

Applying a Cognitive Neuroscience Perspective to Disruptive Behavior Disorders: Implications for Schools.

PubMed

Tyler, Patrick M; White, Stuart F; Thompson, Ronald W; Blair, R J R

2018-02-12

A cognitive neuroscience perspective seeks to understand behavior, in this case disruptive behavior disorders (DBD), in terms of dysfunction in cognitive processes underpinned by neural processes. While this type of approach has clear implications for clinical mental health practice, it also has implications for school-based assessment and intervention with children and adolescents who have disruptive behavior and aggression. This review articulates a cognitive neuroscience account of DBD by discussing the neurocognitive dysfunction related to emotional empathy, threat sensitivity, reinforcement-based decision-making, and response inhibition. The potential implications for current and future classroom-based assessments and interventions for students with these deficits are discussed.

Cognitive performance, symptoms and counter-regulation during hypoglycaemia in patients with type 1 diabetes and high or low renin-angiotensin system activity.

PubMed

Høi-Hansen, Thomas; Pedersen-Bjergaard, Ulrik; Andersen, Rikke Due; Kristensen, Peter Lommer; Thomsen, Carsten; Kjaer, Troels; Høgenhaven, Hans; Smed, Annelise; Holst, Jens Juul; Dela, Flemming; Boomsma, Frans; Thorsteinsson, Birger

2009-12-01

High basal renin-angiotensin system (RAS) activity is associated with increased risk of severe hypoglycaemia in type 1 diabetes. We tested whether this might be explained by more pronounced cognitive dysfunction during hypoglycaemia in patients with high RAS activity than in patients with low RAS activity. Nine patients with type 1 diabetes and high and nine with low RAS activity were subjected to hypoglycaemia and euglycaemia in a cross-over study using an intravenous insulin infusion protocol. Cognitive function, electroencephalography, auditory evoked potentials and hypoglycaemic symptoms were recorded. At a hypoglycaemic nadir of 2.2 (SD 0.3) mmol/L the high RAS group displayed significant deterioration in cognitive performance during hypoglycaemia in the three most complex reaction time tasks. In the low RAS group, hypoglycaemia led to cognitive dysfunction in only one reaction time task. The high RAS group reported lower symptom scores during hypoglycaemia than the low RAS group, suggesting poorer hypoglycaemia awareness. High RAS activity is associated with increased cognitive dysfunction and blunted symptoms during mild hypoglycaemia compared to low RAS activity. This may explain why high RAS activity is a risk factor for severe hypoglycaemia in type 1 diabetes.

Nitrogen dioxide pollution exposure is associated with olfactory dysfunction in older US adults

PubMed Central

Adams, Dara R.; Ajmani, Gaurav S.; Pun, Vivian C.; Wroblewski, Kristen E.; Kern, David W.; Schumm, L. Philip; McClintock, Martha K.; Suh, Helen H.; Pinto, Jayant M.

2017-01-01

Background Olfactory dysfunction has profound effects on quality of life, physical and social function, and mortality itself. Nitrogen dioxide (NO2) is a pervasive air pollutant that is associated with respiratory diseases. Given the olfactory nerve’s anatomic exposure to airborne pollutants, we investigated the relationship between NO2 exposure and olfactory dysfunction. Methods The ability to identify odors was evaluated using a validated test in respondents from the National Social Life, Health, and Aging Project (NSHAP), a representative probability sample of home-dwelling, older US adults ages 57–85. Exposure to NO2 pollution was assessed using measurements obtained from the US EPA AIRS ambient monitoring site closest to each respondent’s home. We tested the association between NO2 exposure and olfactory dysfunction using multivariate logistic regression. Results Among older adults in the US, 22.6% had impaired olfactory function, defined as ≤ 3 correct (out of 5) on the odor identification test. Median NO2 exposure during the 365 days prior to the interview date was 14.7 ppb (interquartile range [IQR] 10.8–19.7 ppb). An IQR increase in NO2 exposure was associated with increased odds of olfactory dysfunction (OR 1.35, 95% CI: 1.07–1.72), adjusting for age, gender, race/ethnicity, education, cognition, comorbidity, smoking, and season of the home interview (n=1,823). Conclusion We show for the first time that NO2 exposure is associated with olfactory dysfunction in older US adults. These results suggest an important role for NO2 exposure on olfactory dysfunction, and, potentially, nasal disease more broadly. PMID:27620703

Detecting social-cognitive deficits after traumatic brain injury: An ALE meta-analysis of fMRI studies.

PubMed

Xiao, Hui; Jacobsen, Andre; Chen, Ziqian; Wang, Yang

2017-01-01

Traumatic brain injury (TBI) can result in significant social dysfunction, which is represented by impairment to social-cognitive abilities (i.e. social cognition, social attention/executive function and communication). This study is aimed to explore brain networks mediating the social dysfunction after TBI and its underlying mechanisms. We performed a quantitative meta-analysis using the activation likelihood estimation (ALE) approach on functional magnetic resonance imaging (fMRI) studies of social-cognitive abilities following TBI. Sixteen studies fulfilled the inclusion criteria resulting in a total of 190 patients with TBI and 206 controls enrolled in the ALE meta-analysis. The temporoparietal junction (TPJ) and the medial prefrontal cortex (mPFC) were the specific regions that social cognition predominantly engaged. The cingulate gyrus, frontal gyrus and inferior parietal lobule were the main regions related to social attention/executive functions. Communication dysfunction, especially related to language deficits, was found to show greater activation of the temporal gyrus and fusiform gyrus in TBI. The current ALE meta-analytic findings provide evidence that patients have significant social-cognitive disabilities following TBI. The relatively limited pool of literature and the varied fMRI results from published studies indicate that social-cognitive abilities following TBI is an area that would greatly benefit from further investigation.

Cognitive Attentional Syndrome and Metacognitive Beliefs in Male Sexual Dysfunction: An Exploratory Study.

PubMed

Giuri, Simona; Caselli, Gabriele; Manfredi, Chiara; Rebecchi, Daniela; Granata, Antonio; Ruggiero, Giovanni Maria; Veronese, Guido

2017-05-01

Erectile dysfunction (ED) and premature ejaculation (PE) are two forms of male sexual disorder with both psychological and physical features. While their cognitive, attentional, and affective components have been investigated separately, there is a lack of knowledge about the role played by cognitive attentional syndrome in their onset and maintenance. The aim of the present study was to investigate the possible contribution of perseverative thinking styles and thought control strategies to the development and maintenance of ED and PE. The authors hypothesized that such modes of processing might constitute a cognitive attentional syndrome specific to these disorders and sustained by particular metacognitive beliefs. A semistructured interview was administered to 11 participants with ED and 10 with PE in order to assess their metacognitive beliefs and cognitive attentional processes. The results suggest that individuals with ED and PE adopt a range of cognitive attentional strategies aimed at improving their sexual performance, and endorse both positive and negative metacognitive beliefs about these thinking responses. Overall, their cognitive and attentional patterns worsened negative internal states, reduced sexual excitement, detached them from their bodily sensations, and hindered sexual functioning. These preliminary findings suggest that perseverative thinking, thought control strategies, and metacognitive beliefs may play a key role in the onset and maintenance of male sexual dysfunction.

Role of brain iron accumulation in cognitive dysfunction: evidence from animal models and human studies.

PubMed

Schröder, Nadja; Figueiredo, Luciana Silva; de Lima, Maria Noêmia Martins

2013-01-01

Over the last decades, studies from our laboratory and other groups using animal models have shown that iron overload, resulting in iron accumulation in the brain, produces significant cognitive deficits. Iron accumulation in the hippocampus and the basal ganglia has been related to impairments in spatial memory, aversive memory, and recognition memory in rodents. These results are corroborated by studies showing that the administration of iron chelators attenuates cognitive deficits in a variety of animal models of cognitive dysfunction, including aging and Alzheimer's disease models. Remarkably, recent human studies using magnetic resonance image techniques have also shown a consistent correlation between cognitive dysfunction and iron deposition, mostly in the hippocampus, cortical areas, and basal ganglia. These findings may have relevant implications in the light of the knowledge that iron accumulates in brain regions of patients suffering from neurodegenerative diseases. A better understanding of the functional consequences of iron dysregulation in aging and neurological diseases may help to identify novel targets for treating memory problems that afflict a growing aging population.

Early Developmental Disturbances of Cortical Inhibitory Neurons: Contribution to Cognitive Deficits in Schizophrenia

PubMed Central

Volk, David W.; Lewis, David A.

2014-01-01

Cognitive dysfunction is a disabling and core feature of schizophrenia. Cognitive impairments have been linked to disturbances in inhibitory (gamma-aminobutyric acid [GABA]) neurons in the prefrontal cortex. Cognitive deficits are present well before the onset of psychotic symptoms and have been detected in early childhood with developmental delays reported during the first year of life. These data suggest that the pathogenetic process that produces dysfunction of prefrontal GABA neurons in schizophrenia may be related to altered prenatal development. Interestingly, adult postmortem schizophrenia brain tissue studies have provided evidence consistent with a disease process that affects different stages of prenatal development of specific subpopulations of prefrontal GABA neurons. Prenatal ontogeny (ie, birth, proliferation, migration, and phenotypic specification) of distinct subpopulations of cortical GABA neurons is differentially regulated by a host of transcription factors, chemokine receptors, and other molecular markers. In this review article, we propose a strategy to investigate how alterations in the expression of these developmental regulators of subpopulations of cortical GABA neurons may contribute to the pathogenesis of cortical GABA neuron dysfunction and consequently cognitive impairments in schizophrenia. PMID:25053651

Task-Specific and General Cognitive Effects in Chiari Malformation Type I

PubMed Central

Allen, Philip A.; Houston, James R.; Pollock, Joshua W.; Buzzelli, Christopher; Li, Xuan; Harrington, A. Katherine; Martin, Bryn A.; Loth, Francis; Lien, Mei-Ching; Maleki, Jahangir; Luciano, Mark G.

2014-01-01

Objective Our objective was to use episodic memory and executive function tests to determine whether or not Chiari Malformation Type I (CM) patients experience cognitive dysfunction. Background CM is a neurological syndrome in which the cerebellum descends into the cervical spine causing neural compression, severe headaches, neck pain, and number of other physical symptoms. While primarily a disorder of the cervico-medullary junction, both clinicians and researchers have suspected deficits in higher-level cognitive function. Design and Methods We tested 24 CM patients who had undergone decompression neurosurgery and 24 age- and education-matched controls on measures of immediate and delayed episodic memory, as well as three measures of executive function. Results The CM group showed performance decrements relative to the controls in response inhibition (Stroop interference), working memory computational speed (Ospan), and processing speed (automated digit symbol substitution task), but group differences in recall did not reach statistical significance. After statistical control for depression and anxiety scores, the group effects for working memory and processing speed were eliminated, but not for response inhibition. This response inhibition difference was not due to overall general slowing for the CM group, either, because when controls' data were transformed using the linear function fit to all of the reaction time tasks, the interaction with group remained statistically significant. Furthermore, there was a multivariate group effect for all of the response time measures and immediate and delayed recall after statistical control of depression and anxiety scores. Conclusion These results suggest that CM patients with decompression surgery exhibit cognitive dysfunction compared to age- and education-matched controls. While some of these results may be related to anxiety and depression (likely proxies for chronic pain), response inhibition effects, in particular, as well as a general cognitive deficit persisted even after control for anxiety and decompression. PMID:24736676

Selective Cognitive Dysfunction Is Related to a Specific Pattern of Cerebral Damage in Persons With Severe Traumatic Brain Injury.

PubMed

Di Paola, Margherita; Phillips, Owen; Costa, Alberto; Ciurli, Paola; Bivona, Umberto; Catani, Sheila; Formisano, Rita; Caltagirone, Carlo; Carlesimo, Giovanni Augusto

2015-01-01

Cognitive dysfunction is a common sequela of traumatic brain injury (TBI); indeed, patients show a heterogeneous pattern of cognitive deficits. This study was aimed at investigating whether patients who show selective cognitive dysfunction after TBI present a selective pattern of cerebral damage. Post-Coma Unit, IRCCS Santa Lucia Foundation, Rome, Italy. We collected data from 8 TBI patients with episodic memory disorder and without executive deficits, 7 patients with executive function impairment and preserved episodic memory capacities, and 16 healthy controls. We used 2 complementary analyses: (1) an exploratory and qualitative approach in which we investigated the distribution of lesions in the TBI groups, and (2) a hypothesis-driven and quantitative approach in which we calculated the volume of hippocampi of individuals in the TBI and control groups. Neuropsychological scores and hippocampal volumes. We found that patients with TBI and executive functions impairment presented focal lesions involving the frontal lobes, whereas patients with TBI and episodic memory disorders showed atrophic changes of the mesial temporal structure (hippocampus). The complexity of TBI is due to several heterogeneous factors. Indeed, studying patients with TBI and selective cognitive dysfunction should lead to a better understanding of correlations with specific brain impairment and damage, better follow-up of long-term outcome scenarios, and better planning of selective and focused rehabilitation programs.

Post-Operative Cognitive Dysfunction: An exploration of the inflammatory hypothesis and novel therapies.

PubMed

Skvarc, David R; Berk, Michael; Byrne, Linda K; Dean, Olivia M; Dodd, Seetal; Lewis, Matthew; Marriott, Andrew; Moore, Eileen M; Morris, Gerwyn; Page, Richard S; Gray, Laura

2018-01-01

Post-Operative Cognitive Dysfunction (POCD) is a highly prevalent condition with significant clinical, social and financial impacts for patients and their communities. The underlying pathophysiology is becoming increasingly understood, with the role of neuroinflammation and oxidative stress secondary to surgery and anaesthesia strongly implicated. This review aims to describe the putative mechanisms by which surgery-induced inflammation produces cognitive sequelae, with a focus on identifying potential novel therapies based upon their ability to modify these pathways. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

The effect of non-invasive positive pressure ventilation (NIPPV) on cognitive function in amyotrophic lateral sclerosis (ALS): a prospective study

PubMed Central

Newsom-Davis, I; Lyall, R; Leigh, P; Moxham, J; Goldstein, L

2001-01-01

OBJECTIVES—Neuropsychological investigations have shown a degree of cognitive dysfunction in a proportion of non-demented patients with ALS. Respiratory muscle weakness in ALS can lead to nocturnal hypoventilation, resulting in sleep disturbance and daytime somnolence. Sleep deprivation of this type may cause impairments in cognitive function, but this has not been formally evaluated in ALS.
METHODS—Cognitive functioning was evaluated in nine patients with ALS with sleep disturbance caused by nocturnal hypoventilation (NIPPV group), and in a comparison group of 10 similar patients without ventilation problems (control group). The NIPPV group then started non-invasive positive pressure ventilation (NIPPV) at night. After about 6 weeks, change in cognitive function was evaluated.
RESULTS—Statistically significant improvement in scores on two of the seven cognitive tests was demonstrated in the NIPPV group postventilation, and a trend towards significant improvement was found for two further tests. Scores in the control group did not improve significantly for these four tests, although an improvement was found on one other test.
CONCLUSIONS—Nocturnal hypoventilation and sleep disturbance may cause cognitive dysfunction in ALS. These deficits may be partially improved by NIPPV over a 6 week period. This has important implications for investigations of both cognitive dysfunction in non-demented patients with ALS, and the effect of ventilation on quality of life.

 PMID:11561031

A Competing Neurobehavioral Decision Systems Model of SES-Related Health and Behavioral Disparities

PubMed Central

Bickel, W. K.; Moody, L.; Quisenberry, A. J.; Ramey, C. T.; Sheffer, C. E.

2014-01-01

We propose that executive dysfunction is an important component relating the socioeconomic status gradient of select health behaviors. We review and find evidence supporting an SES gradient associated with (1) negative health behaviors (e.g., obesity, excessive use of alcohol, tobacco and other substances), and (2) executive dysfunction. Moreover, the evidence supports that stress and insufficient cognitive resources contribute to executive dysfunction and that executive dysfunction is evident among individuals who smoke cigarettes, are obese, abuse alcohol, and use illicit drugs. Collectively these data supports the dual system model of cognitive control, referred to here as the Competing Neurobehavioral Decision Systems hypothesis. The implications of these relationships for intervention and social justice considerations are discussed. PMID:25008219

Relationships between self-reported sleep quality components and cognitive functioning in breast cancer survivors up to 10 years following chemotherapy.

PubMed

Henneghan, Ashley M; Carter, Patricia; Stuifbergan, Alexa; Parmelee, Brennan; Kesler, Shelli

2018-04-23

Links have been made between aspects of sleep quality and cognitive function in breast cancer survivors (BCS), but findings are heterogeneous. The objective of this study is to examine relationships between specific sleep quality components (latency, duration, efficiency, daytime sleepiness, sleep disturbance, use of sleep aids) and cognitive impairment (performance and perceived), and determine which sleep quality components are the most significant contributors to cognitive impairments in BCS 6 months to 10 years post chemotherapy. Women 21 to 65 years old with a history of non-metastatic breast cancer following chemotherapy completion were recruited. Data collection included surveys to evaluate sleep quality and perceived cognitive impairments, and neuropsychological testing to evaluate verbal fluency and memory. Descriptive statistics, bivariate correlations, and hierarchical multiple regression were calculated. 90 women (mean age 49) completed data collection. Moderate significant correlations were found between daytime dysfunction, sleep efficiency, sleep latency, and sleep disturbance and perceived cognitive impairment (Rs = -0.37 to -0.49, Ps<.00049), but not objective cognitive performance of verbal fluency, memory or attention. After accounting for individual and clinical characteristics, the strongest predictors of perceived cognitive impairments were daytime dysfunction, sleep efficiency, and sleep disturbance. Findings support links between sleep quality and perceived cognitive impairments in BCS and suggest specific components of sleep quality (daytime dysfunction, sleep efficiency, and sleep disturbance) are associated with perceived cognitive functioning in this population. Findings can assist clinicians in guiding survivors to manage sleep and cognitive problems and aid in the design of interventional research. This article is protected by copyright. All rights reserved.

The Effects of a Cognitive Information Processing Career Intervention on the Dysfunctional Career Thoughts, Locus of Control, and Career Decision Self-Efficacy of Underprepared College Students

ERIC Educational Resources Information Center

Henderson, Kristina M.

2009-01-01

This study investigated the impact of a seven-session career intervention in a First Year Experience course on the dysfunctional career thoughts, locus of control, and career decision self-efficacy of underprepared college students. The career intervention was based on the cognitive information processing approach to career decision making…

Personality and cognitive vulnerability in remitted recurrently depressed patients.

PubMed

van Rijsbergen, Gerard D; Kok, Gemma D; Elgersma, Hermien J; Hollon, Steven D; Bockting, Claudi L H

2015-03-01

Personality disorders (PDs) have been associated with a poor prognosis of Major Depressive Disorder (MDD). The aim of the current study was to examine cognitive vulnerability (i.e., dysfunctional beliefs, extremity of beliefs, cognitive reactivity, and rumination) that might contribute to this poor prognosis of patients with PD comorbidity. 309 outpatients with remitted recurrent MDD (SCID-I; HAM-D17 ≤ 10) were included within two comparable RCTs and were assessed at baseline with the Personality Diagnostic Questionnaire-4(+) (PDQ-4(+)), the Dysfunctional Attitude Scale Version-A (DAS-A), the Leiden Index of Depression Sensitivity (LEIDS), the Ruminative Response Scale (RRS), and the Inventory of Depressive Symptomatology-Self Report (IDS-SR). We found an indication that the PD prevalence was 49.5% in this remitted recurrently depressed sample. Having a PD (and higher levels of personality pathology) was associated with dysfunctional beliefs, cognitive reactivity, and rumination. Extreme 'black and white thinking' on the DAS was not associated with personality pathology. Brooding was only associated with a Cluster C classification (t(308) = 4.03, p < .001) and with avoidant PD specifically (t(308) = 4.82, p < .001), while surprisingly not with obsessive-compulsive PD. PDs were assessed by questionnaire and the analyses were cross-sectional in nature. Being the first study to examine cognitive reactivity and rumination in patients with PD and remitted MDD, we demonstrated that even after controlling for depressive symptomatology, dysfunctional beliefs, cognitive reactivity, and rumination were associated with personality pathology. Rumination might be a pathway to relapse for patients with avoidant PD. Replication of our findings concerning cognitive vulnerability and specific PDs is necessary. Copyright © 2014 Elsevier B.V. All rights reserved.

Insula Demonstrates a Non-Linear Response to Varying Demand for Cognitive Control and Weaker Resting Connectivity With the Executive Control Network in Smokers.

PubMed

Fedota, John R; Matous, Allison L; Salmeron, Betty Jo; Gu, Hong; Ross, Thomas J; Stein, Elliot A

2016-09-01

Deficits in cognitive control processes are a primary characteristic of nicotine addiction. However, while network-based connectivity measures of dysfunction have frequently been observed, empirical evidence of task-based dysfunction in these processes has been inconsistent. Here, in a sample of smokers (n=35) and non-smokers (n=21), a previously validated parametric flanker task is employed to characterize addiction-related alterations in responses to varying (ie, high, intermediate, and low) demands for cognitive control. This approach yields a demand-response curve that aims to characterize potential non-linear responses to increased demand for control, including insensitivities or lags in fully activating the cognitive control network. We further used task-based differences in activation between groups as seeds for resting-state analysis of network dysfunction in an effort to more closely link prior inconsistencies in task-related activation with evidence of impaired network connectivity in smokers. For both smokers and non-smokers, neuroimaging results showed similar increases in activation in brain areas associated with cognitive control. However, reduced activation in right insula was seen only in smokers and only when processing intermediate demand for cognitive control. Further, in smokers, this task-modulated right insula showed weaker functional connectivity with the superior frontal gyrus, a component of the task-positive executive control network. These results demonstrate that the neural instantiation of salience attribution in smokers is both more effortful to fully activate and has more difficulty communicating with the exogenous, task-positive, executive control network. Together, these findings further articulate the cognitive control dysfunction associated with smoking and illustrate a specific brain circuit potentially responsible.

Memory deficits in amyotrophic lateral sclerosis are not exclusively caused by executive dysfunction: a comparative neuropsychological study of amnestic mild cognitive impairment.

PubMed

Machts, Judith; Bittner, Verena; Kasper, Elisabeth; Schuster, Christina; Prudlo, Johannes; Abdulla, Susanne; Kollewe, Katja; Petri, Susanne; Dengler, Reinhard; Heinze, Hans-Jochen; Vielhaber, Stefan; Schoenfeld, Mircea A; Bittner, Daniel M

2014-06-30

Recent work suggests that ALS and frontotemporal dementia can occur together and share at least in part the same underlying pathophysiology. However, it is unclear at present whether memory deficits in ALS stem from a temporal lobe dysfunction, or are rather driven by frontal executive dysfunction. In this study we sought to investigate the nature of memory deficits by analyzing the neuropsychological performance of 40 ALS patients in comparison to 39 amnestic mild cognitive impairment (aMCI) patients and 40 healthy controls (HC). The neuropsychological battery tested for impairment in executive functions, as well as memory and visuo-spatial skills, the results of which were compared across study groups. In addition, we calculated composite scores for memory (learning, recall, recognition) and executive functions (verbal fluency, cognitive flexibility, working memory). We hypothesized that the nature of memory impairment in ALS will be different from those exhibited by aMCI patients. Patient groups exhibited significant differences in their type of memory deficit, with the ALS group showing impairment only in recognition, whereas aMCI patients showed short and delayed recall performance deficits as well as reduced short-term capacity. Regression analysis revealed a significant impact of executive function on memory performance exclusively for the ALS group, accounting for one fifth of their memory performance. Interestingly, merging all sub scores into a single memory and an executive function score obscured these differences. The presented results indicate that the interpretation of neuropsychological scores needs to take the distinct cognitive profiles in ALS and aMCI into consideration. Importantly, the observed memory deficits in ALS were distinctly different from those observed in aMCI and can be explained only to some extent in the context of comorbid (coexisting) executive dysfunction. These findings highlight the qualitative differences in temporal lobe dysfunction between ALS and aMCI patients, and support temporal lobe dysfunction as a mechanism underlying the distinct cognitive impairments observed in ALS.

Acidosis-Induced Dysfunction of Cortical GABAergic Neurons through Astrocyte-Related Excitotoxicity

PubMed Central

Guan, Sudong; Zhu, Yan; Wang, Jin-Hui

2015-01-01

Background Acidosis impairs cognitions and behaviors presumably by acidification-induced changes in neuronal metabolism. Cortical GABAergic neurons are vulnerable to pathological factors and their injury leads to brain dysfunction. How acidosis induces GABAergic neuron injury remains elusive. As the glia cells and neurons interact each other, we intend to examine the role of the astrocytes in acidosis-induced GABAergic neuron injury. Results Experiments were done at GABAergic cells and astrocytes in mouse cortical slices. To identify astrocytic involvement in acidosis-induced impairment, we induced the acidification in single GABAergic neuron by infusing proton intracellularly or in both neurons and astrocytes by using proton extracellularly. Compared the effects of intracellular acidification and extracellular acidification on GABAergic neurons, we found that their active intrinsic properties and synaptic outputs appeared more severely impaired in extracellular acidosis than intracellular acidosis. Meanwhile, extracellular acidosis deteriorated glutamate transporter currents on the astrocytes and upregulated excitatory synaptic transmission on the GABAergic neurons. Moreover, the antagonists of glutamate NMDA-/AMPA-receptors partially reverse extracellular acidosis-induced injury in the GABAergic neurons. Conclusion Our studies suggest that acidosis leads to the dysfunction of cortical GABAergic neurons by astrocyte-mediated excitotoxicity, in addition to their metabolic changes as indicated previously. PMID:26474076

Rumination, distraction and mindful self-focus: effects on mood, dysfunctional attitudes and cortisol stress response.

PubMed

Kuehner, C; Huffziger, S; Liebsch, K

2009-02-01

Although aggravating effects of rumination on dysfunctional cognitions and endocrine stress responses have been proposed, experimental studies testing these assumptions are lacking. In parallel, mindfulness theory suggests beneficial effects of mindfulness on dysfunctional cognitions. This study aimed to investigate the effects of induced rumination, distraction and mindful self-focus on mood and dysfunctional attitudes and to assess the possible impact of induced rumination on participants' cortisol responses. Sixty university students were subjected to negative mood induction and subsequently randomly assigned to a rumination, distraction or mindful self-focus condition. The latter included statements focusing on self-acceptance and awareness of the breath. Four saliva cortisol samples were selected during the session. Compared to induced rumination, distraction showed a clear beneficial effect on the course of dysphoric mood, whereas a mindful self-focus did not. In contrast to distraction and mindful self-focus, participants induced to ruminate showed significant increases in dysfunctional attitudes from baseline to post-induction. Although rumination was not itself linked to higher cortisol responses, participants scoring high on the Beck Depression Inventory (BDI)-II who were induced to ruminate showed a smaller decrease in cortisol levels than those scoring low on the BDI-II. This study indicates that rumination as a dysfunctional mode of cognitive processing is able to maintain depression-linked dysfunctional thought content. Furthermore, our study revealed preliminary indications for a link between induced rumination and the cortisol stress response in vulnerable individuals.

Decision-Making in Multiple Sclerosis Patients: A Systematic Review

PubMed Central

2018-01-01

Background Multiple sclerosis (MS) is frequently associated with cognitive and behavioural deficits. A growing number of studies suggest an impact of MS on decision-making abilities. The aim of this systematic review was to assess if (1) performance of MS patients in decision-making tasks was consistently different from controls and (2) whether this modification was associated with cognitive dysfunction and emotional alterations. Methods The search was conducted on Pubmed/Medline database. 12 studies evaluating the difference between MS patients and healthy controls using validated decision-making tasks were included. Outcomes considered were quantitative (net scores) and qualitative measurements (deliberation time and learning from feedback). Results Quantitative and qualitative decision-making impairment in MS was present in 64.7% of measurements. Patients were equally impaired in tasks for decision-making under risk and ambiguity. A correlation to other cognitive functions was present in 50% of cases, with the highest associations in the domains of processing speed and attentional capacity. Conclusions In MS patients, qualitative and quantitative modifications may be present in any kind of decision-making task and can appear independently of other cognitive measures. Since decision-making abilities have a significant impact on everyday life, this cognitive aspect has an influential importance in various MS-related treatment settings. PMID:29721338

BDNF pathway is involved in the protective effects of SS-31 on isoflurane-induced cognitive deficits in aging mice.

PubMed

Wu, Jing; Zhang, Mingqiang; Li, Huihui; Sun, Xiaoru; Hao, Shuangying; Ji, Muhuo; Yang, Jianjun; Li, Kuanyu

2016-05-15

Mitochondrial dysfunction has been linked to the earliest pathogenesis of isoflurane-induced cognitive impairments in developing or aging mammalian brain. However, its molecular mechanism is poorly understood and a pharmacologic treatment to rapidly reverse mitochondrial dysfunction is lacking. Fifteen-month-old male C57BL/6 mice were exposed to isoflurane for two hours following intraperitoneal administration of mitochondrion-targeted peptide SS-31 or vehicle with 30min interval. The hippocampus was immediately removed for biochemical assays and mitochondria isolation after inhalation. Behavioral tests were evaluated by the open field test and fear conditioning test 24h after the experiment. We showed that cognitive deficits induced by exposure of the aging mice to isoflurane were accompanied by mitochondrial dysfunction in hippocampus due to loss of the enzymatic activity of complex I. This loss resulted in the increase of reactive oxygen species production, decrease of ATP production and mitochondrial membrane potential, and opening of mitochondrial permeability transition pore. Further, we provided evidence that the BDNF signaling pathway was involved in this process to regulate synaptic plasticity-related proteins, for instance, downregulation of synapsin 1, PSD-95 and p-CREB, and upregulation of NR2A, NR2B, CaMKIIα and CaMKIIβ. Of note, the isoflurane-induced cognitive deficits were rescued by SS-31 through reversal of mitochondrial dysfunction, which facilitated the regulation of BDNF signaling including the expression reversal of aforementioned important synaptic-signaling proteins in aging mice. Our data demonstrate that reversing mitochondrial dysfunction by SS-31 enhances BDNF signaling pathway and synaptic plasticity, and provides protective effects on cognitive function, thereby support the notion that SS-31 may have therapeutic benefits for elderly humans undertaking anesthesia. Copyright © 2016 Elsevier B.V. All rights reserved.

Roles of vascular and metabolic components in cognitive dysfunction of Alzheimer disease: short- and long-term modification by non-genetic risk factors.

PubMed

Sato, Naoyuki; Morishita, Ryuichi

2013-11-05

It is well known that a specific set of genetic and non-genetic risk factors contributes to the onset of Alzheimer disease (AD). Non-genetic risk factors include diabetes, hypertension in mid-life, and probably dyslipidemia in mid-life. This review focuses on the vascular and metabolic components of non-genetic risk factors. The mechanisms whereby non-genetic risk factors modify cognitive dysfunction are divided into four components, short- and long-term effects of vascular and metabolic factors. These consist of (1) compromised vascular reactivity, (2) vascular lesions, (3) hypo/hyperglycemia, and (4) exacerbated AD histopathological features, respectively. Vascular factors compromise cerebrovascular reactivity in response to neuronal activity and also cause irreversible vascular lesions. On the other hand, representative short-term effects of metabolic factors on cognitive dysfunction occur due to hypoglycemia or hyperglycemia. Non-genetic risk factors also modify the pathological manifestations of AD in the long-term. Therefore, vascular and metabolic factors contribute to aggravation of cognitive dysfunction in AD through short-term and long-term effects. β-amyloid could be involved in both vascular and metabolic components. It might be beneficial to support treatment in AD patients by appropriate therapeutic management of non-genetic risk factors, considering the contributions of these four elements to the manifestation of cognitive dysfunction in individual patients, though all components are not always present. It should be clarified how these four components interact with each other. To answer this question, a clinical prospective study that follows up clinical features with respect to these four components: (1) functional MRI or SPECT for cerebrovascular reactivity, (2) MRI for ischemic lesions and atrophy, (3) clinical episodes of hypoglycemia and hyperglycemia, (4) amyloid-PET and tau-PET for pathological features of AD, would be required.

Prefrontal Cortical GABA Modulation of Spatial Reference and Working Memory

PubMed Central

Auger, Meagan L.

2015-01-01

Background: Dysfunction in prefrontal cortex (PFC) GABA transmission has been proposed to contribute to cognitive dysfunction in schizophrenia, yet how this system regulates different cognitive and mnemonic functions remains unclear. Methods: We assessed the effects of pharmacological reduction of GABAA signaling in the medial PFC of rats on spatial reference/working memory using different versions of the radial-arm maze task. We used a massed-trials procedure to probe how PFC GABA regulates susceptibility to proactive interference. Male rats were well-trained to retrieve food from the same 4 arms of an 8-arm maze, receiving 5 trials/day (1–2min intervals). Results: Infusions of the GABAA receptor antagonist bicuculline (12.5–50ng) markedly increased working and reference memory errors and response latencies. Similar treatments also impaired short-term memory on an 8-baited arm task. These effects did not appear to be due to increased susceptibility to proactive interference. In contrast, PFC inactivation via infusion of GABA agonists baclofen/muscimol did not affect reference/working memory. In comparison to the pronounced effects on the 8-arm maze tasks, PFC GABAA antagonism only causes a slight and transient decrease in accuracy on a 2-arm spatial discrimination. Conclusions: These findings demonstrate that prefrontal GABA hypofunction severely disrupts spatial reference and short-term memory and that disinhibition of the PFC can, in some instances, perturb memory processes not normally dependent on the frontal lobes. Moreover, these impairments closely resemble those observed in schizophrenic patients, suggesting that perturbation in PFC GABA signaling may contribute to these types of cognitive deficits associated with the disorder. PMID:25552433

Evaluating the Effect of Cognitive Dysfunction on Mental Imagery in Patients with Stroke Using Temporal Congruence and the Imagined 'Timed Up and Go' Test (iTUG).

PubMed

Geiger, Maxime; Bonnyaud, Céline; Fery, Yves-André; Bussel, Bernard; Roche, Nicolas

2017-01-01

Motor imagery (MI) capacity may be altered following stroke. MI is evaluated by measuring temporal congruence between the timed performance of an imagined and an executed task. Temporal congruence between imagined and physical gait-related activities has not been evaluated following stroke. Moreover, the effect of cognitive dysfunction on temporal congruence is not known. To assess temporal congruence between the Timed Up and Go test (TUG) and the imagined TUG (iTUG) tests in patients with stroke and to investigate the role played by cognitive dysfunctions in changes in temporal congruence. TUG and iTUG performance were recorded and compared in twenty patients with chronic stroke and 20 controls. Cognitive function was measured using the Montreal Cognitive Assessment (MOCA), the Frontal Assessment Battery at Bedside (FAB) and the Bells Test. The temporal congruence of the patients with stroke was significantly altered compared to the controls, indicating a loss of MI capacity (respectively 45.11 ±35.11 vs 24.36 ±17.91, p = 0.02). Furthermore, iTUG test results were positively correlated with pathological scores on the Bells Test (r = 0.085, p = 0.013), likely suggesting that impairment of attention was a contributing factor. These results highlight the importance of evaluating potential attention disorder in patients with stroke to optimise the use of MI for rehabilitation and recovery. However further study is needed to determine how MI should be used in the case of cognitive dysfunction.

The effects and mechanisms of mitochondrial nutrient alpha-lipoic acid on improving age-associated mitochondrial and cognitive dysfunction: an overview.

PubMed

Liu, Jiankang

2008-01-01

We have identified a group of nutrients that can directly or indirectly protect mitochondria from oxidative damage and improve mitochondrial function and named them "mitochondrial nutrients". The direct protection includes preventing the generation of oxidants, scavenging free radicals or inhibiting oxidant reactivity, and elevating cofactors of defective mitochondrial enzymes with increased Michaelis-Menten constant to stimulate enzyme activity, and also protect enzymes from further oxidation, and the indirect protection includes repairing oxidative damage by enhancing antioxidant defense systems either through activation of phase 2 enzymes or through increase in mitochondrial biogenesis. In this review, we take alpha-lipoic acid (LA) as an example of mitochondrial nutrients by summarizing the protective effects and possible mechanisms of LA and its derivatives on age-associated cognitive and mitochondrial dysfunction of the brain. LA and its derivatives improve the age-associated decline of memory, improve mitochondrial structure and function, inhibit the age-associated increase of oxidative damage, elevate the levels of antioxidants, and restore the activity of key enzymes. In addition, co-administration of LA with other mitochondrial nutrients, such as acetyl-L: -carnitine and coenzyme Q10, appears more effective in improving cognitive dysfunction and reducing oxidative mitochondrial dysfunction. Therefore, administrating mitochondrial nutrients, such as LA and its derivatives in combination with other mitochondrial nutrients to aged people and patients suffering from neurodegenerative diseases, may be an effective strategy for improving mitochondrial and cognitive dysfunction.

Myopia and cognitive dysfunction among elderly Chinese adults: a propensity score matching analysis.

PubMed

Sun, Hong-Peng; Liu, Hu; Xu, Yong; Pan, Chen-Wei

2016-03-01

The association between myopia and cognitive dysfunction among elderly adults was assessed by applying a Propensity Score Matching (PSM) approach. This is a statistical method which allows investigators to estimate causal treatment effects using observational or nonrandomised data. The study was designed as a community-based cross-sectional study based on a Chinese cohort aged 60 years or older in China. Objective refraction was measured using an autorefractor and subjective refraction was used to refine vision, using the results of the objective refraction as the starting point. Myopia was defined as a spherical equivalent value of less than -0.50 dioptre (D) in the right eye. The Abbreviated Mental Test (AMT) was used for cognitive assessment. The propensity scores for myopia were formulated using 13 potential confounders. We matched the propensity scores for subjects with and without myopia within a caliper of 0.01 of logit function of propensity scores. About 4123 elderly adults who successfully completed the AMT were included in this analysis. The odds ratio (OR) of cognitive dysfunction for myopia before matching was 1.98 (95% confidence interval [CI] 1.61, 2.44; p < 0.001). There were significant covariate imbalances between comparison groups and after propensity score matching, covariate imbalance was significantly reduced. After propensity score matching, the OR of cognitive dysfunction was marginally significant and the magnitude of association was reduced (OR: 1.31 95% CI 1.00, 1.71; p = 0.05). Traditional multivariate logistic regression modelling found an OR of 1.52 (95% CI 1.23, 2.06; p < 0.001) after adjusting for the 13 potential confounders. Myopia was associated with a higher prevalence of cognitive dysfunction among elderly Chinese aged 60 years or older in China. The PSM approach may be a useful method to address selection bias in observational studies when randomised trials cannot ethically be conducted. © 2015 The Authors Ophthalmic & Physiological Optics © 2015 The College of Optometrists.

Effect of Area-Level Socioeconomic Deprivation on Risk of Cognitive Dysfunction in Older Adults.

PubMed

McCann, Adrian; McNulty, Helene; Rigby, Jan; Hughes, Catherine F; Hoey, Leane; Molloy, Anne M; Cunningham, Conal J; Casey, Miriam C; Tracey, Fergal; O'Kane, Maurice J; McCarroll, Kevin; Ward, Mary; Moore, Katie; Strain, J J; Moore, Adrian

2018-02-12

To investigate the relationship between area-level deprivation and risk of cognitive dysfunction. Cross-sectional analysis. The Trinity, Ulster, and Department of Agriculture (TUDA) study from 2008 to 2012. Community-dwelling adults aged 74.0 ± 8.3 without dementia (N = 5,186; 67% female). Adopting a cross-jurisdictional approach, geo-referenced address-based information was used to map and link participants to official socioeconomic indicators of deprivation within the United Kingdom and the Republic of Ireland. Participants were assigned an individual deprivation score related to the smallest administrative area in which they lived. These scores were categorized into comparable quintiles, that were then used to integrate the datasets from both countries. Cognitive health was assessed using the Mini-Mental State Examination (MMSE); cognitive dysfunction was defined as a MMSE score of 24 or less. Approximately one-quarter of the cohort resided within the most-deprived districts in both countries. Greater area-level deprivation was associated with significantly lower MMSE scores; fewer years of formal education; greater anxiety, depression, smoking and alcohol use, and obesity; and more adverse outcomes, including higher blood pressure and diabetes risk. After adjustment for relevant covariates, area deprivation was associated with significantly higher risk of cognitive dysfunction (odds ratio =1.40, 95% confidence interval = 1.05-1.87, P = .02, for most vs least deprived). This analysis combining data from two health systems shows that area deprivation is an independent risk factor for cognitive dysfunction in older adults. Adults living in areas of greatest socioeconomic deprivation may benefit from targeted strategies aimed at improving modifiable risk factors for dementia. Further cross-national analysis investigating the impact of area-level deprivation is needed to address socioeconomic disparities and shape future policy to improve health outcomes in older adults. © 2018, Copyright the Authors Journal compilation © 2018, The American Geriatrics Society.

Negative Mood States or Dysfunctional Cognitions: Their Independent and Interactional Effects in Influencing Severity of Gambling Among Chinese Problem Gamblers in Hong Kong.

PubMed

Wong, Daniel Fu Keung; Zhuang, Xiao Yu; Jackson, Alun; Dowling, Nicki; Lo, Herman Hay Ming

2017-09-04

Gambling-related cognitions and negative psychological states have been proposed as major factors in the initiation and maintenance of problem gambling (PG). While there are a substantial number of studies supporting the role of cognitive dysfunctions in the initiation and maintenance of PG, very few empirical studies have explored the specific role of negative psychological states in influencing PG behaviours. In addition, very few studies have examined the interaction effects of cognitive dysfunctions and negative psychological states in exerting influence on PG behaviours. Therefore, the present study aims to examine the main and interaction effects of gambling-related cognitions and psychological states on the gambling severity among a group of problem gamblers in Hong Kong. A cross-sectional research design was adopted. A purposive sample of 177 problem gamblers who sought treatment from a social service organization in Hong Kong completed a battery of standardised questionnaires. While gambling-related cognitions were found to exert significant effects on gambling severity, negative psychological states (i.e. stress) significantly moderated the relationship between gambling cognitions and gambling severity. In essence, those participants who reported a higher level of stress had more stable and serious gambling problems than those who reported a lower level of stress irrespective of the level of gambling-related cognitions. The findings of the moderating role of negative emotions in the relationship between cognitive distortions and severity of gambling provide insight towards developing an integrated intervention model which includes both cognitive-behavioural and emotion regulation strategies in helping people with PG.

Meta-Analysis of Functional Neuroimaging and Cognitive Control Studies in Schizophrenia: Preliminary Elucidation of a Core Dysfunctional Timing Network

PubMed Central

Alústiza, Irene; Radua, Joaquim; Albajes-Eizagirre, Anton; Domínguez, Manuel; Aubá, Enrique; Ortuño, Felipe

2016-01-01

Timing and other cognitive processes demanding cognitive control become interlinked when there is an increase in the level of difficulty or effort required. Both functions are interrelated and share neuroanatomical bases. A previous meta-analysis of neuroimaging studies found that people with schizophrenia had significantly lower activation, relative to normal controls, of most right hemisphere regions of the time circuit. This finding suggests that a pattern of disconnectivity of this circuit, particularly in the supplementary motor area, is a trait of this mental disease. We hypothesize that a dysfunctional temporal/cognitive control network underlies both cognitive and psychiatric symptoms of schizophrenia and that timing dysfunction is at the root of the cognitive deficits observed. The goal of our study was to look, in schizophrenia patients, for brain structures activated both by execution of cognitive tasks requiring increased effort and by performance of time perception tasks. We conducted a signed differential mapping (SDM) meta-analysis of functional neuroimaging studies in schizophrenia patients assessing the brain response to increasing levels of cognitive difficulty. Then, we performed a multimodal meta-analysis to identify common brain regions in the findings of that SDM meta-analysis and our previously-published activation likelihood estimate (ALE) meta-analysis of neuroimaging of time perception in schizophrenia patients. The current study supports the hypothesis that there exists an overlap between neural structures engaged by both timing tasks and non-temporal cognitive tasks of escalating difficulty in schizophrenia. The implication is that a deficit in timing can be considered as a trait marker of the schizophrenia cognitive profile. PMID:26925013

Cognitive deficits in recent-onset and chronic schizophrenia☆

PubMed Central

Sponheim, S.R.; Jung, R.E.; Seidman, L.J.; Mesholam-Gately, R.I.; Manoach, D.S.; O'Leary, D.S.; Ho, B.C.; Andreasen, N.C.; Lauriello, J.; Schulz, S.C.

2014-01-01

Although cognitive dysfunction is a primary characteristic of schizophrenia, only recently have investigations begun to pinpoint when the dysfunction develops in the individual afflicted by the disorder. Research to date provides evidence for significant cognitive impairments prior to disorder onset. Less is known about the course of cognitive dysfunction from onset to the chronic phase of schizophrenia. Although longitudinal studies are optimal for assessing stability of cognitive deficits, practice effects often confound assessments, and large and representative subject samples have not been followed over long periods of time. We report results of a cross-sectional study of cognitive deficits early and late in the course of schizophrenia carried out at four different geographic locations to increase sample size and generalizability of findings. We examined a broad set of cognitive functions in 41 recent-onset schizophrenia patients and 106 chronic schizophrenia patients. The study included separate groups of 43 matched controls for the recent-onset sample and 105 matched controls for the chronic schizophrenia sample in order to evaluate the effects of cohort (i.e., age) and diagnosis (i.e., schizophrenia) on cognitive functions. All measures of cognitive function showed effects of diagnosis; however, select time-based measures of problem solving and fine motor dexterity exhibited interactions of diagnosis and cohort indicating that these deficits may progress beyond what is expected with normal aging. Also, worse recall of material in episodic memory was associated with greater length of illness. Nevertheless, findings indicate that nearly all cognitive deficits are comparably impaired across recent-onset and chronic schizophrenia. PMID:19878956

Cognitive deficits in recent-onset and chronic schizophrenia.

PubMed

Sponheim, S R; Jung, R E; Seidman, L J; Mesholam-Gately, R I; Manoach, D S; O'Leary, D S; Ho, B C; Andreasen, N C; Lauriello, J; Schulz, S C

2010-05-01

Although cognitive dysfunction is a primary characteristic of schizophrenia, only recently have investigations begun to pinpoint when the dysfunction develops in the individual afflicted by the disorder. Research to date provides evidence for significant cognitive impairments prior to disorder onset. Less is known about the course of cognitive dysfunction from onset to the chronic phase of schizophrenia. Although longitudinal studies are optimal for assessing stability of cognitive deficits, practice effects often confound assessments, and large and representative subject samples have not been followed over long periods of time. We report results of a cross-sectional study of cognitive deficits early and late in the course of schizophrenia carried out at four different geographic locations to increase sample size and generalizability of findings. We examined a broad set of cognitive functions in 41 recent-onset schizophrenia patients and 106 chronic schizophrenia patients. The study included separate groups of 43 matched controls for the recent-onset sample and 105 matched controls for the chronic schizophrenia sample in order to evaluate the effects of cohort (i.e., age) and diagnosis (i.e., schizophrenia) on cognitive functions. All measures of cognitive function showed effects of diagnosis; however, select time-based measures of problem solving and fine motor dexterity exhibited interactions of diagnosis and cohort indicating that these deficits may progress beyond what is expected with normal aging. Also, worse recall of material in episodic memory was associated with greater length of illness. Nevertheless, findings indicate that nearly all cognitive deficits are comparably impaired across recent-onset and chronic schizophrenia. Published by Elsevier Ltd.

Peripheral DNA methylation, cognitive decline and brain aging: pilot findings from the Whitehall II imaging study.

PubMed

Chouliaras, Leonidas; Pishva, Ehsan; Haapakoski, Rita; Zsoldos, Eniko; Mahmood, Abda; Filippini, Nicola; Burrage, Joe; Mill, Jonathan; Kivimäki, Mika; Lunnon, Katie; Ebmeier, Klaus P

2018-05-01

The present study investigated the link between peripheral DNA methylation (DNAm), cognitive impairment and brain aging. We tested the association between blood genome-wide DNAm profiles using the Illumina 450K arrays, cognitive dysfunction and brain MRI measures in selected participants of the Whitehall II imaging sub-study. Eight differentially methylated regions were associated with cognitive impairment. Accelerated aging based on the Hannum epigenetic clock was associated with mean diffusivity and global fractional anisotropy. We also identified modules of co-methylated loci associated with white matter hyperintensities. These co-methylation modules were enriched among pathways relevant to β-amyloid processing and glutamatergic signaling. Our data support the notion that blood DNAm changes may have utility as a biomarker for cognitive dysfunction and brain aging.

The anatomy of cognitive impairment in amyotrophic lateral sclerosis: more than frontal lobe dysfunction.

PubMed

Tsermentseli, Stella; Leigh, P Nigel; Goldstein, Laura H

2012-02-01

Cognitive and behavioural impairments accompanying amyotrophic lateral sclerosis (ALS) have been reported since the early 20th century. Typically, these changes can be associated with a dysexecutive syndrome or manifest as a frontotemporal dementia (FTD). Although the nature of specific frontotemporal dysfunction in ALS remains to be refined, as with the clinical presentation, there is likely to be significant heterogeneity. This article will review the current state of knowledge regarding the neuropathological and neuroanatomical basis for cognitive dysfunction in ALS. Neuropathological findings suggest that ALS does not selectively affect the frontotemporal network but rather is part of a broad clinico-pathological spectrum now known as TAR-DNA binding protein (TDP)-43 proteinopathies. Functional neuroimaging has supported neuropsychological findings of frontotemporal dysfunction but has also implied the involvement of somatosensory areas. Structural neuroimaging has not been able to establish a specific hypothesis of extra-motor cortical atrophy beyond the combination of various frontal, temporal and limbic areas. The finding of reduction in the integrity of white matter in the frontal, temporal and parietal lobes including long association fibers suggests that subcortical involvement may underlie both cognitive and functional changes in ALS. Future perspectives for further investigations are highlighted. Copyright © 2011 Elsevier Srl. All rights reserved.

Selective cognitive empathy deficit in adolescents with restrictive anorexia nervosa

PubMed Central

Calderoni, Sara; Fantozzi, Pamela; Maestro, Sandra; Brunori, Elena; Narzisi, Antonio; Balboni, Giulia; Muratori, Filippo

2013-01-01

Background A growing, but conflicting body of literature suggests altered empathic abilities in subjects with anorexia nervosa-restricting type (AN-R). This study aims to characterize the cognitive and affective empathic profiles of adolescents with purely AN-R. Methods As part of a standardized clinical and research protocol, the Interpersonal Reactivity Index (IRI), a valid and reliable self-reported instrument to measure empathy, was administered to 32 female adolescents with AN-R and in 41 healthy controls (HC) comparisons, matched for age and gender. Correlational analyses were performed to evaluate the links between empathy scores and psychopathological measures. Results Patients scored significantly lower than HC on cognitive empathy (CE), while they did not differ from controls on affective empathy (AE). The deficit in CE was not related to either disease severity nor was it related to associated psychopathology. Conclusion These results, albeit preliminary, suggest that a dysfunctional pattern of CE capacity may be a stable trait of AN-R that should be taken into account not only for the clinical management, but also in preventive and therapeutic intervention. PMID:24204149

Comparisons of Korsakoff and Non-Korsakoff Alcoholics on Neuropsychological Tests of Prefrontal Brain Functioning

PubMed Central

Oscar-Berman, Marlene; Kirkley, Shalene M.; Gansler, David A.; Couture, Ashley

2014-01-01

Background Evidence suggests that alcoholics exhibit particular deficits in brain systems involving the prefrontal cortex, but few studies have directly compared patients with and without Korsakoff’s syndrome on measures of prefrontal integrity. Methods Neuropsychological tasks sensitive to dysfunction of frontal brain systems were administered, along with standard tests of memory, intelligence, and visuospatial abilities, to 50 healthy, abstinent, nonamnesic alcoholics, 6 patients with alcohol-induced persisting amnestic disorder (Korsakoff’s syndrome), 6 brain-damaged controls with right hemisphere lesions, and 82 healthy nonalcoholic controls. Results Korsakoff patients were impaired on tests of memory, fluency, cognitive flexibility, and perseveration. Non-Korsakoff alcoholics showed some frontal system deficits as well, but these were mild. Cognitive deficits in non-Korsakoff alcoholics were related to age, duration of abstinence (less than 5 years), duration of abuse (more than 20 years), and amount of alcohol intake. Conclusions Abnormalities of frontal system functioning are most apparent in alcoholics with Korsakoff’s syndrome. In non-Korsakoff alcoholics, factors contributing to cognitive performance are age, duration of abstinence, duration of alcoholism, and amount of alcohol consumed. PMID:15100620

Diagnosis and treatment of vascular damage in dementia.

PubMed

Biessels, Geert Jan

2016-05-01

This paper provides an overview of cognitive impairment due to vascular brain damage, which is referred to as vascular cognitive impairment (VCI). Over the past decades, we have seen marked progress in detecting VCI, both through maturation of diagnostic concepts and through advances in brain imaging, especially MRI. Yet in daily practice, it is often challenging to establish the diagnosis, particularly in patients where there is no evident temporal relation between a cerebrovascular event and cognitive dysfunction. Because vascular damage is such a common cause of cognitive dysfunction, it provides an obvious target for treatment. In patients whose cognitive dysfunction follows directly after a stroke, the etiological classification of this stroke will direct treatment. In many patients however, VCI develops due to so-called "silent vascular damage," without evident cerebrovascular events. In these patients, small vessel diseases (SVDs) are the most common cause. Yet no SVD-specific treatments currently exist, which is due to incomplete understanding of the pathophysiology. This review addresses developments in this field. It offers a framework to translate diagnostic criteria to daily practice, addresses treatment, and highlights some future perspectives. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia, edited by M. Paul Murphy, Roderick A. Corriveau, and Donna M. Wilcock. Copyright © 2015 Elsevier B.V. All rights reserved.

The influence of cognitive dysfunction on benefit from learning and memory rehabilitation in MS: A sub-analysis of the MEMREHAB trial.

PubMed

Chiaravalloti, Nancy D; DeLuca, John

2015-10-01

This study examined the influence of processing speed (PS) on benefit from treatment with the modified Story Memory Technique(©) (mSMT), a behavioral intervention shown to improve new learning and memory in multiple sclerosis (MS). This double-blind, placebo-controlled, randomized clinical trial included 85 participants with clinically definite MS, 45 assigned to the treatment group and 40 to the placebo-control group. Participants completed baseline and follow-up neuropsychological assessment. The present study represents a post-hoc analysis to examine the role of PS on treatment efficacy. The treatment group showed a significantly improved CVLT learning slope relative to the placebo group post-treatment, after co-varying PS performance. SDMT performance was a significant predictor of benefit from mSMT treatment, beyond group assignment. Post-hoc analysis indicated a significant correlation between the SDMT and overall cognition, indicating that the SDMT may be serving as a proxy for overall cognitive impairment. Performance on measures of cognitive dysfunction aside from learning and memory impact the benefit of mSMT treatment. While the current study focused on PS as a critical factor, PS may be serving as a marker for generalized cognitive dysfunction. Implications for cognitive rehabilitation in MS are discussed. © The Author(s), 2015.

Interictal epileptic discharge correlates with global and frontal cognitive dysfunction in temporal lobe epilepsy.

PubMed

Dinkelacker, Vera; Xin, Xu; Baulac, Michel; Samson, Séverine; Dupont, Sophie

2016-09-01

Temporal lobe epilepsy (TLE) with hippocampal sclerosis has widespread effects on structural and functional connectivity and often entails cognitive dysfunction. EEG is mandatory to disentangle interactions in epileptic and physiological networks which underlie these cognitive comorbidities. Here, we examined how interictal epileptic discharges (IEDs) affect cognitive performance. Thirty-four patients (right TLE=17, left TLE=17) were examined with 24-hour video-EEG and a battery of neuropsychological tests to measure intelligence quotient and separate frontal and temporal lobe functions. Hippocampal segmentation of high-resolution T1-weighted imaging was performed with FreeSurfer. Partial correlations were used to compare the number and distribution of clinical interictal spikes and sharp waves with data from imagery and psychological tests. The number of IEDs was negatively correlated with executive functions, including verbal fluency and intelligence quotient (IQ). Interictal epileptic discharge affected cognitive function in patients with left and right TLE differentially, with verbal fluency strongly related to temporofrontal spiking. In contrast, IEDs had no clear effects on memory functions after corrections with partial correlations for age, age at disease onset, disease duration, and hippocampal volume. In patients with TLE of long duration, IED occurrence was strongly related to cognitive deficits, most pronounced for frontal lobe function. These data suggest that IEDs reflect dysfunctional brain circuitry and may serve as an independent biomarker for cognitive comorbidity. Copyright © 2016. Published by Elsevier Inc.

Brain 18F-FDG PET Metabolic Abnormalities in Patients with Long-Lasting Macrophagic Myofascitis.

PubMed

Van Der Gucht, Axel; Aoun Sebaiti, Mehdi; Guedj, Eric; Aouizerate, Jessie; Yara, Sabrina; Gherardi, Romain K; Evangelista, Eva; Chalaye, Julia; Cottereau, Anne-Ségolène; Verger, Antoine; Bachoud-Levi, Anne-Catherine; Abulizi, Mukedaisi; Itti, Emmanuel; Authier, François-Jérôme

2017-03-01

The aim of this study was to characterize brain metabolic abnormalities in patients with macrophagic myofascitis (MMF) and the relationship with cognitive dysfunction through the use of PET with 18 F-FDG. Methods: 18 F-FDG PET brain imaging and a comprehensive battery of neuropsychological tests were performed in 100 consecutive MMF patients (age [mean ± SD], 45.9 ± 12 y; 74% women). Images were analyzed with statistical parametric mapping (SPM12). Through the use of analysis of covariance, all 18 F-FDG PET brain images of MMF patients were compared with those of a reference population of 44 healthy subjects similar in age (45.4 ± 16 y; P = 0.87) and sex (73% women; P = 0.88). The neuropsychological assessment identified 4 categories of patients: those with no significant cognitive impairment ( n = 42), those with frontal subcortical (FSC) dysfunction ( n = 29), those with Papez circuit dysfunction ( n = 22), and those with callosal disconnection ( n = 7). Results: In comparison with healthy subjects, the whole population of patients with MMF exhibited a spatial pattern of cerebral glucose hypometabolism ( P < 0.001) involving the occipital lobes, temporal lobes, limbic system, cerebellum, and frontoparietal cortices, as shown by analysis of covariance. The subgroup of patients with FSC dysfunction exhibited a larger extent of involved areas (35,223 voxels vs. 13,680 voxels in the subgroup with Papez circuit dysfunction and 5,453 voxels in patients without cognitive impairment). Nonsignificant results were obtained for the last subgroup because of its small population size. Conclusion: Our study identified a peculiar spatial pattern of cerebral glucose hypometabolism that was most marked in MMF patients with FSC dysfunction. Further studies are needed to determine whether this pattern could represent a diagnostic biomarker of MMF in patients with chronic fatigue syndrome and cognitive dysfunction. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Validity of Montreal Cognitive Assessment in non-english speaking patients with Parkinson's disease.

PubMed

Krishnan, Syam; Justus, Sunitha; Meluveettil, Radhamani; Menon, Ramshekhar N; Sarma, Sankara P; Kishore, Asha

2015-01-01

The Montreal Cognitive Assessment is a brief and easy screening tool for accurately testing cognitive dysfunction in Parkinson's disease. We tested its validity for use in non-English (Malayalam) speaking patients with Parkinson's disease. We developed a Malayalam (a south-Indian language) version of Montreal Cognitive Assessment and applied to 70 patients with Parkinson's disease and 60 age- and education-matched healthy controls. Metric properties were assessed, and the scores were compared with the performance in validated Malayalam versions of Mini Mental Status Examination and Addenbrooke's Cognitive Examination. The Montreal Cognitive Assessment-Malayalam showed good internal consistency and test-retest reliability and its scores correlated with Mini Mental Status Examination (patients: R = 0.70; P < 0.001; healthy controls: R = 0.26; P = 0.04) and Addenbrooke's Cognitive Examination (patients: R = 0.8; P < 0.001; healthy controls: R = 0.52; P < 0.001) scores. This study establishes the reliability of cross-cultural adaptation of Montreal Cognitive Assessment for assessing cognition in Malayalam-speaking Parkinson's disease patients for early screening and potential future interventions for cognitive dysfunction.

Postoperative cognitive dysfunction in older adults: a call for nursing involvement.

PubMed

Sorrell, Jeanne M

2014-11-01

As the population continues to age and new medical developments make surgery at advanced ages increasingly possible, it is important to consider how older adults tolerate surgery and anesthesia. Considerable evidence shows that older adults have a higher risk of developing postoperative cognitive dysfunction (POCD), which leads to transient and sometimes long-term cognitive changes that may affect quality of life. Because little is known about how to prevent or treat POCD, it is important that nurses identify ways in which they can intervene to help patients who experience this disorder. Copyright 2014, SLACK Incorporated.

Houttuynia cordata Improves Cognitive Deficits in Cholinergic Dysfunction Alzheimer's Disease-Like Models.

PubMed

Huh, Eugene; Kim, Hyo Geun; Park, Hanbyeol; Kang, Min Seo; Lee, Bongyong; Oh, Myung Sook

2014-05-01

Cognitive impairment is a result of dementia of diverse causes, such as cholinergic dysfunction and Alzheimer's disease (AD). Houttuynia cordata Thunb. (Saururaceae) has long been used as a traditional herbal medicine. It has biological activities including protective effects against amyloid beta (Aβ) toxicity, via regulation of calcium homeostasis, in rat hippocampal cells. To extend previous reports, we investigated the effects of water extracts of H. cordata herb (HCW) on tauopathies, also involving calcium influx. We then confirmed the effects of HCW in improving memory impairment and neuronal damage in mice with Aβ-induced neurotoxicity. We also investigated the effects of HCW against scopolamine-induced cholinergic dysfunction in mice. In primary neuronal cells, HCW inhibited the phosphorylation of tau by regulating p25/p35 expression in Aβ-induced neurotoxicity. In mice with Aβ-induced neurotoxicity, HCW improved cognitive impairment, as assessed with behavioral tasks, such as novel object recognition, Y-maze, and passive avoidance tasks. HCW also inhibited the degeneration of neurons in the CA3 region of the hippocampus in Aβ-induced neurotoxicity. Moreover, HCW, which had an IC50 value of 79.7 μg/ml for acetylcholinesterase inhibition, ameliorated scopolamine-induced cognitive impairment significantly in Y-maze and passive avoidance tasks. These results indicate that HCW improved cognitive impairment, due to cholinergic dysfunction, with inhibitory effects against tauopathies and cholinergic antagonists, suggesting that HCW may be an interesting candidate to investigate for the treatment of AD.

Houttuynia cordata Improves Cognitive Deficits in Cholinergic Dysfunction Alzheimer’s Disease-Like Models

PubMed Central

Huh, Eugene; Kim, Hyo Geun; Park, Hanbyeol; Kang, Min Seo; Lee, Bongyong; Oh, Myung Sook

2014-01-01

Cognitive impairment is a result of dementia of diverse causes, such as cholinergic dysfunction and Alzheimer’s disease (AD). Houttuynia cordata Thunb. (Saururaceae) has long been used as a traditional herbal medicine. It has biological activities including protective effects against amyloid beta (Aβ) toxicity, via regulation of calcium homeostasis, in rat hippocampal cells. To extend previous reports, we investigated the effects of water extracts of H. cordata herb (HCW) on tauopathies, also involving calcium influx. We then confirmed the effects of HCW in improving memory impairment and neuronal damage in mice with Aβ-induced neurotoxicity. We also investigated the effects of HCW against scopolamine-induced cholinergic dysfunction in mice. In primary neuronal cells, HCW inhibited the phosphorylation of tau by regulating p25/p35 expression in Aβ-induced neurotoxicity. In mice with Aβ-induced neurotoxicity, HCW improved cognitive impairment, as assessed with behavioral tasks, such as novel object recognition, Y-maze, and passive avoidance tasks. HCW also inhibited the degeneration of neurons in the CA3 region of the hippocampus in Aβ-induced neurotoxicity. Moreover, HCW, which had an IC50 value of 79.7 μg/ml for acetylcholinesterase inhibition, ameliorated scopolamine-induced cognitive impairment significantly in Y-maze and passive avoidance tasks. These results indicate that HCW improved cognitive impairment, due to cholinergic dysfunction, with inhibitory effects against tauopathies and cholinergic antagonists, suggesting that HCW may be an interesting candidate to investigate for the treatment of AD. PMID:25009697

The cycle of schizoaffective disorder, cognitive ability, alcoholism, and suicidality.

PubMed

Goldstein, Gerald; Haas, Gretchen L; Pakrashi, Manish; Novero, Ada M; Luther, James F

2006-02-01

In this study we investigated the putative role of cognitive dysfunction, diagnosis (schizoaffective versus schizophrenia disorder), and alcoholism as risk factors for suicidal behavior among individuals with DSM-TV schizophrenia or schizoaffective disorders. Subjects received cognitive tests and medical records were reviewed for evidence of a history of suicide attempts or suicidal ideation. Discriminant analysis was used to identify cognitive test performance measures that distinguished those with versus those without suicidal behavior. None of the cognitive measures discriminated between the two groups. The rates of suicidal behavior (suicidal ideation and suicide attempts) did not differ between participants with versus those without comorbid alcohol use. An association was found between suicidal behavior and the diagnosis of schizoaffective disorder. It was concluded that the history of prominent mood syndromes characteristic of schizoaffective disorder contributes to increased risk of suicidal behaviors. Cognitive dysfunction and/or alcoholism did not contribute additionally to risk in this study.

Persistent anterograde amnesia following limbic encephalitis associated with antibodies to the voltage-gated potassium channel complex.

PubMed

Butler, Christopher R; Miller, Thomas D; Kaur, Manveer S; Baker, Ian W; Boothroyd, Georgie D; Illman, Nathan A; Rosenthal, Clive R; Vincent, Angela; Buckley, Camilla J

2014-04-01

Limbic encephalitis (LE) associated with antibodies to the voltage-gated potassium channel complex (VGKC) is a potentially reversible cause of cognitive impairment. Despite the prominence of cognitive dysfunction in this syndrome, little is known about patients' neuropsychological profile at presentation or their long-term cognitive outcome. We used a comprehensive neuropsychological test battery to evaluate cognitive function longitudinally in 19 patients with VGKC-LE. Before immunotherapy, the group had significant impairment of memory, processing speed and executive function, whereas language and perceptual organisation were intact. At follow-up, cognitive impairment was restricted to the memory domain, with processing speed and executive function having returned to the normal range. Residual memory function was predicted by the antibody titre at presentation. The results show that, despite broad cognitive dysfunction in the acute phase, patients with VGKC-LE often make a substantial recovery with immunotherapy but may be left with permanent anterograde amnesia.

Assessment of subjective and objective cognitive function in bipolar disorder: Correlations, predictors and the relation to psychosocial function.

PubMed

Demant, Kirsa M; Vinberg, Maj; Kessing, Lars V; Miskowiak, Kamilla W

2015-09-30

Cognitive dysfunction is prevalent in bipolar disorder (BD). However, the evidence regarding the association between subjective cognitive complaints, objective cognitive performance and psychosocial function is sparse and inconsistent. Seventy seven patients with bipolar disorder who presented cognitive complaints underwent assessment of objective and subjective cognitive function and psychosocial functioning as part of their participation in two clinical trials. We investigated the association between global and domain-specific objective and subjective cognitive function and between global cognitive function and psychosocial function. We also identified clinical variables that predicted objective and subjective cognitive function and psychosocial functioning. There was a correlation between global subjective and objective measures of cognitive dysfunction but not within the individual cognitive domains. However, the correlation was weak, suggesting that cognitive complaints are not an assay of cognition per se. Self-rated psychosocial difficulties were associated with subjective (but not objective) cognitive impairment and both subjective cognitive and psychosocial difficulties were predicted by depressive symptoms. Our findings indicate that adequate assessment of cognition in the clinical treatment of BD and in drug trials targeting cognition requires implementation of not only subjective measures but also of objective neuropsychological tests. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Electroencephalogram power changes as a correlate of chemotherapy-associated fatigue and cognitive dysfunction.

PubMed

Moore, Halle C F; Parsons, Michael W; Yue, Guang H; Rybicki, Lisa A; Siemionow, Wlodzimierz

2014-08-01

Persistent fatigue and cognitive dysfunction are poorly understood potential long-term effects of adjuvant chemotherapy. In this pilot study, we assessed the value of electroencephalogram (EEG) power measurements as a means to evaluate physical and mental fatigue associated with chemotherapy. Women planning to undergo adjuvant chemotherapy for breast cancer and healthy controls underwent neurophysiologic assessments at baseline, during the time of chemotherapy treatment, and at 1 year. Repeated measures analysis of variance was used to analyze the data. Compared with controls, patients reported more subjective fatigue at baseline that increased during chemotherapy and did not entirely resolve by 1 year. Performance on endurance testing was similar in patients versus controls at all time points; however, values of EEG power increased after a physical task in patients during chemotherapy but not controls. Compared with controls, subjective mental fatigue was similar for patients at baseline and 1 year but worsened during chemotherapy. Patients performed similarly to controls on formal cognitive testing at all time points, but EEG activity after the cognitive task was increased in patients only during chemotherapy. EEG power measurement has the potential to provide a sensitive neurophysiologic correlate of cancer treatment-related fatigue and cognitive dysfunction.

Does True Neurocognitive Dysfunction Contribute to Minnesota Multiphasic Personality Inventory-2nd Edition-Restructured Form Cognitive Validity Scale Scores?

PubMed

Martin, Phillip K; Schroeder, Ryan W; Heinrichs, Robin J; Baade, Lyle E

2015-08-01

Previous research has demonstrated RBS and FBS-r to identify non-credible reporters of cognitive symptoms, but the extent that these scales might be influenced by true neurocognitive dysfunction has not been previously studied. The present study examined the relationship between these cognitive validity scales and neurocognitive performance across seven domains of cognitive functioning, both before and after controlling for PVT status in 120 individuals referred for neuropsychological evaluations. Variance in RBS, but not FBS-r, was significantly accounted for by neurocognitive test performance across most cognitive domains. After controlling for PVT status, however, relationships between neurocognitive test performance and validity scales were no longer significant for RBS, and remained non-significant for FBS-r. Additionally, PVT failure accounted for a significant proportion of the variance in both RBS and FBS-r. Results support both the convergent and discriminant validity of RBS and FBS-r. As neither scale was impacted by true neurocognitive dysfunction, these findings provide further support for the use of RBS and FBS-r in neuropsychological evaluations. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Cognitive dysfunction and depression in adult kidney transplant recipients: baseline findings from the FAVORIT Ancillary Cognitive Trial (FACT)

USDA-ARS?s Scientific Manuscript database

Hyperhomocysteinemia and B-vitamin deficiency may be treatable risk factors for cognitive impairment and decline. Hyperhomocysteinemia, cognitive impairment and depression all are common in individuals with kidney disease, including kidney transplant recipient. Accordingly, we assessed the prevalenc...

Noradrenergic Dysfunction in Alzheimer's and Parkinson's Diseases-An Overview of Imaging Studies.

PubMed

Peterson, Andrew C; Li, Chiang-Shan R

2018-01-01

Noradrenergic dysfunction contributes to cognitive impairment in Alzheimer's Disease (AD) and Parkinson's Disease (PD). Conventional therapeutic strategies seek to enhance cholinergic and dopaminergic neurotransmission in AD and PD, respectively, and few studies have examined noradrenergic dysfunction as a target for medication development. We review the literature of noradrenergic dysfunction in AD and PD with a focus on human imaging studies that implicate the locus coeruleus (LC) circuit. The LC sends noradrenergic projections diffusely throughout the cerebral cortex and plays a critical role in attention, learning, working memory, and cognitive control. The LC undergoes considerable degeneration in both AD and PD. Advances in magnetic resonance imaging have facilitated greater understanding of how structural and functional alteration of the LC may contribute to cognitive decline in AD and PD. We discuss the potential roles of the noradrenergic system in the pathogenesis of AD and PD with an emphasis on postmortem anatomical studies, structural MRI studies, and functional MRI studies, where we highlight changes in LC connectivity with the default mode network (DMN). LC degeneration may accompany deficient capacity in suppressing DMN activity and increasing saliency and task control network activities to meet behavioral challenges. We finish by proposing potential and new directions of research to address noradrenergic dysfunction in AD and PD.

The role of objective cognitive dysfunction in subjective cognitive complaints after stroke.

PubMed

van Rijsbergen, M W A; Mark, R E; Kop, W J; de Kort, P L M; Sitskoorn, M M

2017-03-01

Objective cognitive performance (OCP) is often impaired in patients post-stroke but the consequences of OCP for patient-reported subjective cognitive complaints (SCC) are poorly understood. We performed a detailed analysis on the association between post-stroke OCP and SCC. Assessments of OCP and SCC were obtained in 208 patients 3 months after stroke. OCP was evaluated using conventional and ecologically valid neuropsychological tests. Levels of SCC were measured using the CheckList for Cognitive and Emotional (CLCE) consequences following stroke inventory. Multivariate hierarchical regression analyses were used to evaluate the association of OCP with CLCE scores adjusting for age, sex and intelligence quotient. Analyses were performed to examine the global extent of OCP dysfunction (based on the total number of impaired neuropsychological tests, i.e. objective cognitive impairment index) and for each OCP test separately using the raw neuropsychological (sub)test scores. The objective cognitive impairment index for global OCP was positively correlated with the CLCE score (Spearman's rho = 0.22, P = 0.003), which remained significant in multivariate adjusted models (β = 0.25, P = 0.01). Results for the separate neuropsychological tests indicated that only one task (the ecologically valid Rivermead Behavioural Memory Test) was independently associated with the CLCE in multivariate adjusted models (β = -0.34, P < 0.001). Objective neuropsychological test performance, as measured by the global dysfunction index or an ecologically valid memory task, was associated with SCC. These data suggest that cumulative deficits in multiple cognitive domains contribute to subjectively experienced poor cognitive abilities in daily life in patients post-stroke. © 2016 EAN.

Children with chronic lung diseases have cognitive dysfunction as assessed by event-related potential (auditory P300) and Stanford-Binet IQ (SB-IV) test.

PubMed

Kamel, Terez Boshra; Abd Elmonaem, Mahmoud Tarek; Khalil, Lobna Hamed; Goda, Mona Hamdy; Sanyelbhaa, Hossam; Ramzy, Mourad Alfy

2016-10-01

Chronic lung disease (CLD) in children represents a heterogeneous group of many clinico-pathological entities with risk of adverse impact of chronic or intermittent hypoxia. So far, few researchers have investigated the cognitive function in these children, and the role of auditory P300 in the assessment of their cognitive function has not been investigated yet. This study was designed to assess the cognitive functions among schoolchildren with different chronic pulmonary diseases using both auditory P300 and Stanford-Binet test. This cross-sectional study included 40 school-aged children who were suffering from chronic chest troubles other than asthma and 30 healthy children of similar age, gender and socioeconomic state as a control group. All subjects were evaluated through clinical examination, radiological evaluation and spirometry. Audiological evaluation included (basic otological examination, pure-tone, speech audiometry and immittancemetry). Cognitive function was assessed by auditory P300 and psychological evaluation using Stanford-Binet test (4th edition). Children with chronic lung diseases had significantly lower anthropometric measures compared to healthy controls. They had statistically significant lower IQ scores and delayed P300 latencies denoting lower cognitive abilities. Cognitive dysfunction correlated to severity of disease. P300 latencies were prolonged among hypoxic patients. Cognitive deficits in children with different chronic lung diseases were best detected using both Stanford-Binet test and auditory P300. P300 is an easy objective tool. P300 is affected early with hypoxia and could alarm subtle cognitive dysfunction.

Cognitive Impairment in Chronic Alcoholics: Some Cause for Optimism.

ERIC Educational Resources Information Center

Goldman, Mark S.

1983-01-01

It appears that, although the cognitive functioning of many alcoholics remains impaired even after drinking has stopped, considerable recovery can occur. New findings now suggest the possibility of reducing cognitive dysfunction and enhancing alcoholism treatment outcomes. (CMG)

Postoperative Structural Brain Changes and Cognitive Dysfunction in Patients with Breast Cancer.

PubMed

Sato, Chiho; Sekiguchi, Atsushi; Kawai, Masaaki; Kotozaki, Yuka; Nouchi, Rui; Tada, Hiroshi; Takeuchi, Hikaru; Ishida, Takanori; Taki, Yasuyuki; Kawashima, Ryuta; Ohuchi, Noriaki

2015-01-01

The primary purpose of this study was to clarify the influence of the early response to surgery on brain structure and cognitive function in patients with breast cancer. It was hypothesized that the structure of the thalamus would change during the early response after surgery due to the effects of anesthesia and would represent one aspect of an intermediate phenotype of postoperative cognitive dysfunction (POCD). We examined 32 postmenopausal females with breast cancer and 20 age-matched controls. We assessed their cognitive function (attention, memory, and executive function), and performed brain structural MRI 1.5 ± 0.5 days before and 5.6 ± 1.2 days after surgery. We found a significant interaction between regional grey matter volume (rGMV) in the thalamus (P < 0.05, familywise error (FWE), small volume correction (SVC)) and one attention domain subtest (P = 0.001, Bonferroni correction) after surgery in the patient group compared with the control group. Furthermore, the changes in attention were significantly associated with sevoflurane anesthetic dose (r2 = 0.247, β = ‒0.471, P = 0.032) and marginally associated with rGMV changes in the thalamus (P = 0.07, FWE, SVC) in the Pt group. Our findings suggest that alterations in brain structure, particularly in the thalamus, may occur shortly after surgery and may be associated with attentional dysfunction. This early postoperative response to anesthesia may represent an intermediate phenotype of POCD. It was assumed that patients experiencing other risk factors of POCD, such as the severity of surgery, the occurrence of complications, and pre-existing cognitive impairments, would develop clinical POCD with broad and multiple types of cognitive dysfunction.

Hydrogen Sulfide Ameliorates Homocysteine-Induced Cognitive Dysfunction by Inhibition of Reactive Aldehydes Involving Upregulation of ALDH2.

PubMed

Li, Min; Zhang, Ping; Wei, Hai-Jun; Li, Man-Hong; Zou, Wei; Li, Xiang; Gu, Hong-Feng; Tang, Xiao-Qing

2017-04-01

Homocysteine, a risk factor for Alzheimer's disease, induces cognitive dysfunction. Reactive aldehydes play an important role in cognitive dysfunction. Aldehyde-dehydrogenase 2 detoxifies reactive aldehydes. Hydrogen sulfide, a novel neuromodulator, has neuroprotective effects and regulates learning and memory. Our previous work confirmed that the disturbance of hydrogen sulfide synthesis is invovled in homocysteine-induced defects in learning and memory. Therefore, the present work was to explore whether hydrogen sulfide ameliorates homocysteine-generated cognitive dysfunction and to investigate whether its underlying mechanism is related to attenuating accumulation of reactive aldehydes by upregulation of aldehyde-dehydrogenase 2. The cognitive function of rats was assessed by the Morris water maze test and the novel object recognition test. The levels of malondialdehyde, 4-hydroxynonenal, and glutathione as well as the activity of aldehyde-dehydrogenase 2 were determined by enzyme linked immunosorbent assay; the expression of aldehyde-dehydrogenase 2 was detected by western blot. The behavior experiments, Morris water maze test and novel objects recognition test, showed that homocysteine induced deficiency in learning and memory in rats, and this deficiency was reversed by treatment of NaHS (a donor of hydrogen sulfide). We demonstrated that NaHS inhibited homocysteine-induced increases in generations of MDA and 4-HNE in the hippocampus of rats and that hydrogen sulfide reversed homocysteine-induced decreases in the level of glutathione as well as the activity and expression of aldehyde-dehydrogenase 2 in the hippocampus of rats. Hydrogen sulfide ameliorates homocysteine-induced impairment in cognitive function by decreasing accumulation of reactive aldehydes as a result of upregulations of glutathione and aldehyde-dehydrogenase 2. © The Author 2016. Published by Oxford University Press on behalf of CINP.

Cognitive Impairment in Bipolar Disorder: Treatment and Prevention Strategies

PubMed Central

Solé, Brisa; Jiménez, Esther; Torrent, Carla; Reinares, Maria; Bonnin, Caterina del Mar; Torres, Imma; Varo, Cristina; Grande, Iria; Valls, Elia; Salagre, Estela; Sanchez-Moreno, Jose; Martinez-Aran, Anabel; Carvalho, André F

2017-01-01

Abstract Over the last decade, there has been a growing appreciation of the importance of identifying and treating cognitive impairment associated with bipolar disorder, since it persists in remission periods. Evidence indicates that neurocognitive dysfunction may significantly influence patients’ psychosocial outcomes. An ever-increasing body of research seeks to achieve a better understanding of potential moderators contributing to cognitive impairment in bipolar disorder in order to develop prevention strategies and effective treatments. This review provides an overview of the available data from studies examining treatments for cognitive dysfunction in bipolar disorder as well as potential novel treatments, from both pharmacological and psychological perspectives. All these data encourage the development of further studies to find effective strategies to prevent and treat cognitive impairment associated with bipolar disorder. These efforts may ultimately lead to an improvement of psychosocial functioning in these patients. PMID:28498954

T cell deficiency leads to cognitive dysfunction: Implications for therapeutic vaccination for schizophrenia and other psychiatric conditions

PubMed Central

Kipnis, Jonathan; Cohen, Hagit; Cardon, Michal; Ziv, Yaniv; Schwartz, Michal

2004-01-01

The effects of the adaptive immune system on the cognitive performance and abnormal behaviors seen in mental disorders such as schizophrenia have never been documented. Here, we show that mice deprived of mature T cells manifested cognitive deficits and behavioral abnormalities, which were remediable by T cell restoration. T cell-based vaccination, using glatiramer acetate (copolymer-1, a weak agonist of numerous self-reactive T cells), can overcome the behavioral and cognitive abnormalities that accompany neurotransmitter imbalance induced by (+)dizocilpine maleate (MK-801) or amphetamine. The results, by suggesting that peripheral T cell deficit can lead to cognitive and behavioral impairment, highlight the importance of properly functioning adaptive immunity in the maintenance of mental activity and in coping with conditions leading to cognitive deficits. These findings point to critical factors likely to contribute to age- and AIDS-related dementias and might herald the development of a therapeutic vaccination for fighting off cognitive dysfunction and psychiatric conditions. PMID:15141078

Neurofeedback and its possible relevance for the treatment of Tourette syndrome.

PubMed

Farkas, Aniko; Bluschke, Annet; Roessner, Veit; Beste, Christian

2015-04-01

Neurofeedback is an increasingly recognized therapeutic option in various neuropsychiatric disorders to treat dysfunctions in cognitive control as well as disorder-specific symptoms. In this review we propose that neurofeedback may also reflect a valuable therapeutic option to treat executive control functions in Gilles-de-la-Tourette syndrome (GTS). Deficits in executive control functions when ADHD symptoms appear in GTS likely reflect pathophysiological processes in cortico-thalamic-striatal circuits and may also underlie the motor symptoms in GTS. Such executive control deficits evident in comorbid GTS/ADHD depend on neurophysiological processes well-known to be modifiable by neurofeedback. However, so far efforts to use neurofeedback to treat cognitive dysfunctions are scarce. We outline why neurofeedback should be considered a promising treatment option, what forms of neurofeedback may prove to be most effective and how neurofeedback may be implemented in existing intervention strategies to treat comorbid GTS/ADHD and associated dysfunctions in cognitive control. As cognitive control deficits in GTS mostly appear in comorbid GTS/ADHD, neurofeedback may be most useful in this frequent combination of disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.

Unifying the field: developing an integrative paradigm for behavior therapy.

PubMed

Eifert, G H; Forsyth, J P; Schauss, S L

1993-06-01

The limitations of early conditioning models and treatments have led many behavior therapists to abandon conditioning principles and replace them with loosely defined cognitive theories and treatments. Systematic theory extensions to human behavior, using new concepts and processes derived from and built upon the basic principles, could have prevented the divisive debates over whether psychological dysfunctions are the results of conditioning or cognition and whether they should be treated with conditioning or cognitive techniques. Behavior therapy could also benefit from recent advances in experimental cognitive psychology that provide objective behavioral methods of studying dysfunctional processes. We suggest a unifying paradigm for explaining abnormal behavior that links and integrates different fields of study and processes that are frequently believed to be incompatible or antithetical such as biological vulnerability variables, learned behavioral repertoires, and that also links historical and current antecedents of the problem. An integrative paradigmatic behavioral approach may serve a unifying function in behavior therapy (a) by promoting an understanding of the dysfunctional processes involved in different disorders and (b) by helping clinicians conduct functional analyses that lead to theory-based, individualized, and effective treatments.

Protective effect of curcumin (Curcuma longa) against D-galactose-induced senescence in mice.

PubMed

Kumar, Anil; Prakash, Atish; Dogra, Samrita

2011-01-01

Brain senescence plays an important role in cognitive dysfunction and neurodegenerative disorders. Curcumin was reported to have beneficial effect against several neurodegenerative disorders including Alzheimer's disease. Therefore, the present study was conducted in order to explore the possible role of curcumin against D-galactose-induced cognitive dysfunction, oxidative damage, and mitochondrial dysfunction in mice. Chronic administration of D-galactose for 6 weeks significantly impaired cognitive function (both in Morris water maze and elevated plus maze), locomotor activity, oxidative defense (raised lipid peroxidation, nitrite concentration, depletion of reduced glutathione and catalase activity), and mitochondrial enzyme complex activities (I, II, and III) as compared to vehicle treated group. Curcumin (15 and 30 mg/kg) and galantamine (5 mg/kg) treatment for 6 weeks significantly improved cognitive tasks, locomotor activity, oxidative defense, and restored mitochondrial enzyme complex activity as compared to control (D-galactose). Chronic D-galactose treatment also significantly increased acetylcholine esterase activity that was attenuated by curcumin (15 and 30 mg/kg) and galantamine (5 mg/kg) treatment. In conclusion, the present study highlights the therapeutic potential of curcumin against d-galactose induced senescence in mice.

Culture and Sexuality: Cognitive-Emotional Determinants of Sexual Dissatisfaction Among Iranian and New Zealand Women.

PubMed

Abdolmanafi, Atefe; Nobre, Pedro; Winter, Sam; Tilley, P J Matt; Jahromi, Reza Ghorban

2018-05-01

Several studies have demonstrated that culture plays a fundamental role in individuals' beliefs, attitudes, and values toward sexuality, and influences their ability to enjoy sex. It follows that culture may influence sexual satisfaction or dissatisfaction. To examine and compare cognitive-emotional variables related to women's sexual dissatisfaction in Iran and New Zealand. In total, 196 Iranian women and 207 New Zealand women participated in the study, answering questionnaires evaluating dysfunctional sexual beliefs, automatic thoughts, emotional and sexual response during sexual activity, as well as sexual satisfaction. Sexual beliefs were measured by the Sexual Dysfunctional Beliefs Questionnaire, thoughts and emotional responses were measured by the Sexual Modes Questionnaire, and sexual satisfaction was measured by the Sexual Satisfaction Index. Findings indicated that in both Iranian and New Zealand women, failure and disengagement thoughts, lack of erotic thoughts, and emotions of fear during sexual activity were significant predictors of sexual dissatisfaction. Besides these common predictors, results also indicated that sexual conservatism and women's sexual passivity beliefs, sexual abuse thoughts, and fear during sexual activity were significant predictors of sexual dissatisfaction in Iranian women. Beliefs of sexual desire and pleasure as a sin; age-related beliefs; and emotions such as sadness, disillusion, and hurt were significant predictors of sexual dissatisfaction in New Zealand women. The present findings could facilitate a better understanding of cultural differences in the roles played by dysfunctional sexual beliefs, negative automatic thoughts, and negative emotions during sexual activity, and the value of these beliefs, thoughts, and emotions in predicting sexual dissatisfaction. The strength of this study is in providing an examination of the role of culturally bound beliefs in predicting sexual dissatisfaction in women from different cultural backgrounds. Limitations include the lack of evaluation of psychological and interpersonal variables that may impact on women's sexual dissatisfaction. These findings suggest that there may be a role of culture in shaping beliefs, attitudes, and values toward sexuality; and provide evidence for the effect of cognitive-emotional variables in predicting women's sexual dissatisfaction. Abdolmanafi A, Nobre P, Winter S, et al. Culture and Sexuality: Cognitive-Emotional Determinants of Sexual Dissatisfaction Among Iranian and New Zealand Women. J Sex Med 2018;15:687-697. Copyright © 2018 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

[Minimal emotional dysfunction and first impression formation in personality disorders].

PubMed

Linden, M; Vilain, M

2011-01-01

"Minimal cerebral dysfunctions" are isolated impairments of basic mental functions, which are elements of complex functions like speech. The best described are cognitive dysfunctions such as reading and writing problems, dyscalculia, attention deficits, but also motor dysfunctions such as problems with articulation, hyperactivity or impulsivity. Personality disorders can be characterized by isolated emotional dysfunctions in relation to emotional adequacy, intensity and responsivity. For example, paranoid personality disorders can be characterized by continuous and inadequate distrust, as a disorder of emotional adequacy. Schizoid personality disorders can be characterized by low expressive emotionality, as a disorder of effect intensity, or dissocial personality disorders can be characterized by emotional non-responsivity. Minimal emotional dysfunctions cause interactional misunderstandings because of the psychology of "first impression formation". Studies have shown that in 100 ms persons build up complex and lasting emotional judgements about other persons. Therefore, minimal emotional dysfunctions result in interactional problems and adjustment disorders and in corresponding cognitive schemata.From the concept of minimal emotional dysfunctions specific psychotherapeutic interventions in respect to the patient-therapist relationship, the diagnostic process, the clarification of emotions and reality testing, and especially an understanding of personality disorders as impairment and "selection, optimization, and compensation" as a way of coping can be derived.

Cerebrovascular Complications of Diabetes: Focus on Cognitive Dysfunction

PubMed Central

Hardigan, Trevor; Ward, Rebecca; Ergul, Adviye

2017-01-01

The incidence of diabetes has more than doubled in the United States in the last 30 years and the global disease rate is projected to double by 2030. Cognitive impairment has been associated with diabetes, worsening quality of life in patients. The structural and functional interaction of neurons with the surrounding vasculature is critical for proper function of the central nervous system including domains involved in learning and memory. Thus, in this review we explore cognitive impairment in patients and experimental models, focusing on links to vascular dysfunction and structural changes. Lastly, we propose a role for the innate immunity--mediated inflammation in neurovascular changes in diabetes. PMID:27634842

Gambling with Rose-Tinted Glasses on: Use of Emotion-Regulation Strategies Correlates with Dysfunctional Cognitions in Gambling Disorder Patients

PubMed Central

Navas, Juan F.; Verdejo-García, Antonio; LÓpez-GÓmez, Marta; Maldonado, Antonio; Perales, José C.

2016-01-01

Background and aims Existing research shows that gambling disorder patients (GDPs) process gambling outcomes abnormally when compared against healthy controls (HCs). These anomalies present the form of exaggerated or distorted beliefs regarding the expected utility of outcomes and one’s ability to predict or control gains and losses, as well as retrospective reinterpretations of what caused them. This study explores the possibility that the emotional regulation strategies GDPs use to cope with aversive events are linked to these cognitions. Methods 41 GDPs and 45 HCs, matched in sociodemographic variables, were assessed in gambling severity, emotion-regulation strategies (cognitive emotion-regulation questionnaire, CERQ), and gambling-related cognitions (gambling-related cognitions scale, GRCS). Results GDPs showed higher scores in all gambling-related cognition dimensions. Regarding emotion regulation, GDPs were observed to use self-blame and catastrophizing, but also positive refocusing, more often than controls. Additionally, in GDPs, putatively adaptive CERQ strategies shared a significant portion of variance with South Oaks gambling screen severity and GRCS beliefs. Shared variability was mostly attributable to the roles of refocusing on planning and putting into perspective at positively predicting severity and the interpretative bias (GDPs propensity to reframe losses in a more benign way), respectively. Discussion and conclusions Results show links between emotion-regulation strategies and problematic gambling-related behaviors and cognitions. The pattern of those links supports the idea that GDPs use emotion-regulation strategies, customarily regarded as adaptive, to cope with negative emotions, so that the motivational and cognitive processing of gambling outcomes becomes less effective in shaping gambling-related behavior. PMID:27363462

Heterogeneity of Developmental Dyscalculia: Cases with Different Deficit Profiles

PubMed Central

Träff, Ulf; Olsson, Linda; Östergren, Rickard; Skagerlund, Kenny

2017-01-01

Developmental Dyscalculia (DD) has long been thought to be a monolithic learning disorder that can be attributed to a specific neurocognitive dysfunction. However, recent research has increasingly recognized the heterogeneity of DD, where DD can be differentiated into subtypes in which the underlying cognitive deficits and neural dysfunctions may differ. The aim was to further understand the heterogeneity of developmental dyscalculia (DD) from a cognitive psychological perspective. Utilizing four children (8–9 year-old) we administered a comprehensive cognitive test battery that shed light on the cognitive-behavioral profile of each child. The children were compared against norm groups of aged-matched peers. Performance was then contrasted against predominant hypotheses of DD, which would also give insight into candidate neurocognitive correlates. Despite showing similar mathematical deficits, these children showed remarkable interindividual variability regarding cognitive profile and deficits. Two cases were consistent with the approximate number system deficit account and also the general magnitude-processing deficit account. These cases showed indications of having domain-general deficits as well. One case had an access deficit in combination with a general cognitive deficit. One case suffered from general cognitive deficits only. The results showed that DD cannot be attributed to a single explanatory factor. These findings support a multiple deficits account of DD and suggest that some cases have multiple deficits, whereas other cases have a single deficit. We discuss a previously proposed distinction between primary DD and secondary DD, and suggest hypotheses of dysfunctional neurocognitive correlates responsible for the displayed deficits. PMID:28101068

Heterogeneity of Developmental Dyscalculia: Cases with Different Deficit Profiles.

PubMed

Träff, Ulf; Olsson, Linda; Östergren, Rickard; Skagerlund, Kenny

2016-01-01

Developmental Dyscalculia (DD) has long been thought to be a monolithic learning disorder that can be attributed to a specific neurocognitive dysfunction. However, recent research has increasingly recognized the heterogeneity of DD, where DD can be differentiated into subtypes in which the underlying cognitive deficits and neural dysfunctions may differ. The aim was to further understand the heterogeneity of developmental dyscalculia (DD) from a cognitive psychological perspective. Utilizing four children (8-9 year-old) we administered a comprehensive cognitive test battery that shed light on the cognitive-behavioral profile of each child. The children were compared against norm groups of aged-matched peers. Performance was then contrasted against predominant hypotheses of DD, which would also give insight into candidate neurocognitive correlates. Despite showing similar mathematical deficits, these children showed remarkable interindividual variability regarding cognitive profile and deficits. Two cases were consistent with the approximate number system deficit account and also the general magnitude-processing deficit account. These cases showed indications of having domain-general deficits as well. One case had an access deficit in combination with a general cognitive deficit. One case suffered from general cognitive deficits only. The results showed that DD cannot be attributed to a single explanatory factor. These findings support a multiple deficits account of DD and suggest that some cases have multiple deficits, whereas other cases have a single deficit. We discuss a previously proposed distinction between primary DD and secondary DD, and suggest hypotheses of dysfunctional neurocognitive correlates responsible for the displayed deficits.

PERFORMANCE OF A COMPUTER-BASED ASSESSMENT OF COGNITIVE FUNCTION MEASURES IN TWO COHORTS OF SENIORS

PubMed Central

Espeland, Mark A.; Katula, Jeffrey A.; Rushing, Julia; Kramer, Arthur F.; Jennings, Janine M.; Sink, Kaycee M.; Nadkarni, Neelesh K.; Reid, Kieran F.; Castro, Cynthia M.; Church, Timothy; Kerwin, Diana R.; Williamson, Jeff D.; Marottoli, Richard A.; Rushing, Scott; Marsiske, Michael; Rapp, Stephen R.

2013-01-01

Background Computer-administered assessment of cognitive function is being increasingly incorporated in clinical trials, however its performance in these settings has not been systematically evaluated. Design The Seniors Health and Activity Research Program (SHARP) pilot trial (N=73) developed a computer-based tool for assessing memory performance and executive functioning. The Lifestyle Interventions and Independence for Seniors (LIFE) investigators incorporated this battery in a full scale multicenter clinical trial (N=1635). We describe relationships that test scores have with those from interviewer-administered cognitive function tests and risk factors for cognitive deficits and describe performance measures (completeness, intra-class correlations). Results Computer-based assessments of cognitive function had consistent relationships across the pilot and full scale trial cohorts with interviewer-administered assessments of cognitive function, age, and a measure of physical function. In the LIFE cohort, their external validity was further demonstrated by associations with other risk factors for cognitive dysfunction: education, hypertension, diabetes, and physical function. Acceptable levels of data completeness (>83%) were achieved on all computer-based measures, however rates of missing data were higher among older participants (odds ratio=1.06 for each additional year; p<0.001) and those who reported no current computer use (odds ratio=2.71; p<0.001). Intra-class correlations among clinics were at least as low (ICC≤0.013) as for interviewer measures (ICC≤0.023), reflecting good standardization. All cognitive measures loaded onto the first principal component (global cognitive function), which accounted for 40% of the overall variance. Conclusion Our results support the use of computer-based tools for assessing cognitive function in multicenter clinical trials of older individuals. PMID:23589390

Psychometrics of the AAN Caregiver Driving Safety Questionnaire and contributors to caregiver concern about driving safety in older adults.

PubMed

Carvalho, Janessa O; Springate, Beth; Bernier, Rachel A; Davis, Jennifer

2018-03-01

ABSTRACTBackground:The American Academy of Neurology (AAN) updated their practice parameters in the evaluation of driving risk in dementia and developed a Caregiver Driving Safety Questionnaire, detailed in their original manuscript (Iverson Gronseth, Reger, Classen, Dubinsky, & Rizzo, 2010). They described four factors associated with decreased driving ability in dementia patients: history of crashes or citations, informant-reported concerns, reduced mileage, and aggressive driving. An informant-reported AAN Caregiver Driving Safety Questionnaire was designed with these elements, and the current study was the first to explore the factor structure of this questionnaire. Additionally, we examined associations between these factors and cognitive and behavioral measures in patients with mild cognitive impairment or early Alzheimer's disease and their informants. Exploratory factor analysis revealed a four-component structure, consistent with the theory behind the AAN scale composition. These four factor scores also were significantly associated with performance on cognitive screening instruments and informant reported behavioral dysfunction. Regressions revealed that behavioral dysfunction predicted caregiver concerns about driving safety beyond objective patient cognitive dysfunction. In this first known quantitative exploration of the scale, our results support continued use of this scale in office driving safety assessments. Additionally, patient behavioral changes predicted caregiver concerns about driving safety over and above cognitive status, which suggests that caregivers may benefit from psychoeducation about cognitive factors that may negatively impact driving safety.

Insulin-like growth factor-1: a possible marker for emotional and cognitive disturbances, and treatment effectiveness in major depressive disorder.

PubMed

Levada, Oleg A; Troyan, Alexandra S

2017-01-01

Depression and cognitive dysfunction share a common neuropathological platform. Abnormal neural plasticity in the frontolimbic circuits has been linked to changes in the expression of neurotrophic factors, including IGF-1. These changes may result in clinical abnormalities observed over the course of major depressive disorder (MDD), including cognitive dysfunction. The present review aimed to summarize evidence regarding abnormalities of peripheral IGF-1 in MDD patients and assess a marker and predictive role of the neurotrophin for emotional and cognitive disturbances, and treatment effectiveness. A literature search of the PubMed database was conducted for studies, in which peripheral IGF-1 levels were evaluated. Our analysis revealed four main findings: (1) IGF-1 levels in MDD patients mismatch across the studies, which may arise from various factors, e.g., age, gender, the course of the disease, presence of cognitive impairment, ongoing therapy, or general health conditions; (2) the initial peripheral IGF-1 levels may predict the occurrence of depression in future; (3) peripheral IGF-1 levels may reflect cognitive dysfunction, although the data is limited; (4) it is difficult to evaluate the influence of treatment on IGF-1 levels as there is discrepancy of this growth factor among the studies at baseline, although most of them showed a decrease in IGF-1 levels after treatment.

Conversion of elderly to Alzheimer's dementia: role of confluence of hypothermia and senescent stigmata--the plausible pathway.

PubMed

Daulatzai, Mak Adam

2010-01-01

Aging is a consequence of progressive decline in special and somatosensory functions and specific brain stem nuclei. Many senescent stigmata, including hypoxia, hypoxemia, depressed cerebral blood flow and glucose metabolism, diseases of senescence, and their medications all enhance hypothermia as do alcohol, cold environment, and malnutrition. Hypothermia is a critical factor having deleterious impact on brain stem and neocortical functions. Additionally, anesthesia in elderly also promotes hypothermia; anesthetics not only cause consciousness (sensory and motor) changes, but memory impairment as well. Anesthesia inhibits cholinergic pathways, reticular and thalamocortical systems, cortico-cortical connectivity, and causes post-operative delirium and cognitive dysfunction. Increasing evidence indicates that anesthetic exposures may contribute to dementia onset and Alzheimer's disease (AD) in hypothermic elderly. Inhaled anesthetics potentiate caspases, BACE, tau hyperphosphorylation, and apoptosis. This paper addresses the important question: "Why do only some elderly fall victim to AD"? Based on information on the pathogenesis of early stages of cognitive dysfunction in elderly (i.e., due to senescent stigmata), and the effects of anesthesia superimposed, a detailed plausible neuropathological substrate (mechanism/pathway) is delineated here that reveals the possible cause(s) of AD. Basically, it encompasses several risk factors for cognitive dysfunction during senescence plus several hypothermia-enhancing routes; they all converge and tip the balance towards dementia onset. This knowledge of the confluence of heterogeneous risk factors in perpetuating dementia relentlessly is of importance in order to: (a) avoid their convergence; (b) take measures to stop/reverse cognitive dysfunction; and (c) to develop therapeutic strategies to enhance cognitive function and attenuate AD.

Amyloid-β Homeostasis Bridges Inflammation, Synaptic Plasticity Deficits and Cognitive Dysfunction in Multiple Sclerosis.

PubMed

Stampanoni Bassi, Mario; Garofalo, Sara; Marfia, Girolama A; Gilio, Luana; Simonelli, Ilaria; Finardi, Annamaria; Furlan, Roberto; Sancesario, Giulia M; Di Giandomenico, Jonny; Storto, Marianna; Mori, Francesco; Centonze, Diego; Iezzi, Ennio

2017-01-01

Cognitive deficits are frequently observed in multiple sclerosis (MS), mainly involving processing speed and episodic memory. Both demyelination and gray matter atrophy can contribute to cognitive deficits in MS. In recent years, neuroinflammation is emerging as a new factor influencing clinical course in MS. Inflammatory cytokines induce synaptic dysfunction in MS. Synaptic plasticity occurring within hippocampal structures is considered as one of the basic physiological mechanisms of learning and memory. In experimental models of MS, hippocampal plasticity is profoundly altered by proinflammatory cytokines. Although mechanisms of inflammation-induced hippocampal pathology in MS are not completely understood, alteration of Amyloid-β (Aβ) metabolism is emerging as a key factor linking together inflammation, synaptic plasticity and neurodegeneration in different neurological diseases. We explored the correlation between concentrations of Aβ 1-42 and the levels of some proinflammatory and anti-inflammatory cytokines (interleukin-1β (IL-1β), IL1-ra, IL-8, IL-10, IL-12, tumor necrosis factor α (TNFα), interferon γ (IFNγ)) in the cerebrospinal fluid (CSF) of 103 remitting MS patients. CSF levels of Aβ 1-42 were negatively correlated with the proinflammatory cytokine IL-8 and positively correlated with the anti-inflammatory molecules IL-10 and interleukin-1 receptor antagonist (IL-1ra). Other correlations, although noticeable, were either borderline or not significant. Our data show that an imbalance between proinflammatory and anti-inflammatory cytokines may lead to altered Aβ homeostasis, representing a key factor linking together inflammation, synaptic plasticity and cognitive dysfunction in MS. This could be relevant to identify novel therapeutic approaches to hinder the progression of cognitive dysfunction in MS.

Cognitive sequelae of methanol poisoning involve executive dysfunction and memory impairment in cross-sectional and long-term perspective.

PubMed

Bezdicek, O; Michalec, J; Vaneckova, M; Klempir, J; Liskova, I; Seidl, Z; Janikova, B; Miovsky, M; Hubacek, J; Diblik, P; Kuthan, P; Pilin, A; Kurcova, I; Fenclova, Z; Petrik, V; Navratil, T; Pelclova, D; Zakharov, S; Ruzicka, E

2017-03-01

Methanol poisoning leads to lesions in the basal ganglia and subcortical white matter, as well as to demyelination and atrophy of the optic nerve. However, information regarding cognitive deficits in a large methanol sample is lacking. The principal aim of the present study was to identify the cognitive sequelae of methanol poisoning and their morphological correlates. A sample of 50 patients (METH; age 48 ± 13 years), 3-8 months after methanol poisoning, and 57 control subjects (CS; age 49 ± 13 years) were administered a neuropsychological battery. Forty-six patients were followed in 2 years' perspective. Patients additionally underwent 1.5T magnetic resonance imaging (MRI). Three biochemical and toxicological metabolic markers and a questionnaire regarding alcohol abuse facilitated the classification of 24 patients with methanol poisoning without alcohol abuse (METHna) and 22 patients with methanol poisoning and alcohol abuse (METHa). All groups were compared to a control group of similar size, and matched for age, education, premorbid intelligence level, global cognitive performance, and level of depressive symptoms. Using hierarchical multiple regression we found significant differences between METH and CS, especially in executive and memory domains. METHa showed a similar pattern of cognitive impairment with generally more severe executive dysfunction. Moreover, all METH patients with extensive involvement on brain MRI (lesions in ≥2 anatomical regions) had a more severe cognitive impairment. From a longitudinal perspective, we did not find any changes in their cognitive functioning after 2 years' follow-up. Our findings suggest that methanol poisoning is associated with executive dysfunction and explicit memory impairment, supposedly due to basal ganglia dysfunction and disruption of frontostriatal circuitry proportional to the number of brain lesions, and that these changes are persistent after 2 years' follow-up. Copyright © 2016 Elsevier Inc. All rights reserved.

Role of silent information regulator 1 in the protective effect of hydrogen sulfide on homocysteine-induced cognitive dysfunction: Involving reduction of hippocampal ER stress.

PubMed

Tang, Yi-Yun; Wang, Ai-Ping; Wei, Hai-Jun; Li, Man-Hong; Zou, Wei; Li, Xiang; Wang, Chun-Yan; Zhang, Ping; Tang, Xiao-Qing

2018-04-16

Homocysteine (Hcy) causes cognitive deficits and hippocampal endoplasmic reticulum (ER) stress. Our previous study has confirmed that Hydrogen sulfide (H 2 S) attenuates Hcy-induced cognitive dysfunction and hippocampal ER stress. Silent information regulator 1 (Sirt-1) is indispensable in the formation of learning and memory. Therefore, the aim of this study was to explore the role of Sirt-1 in the protective effect of H 2 S against Hcy-induced cognitive dysfunction. We found that NaHS (a donor of H 2 S) markedly up-regulated the expression of Sirt-1 in the hippocampus of Hcy-exposed rats. Sirtinol, a specific inhibitor of Sirt-1, reversed the improving role of NaHS in the cognitive function of Hcy-exposed rats, as evidenced by that sirtinol increased the escape latency and the swim distance in the acquisition trial of morris water maze (MWM) test, decreased the times crossed through and the time spent in the target quadrant in the probe trail of MWM test, and reduced the discrimination index in the novel object recognition test (NORT) in the rats cotreated with NaHS and Hcy. We also found that sirtinol reversed the protection of NaHS against Hcy-induced hippocampal ER-stress, as evidenced by up-regulating the expressions of GRP78, CHOP, and cleaved caspase-12 in the hippocampus of rats cotreated with NaHS and Hcy. These results suggested the contribution of upregulation of hippocampal Sirt-1 to the improving role of H 2 S in the cognitive function of Hcy-exposed rats, which involves suppression of hippocampal ER stress. Our finding provides a new insight into the mechanism underlying the inhibitory role of H 2 S in Hcy-induced cognitive dysfunction. Copyright © 2018 Elsevier B.V. All rights reserved.

Coping with cancer-related cognitive dysfunction: a scoping review of the literature.

PubMed

Sleight, Alix

2016-01-01

Cancer-related cognitive dysfunction (CRCD) impacts memory, attention, concentration, language, multi-tasking, and organizational skills and decreases participation and quality of life for cancer survivors. The objectives of this article are: (1) to outline the neuroscience of CRCD, its risk factors, and its effect on participation; and (2) to identify and summarize the literature on rehabilitation interventions and coping techniques for CRCD in cancer survivors. A scoping review of articles cited in PubMed, MEDLINE, PsychINFO, and CINAHL was performed. To be included, articles must have been published in a peer-reviewed scientific journal between 1996 and 2014, written in English, and included a quantitative or qualitative non-pharmacological study of interventions and/or coping strategies for adult cancer survivors experiencing CRCD. Ten articles met the inclusion criteria for final review. Six studies tested the efficacy of rehabilitation treatments on CRCD. Three involved cognitive-behavioral therapy (CBT), while three tested neuropsychological and/or cognitive training interventions. Four qualitative studies investigated coping strategies used by survivors with CRCD. CBT-based treatments and neuropsychological/cognitive training methods may ameliorate symptoms of CRCD. The most commonly-reported coping strategy is utilization of assistive technology and memory aids. Further research is needed about efficacious rehabilitation techniques for this population. Implications for Rehabilitation Cancer-related cognitive dysfunction (CRCD) may impact up to 50% of cancer survivors. CRCD can significantly decrease participation and quality of life during survivorship. Cognitive-behavioral therapy (CBT) and neuropsychological/cognitive training methods may ameliorate symptoms of CRCD. The most common coping strategy reported by cancer survivors with CRCD is the use of assistive technology and memory aids.

Kidney function and cognitive decline in frail elderly: two faces of the same coin?

PubMed

Coppolino, Giuseppe; Bolignano, Davide; Gareri, Pietro; Ruberto, Carmen; Andreucci, Michele; Ruotolo, Giovanni; Rocca, Maurizio; Castagna, Alberto

2018-06-04

Cognitive and renal impairment are pervasive among elderly frails, a high-risk, geriatric sub-population with peculiar clinical characteristics. In a series of frail individuals with non-advanced chronic kidney disease (CKD), we aimed at assessing the entity of functional, general health and cognitive impairment and the possible relationship between these types of dysfunction and the severity of renal impairment. 2229 geriatric subjects were screened for frailty and CKD. Severity of CKD was assessed by eGFR (CKD-EPI formula). Frailty was established by the Fried Index. Functional, general health and cognitive status were assessed by validated score measures. Final analysis included 271 frail CKD subjects (162 women, 109 men). Mean eGFR was 64.25 ± 25.04 mL/min/1.73 m 2 . Prevalence of mild-to-moderate CKD (stage 3-4) was 44%. Twenty-six percent of patients had severe cognitive impairment, while mild and moderate impairment was found in 7 and 67% of individuals, respectively. All subjects had poor functional and general health status. Cognitive capacities significantly decreased across CKD stages (p for trend < 0.0001). In fully adjusted multivariate analyses, cognitive status remained an independent predictor of eGFR (β = 0.465; p < 0.0001). Mild-to-moderate CKD is highly pervasive among frail elderly individuals and the severity of renal dysfunction is independently correlated with that of cognitive impairment. Future studies are advocated to clarify whether the combination of kidney and mental dysfunction may portend a higher risk of worsen outcomes in this high-risk population.

Obstructive sleep apnea exaggerates cognitive dysfunction in stroke patients.

PubMed

Zhang, Yan; Wang, Wanhua; Cai, Sijie; Sheng, Qi; Pan, Shenggui; Shen, Fang; Tang, Qing; Liu, Yang

2017-05-01

Obstructive sleep apnea (OSA) is very common in stroke survivors. It potentially worsens the cognitive dysfunction and inhibits their functional recovery. However, whether OSA independently damages the cognitive function in stroke patients is unclear. A simple method for evaluating OSA-induced cognitive impairment is also missing. Forty-four stroke patients six weeks after onset and 24 non-stroke patients with snoring were recruited for the polysomnographic study of OSA and sleep architecture. Their cognitive status was evaluated with a validated Chinese version of Cambridge Prospective Memory Test. The relationship between memory deficits and respiratory, sleeping, and dementia-related clinical variables were analyzed with correlation and multiple linear regression tests. OSA significantly and independently damaged time- and event-based prospective memory in stroke patients, although it had less power than the stroke itself. The impairment of prospective memory was correlated with increased apnea-hypopnea index, decreased minimal and mean levels of peripheral oxygen saturation, and disrupted sleeping continuity (reduced sleep efficiency and increased microarousal index). The further regression analysis identified minimal levels of peripheral oxygen saturation and sleep efficiency to be the two most important predictors for the decreased time-based prospective memory in stroke patients. OSA independently contributes to the cognitive dysfunction in stroke patients, potentially through OSA-caused hypoxemia and sleeping discontinuity. The prospective memory test is a simple but sensitive method to detect OSA-induced cognitive impairment in stroke patients. Proper therapies of OSA might improve the cognitive function and increase the life quality of stroke patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Experiential Avoidance as a Mediator of Relationships between Cognitions and Hair-Pulling Severity

ERIC Educational Resources Information Center

Norberg, Melissa M.; Wetterneck, Chad T.; Woods, Douglas W.; Conelea, Christine A.

2007-01-01

Cognitive-behavioral models suggest that certain cognitions and beliefs are functionally related to hair pulling in persons with trichotillomania (TTM), but little empirical data have been collected to test such claims. This study assessed dysfunctional beliefs about appearance, shameful cognitions, and fear of negative evaluation and their…

Neurobiology of cognitive remediation therapy for schizophrenia: a systematic review.

PubMed

Thorsen, Anders Lillevik; Johansson, Kyrre; Løberg, Else-Marie

2014-01-01

Cognitive impairment is an important aspect of schizophrenia, where cognitive remediation therapy (CRT) is a promising treatment for improving cognitive functioning. While neurobiological dysfunction in schizophrenia has been the target of much research, the neural substrate of cognitive remediation and recovery has not been thoroughly examined. The aim of the present article is to systematically review the evidence for neural changes after CRT for schizophrenia. The reviewed studies indicate that CRT affects several brain regions and circuits, including prefrontal, parietal, and limbic areas, both in terms of activity and structure. Changes in prefrontal areas are the most reported finding, fitting to previous evidence of dysfunction in this region. Two limitations of the current research are the few studies and the lack of knowledge on the mechanisms underlying neural and cognitive changes after treatment. Despite these limitations, the current evidence suggests that CRT is associated with both neurobiological and cognitive improvement. The evidence from these findings may shed light on both the neural substrate of cognitive impairment in schizophrenia, and how better treatment can be developed and applied.

Alterations in Cerebral White Matter and Neuropsychology in Patients with Cirrhosis and Falls

PubMed Central

Gómez-Ansón, Beatriz; Román, Eva; Fernández de Bobadilla, Ramón; Pires-Encuentra, Patricia; Díaz-Manera, Jordi; Núñez, Fidel; Martinez-Horta, Saül; Vives-Gilabert, Yolanda; Pagonabarraga, Javier; Kulisevsky, Jaume; Guarner, Carlos; Soriano, Germán

2015-01-01

Background & Aim Falls are frequent in patients with cirrhosis but underlying mechanisms are unknown. The aim was to determine the neuropsychological, neurological and brain alterations using magnetic resonance-diffusion tensor imaging (MR-DTI) in cirrhotic patients with falls. Patients and methods Twelve patients with cirrhosis and falls in the previous year were compared to 9 cirrhotic patients without falls. A comprehensive neuropsychological and neurological evaluation of variables that may predispose to falls included: the Mini-Mental State Examination, Psychometric Hepatic Encephalopathy Score (PHES), Parkinson’s Disease-Cognitive Rating Scale, specific tests to explore various cognitive domains, Unified Parkinson’s Disease Rating Scale to evaluate parkinsonism, scales for ataxia and muscular strength, and electroneurography. High-field MR (3T) including DTI and structural sequences was performed in all patients. Results The main neuropsychological findings were impairment in PHES (p = 0.03), Parkinson’s Disease-Cognitive Rating Scale (p = 0.04) and in executive (p<0.05) and visuospatial-visuoconstructive functions (p<0.05) in patients with falls compared to those without. There were no statistical differences between the two groups in the neurological evaluation or in the visual assessment of MRI. MR-DTI showed alterations in white matter integrity in patients with falls compared to those without falls (p<0.05), with local maxima in the superior longitudinal fasciculus and corticospinal tract. These alterations were independent of PHES as a covariate and correlated with executive dysfunction (p<0.05). Conclusions With the limitation of the small sample size, our results suggest that patients with cirrhosis and falls present alterations in brain white matter tracts related to executive dysfunction. These alterations are independent of PHES impairment. PMID:25793766

Feeling, caring, knowing: different types of empathy deficit in boys with psychopathic tendencies and autism spectrum disorder

PubMed Central

Jones, Alice P; Happé, Francesca GE; Gilbert, Francesca; Burnett, Stephanie; Viding, Essi

2010-01-01

Background Empathy dysfunction is one of the hallmarks of psychopathy, but it is also sometimes thought to characterise autism spectrum disorders (ASD). Individuals with either condition can appear uncaring towards others. This study set out to compare and contrast directly boys with psychopathic tendencies and boys with ASD on tasks assessing aspects of affective empathy and cognitive perspective taking. The main aim of the study was to assess whether a distinct profile of empathy deficits would emerge for boys with psychopathic tendencies and ASD, and whether empathy deficits would be associated with conduct problems in general, rather than psychopathic tendencies or ASD specifically. Methods Four groups of boys aged between 9 and 16 years (N = 96) were compared: 1) psychopathic tendencies, 2) ASD, 3) conduct problems and 4) comparison. Tasks were included to probe attribution of emotions to self, empathy for victims of aggression and cognitive perspective-taking ability. Results Boys with psychopathic tendencies had a profile consistent with dysfunctional affective empathy. They reported experiencing less fear and less empathy for victims of aggression than comparison boys. Their cognitive perspective-taking abilities were not statistically significantly different from those of comparison boys. In contrast, boys with ASD had difficulties with tasks requiring cognitive perspective taking, but reported emotional experiences and victim empathy that were in line with comparison boys. Boys with conduct problems did not differ from comparison boys, suggesting that the affective empathy deficit seen in boys with psychopathic tendencies was specific to that group, rather than common to all boys with conduct problems. Conclusions Although both groups can appear uncaring, our findings suggest that the affective/information processing correlates of psychopathic tendencies and ASD are quite different. Psychopathic tendencies are associated with difficulties in resonating with other people’s distress, whereas ASD is characterised by difficulties in knowing what other people think. PMID:20633070

MicroRNAs in Neurocognitive Dysfunctions: New Molecular Targets for Pharmacological Treatments?

PubMed Central

Nadim, Wissem Deraredj; Simion, Viorel; Bénédetti, Hélène; Pichon, Chantal; Baril, Patrick; Morisset-Lopez, Séverine

2017-01-01

Background Neurodegenerative and cognitive disorders are multifactorial diseases (i.e., involving neurodevelopmental, genetic, age or environmental factors) characterized by an abnormal development that affects neuronal function and integrity. Recently, an increasing number of studies revealed that the dysregulation of microRNAs (miRNAs) may be involved in the etiology of cognitive disorders as Alzheimer, Parkinson, and Huntington‘s diseases, Schizophrenia and Autism spectrum disorders. Methods From an extensive search in bibliographic databases of peer-reviewed research literature, 
we identified relevant published studies related to specific key words such as memory, cognition, neurodegenerative disorders, neurogenesis and miRNA. We then analysed, evaluated and summerized scientific evidences derived from these studies. Results We first briefly summarize the basic molecular events involved in memory, a process inherent to cognitive disease, and then describe the role of miRNAs in neurodevelopment, synaptic plasticity and memory. Secondly, we provide an overview of the impact of miRNA dysregulation in the pathogenesis of different neurocognitive disorders, and lastly discuss the feasibility of miRNA-based therapeutics in the treatment of these disorders. Conclusion This review highlights the molecular basis of neurodegenerative and cognitive disorders by focusing on the impact of miRNAs dysregulation in these pathological phenotypes. Altogether, the published reports suggest that miRNAs-based therapy could be a viable therapeutic alternative to current treatment options in the future. PMID:27396304

Cognitive Impairment in Bipolar Disorder: Treatment and Prevention Strategies.

PubMed

Solé, Brisa; Jiménez, Esther; Torrent, Carla; Reinares, Maria; Bonnin, Caterina Del Mar; Torres, Imma; Varo, Cristina; Grande, Iria; Valls, Elia; Salagre, Estela; Sanchez-Moreno, Jose; Martinez-Aran, Anabel; Carvalho, André F; Vieta, Eduard

2017-08-01

Over the last decade, there has been a growing appreciation of the importance of identifying and treating cognitive impairment associated with bipolar disorder, since it persists in remission periods. Evidence indicates that neurocognitive dysfunction may significantly influence patients' psychosocial outcomes. An ever-increasing body of research seeks to achieve a better understanding of potential moderators contributing to cognitive impairment in bipolar disorder in order to develop prevention strategies and effective treatments. This review provides an overview of the available data from studies examining treatments for cognitive dysfunction in bipolar disorder as well as potential novel treatments, from both pharmacological and psychological perspectives. All these data encourage the development of further studies to find effective strategies to prevent and treat cognitive impairment associated with bipolar disorder. These efforts may ultimately lead to an improvement of psychosocial functioning in these patients. © The Author 2017. Published by Oxford University Press on behalf of CINP.

Reduced Physical Fitness in Patients With Heart Failure as a Possible Risk Factor for Impaired Driving Performance

PubMed Central

Alosco, Michael L.; Penn, Marc S.; Spitznagel, Mary Beth; Cleveland, Mary Jo; Ott, Brian R.

2015-01-01

OBJECTIVE. Reduced physical fitness secondary to heart failure (HF) may contribute to poor driving; reduced physical fitness is a known correlate of cognitive impairment and has been associated with decreased independence in driving. No study has examined the associations among physical fitness, cognition, and driving performance in people with HF. METHOD. Eighteen people with HF completed a physical fitness assessment, a cognitive test battery, and a validated driving simulator scenario. RESULTS. Partial correlations showed that poorer physical fitness was correlated with more collisions and stop signs missed and lower scores on a composite score of attention, executive function, and psychomotor speed. Cognitive dysfunction predicted reduced driving simulation performance. CONCLUSION. Reduced physical fitness in participants with HF was associated with worse simulated driving, possibly because of cognitive dysfunction. Larger studies using on-road testing are needed to confirm our findings and identify clinical interventions to maximize safe driving. PMID:26122681

Piracetam improves children's memory after general anaesthesia.

PubMed

Fesenko, Ułbołgan A

2009-01-01

Surgery and anaesthesia may account for postoperative complications including cognitive impairment. The purpose of the study was to assess the influence of general anaesthetics on children's memory and effectiveness of piracetam for prevention of postoperative cognitive dysfunction. The study included patients receiving different kinds of anaesthesia for various surgical procedures, randomly allocated to two groups. According to immediate postoperative treatment, the study group received intravenous piracetam 30 mg kg(-1) and the control group--placebo. The cognitive functions were examined preoperatively and within 10 consecutive postoperative days using the ten-word memory test. The study group consisted of 123 children, the control one--of 127. Declines in memory indexes were observed in all anaesthetized patients. The most injured function was long-term memory. The intravenous administration of piracetam improved this cognitive function. The study results confirm that general anaesthesia affects the memory function in children. Piracetam is effective for prevention of postoperative cognitive dysfunction after anaesthesia.

GABA neuron alterations, cortical circuit dysfunction and cognitive deficits in schizophrenia.

PubMed

Gonzalez-Burgos, Guillermo; Fish, Kenneth N; Lewis, David A

2011-01-01

Schizophrenia is a brain disorder associated with cognitive deficits that severely affect the patients' capacity for daily functioning. Whereas our understanding of its pathophysiology is limited, postmortem studies suggest that schizophrenia is associated with deficits of GABA-mediated synaptic transmission. A major role of GABA-mediated transmission may be producing synchronized network oscillations which are currently hypothesized to be essential for normal cognitive function. Therefore, cognitive deficits in schizophrenia may result from a GABA synapse dysfunction that disturbs neural synchrony. Here, we highlight recent studies further suggesting alterations of GABA transmission and network oscillations in schizophrenia. We also review current models for the mechanisms of GABA-mediated synchronization of neural activity, focusing on parvalbumin-positive GABA neurons, which are altered in schizophrenia and whose function has been strongly linked to the production of neural synchrony. Alterations of GABA signaling that impair gamma oscillations and, as a result, cognitive function suggest paths for novel therapeutic interventions.

The Link Between Physical Activity and Cognitive Dysfunction in Alzheimer Disease.

PubMed

Phillips, Cristy; Baktir, Mehmet Akif; Das, Devsmita; Lin, Bill; Salehi, Ahmad

2015-07-01

Alzheimer disease (AD) is a primary cause of cognitive dysfunction in the elderly population worldwide. Despite the allocation of enormous amounts of funding and resources to studying this brain disorder, there are no effective pharmacological treatments for reducing the severity of pathology and restoring cognitive function in affected people. Recent reports on the failure of multiple clinical trials for AD have highlighted the need to diversify further the search for new therapeutic strategies for cognitive dysfunction. Thus, studies detailing the neuroprotective effects of physical activity (PA) on the brain in AD were reviewed, and mechanisms by which PA might mitigate AD-related cognitive decline were explored. A MEDLINE database search was used to generate a list of studies conducted between January 2007 and September 2014 (n=394). These studies, along with key references, were screened to identify those that assessed the effects of PA on AD-related biomarkers and cognitive function. The search was not limited on the basis of intensity, frequency, duration, or mode of activity. However, studies in which PA was combined with another intervention (eg, diet, pharmacotherapeutics, ovariectomy, cognitive training, behavioral therapy), and studies not written in English were excluded. Thirty-eight animal and human studies met entry criteria. Most of the studies suggested that PA attenuates neuropathology and positively affects cognitive function in AD. Although the literature lacked sufficient evidence to support precise PA guidelines, convergent evidence does suggest that the incorporation of regular PA into daily routines mitigates AD-related symptoms, especially when deployed earlier in the disease process. Here the protocols used to alter the progression of AD-related neuropathology and cognitive decline are highlighted, and the implications for physical therapist practice are discussed. © 2015 American Physical Therapy Association.

A study of donepezil in female breast cancer survivors with self-reported cognitive dysfunction 1 to 5 years following adjuvant chemotherapy.

PubMed

Lawrence, J A; Griffin, L; Balcueva, E P; Groteluschen, D L; Samuel, T A; Lesser, G J; Naughton, M J; Case, L D; Shaw, E G; Rapp, S R

2016-02-01

Some breast cancer survivors report cognitive difficulties greater than 1 year after chemotherapy. Acetylcholinesterase inhibitors (AChEI) may improve cognitive impairment. We conducted a randomized, placebo-controlled, pilot study to assess the feasibility of using the AChEI, donepezil, to improve subjective and objective measures of cognitive function in breast cancer survivors. Women who received adjuvant chemotherapy 1-5 years prior with current cognitive dysfunction symptoms were randomized to 5 mg of donepezil/day vs placebo for 6 weeks and if tolerated 10 mg/day for 18 weeks for a total of 24 weeks. A battery of validated measures of attention, memory, language, visuomotor skills, processing speed, executive function, and motor dexterity and speed was administered at baseline and at 24 and 36 weeks. Subjective cognitive function, fatigue, sleep, mood, and health-related quality of life were evaluated at baseline and at 12, 24, and 36 weeks. Sixty-two patients were enrolled, 76 % completed the study, self-reported compliance was 98 %, and toxicities were minimal. At the end of treatment, the donepezil group performed significantly better than the control group on two parameters of memory-the Hopkins Verbal Learning Test -Revised (HVLT-R) Total Recall (p = 0.033) and HVLT-R Discrimination (p = 0.036). There were no significant differences on other cognitive variables or in subjective cognitive function or quality of life. Accrual to this feasibility trial was robust, retention was good, compliance was excellent, and toxicities were minimal. Randomized clinical trials in breast cancer survivors to improve cognitive dysfunction are feasible. A phase III trial testing the efficacy of donepezil is warranted given these pilot results.

Affective and cognitive reactivity to mood induction in chronic depression.

PubMed

Guhn, Anne; Sterzer, Philipp; Haack, Friderike H; Köhler, Stephan

2018-03-15

Chronic depression (CD) is strongly associated with childhood maltreatment, which has been proposed to lead to inefficient coping styles that are characterized by abnormal affective responsiveness and dysfunctional cognitive attitudes. However, while this notion forms an important basis for psychotherapeutic strategies in the treatment of CD, there is still little direct empirical evidence for a role of altered affective and cognitive reactivity in CD. The present study therefore experimentally investigated affective and cognitive reactivity to two forms of negative mood induction in CD patients versus a healthy control sample (HC). For the general mood induction procedure, a combination of sad pictures and sad music was used, while for individualized mood induction, negative mood was induced by individualized scripts with autobiographical content. Both experiments included n = 15 CD patients versus n = 15 HC, respectively. Interactions between affective or cognitive reactivity and group were analyzed by repeated measurements ANOVAs. General mood induction neither revealed affective nor cognitive reactivity in the patient group while the control group reported the expected decrease of positive affect [interaction (IA) affective reactivity x group: p = .011, cognitive reactivity x group: n.s.]. In contrast, individualized mood induction specifically increased affective reactivity (IA: p = .037) as well as the amount of dysfunctional cognitions in patients versus controls (IA: p = .014). The experiments were not balanced in a crossover design, causal conclusions are thus limited. Additionally, the differences to non-chronic forms of depression are still outstanding. The results suggest that in patients with CD, specific emotional activation through autobiographical memories is a key factor in dysfunctional coping styles. Psychotherapeutic interventions aimed at modifying affective and cognitive reactivity are thus of high relevance in the treatment of CD. Copyright © 2018 Elsevier B.V. All rights reserved.

Kant, cognitive psychotherapy, and the hardening of the categories.

PubMed

Nevid, Jeffrey S

2007-12-01

Contemporary models of psychotherapy owe a considerable intellectual debt to philosophy, even though the contributions of philosophers to contemporary practice in the field often go unrecognized. A case in point is Kant's epistemology, which is foundational to cognitive approaches to psychotherapy. Here, it is argued that the rigid use of certain judgments represented in Kant's conceptual scheme underlies patterns of distorted or dysfunctional thinking associated with emotional disorders. Kantian judgments of necessity, disjunction, particularity and universality have counterpoints in contemporary conceptions of cognitive distortions. Moreover, Kantian epistemology has important therapeutic implications with respect to helping people with emotional disorders recognize and challenge rigidly held judgments or categories of understanding. The Kantian perspective also leads us to consider the cognitive frameworks or thought structures that underlie dysfunctional thinking patterns.

Early cognitive impairment along with decreased stress-induced BDNF in male and female patients with newly diagnosed multiple sclerosis.

PubMed

Prokopova, Barbora; Hlavacova, Natasa; Vlcek, Miroslav; Penesova, Adela; Grunnerova, Lucia; Garafova, Alexandra; Turcani, Peter; Kollar, Branislav; Jezova, Daniela

2017-01-15

The aim of this study was to evaluate neuroendocrine activation during stress in patients with recently diagnosed multiple sclerosis before starting the immunomodulatory therapy (EDSS score≤2.0). We verified the hypothesis that certain cognitive and affective dysfunction is present already at this early stage of the disease. The sample consisted of 38 subjects, which involved patients who were recently diagnosed multiple sclerosis and age- and sex-matched healthy volunteers. Stroop test served as mental stress model enabling measurement of cognitive performance. Present results showed increased state anxiety, depression scores and poorer performance in the Stroop test in the group of patients compared to healthy subjects. The cognitive dysfunction was particularly evident in male patients with simultaneously decreased concentrations of the brain-derived neurotrophic factor (BDNF) in plasma. The patients at this stage of the disease have not yet developed the hyperactivity of the hypothalamic-pituitary-adrenocortical axis. They showed normal levels of plasma copeptin and reduced aldosterone response to mental stress test in women only. Concentrations of plasma copeptin were higher in men compared to women. Very early stages of multiple sclerosis are accompanied by disturbances in psychological well-being, mild cognitive dysfunction and decreased plasma concentrations of BDNF, particularly in male patients. Copyright © 2016. Published by Elsevier B.V.

Sleep disruption among cancer patients following autologous hematopoietic cell transplantation.

PubMed

Nelson, Ashley M; Jim, Heather S L; Small, Brent J; Nishihori, Taiga; Gonzalez, Brian D; Cessna, Julie M; Hyland, Kelly A; Rumble, Meredith E; Jacobsen, Paul B

2018-03-01

Despite a high prevalence of sleep disruption among hematopoietic cell transplant (HCT) recipients, relatively little research has investigated its relationships with modifiable cognitive or behavioral factors or used actigraphy to characterize sleep disruption in this population. Autologous HCT recipients who were 6-18 months post transplant completed self-report measures of cancer-related distress, fear of cancer recurrence, dysfunctional sleep cognitions, and inhibitory sleep behaviors upon enrollment. Patients then wore an actigraph for 7 days and completed a self-report measure of sleep disruption on day 7 of the study. Among the 84 participants (age M = 60, 45% female), 41% reported clinically relevant sleep disruption. Examination of actigraph data confirmed that, on average, sleep was disrupted (wake after sleep onset M = 66 min) and sleep efficiency was less than recommended (sleep efficiency M = 78%). Cancer-related distress, fear of recurrence, dysfunctional sleep cognitions, and inhibitory sleep behaviors were related to self-reported sleep disruption (p values<0.05) but not objective sleep indices. Results suggest that many HCT recipients experience sleep disruption after transplant. Cancer-related distress, fear of recurrence, dysfunctional sleep cognitions, and maladaptive sleep behaviors are related to self-reported sleep disruption and should be considered targets for cognitive behavioral intervention in this population.

Cannabis-induced Moto-Cognitive Dysfunction in Wistar Rats: Ameliorative Efficacy of Nigella Sativa.

PubMed

Imam, Aminu; Ajao, Moyosore Saliu; Amin, Abdulbasit; Abdulmajeed, Wahab Imam; Ibrahim, Abdulmumin; Olajide, Olayemi Joseph; Ajibola, Musa Iyiola; Alli-Oluwafuyi, Abdulmusawir; Balogun, Wasiu Gbolahan

2016-09-01

Cannabis is a widely used illicit drug with various threats of personality syndrome, and Nigella sativa has been widely implicated as having therapeutic efficacy in many neurological diseases. The present study investigates the ameliorative efficacy of Nigella sativa oil (NSO) on cannabis-induced moto-cognitive defects. Scopolamine (1 mg/kg i.p.) was given to induce dementia as a standard base line for cannabis (20 mg/kg)-induced cognitive impairment, followed by an oral administration of NSO (1 ml/kg) for 14 consecutive days. The Morris water maze (MWM) paradigm was used to assess the memory index, the elevated plus maze was used for anxiety-like behaviour, and the open field test was used for locomotor activities; thereafter, the rats were sacrificed and their brains were removed for histopathologic studies. Cannabis-like Scopolamine caused memory impairment, delayed latency in the MWM, and anxiety-like behaviour, coupled with alterations in the cerebello-hippocampal neurons. The post-treatment of rats with NSO mitigated cannabis-induced cognitive dysfunction as with scopolamine and impaired anxiety-like behaviour by increasing open arm entry, line crossing, and histological changes. The observed ameliorative effects of NSO make it a promising agent against moto-cognitive dysfunction and cerebelo-hippocampal alterations induced by cannabis.

Radiation-induced cognitive dysfunction and cerebellar oxidative stress in mice: protective effect of alpha-lipoic acid.

PubMed

Manda, Kailash; Ueno, Megumi; Moritake, Takashi; Anzai, Kazunori

2007-02-12

Reactive oxygen species are implicated in neurodegeneration and cognitive disorders due to higher vulnerability of neuronal tissues. The cerebellum is recently reported to be involved in cognitive function. Therefore, present study aimed at investigating the role alpha-lipoic acid against radiation-induced oxidative stress and antioxidant status in cerebellum and its correlation with cognitive dysfunction. We observed spontaneous motor activities and spatial memory task of mice using pyroelectric infrared sensor and programmed video tracking system, respectively. Whole body X-irradiation (6 Gy) of mice substantially impaired the reference memory and motor activities of mice. However, acute intraperitoneal treatment of mice with alpha-lipoic acid prior to irradiation significantly attenuated such cognitive dysfunction. Alpha-lipoic acid pretreatment exerted a very high magnitude of protection against radiation-induced augmentation of protein carbonyls and thiobarbituric acid reactive substance (TBARS) in mice cerebellum. Further, radiation-induced deficit of total, nonprotein and protein-bound sulfhydryl (T-SH, NP-SH, PB-SH) contents of cerebellum and plasma ferric reducing power (FRAP) was also inhibited by alpha-lipoic acid pre-treatment. Moreover, alpha-lipoic acid treated mice showed an intact cytoarchitecture of cerebellum, higher counts of intact Purkinje cells and granular cells in comparison to untreated irradiated mice. Results clearly indicate that alpha-lipoic acid is potent neuroprotective antioxidant.

Role of Oxidative Stress in the Neurocognitive Dysfunction of Obstructive Sleep Apnea Syndrome.

PubMed

Zhou, Li; Chen, Ping; Peng, Yating; Ouyang, Ruoyun

2016-01-01

Obstructive sleep apnea syndrome (OSAS) is characterized by chronic nocturnal intermittent hypoxia and sleep fragmentations. Neurocognitive dysfunction, a significant and extraordinary complication of OSAS, influences patients' career, family, and social life and reduces quality of life to some extent. Previous researches revealed that repetitive hypoxia and reoxygenation caused mitochondria and endoplasmic reticulum dysfunction, overactivated NADPH oxidase, xanthine oxidase, and uncoupling nitric oxide synthase, induced an imbalance between prooxidants and antioxidants, and then got rise to a series of oxidative stress (OS) responses, such as protein oxidation, lipid peroxidation, and DNA oxidation along with inflammatory reaction. OS in brain could trigger neuron injury especially in the hippocampus and cerebral cortex regions. Those two regions are fairly susceptible to hypoxia and oxidative stress production which could consequently result in cognitive dysfunction. Apart from continuous positive airway pressure (CPAP), antioxidant may be a promising therapeutic method to improve partially reversible neurocognitive function. Understanding the role that OS played in the cognitive deficits is crucial for future research and therapeutic strategy development. In this paper, recent important literature concerning the relationship between oxidative stress and cognitive impairment in OSAS will be summarized and the results can provide a rewarding overview for future breakthrough in this field.

White matter damage and glymphatic dysfunction in a model of vascular dementia in rats with no prior vascular pathologies

PubMed Central

Venkat, Poornima; Chopp, Michael; Zacharek, Alex; Cui, Chengcheng; Zhang, Li; Li, Qingjiang; Lu, Mei; Zhang, Talan; Liu, Amy; Chen, Jieli

2016-01-01

We investigated cognitive function, axonal/white matter (WM) changes and glymphatic function of vascular dementia (VaD) using a multiple microinfarction (MMI) model in retired breeder (RB) rats. The MMI model induces significant (p<0.05) cognitive decline that worsens with age starting at 2 weeks, which persists until at least 6 weeks after MMI. RB rats subjected to MMI exhibit significant axonal/WM damage identified by decreased myelin thickness, oligodendrocyte progenitor cell numbers, axon density, synaptic protein expression in the cortex and striatum, cortical neuronal branching, and dendritic spine density in the cortex and hippocampus compared with age matched controls. MMI evokes significant dilation of perivascular spaces as well as water channel dysfunction indicated by decreased Aquaporin-4 (AQP-4) expression around blood vessels. MMI induced glymphatic dysfunction with delayed cerebrospinal fluid (CSF) penetration into the brain parenchyma via paravascular pathways as well as delayed waste clearance from the brain. The MMI model in RB rats decreases AQP-4 and induces glymphatic dysfunction which may play an important role in MMI induced axonal/WM damage and cognitive deficits. PMID:27940353

White matter damage and glymphatic dysfunction in a model of vascular dementia in rats with no prior vascular pathologies.

PubMed

Venkat, Poornima; Chopp, Michael; Zacharek, Alex; Cui, Chengcheng; Zhang, Li; Li, Qingjiang; Lu, Mei; Zhang, Talan; Liu, Amy; Chen, Jieli

2017-02-01

We investigated cognitive function, axonal/white matter (WM) changes and glymphatic function of vascular dementia using a multiple microinfarction (MMI) model in retired breeder (RB) rats. The MMI model induces significant (p < 0.05) cognitive decline that worsens with age starting at 2 weeks, which persists until at least 6 weeks after MMI. RB rats subjected to MMI exhibit significant axonal/WM damage identified by decreased myelin thickness, oligodendrocyte progenitor cell numbers, axon density, synaptic protein expression in the cortex and striatum, cortical neuronal branching, and dendritic spine density in the cortex and hippocampus compared with age-matched controls. MMI evokes significant dilation of perivascular spaces as well as water channel dysfunction indicated by decreased Aquaporin-4 expression around blood vessels. MMI-induced glymphatic dysfunction with delayed cerebrospinal fluid penetration into the brain parenchyma via paravascular pathways as well as delayed waste clearance from the brain. The MMI model in RB rats decreases Aquaporin-4 and induces glymphatic dysfunction which may play an important role in MMI-induced axonal/WM damage and cognitive deficits. Copyright © 2016 Elsevier Inc. All rights reserved.

Improvement in social-interpersonal functioning after cognitive therapy for recurrent depression

PubMed Central

VITTENGL, J. R.; CLARK, L. A.; JARRETT, R. B.

2005-01-01

Background. Cognitive therapy reduces depressive symptoms of major depressive disorder, but little is known about concomitant reduction in social-interpersonal dysfunction. Method. We evaluated social-interpersonal functioning (self-reported social adjustment, interpersonal problems and dyadic adjustment) and depressive symptoms (two self-report and two clinician scales) in adult outpatients (n=156) with recurrent major depressive disorder at several points during a 20-session course of acute phase cognitive therapy. Consenting acute phase responders (n=84) entered a 2-year follow-up phase, which included an 8-month experimental trial comparing continuation phase cognitive therapy to assessment-only control. Results. Social-interpersonal functioning improved after acute phase cognitive therapy (dyadic adjustment d=0.47; interpersonal problems d=0.91; social adjustment d=1.19), but less so than depressive symptoms (d=1.55). Improvement in depressive symptoms and social-interpersonal functioning were moderately to highly correlated (r=0.39–0.72). Improvement in depressive symptoms was partly independent of social-interpersonal functioning (r=0.55–0.81), but improvement in social-interpersonal functioning independent of change in depressive symptoms was not significant (r=0.01–0.06). In acute phase responders, continuation phase therapy did not further enhance social-interpersonal functioning, but improvements in social-interpersonal functioning were maintained through the follow-up. Conclusions. Social-interpersonal functioning is improved after acute phase cognitive therapy and maintained in responders over 2 years. Improvement in social-interpersonal functioning is largely accounted for by decreases in depressive symptoms. PMID:15099419

Parvalbumin-positive interneurons of the prefrontal cortex support working memory and cognitive flexibility

PubMed Central

Murray, Andrew J.; Woloszynowska-Fraser, Marta U.; Ansel-Bollepalli, Laura; Cole, Katy L. H.; Foggetti, Angelica; Crouch, Barry; Riedel, Gernot; Wulff, Peer

2015-01-01

Dysfunction of parvalbumin (PV)-positive GABAergic interneurons (PVIs) within the prefrontal cortex (PFC) has been implicated in schizophrenia pathology. It is however unclear, how impaired signaling of these neurons may contribute to PFC dysfunction. To identify how PVIs contribute to PFC-dependent behaviors we inactivated PVIs in the PFC in mice using region- and cell-type-selective expression of tetanus toxin light chain (TeLC) and compared the functional consequences of this manipulation with non-cell-type-selective perturbations of the same circuitry. By sampling for behavioral alterations that map onto distinct symptom categories in schizophrenia, we show that dysfunction of PVI signaling in the PFC specifically produces deficits in the cognitive domain, but does not give rise to PFC-dependent correlates of negative or positive symptoms. Our results suggest that distinct aspects of the complex symptomatology of PFC dysfunction in schizophrenia can be attributed to specific prefrontal circuit elements. PMID:26608841

Age-Associated Differences in Cognitive Performance in Older Community Dwelling Schizophrenia Patients: Differential Sensitivity of Clinical Neuropsychological and Experimental Information Processing Tests

PubMed Central

Bowie, Christopher R.; Reichenberg, Abraham; McClure, Margaret M.; Leung, Winnie L.; Harvey, Philip D.

2008-01-01

Cognitive dysfunction is a common feature of schizophrenia and deficits are present before the onset of psychosis, and are moderate to severe by the time of the first episode. Controversy exists over the course of cognitive dysfunction after the first episode. This study examined age-associated differences in performance on clinical neuropsychological (NP) and information processing tasks in a sample of geriatric community living schizophrenia patients (n=172). Compared to healthy control subjects (n=70), people with schizophrenia did not differ on NP tests across age groups but showed evidence for age-associated cognitive worsening on the more complex components of an information-processing test. Age-related changes in cognitive function in schizophrenia may be a function of both the course of illness and the processing demands of the cognitive measure of interest. Tests with fixed difficulty, such as clinical NP tests, may differ in their sensitivity from tests for which parametric difficulty manipulations can be performed. PMID:18053687

Pharmacological cognitive enhancement: treatment of neuropsychiatric disorders and lifestyle use by healthy people.

PubMed

Sahakian, Barbara J; Morein-Zamir, Sharon

2015-04-01

Neuropsychiatric disorders typically manifest as problems with attentional biases, aberrant learning, dysfunctional reward systems, and an absence of top-down cognitive control by the prefrontal cortex. In view of the cost of common mental health disorders, in terms of distress to the individual and family in addition to the financial cost to society and governments, new developments for treatments that address cognitive dysfunction should be a priority so that all members of society can flourish. Cognitive enhancing drugs, such as cholinesterase inhibitors and methylphenidate, are used as treatments for the cognitive symptoms of Alzheimer's disease and attention deficit hyperactivity disorder. However, these drugs and others, including modafinil, are being increasingly used by healthy people for enhancement purposes. Importantly for ethical and safety reasons, the drivers for this increasing lifestyle use of so-called smart drugs by healthy people should be considered and discussions must occur about how to ensure present and future pharmacological cognitive enhancers are used for the benefit of society. Copyright © 2015 Elsevier Ltd. All rights reserved.

Micro-RNAs in cognition and cognitive disorders: Potential for novel biomarkers and therapeutics.

PubMed

Woldemichael, Bisrat T; Mansuy, Isabelle M

2016-03-15

Micro-RNAs (miRNAs) are small regulatory non-coding RNAs involved in the regulation of many biological functions. In the brain, they have distinct expression patterns depending on region, cell-type and developmental stage. Their expression profile is altered by neuronal activation in response to behavioral training or chemical/electrical stimulation. The dynamic changes in miRNA level regulate the expression of genes required for cognitive processes such as learning and memory. In addition, in cognitive dysfunctions such as dementias, expression levels of many miRNAs are perturbed, not only in brain areas affected by the pathology, but also in peripheral body fluids such as serum and cerebrospinal fluid. This presents an opportunity to utilize miRNAs as biomarkers for early detection and assessment of cognitive dysfunctions. Further, since miRNAs target many genes and pathways, they may represent key molecular signatures that can help understand the mechanisms of cognitive disorders and the development of potential therapeutic agents. Copyright © 2015 Elsevier Inc. All rights reserved.

Cognitive outcome of cerebral fat embolism.

PubMed

Manousakis, Georgios; Han, Dong Y; Backonja, Miroslav

2012-11-01

Cerebral fat embolism is an uncommon but serious complication of long-bone fracture. We report a young adult patient who sustained fat embolism after a femoral fracture. He developed stupor and coma within 24 hours from his injury. His acute recovery was characterized by marked frontal dysfunction. A comprehensive neuropsychological evaluation 4 months later revealed overall normal cognitive function, except for mild residual frontal dysfunction and weakness of verbal memory. Copyright © 2012 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Neurocognitive Dysfunction in Systemic Lupus Erythematosus: Association with Antiphospholipid Antibodies, Disease Activity and Chronic Damage

PubMed Central

Conti, Fabrizio; Alessandri, Cristiano; Perricone, Carlo; Scrivo, Rossana; Rezai, Soheila; Ceccarelli, Fulvia; Spinelli, Francesca Romana; Ortona, Elena; Marianetti, Massimo; Mina, Concetta; Valesini, Guido

2012-01-01

Introduction Systemic lupus erythematosus (SLE) is characterized by frequent neuropsychiatric involvement, which includes cognitive impairment (CI). We aimed at assessing CI in a cohort of Italian SLE patients by using a wide range of neurocognitive tests specifically designed to evaluate the fronto-subcortical dysfunction. Furthermore, we aimed at testing whether CI in SLE is associated with serum autoantibodies, disease activity and chronic damage. Methods Fifty-eight consecutive patients were enrolled. Study protocol included data collection, evaluation of serum levels of ANA, anti-dsDNA, anti-cardiolipin, anti-β2-glycoprotein I, anti-P ribosomal, anti-endothelial cell, and anti-Nedd5 antibodies. SLEDAI-2000 and SLICC were used to assess disease activity and chronic damage. Patients were administered a test battery specifically designed to detect fronto-subcortical dysfunction across five domains: memory, attention, abstract reasoning, executive function and visuospatial function. For each patient, the raw scores from each test were compared with published norms, then transformed into Z scores (deviation from normal mean), and finally summed in the Global Cognitive Dysfunction score (GCDs). Results Nineteen percent of patients had mild GCDs impairment (GCDs 2–3), 7% moderate (GCDs 4–5) and 5% severe (GCDs≥6). The visuospatial domain was the most compromised (MDZs = −0.89±1.23). Anti-cardiolipin IgM levels were associated with visuospatial domain impairment (r = 0.331, P = 0.005). SLEDAI correlated with GCDs, and attentional and executive domains; SLICC correlated with GCDs, and with visuospatial and attentional domains impairment. Conclusions Anti-phospholipids, disease activity, and chronic damage are associated with cognitive dysfunction in SLE. The use of a wide spectrum of tests allowed for a better selection of the relevant factors involved in SLE cognitive dysfunction, and standardized neuropsychological testing methods should be used for routine assessment of SLE patients. PMID:22461897

Altered caudate connectivity is associated with executive dysfunction after traumatic brain injury

PubMed Central

De Simoni, Sara; Jenkins, Peter O; Bourke, Niall J; Fleminger, Jessica J; Jolly, Amy E; Patel, Maneesh C; Leech, Robert; Sharp, David J

2018-01-01

Abstract Traumatic brain injury often produces executive dysfunction. This characteristic cognitive impairment often causes long-term problems with behaviour and personality. Frontal lobe injuries are associated with executive dysfunction, but it is unclear how these injuries relate to corticostriatal interactions that are known to play an important role in behavioural control. We hypothesized that executive dysfunction after traumatic brain injury would be associated with abnormal corticostriatal interactions, a question that has not previously been investigated. We used structural and functional MRI measures of connectivity to investigate this. Corticostriatal functional connectivity in healthy individuals was initially defined using a data-driven approach. A constrained independent component analysis approach was applied in 100 healthy adult dataset from the Human Connectome Project. Diffusion tractography was also performed to generate white matter tracts. The output of this analysis was used to compare corticostriatal functional connectivity and structural integrity between groups of 42 patients with traumatic brain injury and 21 age-matched controls. Subdivisions of the caudate and putamen had distinct patterns of functional connectivity. Traumatic brain injury patients showed disruption to functional connectivity between the caudate and a distributed set of cortical regions, including the anterior cingulate cortex. Cognitive impairments in the patients were mainly seen in processing speed and executive function, as well as increased levels of apathy and fatigue. Abnormalities of caudate functional connectivity correlated with these cognitive impairments, with reductions in right caudate connectivity associated with increased executive dysfunction, information processing speed and memory impairment. Structural connectivity, measured using diffusion tensor imaging between the caudate and anterior cingulate cortex was impaired and this also correlated with measures of executive dysfunction. We show for the first time that altered subcortical connectivity is associated with large-scale network disruption in traumatic brain injury and that this disruption is related to the cognitive impairments seen in these patients. PMID:29186356

"Boomerang Neuropathology" of Late-Onset Alzheimer's Disease is Shrouded in Harmful "BDDS": Breathing, Diet, Drinking, and Sleep During Aging.

PubMed

Daulatzai, Mak Adam

2015-07-01

Brain damage begins years before substantial neurodegeneration and Alzheimer's dementia. Crucial fundamental activities of life are breathing, eating, drinking, and sleeping. When these pivotal functions are maligned over a prolonged period, they impart escalating dyshomeostasis. The latter may lead to disastrous consequences including cognitive dysfunction and Alzheimer's disease (AD). The current theme here is that multiple pathophysiological derangements are promoted over a prolonged period by the very fundamental activities of life-when "rendered unhealthy." They may converge on several regulating/modulating factors (e.g., mitochondrial energy production, oxidative stress, innate immunity, and vascular function) and promote insidious neuropathology that culminates in cognitive decline in the aged. This is of course associated with the accumulation of amyloid beta and phosphorylated tau in the brain. Epidemiological, biomarker, and neuroimaging studies have provided significant copious evidence on the presence of indolent prodromal AD neuropathology many years prior to symptomatic onset. Progressive oxidative damage to specific gene promoters may result in gene silencing. A mechanistic link may possibly exist between epigenomic state, DNA damage, and chronically unhealthy/dysfunctional body systems. This paper, therefore, addresses and delineates the deleterious pathophysiological impact triggered by dysfunctional breathing, harmful diet, excess of alcohol consumption, and sleep deprivation; indeed, their impact may alter epigenetic state. It is mandatory, therefore, to abrogate cognitive decline and attenuate AD pathology through adoption of a healthy lifestyle, in conjunction with combination therapy with known moderators of cognitive decline. This strategy may thwart multiple concurrent and synergistic pathologies, including epigenetic dysfunction. A multi-factorial therapeutic intervention is required to overcome wide ranging neuropathology and multi-faceted disease process. Such an approach may attenuate neuropathology and ameliorate memory dysfunction.

Effects of environmental noise on cognitive (dys)functions in schizophrenia: A pilot within-subjects experimental study

PubMed Central

Wright, Bernice; Peters, Emmanuelle; Ettinger, Ulrich; Kuipers, Elizabeth; Kumari, Veena

2016-01-01

Cognitive impairment, particularly in attention, memory and executive function domains, is commonly present and associated with poor functional outcomes in schizophrenia. In healthy adults, environmental noise adversely affects many cognitive domains, including those known to be compromised in schizophrenia. This pilot study examined whether environmental noise causes further cognitive deterioration in a small sample of people with schizophrenia. Eighteen outpatients with schizophrenia on stable doses of antipsychotics and 18 age and sex-matched healthy participants were assessed on a comprehensive cognitive battery including measures of psychomotor speed, attention, executive functioning, working memory, and verbal learning and memory under three different conditions [quiet: ~ 30 dB(A); urban noise: building site noise, 68–78 dB(A); and social noise: background babble and footsteps from a crowded hall without any discernible words, 68–78 dB(A)], 7–14 days apart, with counter-balanced presentation of noise conditions across participants of both groups. The results showed widespread cognitive impairment in patients under all conditions, and noise-induced impairments of equal magnitude on specific cognitive functions in both groups. Both patient and healthy participant groups showed significant disruption of delayed verbal recall and recognition by urban and social noise, and of working memory by social noise, relative to the quiet condition. Performance under urban and social noise did not differ significantly from each other for any cognitive measure in either group. We conclude that noise has adverse effects on the verbal and working memory domains in schizophrenia patients and healthy participants. This may be particularly problematic for patients as it worsens their pre-existing cognitive deficits. PMID:27017491

Effects of environmental noise on cognitive (dys)functions in schizophrenia: A pilot within-subjects experimental study.

PubMed

Wright, Bernice; Peters, Emmanuelle; Ettinger, Ulrich; Kuipers, Elizabeth; Kumari, Veena

2016-05-01

Cognitive impairment, particularly in attention, memory and executive function domains, is commonly present and associated with poor functional outcomes in schizophrenia. In healthy adults, environmental noise adversely affects many cognitive domains, including those known to be compromised in schizophrenia. This pilot study examined whether environmental noise causes further cognitive deterioration in a small sample of people with schizophrenia. Eighteen outpatients with schizophrenia on stable doses of antipsychotics and 18 age and sex-matched healthy participants were assessed on a comprehensive cognitive battery including measures of psychomotor speed, attention, executive functioning, working memory, and verbal learning and memory under three different conditions [quiet: ~30dB(A); urban noise: building site noise, 68-78dB(A); and social noise: background babble and footsteps from a crowded hall without any discernible words, 68-78dB(A)], 7-14days apart, with counter-balanced presentation of noise conditions across participants of both groups. The results showed widespread cognitive impairment in patients under all conditions, and noise-induced impairments of equal magnitude on specific cognitive functions in both groups. Both patient and healthy participant groups showed significant disruption of delayed verbal recall and recognition by urban and social noise, and of working memory by social noise, relative to the quiet condition. Performance under urban and social noise did not differ significantly from each other for any cognitive measure in either group. We conclude that noise has adverse effects on the verbal and working memory domains in schizophrenia patients and healthy participants. This may be particularly problematic for patients as it worsens their pre-existing cognitive deficits. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Frontal dysfunctions of impulse control - a systematic review in borderline personality disorder and attention-deficit/hyperactivity disorder.

PubMed

Sebastian, Alexandra; Jung, Patrick; Krause-Utz, Annegret; Lieb, Klaus; Schmahl, Christian; Tüscher, Oliver

2014-01-01

Disorders such as borderline personality disorder (BPD) or attention-deficit/hyperactivity disorder (ADHD) are characterized by impulsive behaviors. Impulsivity as used in clinical terms is very broadly defined and entails different categories including personality traits as well as different cognitive functions such as emotion regulation or interference resolution and impulse control. Impulse control as an executive function, however, is neither cognitively nor neurobehaviorally a unitary function. Recent findings from behavioral and cognitive neuroscience studies suggest related but dissociable components of impulse control along functional domains like selective attention, response selection, motivational control, and behavioral inhibition. In addition, behavioral and neural dissociations are seen for proactive vs. reactive inhibitory motor control. The prefrontal cortex with its sub-regions is the central structure in executing these impulse control functions. Based on these concepts of impulse control, neurobehavioral findings of studies in BPD and ADHD were reviewed and systematically compared. Overall, patients with BPD exhibited prefrontal dysfunctions across impulse control components rather in orbitofrontal, dorsomedial, and dorsolateral prefrontal regions, whereas patients with ADHD displayed disturbed activity mainly in ventrolateral and medial prefrontal regions. Prefrontal dysfunctions, however, varied depending on the impulse control component and from disorder to disorder. This suggests a dissociation of impulse control related frontal dysfunctions in BPD and ADHD, although only few studies are hitherto available to assess frontal dysfunctions along different impulse control components in direct comparison of these disorders. Yet, these findings might serve as a hypothesis for the future systematic assessment of impulse control components to understand differences and commonalities of prefrontal cortex dysfunction in impulsive disorders.

Global Efficiency of Structural Networks Mediates Cognitive Control in Mild Cognitive Impairment

PubMed Central

Berlot, Rok; Metzler-Baddeley, Claudia; Ikram, M. Arfan; Jones, Derek K.; O’Sullivan, Michael J.

2016-01-01

Background: Cognitive control has been linked to both the microstructure of individual tracts and the structure of whole-brain networks, but their relative contributions in health and disease remain unclear. Objective: To determine the contribution of both localized white matter tract damage and disruption of global network architecture to cognitive control, in older age and Mild Cognitive Impairment (MCI). Materials and Methods: Twenty-five patients with MCI and 20 age, sex, and intelligence-matched healthy volunteers were investigated with 3 Tesla structural magnetic resonance imaging (MRI). Cognitive control and episodic memory were evaluated with established tests. Structural network graphs were constructed from diffusion MRI-based whole-brain tractography. Their global measures were calculated using graph theory. Regression models utilized both global network metrics and microstructure of specific connections, known to be critical for each domain, to predict cognitive scores. Results: Global efficiency and the mean clustering coefficient of networks were reduced in MCI. Cognitive control was associated with global network topology. Episodic memory, in contrast, correlated with individual temporal tracts only. Relationships between cognitive control and network topology were attenuated by addition of single tract measures to regression models, consistent with a partial mediation effect. The mediation effect was stronger in MCI than healthy volunteers, explaining 23-36% of the effect of cingulum microstructure on cognitive control performance. Network clustering was a significant mediator in the relationship between tract microstructure and cognitive control in both groups. Conclusion: The status of critical connections and large-scale network topology are both important for maintenance of cognitive control in MCI. Mediation via large-scale networks is more important in patients with MCI than healthy volunteers. This effect is domain-specific, and true for cognitive control but not for episodic memory. Interventions to improve cognitive control will need to address both dysfunction of local circuitry and global network architecture to be maximally effective. PMID:28018208

Effects of body mass index and education on verbal and nonverbal memory.

PubMed

De Wit, Liselotte; Kirton, Joshua W; O'Shea, Deirdre M; Szymkowicz, Sarah M; McLaren, Molly E; Dotson, Vonetta M

2017-05-01

We previously reported that higher education protects against executive dysfunction related to higher body mass index (BMI) in younger, but not older, adults. We now extend the previous analyses to verbal and nonverbal memory. Fifty-nine healthy, dementia-free community-dwelling adults ranging in age from 18 to 81 years completed the Hopkins Verbal Learning Test - Revised (HVLT-R) and the Brief Visuospatial Memory Test - Revised (BVMT-R). Self-reported years of education served as a proxy for cognitive reserve. We found that more highly educated individuals maintained their BVMT-R immediate recall performance across the range of BMI, but in less educated individuals, higher BMI was associated with worse performance. Our findings suggest that education may play a protective role against BMI-related nonverbal learning deficits, similar to previous reports for verbal memory and executive functioning. Results highlight the importance of considering educational background when determining the risk for BMI-related cognitive impairment in clinical settings.

Does improvement of cognitive functioning by cognitive remediation therapy effect work outcomes in severe mental illness? A secondary analysis of a randomized controlled trial.

PubMed

Ikebuchi, Emi; Sato, Sayaka; Yamaguchi, Sosei; Shimodaira, Michiyo; Taneda, Ayano; Hatsuse, Norifumi; Watanabe, Yukako; Sakata, Masuhiro; Satake, Naoko; Nishio, Masaaki; Ito, Jun-Ichiro

2017-05-01

The aim of this study was to clarify whether improvement of cognitive functioning by cognitive remediation therapy can improve work outcome in schizophrenia and other severe mental illnesses when combined with supported employment. The subjects of this study were persons with severe mental illness diagnosed with schizophrenia, major depression, or bipolar disorder (ICD-10) and cognitive dysfunction who participated in both cognitive remediation using the Thinking Skills for Work program and a supported employment program in a multisite, randomized controlled study. Logistic and multiple linear regression analyses were performed to clarify the influence of cognitive functioning on vocational outcomes, adjusting for demographic and clinical variables. Improvement of cognitive functioning with cognitive remediation significantly contributed to the total days employed and total earnings of competitive employment in supported employment service during the study period. Any baseline demographic and clinical variables did not significantly contribute to the work-related outcomes. A cognitive remediation program transferring learning skills into the real world is useful to increase the quality of working life in supported employment services for persons with severe mental illness and cognitive dysfunction who want to work competitively. © 2016 The Authors. Psychiatry and Clinical Neurosciences © 2016 Japanese Society of Psychiatry and Neurology.

Cognitive Communication Impairments: A Family-Focused Viewpoint.

ERIC Educational Resources Information Center

DePompei, Roberta; And Others

1988-01-01

An active role is recommended for family members involved in rehabilitation of cognitive communicative impairments of head-injured individuals. The paper discusses family systems theory, dysfunctional family reactions to the cognitive communicative behaviors of the head-injured member, and methods of assisting the family to develop the…

Role of fruits, nuts, and vegetables in maintaining cognitive health

USDA-ARS?s Scientific Manuscript database

Population aging is leading to an increase in the incidence of age-related cognitive dysfunction and, with it, the health care burden of caring for older adults. Epidemiological studies have shown that consumption of fruits, nuts, and vegetables is positively associated with cognitive ability; howev...

Development and validation of 26-item dysfunctional attitude scale.

PubMed

Ebrahimi, Amrollah; Samouei, Rahele; Mousavii, Sayyed Ghafour; Bornamanesh, Ali Reza

2013-06-01

Dysfunctional Attitude Scale is one of the most common instruments used to assess cognitive vulnerability. This study aimed to develop and validate a short form of Dysfunctional Attitude Scale appropriate for an Iranian clinical population. Participants were 160 psychiatric patients from medical centers affiliated with Isfahan Medical University, as well as 160 non-patients. Research instruments were clinical interviews based on the Diagnostic and Statistical Manual-IV-TR, Dysfunctional Attitude Scale and General Heath Questionnaire (GHQ-28). Data was analyzed using multicorrelation calculations and factor analysis. Based on the results of factor analysis and item-total correlation, 14 items were judged candidates for omission. Analysis of the 26-item Dysfunctional Attitude Scale (DAS-26) revealed a Cronbach's alpha of 0.92. Evidence for the concurrent criterion validity was obtained through calculating the correlation between the Dysfunctional Attitude Scale and psychiatric diagnosis (r = 0.55), GHQ -28 (r = 0.56) and somatization, anxiety, social dysfunction, and depression subscales (0.45,0.53,0.48, and 0.57, respectively). Factor analysis deemed a four-factor structure the best. The factors were labeled as success-perfectionism, need for approval, need for satisfying others, and vulnerability-performance evaluation. The results showed that the Iranian version of the Dysfunctional Attitude Scale (DAS-26) bears satisfactory psychometric properties suggesting that this cognitive instrument is appropriate for use in an Iranian cultural context. Copyright © 2012 Wiley Publishing Asia Pty Ltd.

Basal ganglia and beyond: The interplay between motor and cognitive aspects in Parkinson's disease rehabilitation.

PubMed

Ferrazzoli, Davide; Ortelli, Paola; Madeo, Graziella; Giladi, Nir; Petzinger, Giselle M; Frazzitta, Giuseppe

2018-07-01

Parkinson's disease (PD) is characterized by motor and cognitive dysfunctions, affecting the motor behaviour. We summarize evidence that the interplay between motor and cognitive approaches is crucial in PD rehabilitation. Rehabilitation is complementary to pharmacological therapy and effective in reducing the PD disturbances, probably acting by inducing neuroplastic effects. The motor behaviour results from a complex integration between cortical and subcortical areas, underlying the motor, cognitive and motivational aspects of movement. The close interplay amongst these areas makes possible to learn, control and express habitual-automatic actions, which are dysfunctional in PD. The physiopathology of PD could be considered the base for the development of effective rehabilitation treatments. As the volitional action control is spared in early-medium stages of disease, rehabilitative approaches engaging cognition permit to achieve motor benefits and appear to be the most effective for PD. We will point out data supporting the relevance of targeting both motor and cognitive aspects in PD rehabilitation. Finally, we will discuss the role of cognitive engagement in motor rehabilitation for PD. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Prevalence of Cognitive Impairment and Association With Survival Among Older Patients With Hematologic Cancers.

PubMed

Hshieh, Tammy T; Jung, Wooram F; Grande, Laura J; Chen, Jiaying; Stone, Richard M; Soiffer, Robert J; Driver, Jane A; Abel, Gregory A

2018-05-01

As the population ages, cognitive impairment has promised to become increasingly common among patients with cancer. Little is known about how specific domains of cognitive impairment may be associated with survival among older patients with hematologic cancers. To determine the prevalence of domain-specific cognitive impairment and its association with overall survival among older patients with blood cancer. This prospective observational cohort study included all patients 75 years and older who presented for initial consultation in the leukemia, myeloma, or lymphoma clinics of a large tertiary hospital in Boston, Massachusetts, from February 1, 2015, to March 31, 2017. Patients underwent screening for frailty and cognitive dysfunction and were followed up for survival. The Clock-in-the-Box (CIB) test was used to screen for executive dysfunction. A 5-word delayed recall test was used to screen for impairment in working memory. The Fried frailty phenotype and Rockwood cumulative deficit model of frailty were also assessed to characterize participants as robust, prefrail, or frail. Among 420 consecutive patients approached, 360 (85.7%) agreed to undergo frailty assessment (232 men [64.4%] and 128 women [35.6%]; mean [SD] age, 79.8 [3.9] years), and 341 of those (94.7%) completed both cognitive screening tests. One hundred twenty-seven patients (35.3%) had probable executive dysfunction on the CIB, and 62 (17.2%) had probable impairment in working memory on the 5-word delayed recall. Impairment in either domain was modestly correlated with the Fried frailty phenotype (CIB, ρ = 0.177; delayed recall, ρ = 0.170; P = .01 for both), and many phenotypically robust patients also had probable cognitive impairment (24 of 104 [23.1%] on CIB and 9 of 104 [8.7%] on delayed recall). Patients with impaired working memory had worse median survival (10.9 [SD, 12.9] vs 12.2 [SD, 14.7] months; log-rank P < .001), including when stratified by indolent cancer (log-rank P = .01) and aggressive cancer (P < .001) and in multivariate analysis when adjusting for age, comorbidities, and disease aggressiveness (odds ratio, 0.26; 95% CI, 0.13-0.50). Impaired working memory was also associated with worse survival for those undergoing intensive treatment (log-rank P < .001). Executive dysfunction was associated with worse survival only among patients who underwent intensive treatment (log-rank P = .03). These data suggest that domains of cognitive dysfunction may be prevalent in older patients with blood cancer and may have differential predictive value for survival. Targeted interventions are needed for this vulnerable patient population.

The Outward Spiral: A vicious cycle model of obesity and cognitive dysfunction.

PubMed

Hargrave, Sara L; Jones, Sabrina; Davidson, Terry L

2016-06-01

Chronic failure to suppress intake during states of positive energy balance leads to weight gain and obesity. The ability to use context - including interoceptive satiety states - to inhibit responding to previously rewarded cues appears to depend on the functional integrity of the hippocampus. Recent evidence implicates energy dense Western diets in several types of hippocampal dysfunction, including reduced expression of neurotrophins and nutrient transporters, increased inflammation, microglial activation, and blood brain barrier permeability. The functional consequences of such insults include impairments in an animal's ability to modulate responding to a previously reinforced cues. We propose that such deficits promote overeating, which can further exacerbate hippocampal dysfunction and thus initiate a vicious cycle of both obesity and progressive cognitive decline.

Child, parent and family dysfunction as predictors of outcome in cognitive-behavioral treatment of antisocial children.

PubMed

Kazdin, A E

1995-03-01

The present study examined factors that predicted favorable treatment outcomes among clinically referred conduct problem children (N = 105, ages 7-13) who received cognitive-behavioral treatment. Three domains (severity and breadth of child impairment, parent stress and psychopathology and family dysfunction) assessed at pretreatment were predicted to affect treatment outcome. The results only partially supported the prediction. Less dysfunction in each of the domains predicted who responded favorably to treatment on parent ratings of deviance and prosocial functioning but not on teacher ratings of these outcomes. The findings have implications for identifying youths who respond to available treatments. The results also underscore fundamental questions about the assessment of treatment effects and the criteria for evaluating outcome.

[Higher Brain Dysfunction in Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis and Stroke-Like Episodes (MELAS)].

PubMed

Ichikawa, Hiroo

2016-02-01

Stroke-like episodes are one of the cardinal features of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS), and occur in 84-99% of the patients. The affected areas detected on neuroimaging do not have classical vascular distribution, and involve predominantly the temporal, parietal and occipital lobes. Thus, the neurological symptoms including higher brain dysfunction correlate with this topographical distribution. In association with the occipital lobe involvement, the most frequent symptom is cortical blindness. Other symptoms have been occasionally reported in case reports: visual agnosia, prosopagnosia, cortical deafness, auditory agnosia, topographical disorientation, various types of aphasia, hemispatial neglect, and so on. On the other hand, cognitive decline associated with more diffuse brain impairment rather than with focal stroke-like lesions has been postulated. This condition is also known as mitochondrial dementia. Domains of cognitive dysfunction include abstract reasoning, verbal memory, visual memory, language (naming and fluency), executive or constructive functions, attention, and visuospatial function. Cognitive functions and intellectual abilities may decline from initially minimal cognitive impairment to dementia. To date, the neuropsychological and neurologic impairment has been reported to be associated with cerebral lactic acidosis as estimated by ventricular spectroscopic lactate levels.

Perceptual Anomalies in Schizophrenia: Integrating Phenomenology and Cognitive Neuroscience

PubMed Central

Uhlhaas, Peter J.; Mishara, Aaron L.

2007-01-01

From phenomenological and experimental perspectives, research in schizophrenia has emphasized deficits in “higher” cognitive functions, including attention, executive function, as well as memory. In contrast, general consensus has viewed dysfunctions in basic perceptual processes to be relatively unimportant in the explanation of more complex aspects of the disorder, including changes in self-experience and the development of symptoms such as delusions. We present evidence from phenomenology and cognitive neuroscience that changes in the perceptual field in schizophrenia may represent a core impairment. After introducing the phenomenological approach to perception (Husserl, the Gestalt School), we discuss the views of Paul Matussek, Klaus Conrad, Ludwig Binswanger, and Wolfgang Blankenburg on perception in schizophrenia. These 4 psychiatrists describe changes in perception and automatic processes that are related to the altered experience of self. The altered self-experience, in turn, may be responsible for the emergence of delusions. The phenomenological data are compatible with current research that conceptualizes dysfunctions in perceptual processing as a deficit in the ability to combine stimulus elements into coherent object representations. Relationships of deficits in perceptual organization to cognitive and social dysfunction as well as the possible neurobiological mechanisms are discussed. PMID:17118973

Social cognition and self-other distinctions in neuropsychiatry: Insights from schizophrenia and Tourette syndrome.

PubMed

Eddy, Clare M

2018-03-02

Impairments in social cognition may reflect dysfunction of disorder specific or disorder general mechanisms. Although cross-disorder comparison may prove insightful, few studies have compared social cognition in different neuropsychiatric disorders. Parallel investigation of schizophrenia and Tourette syndrome (TS) is encouraged by similarities including the presence of problematic social behavior, echophenomena, emotional dysregulation and dopamine dysfunction. Focusing on tests of social cognition administered in both disorders, this review aims to summarize behavioral, neurophysiological and neuroimaging findings, before exploring how these may contribute to clinical symptoms. Studies investigating social cognition (imitation, emotion recognition, and understanding of beliefs or intentions) in patients with schizophrenia or TS were identified through Web of Science and PubMed searches. Although findings indicate that social cognitive deficits are more apparent in schizophrenia, adults with TS can exhibit similar task performance to patients with paranoia. In both disorders, behavioral and neuroimaging findings raise the possibility of increased internal simulation of others' actions and emotions, in combination with a relative under-application of mentalizing. More specifically, dysfunction in neurobiological substrates such as temporo-parietal junction and inferior frontal gyrus may underlie problems with self-other distinctions in both schizophrenia and TS. Difficulties in distinguishing between actions and mental states linked to the self and other may contribute to a range of psychiatric symptoms, including emotional dysregulation, paranoia, social anhedonia and socially disruptive urges. Comparing different patient populations could therefore reveal common neuro-cognitive risk factors for the development of problematic social behaviors, in addition to markers of resilience, coping strategies and potential neuro-compensation mechanisms. Copyright © 2017 Elsevier Inc. All rights reserved.

Elevated Cystatin C Levels Are Associated with Cognitive Impairment and Progression of Parkinson Disease.

PubMed

Hu, Wei-Dong; Chen, Jing; Mao, Cheng-Jie; Feng, Ping; Yang, Ya-Ping; Luo, Wei-Feng; Liu, Chun-Feng

2016-09-01

We investigated the relationship between serum cystatin C (CysC) levels and cognitive dysfunction and disease progression in patients with Parkinson disease. Previous studies have reported altered CysC levels in neurodegenerative disorders, but only a few studies have explored the role of CysC and its relationship to cognitive dysfunction in Parkinson disease. We measured serum levels of CysC, creatinine, urea, and uric acid in 142 patients with Parkinson disease and 146 healthy controls. We assessed disease progression using the Hoehn and Yahr scale, and cognitive function using the Montreal Cognitive Assessment (Beijing version). The patients with Parkinson disease had significantly higher CysC levels than the controls (P<0.001). CysC level correlated significantly with age (r=0.494, P<0.001), sex (r=0.150, P=0.011), and serum creatinine level (r=0.377, P<0.001), but not with levels of urea or uric acid (P>0.05). CysC level was a significant independent predictor of Parkinson disease (odds ratio=23.143, 95% confidence interval: 5.485-97.648, P<0.001) in multivariate logistic regression analysis. In the Parkinson disease group, a higher CysC level was associated with a more advanced Hoehn and Yahr stage (r=0.098, P<0.05) and a lower Montreal Cognitive Assessment score (r=-0.381, P=0.003). Serum CysC levels can predict disease severity and cognitive dysfunction in patients with Parkinson disease. The exact role of CysC remains to be determined.

Adenosine Kinase Inhibition Protects against Cranial Radiation-Induced Cognitive Dysfunction

PubMed Central

Acharya, Munjal M.; Baulch, Janet E.; Lusardi, Theresa A.; Allen, Barrett. D.; Chmielewski, Nicole N.; Baddour, Al Anoud D.; Limoli, Charles L.; Boison, Detlev

2016-01-01

Clinical radiation therapy for the treatment of CNS cancers leads to unintended and debilitating impairments in cognition. Radiation-induced cognitive dysfunction is long lasting; however, the underlying molecular and cellular mechanisms are still not well established. Since ionizing radiation causes microglial and astroglial activation, we hypothesized that maladaptive changes in astrocyte function might be implicated in radiation-induced cognitive dysfunction. Among other gliotransmitters, astrocytes control the availability of adenosine, an endogenous neuroprotectant and modulator of cognition, via metabolic clearance through adenosine kinase (ADK). Adult rats exposed to cranial irradiation (10 Gy) showed significant declines in performance of hippocampal-dependent cognitive function tasks [novel place recognition, novel object recognition (NOR), and contextual fear conditioning (FC)] 1 month after exposure to ionizing radiation using a clinically relevant regimen. Irradiated rats spent less time exploring a novel place or object. Cranial irradiation also led to reduction in freezing behavior compared to controls in the FC task. Importantly, immunohistochemical analyses of irradiated brains showed significant elevation of ADK immunoreactivity in the hippocampus that was related to astrogliosis and increased expression of glial fibrillary acidic protein (GFAP). Conversely, rats treated with the ADK inhibitor 5-iodotubercidin (5-ITU, 3.1 mg/kg, i.p., for 6 days) prior to cranial irradiation showed significantly improved behavioral performance in all cognitive tasks 1 month post exposure. Treatment with 5-ITU attenuated radiation-induced astrogliosis and elevated ADK immunoreactivity in the hippocampus. These results confirm an astrocyte-mediated mechanism where preservation of extracellular adenosine can exert neuroprotection against radiation-induced pathology. These innovative findings link radiation-induced changes in cognition and CNS functionality to altered purine metabolism and astrogliosis, thereby linking the importance of adenosine homeostasis in the brain to radiation injury. PMID:27375429

Reduced Gray Matter Volume Is Associated With Poorer Instrumental Activities of Daily Living Performance in Heart Failure.

PubMed

Alosco, Michael L; Brickman, Adam M; Spitznagel, Mary Beth; Narkhede, Atul; Griffith, Erica Y; Cohen, Ronald; Sweet, Lawrence H; Josephson, Richard; Hughes, Joel; Gunstad, John

2016-01-01

Heart failure patients require assistance with instrumental activities of daily living in part because of the high rates of cognitive impairment in this population. Structural brain insult (eg, reduced gray matter volume) is theorized to underlie cognitive dysfunction in heart failure, although no study has examined the association among gray matter, cognition, and instrumental activities of daily living in heart failure. The aim of this study was to investigate the associations among gray matter volume, cognitive function, and functional ability in heart failure. A total of 81 heart failure patients completed a cognitive test battery and the Lawton-Brody self-report questionnaire to assess instrumental activities of daily living. Participants underwent magnetic resonance imaging to quantify total gray matter and subcortical gray matter volume. Impairments in instrumental activities of daily living were common in this sample of HF patients. Regression analyses controlling for demographic and medical confounders showed that smaller total gray matter volume predicted decreased scores on the instrumental activities of daily living composite, with specific associations noted for medication management and independence in driving. Interaction analyses showed that reduced total gray matter volume interacted with worse attention/executive function and memory to negatively impact instrumental activities of daily living. Smaller gray matter volume is associated with greater impairment in instrumental activities of daily living in persons with heart failure, possibly via cognitive dysfunction. Prospective studies are needed to clarify the utility of clinical correlates of gray matter volume (eg, cognitive dysfunction) in identifying heart failure patients at risk for functional decline and determine whether interventions that target improved brain and cognitive function can preserve functional independence in this high-risk population.

Mood and Memory Deficits in a Model of Gulf War Illness Are Linked with Reduced Neurogenesis, Partial Neuron Loss, and Mild Inflammation in the Hippocampus

PubMed Central

Parihar, Vipan K; Hattiangady, Bharathi; Shuai, Bing; Shetty, Ashok K

2013-01-01

Impairments in mood and cognitive function are the key brain abnormalities observed in Gulf war illness (GWI), a chronic multisymptom health problem afflicting ∼25% of veterans who served in the Persian Gulf War-1. Although the precise cause of GWI is still unknown, combined exposure to a nerve gas prophylaxis drug pyridostigmine bromide (PB) and pesticides DEET and permethrin during the war has been proposed as one of the foremost causes of GWI. We investigated the effect of 4 weeks of exposure to Gulf war illness-related (GWIR) chemicals in the absence or presence of mild stress on mood and cognitive function, dentate gyrus neurogenesis, and neurons, microglia, and astrocytes in the hippocampus. Combined exposure to low doses of GWIR chemicals PB, DEET, and permethrin induced depressive- and anxiety-like behavior and spatial learning and memory dysfunction. Application of mild stress in the period of exposure to chemicals exacerbated the extent of mood and cognitive dysfunction. Furthermore, these behavioral impairments were associated with reduced hippocampal volume and multiple cellular alterations such as chronic reductions in neural stem cell activity and neurogenesis, partial loss of principal neurons, and mild inflammation comprising sporadic occurrence of activated microglia and significant hypertrophy of astrocytes. The results show the first evidence of an association between mood and cognitive dysfunction and hippocampal pathology epitomized by decreased neurogenesis, partial loss of principal neurons, and mild inflammation in a model of GWI. Hence, treatment strategies that are efficacious for enhancing neurogenesis and suppressing inflammation may be helpful for alleviation of mood and cognitive dysfunction observed in GWI. PMID:23807240

Amyloid-β Homeostasis Bridges Inflammation, Synaptic Plasticity Deficits and Cognitive Dysfunction in Multiple Sclerosis

PubMed Central

Stampanoni Bassi, Mario; Garofalo, Sara; Marfia, Girolama A.; Gilio, Luana; Simonelli, Ilaria; Finardi, Annamaria; Furlan, Roberto; Sancesario, Giulia M.; Di Giandomenico, Jonny; Storto, Marianna; Mori, Francesco; Centonze, Diego; Iezzi, Ennio

2017-01-01

Cognitive deficits are frequently observed in multiple sclerosis (MS), mainly involving processing speed and episodic memory. Both demyelination and gray matter atrophy can contribute to cognitive deficits in MS. In recent years, neuroinflammation is emerging as a new factor influencing clinical course in MS. Inflammatory cytokines induce synaptic dysfunction in MS. Synaptic plasticity occurring within hippocampal structures is considered as one of the basic physiological mechanisms of learning and memory. In experimental models of MS, hippocampal plasticity is profoundly altered by proinflammatory cytokines. Although mechanisms of inflammation-induced hippocampal pathology in MS are not completely understood, alteration of Amyloid-β (Aβ) metabolism is emerging as a key factor linking together inflammation, synaptic plasticity and neurodegeneration in different neurological diseases. We explored the correlation between concentrations of Aβ1–42 and the levels of some proinflammatory and anti-inflammatory cytokines (interleukin-1β (IL-1β), IL1-ra, IL-8, IL-10, IL-12, tumor necrosis factor α (TNFα), interferon γ (IFNγ)) in the cerebrospinal fluid (CSF) of 103 remitting MS patients. CSF levels of Aβ1–42 were negatively correlated with the proinflammatory cytokine IL-8 and positively correlated with the anti-inflammatory molecules IL-10 and interleukin-1 receptor antagonist (IL-1ra). Other correlations, although noticeable, were either borderline or not significant. Our data show that an imbalance between proinflammatory and anti-inflammatory cytokines may lead to altered Aβ homeostasis, representing a key factor linking together inflammation, synaptic plasticity and cognitive dysfunction in MS. This could be relevant to identify novel therapeutic approaches to hinder the progression of cognitive dysfunction in MS. PMID:29209169

Exploring neural dysfunction in 'clinical high risk' for psychosis: a quantitative review of fMRI studies.

PubMed

Dutt, Anirban; Tseng, Huai-Hsuan; Fonville, Leon; Drakesmith, Mark; Su, Liang; Evans, John; Zammit, Stanley; Jones, Derek; Lewis, Glyn; David, Anthony S

2015-02-01

Individuals at clinical high risk (CHR) of developing psychosis present with widespread functional abnormalities in the brain. Cognitive deficits, including working memory (WM) problems, as commonly elicited by n-back tasks, are observed in CHR individuals. However, functional MRI (fMRI) studies, comprising a heterogeneous cluster of general and social cognition paradigms, have not necessarily demonstrated consistent and conclusive results in this population. Hence, a comprehensive review of fMRI studies, spanning almost one decade, was carried out to observe for general trends with respect to brain regions and cognitive systems most likely to be dysfunctional in CHR individuals. 32 studies were included for this review, out of which 22 met the criteria for quantitative analysis using activation likelihood estimation (ALE). Task related contrast activations were firstly analysed by comparing CHR and healthy control participants in the total pooled sample, followed by a comparison of general cognitive function studies (excluding social cognition paradigms), and finally by only looking at n-back working memory task based studies. Findings from the ALE implicated four key dysfunctional and distinct neural regions in the CHR group, namely the right inferior parietal lobule (rIPL), the left medial frontal gyrus (lmFG), the left superior temporal gyrus (lSTG) and the right fronto-polar cortex (rFPC) of the superior frontal gyrus (SFG). Narrowing down to relatively few significant dysfunctional neural regions is a step forward in reducing the apparent ambiguity of overall findings, which would help to target specific neural regions and pathways of interest for future research in CHR populations. Copyright © 2014. Published by Elsevier Ltd.

Heavy metals (Pb, Cd, As and MeHg) as risk factors for cognitive dysfunction: A general review of metal mixture mechanism in brain.

PubMed

Karri, Venkatanaidu; Schuhmacher, Marta; Kumar, Vikas

2016-12-01

Human exposure to toxic heavy metals is a global challenge. Concurrent exposure of heavy metals, such as lead (Pb), cadmium (Cd), arsenic (As) and methylmercury (MeHg) are particularly important due to their long lasting effects on the brain. The exact toxicological mechanisms invoked by exposure to mixtures of the metals Pb, Cd, As and MeHg are still unclear, however they share many common pathways for causing cognitive dysfunction. The combination of metals may produce additive/synergetic effects due to their common binding affinity with NMDA receptor (Pb, As, MeHg), Na + - K + ATP-ase pump (Cd, MeHg), biological Ca +2 (Pb, Cd, MeHg), Glu neurotransmitter (Pb, MeHg), which can lead to imbalance between the pro-oxidant elements (ROS) and the antioxidants (reducing elements). In this process, ROS dominates the antioxidants factors such as GPx, GS, GSH, MT-III, Catalase, SOD, BDNF, and CERB, and finally leads to cognitive dysfunction. The present review illustrates an account of the current knowledge about the individual metal induced cognitive dysfunction mechanisms and analyse common Mode of Actions (MOAs) of quaternary metal mixture (Pb, Cd, As, MeHg). This review aims to help advancement in mixture toxicology and development of next generation predictive model (such as PBPK/PD) combining both kinetic and dynamic interactions of metals. Copyright © 2016 Elsevier B.V. All rights reserved.

Cognition and event-related potentials in adult-onset non-demented myotonic dystrophy type 1.

PubMed

Tanaka, H; Arai, M; Harada, M; Hozumi, A; Hirata, K

2012-02-01

To clarify the cognitive and event-related potentials (ERPs) profiles of adult-onset genetically-proven non-demented myotonic dystrophy type 1 (DM1). Fourteen DM1 patients and matched 14 normal controls were enrolled. DM1 patients were compared with normal controls, using a variety of neuropsychological tests; an auditory "oddball" counting paradigm for the ERPs, and low-resolution brain electromagnetic tomography (LORETA). For patients, ERPs and neuropsychological parameters were correlated with CTG repeat size, duration of illness, grip strength, and arterial blood gas analysis. Frontal lobe dysfunction, prolonged N1 latency, and attenuated N2/P3 amplitudes were observed in DM1. Longer CTG repeat size was associated with fewer categories achieved on Wisconsin Card Sorting Test. Greater grip strength was associated with better scores on color-word "interference" of Stroop test. P3 latency was negatively correlated with PaO(2). LORETA revealed significant hypoactivities at the orbitofrontal and medial temporal lobe, cingulate, and insula. There was no correlation between ERPs and CTG expansion. Adult-onset non-demented DM1 presented frontal lobe dysfunction. Absence of correlations between CTG repeat size and objective ERP parameters suggested CTG expansion in lymphocytes does not directly contribute to cognitive dysfunction. CTG expansion in lymphocytes does not directly contribute to cognitive dysfunction of adult-onset non-demented DM1. Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Obsessive Compulsive Disorder Networks: Positron Emission Tomography and Neuropsychology Provide New Insights

PubMed Central

Millet, Bruno; Dondaine, Thibaut; Reymann, Jean-Michel; Bourguignon, Aurélie; Naudet, Florian; Jaafari, Nematollah; Drapier, Dominique; Turmel, Valérie; Mesbah, Habiba; Vérin, Marc; Le Jeune, Florence

2013-01-01

Background Deep brain stimulation has shed new light on the central role of the prefrontal cortex (PFC) in obsessive compulsive disorder (OCD). We explored this structure from a functional perspective, synchronizing neuroimaging and cognitive measures. Methods and Findings This case-control cross-sectional study compared 15 OCD patients without comorbidities and not currently on serotonin reuptake inhibitors or cognitive behavioural therapy with 15 healthy controls (matched for age, sex and education level) on resting-state 18FDG-PET scans and a neuropsychological battery assessing executive functions. We looked for correlations between metabolic modifications and impaired neuropsychological scores. Modifications in glucose metabolism were found in frontal regions (orbitofrontal cortex and dorsolateral cortices), the cingulate gyrus, insula and parietal gyrus. Neuropsychological differences between patients and controls, which were subtle, were correlated with the metabolism of the prefrontal, parietal, and temporal cortices. Conclusion As expected, we confirmed previous reports of a PFC dysfunction in OCD patients, and established a correlation with cognitive deficits. Other regions outside the prefrontal cortex, including the dorsoparietal cortex and the insula, also appeared to be implicated in the pathophysiology of OCD, providing fresh insights on the complexity of OCD syndromes. PMID:23326403

Effect of Psilocybin on Empathy and Moral Decision-Making

PubMed Central

Preller, Katrin H; Kometer, Michael; Dziobek, Isabel; Vollenweider, Franz X

2017-01-01

Abstract Background Impaired empathic abilities lead to severe negative social consequences and influence the development and treatment of several psychiatric disorders. Furthermore, empathy has been shown to play a crucial role in moral and prosocial behavior. Although the serotonin system has been implicated in modulating empathy and moral behavior, the relative contribution of the various serotonin receptor subtypes is still unknown. Methods We investigated the acute effect of psilocybin (0.215 mg/kg p.o.) in healthy human subjects on different facets of empathy and hypothetical moral decision-making using the multifaceted empathy test (n=32) and the moral dilemma task (n=24). Results Psilocybin significantly increased emotional, but not cognitive empathy compared with placebo, and the increase in implicit emotional empathy was significantly associated with psilocybin-induced changed meaning of percepts. In contrast, moral decision-making remained unaffected by psilocybin. Conclusions These findings provide first evidence that psilocybin has distinct effects on social cognition by enhancing emotional empathy but not moral behavior. Furthermore, together with previous findings, psilocybin appears to promote emotional empathy presumably via activation of serotonin 2A/1A receptors, suggesting that targeting serotonin 2A/1A receptors has implications for potential treatment of dysfunctional social cognition. PMID:28637246

Associations of NEUROD2 polymorphisms and change of cognitive dysfunctions in schizophrenia and schizoaffective disorder after eight weeks of antipsychotic treatment.

PubMed

Spellmann, Ilja; Riedel, Michael; Städtler, Julia; Zill, Peter; Obermeier, Michael; Cerovecki, Anja; Dehning, Sandra; Schennach, Rebecca; Epple, Maria; Opgen-Rhein, Markus; Müller, Norbert; Bondy, Brigitta; Möller, Hans-Jürgen; Musil, Richard

2017-07-01

NEUROD2 is a neurospecific helix-loop-helix transcription factor which has an impact on the regulation of glutamatergic and GABAergic genes. We investigated an association of NEUROD2 with neurocognitive dysfunctions in schizophrenia and schizoaffective disorder patients before and during treatment with different second-generation antipsychotics. Patients were genotyped for four different polymorphisms of the NEUROD2 gene ((rs9889354(A/G), rs1877032(C/T), rs12453682(C/T) and rs11078918(C/G)). Cognitive function was assessed at baseline and week 8. Results of individual neuropsychological tests were assigned to six cognitive domains (reaction time and quality; executive function; working, verbal and visual memory) and a general cognitive index. 167 patients were included in the study. The NEUROD2 exonic polymorphism rs11078918 showed significant associations with verbal memory and executive functions, whereas the NEUROD2 polymorphism rs12453682 was significantly associated with working and verbal memory, executive functions and with a cognitive index. Significant associations were found at baseline and after eight weeks. Moreover, significant associations between the change in neuropsychological test results during antipsychotic treatment and the NEUROD2 polymorphisms rs11078918 and rs12453682 were observed. Our findings suggest that the NEUROD2 gene could play a role in the pathophysiology of neurocognitive dysfunctions as well as in the change of cognitive symptoms under antipsychotic treatment in schizophrenia and schizoaffective disorder.

Integrating Functional Brain Neuroimaging and Developmental Cognitive Neuroscience in Child Psychiatry Research

ERIC Educational Resources Information Center

Pavuluri, Mani N.; Sweeney, John A.

2008-01-01

The use of cognitive neuroscience and functional brain neuroimaging to understand brain dysfunction in pediatric psychiatric disorders is discussed. Results show that bipolar youths demonstrate impairment in affective and cognitive neural systems and in these two circuits' interface. Implications for the diagnosis and treatment of psychiatric…

The Cycle of Schizoaffective Disorder, Cognitive Ability, Alcoholism, and Suicidality

ERIC Educational Resources Information Center

Goldstein, Gerald; Haas, Gretchen L.; Pakrashi, Manish; Novero, Ada M.; Luther, James F.

2006-01-01

In this study we investigated the putative role of cognitive dysfunction, diagnosis (schizoaffective versus schizophrenia disorder), and alcoholism as risk factors for suicidal behavior among individuals with DSM-IV schizophrenia or schizoaffective disorders. Subjects received cognitive tests and medical records were reviewed for evidence of a…

The Evaluation of Relationship between Sexual Self-concept and Sexual Dysfunction in Individuals Undergoing Methadone Maintenance Treatment

PubMed Central

Rajabizadeh, Ghodratolah; Yazdanpanah, Fatemeh; Ramezani, Mohammad Arash

2017-01-01

Background The present study was conducted with the aim of designing a causal model for the evaluation of sexual dysfunctions based on the variables of methadone dosage and sexual self-concept among individuals undergoing methadone maintenance treatment (MMT). Methods The study population of the present study consisted of married men of 20 to 45 years of age with sexual ýrelations and undergoing MMT for a minimum of 8 weeks referring to all MMT clinics of Kerman, Iran, in ýý2015-2016. ýThe subjects were selected through multi-stage cluster sampling (n = 250). Data were collected using the General Health Questionnaire (GHQ-28), Multi-Dimensional Sexual Self-concept Questionnaire (MSSQ), and Internal Index for Erectile Function (IIEF). Data were analyzed using path analysis method and Pearson correlation coefficient. The suggested model was evaluated using structural equation model (SEM), and indirect relationships were assessed using Bootstrap method. Findings The suggested model showed acceptable fitness with the data, and all routes, except methadone use route, to sexual function were significant. The result of the multiple ýindirect route showed that sexual function had a significant relationship with methadone use through ýsexual self-concept. In total, 60% of variance in sexual dysfunction was explained using the variables of the suggested model. Conclusion Further studies are suggested to be conducted regarding psychological factors effective on the sexual dysfunctions among individuals undergoing MMT, such as sexual self-concept. Moreover, more detailed evaluation of each subscale of positive and negative sexual self-concept is recommended to assess the psychological causes of sexual dysfunctions in these individuals and design psychological, behavioral, and cognitive-behavioral treatment interventions for them. PMID:29299211

New insights into environmental enteric dysfunction

USDA-ARS?s Scientific Manuscript database

Environmental enteric dysfunction (EED) has been recognised as an important contributing factor to physical and cognitive stunting, poor response to oral vaccines, limited resilience to acute infections and ultimately global childhood mortality. The aetiology of EED remains poorly defined but the ep...

Exposure therapy changes dysfunctional evaluations of somatic symptoms in patients with hypochondriasis (health anxiety). A randomized controlled trial.

PubMed

Weck, Florian; Neng, Julia M B; Schwind, Julia; Höfling, Volkmar

2015-08-01

Dysfunctional evaluations of somatic symptoms are considered a central factor in maintaining hypochondriasis. The aim of the current study was to investigate whether exposure therapy (ET) without cognitive restructuring is sufficient to change dysfunctional evaluations of somatic symptoms. The current study was based on a randomized controlled trial and compared patients with hypochondriasis (N=73) receiving ET or cognitive therapy (CT) to a wait list (WL) control group. In both the ET and CT groups, dysfunctional symptom evaluations changed significantly compared with the WL group. No differences between the ET and CT groups emerged. The relationship between the treatment condition (active treatment vs. WL) and reductions in health anxiety was mediated by changes in somatic symptom evaluations only in a specific card sorting procedure. We conclude that addressing dysfunctional symptom evaluations is a necessary precondition for the effective treatment of hypochondriasis. However, the results indicate that ET and CT appear to change those processes to a similar degree. Copyright © 2015 Elsevier Ltd. All rights reserved.

Bridging disparate symptoms of schizophrenia: a triple network dysfunction theory

PubMed Central

Nekovarova, Tereza; Fajnerova, Iveta; Horacek, Jiri; Spaniel, Filip

2014-01-01

Schizophrenia is a complex neuropsychiatric disorder with variable symptomatology, traditionally divided into positive and negative symptoms, and cognitive deficits. However, the etiology of this disorder has yet to be fully understood. Recent findings suggest that alteration of the basic sense of self-awareness may be an essential distortion of schizophrenia spectrum disorders. In addition, extensive research of social and mentalizing abilities has stressed the role of distortion of social skills in schizophrenia.This article aims to propose and support a concept of a triple brain network model of the dysfunctional switching between default mode and central executive network (CEN) related to the aberrant activity of the salience network. This model could represent a unitary mechanism of a wide array of symptom domains present in schizophrenia including the deficit of self (self-awareness and self-representation) and theory of mind (ToM) dysfunctions along with the traditional positive, negative and cognitive domains. We review previous studies which document the dysfunctions of self and ToM in schizophrenia together with neuroimaging data that support the triple brain network model as a common neuronal substrate of this dysfunction. PMID:24910597

Cognitive Impairment in Folate-Deficient Rats Corresponds to Depleted Brain Phosphatidylcholine and Is Prevented by Dietary Methionine without Lowering Plasma Homocysteine12

PubMed Central

Troen, Aron M.; Chao, Wei-Hsun; Crivello, Natalia A.; D'Anci, Kristen E.; Shukitt-Hale, Barbara; Smith, Don E.; Selhub, Jacob; Rosenberg, Irwin H.

2008-01-01

Poor folate status is associated with cognitive decline and dementia in older adults. Although impaired brain methylation activity and homocysteine toxicity are widely thought to account for this association, how folate deficiency impairs cognition is uncertain. To better define the role of folate deficiency in cognitive dysfunction, we fed rats folate-deficient diets (0 mg FA/kg diet) with or without supplemental L-methionine for 10 wk, followed by cognitive testing and tissue collection for hematological and biochemical analysis. Folate deficiency with normal methionine impaired spatial memory and learning; however, this impairment was prevented when the folate-deficient diet was supplemented with methionine. Under conditions of folate deficiency, brain membrane content of the methylated phospholipid phosphatidylcholine was significantly depleted, which was reversed with supplemental methionine. In contrast, neither elevated plasma homocysteine nor brain S-adenosylmethionine and S-adenosylhomocysteine concentrations predicted cognitive impairment and its prevention by methionine. The correspondence of cognitive outcomes to changes in brain membrane phosphatidylcholine content suggests that altered phosphatidylcholine and possibly choline metabolism might contribute to the manifestation of folate deficiency-related cognitive dysfunction. PMID:19022979

Cognition and dementia in older patients with epilepsy

PubMed Central

Sen, Arjune; Capelli, Valentina

2018-01-01

Abstract With advances in healthcare and an ageing population, the number of older adults with epilepsy is set to rise substantially across the world. In developed countries the highest incidence of epilepsy is already in people over 65 and, as life expectancy increases, individuals who developed epilepsy at a young age are also living longer. Recent findings show that older persons with epilepsy are more likely to suffer from cognitive dysfunction and that there might be an important bidirectional relationship between epilepsy and dementia. Thus some people with epilepsy may be at a higher risk of developing dementia, while individuals with some forms of dementia, particularly Alzheimer’s disease and vascular dementia, are at significantly higher risk of developing epilepsy. Consistent with this emerging view, epidemiological findings reveal that people with epilepsy and individuals with Alzheimer’s disease share common risk factors. Recent studies in Alzheimer’s disease and late-onset epilepsy also suggest common pathological links mediated by underlying vascular changes and/or tau pathology. Meanwhile electrophysiological and neuroimaging investigations in epilepsy, Alzheimer’s disease, and vascular dementia have focused interest on network level dysfunction, which might be important in mediating cognitive dysfunction across all three of these conditions. In this review we consider whether seizures promote dementia, whether dementia causes seizures, or if common underlying pathophysiological mechanisms cause both. We examine the evidence that cognitive impairment is associated with epilepsy in older people (aged over 65) and the prognosis for patients with epilepsy developing dementia, with a specific emphasis on common mechanisms that might underlie the cognitive deficits observed in epilepsy and Alzheimer’s disease. Our analyses suggest that there is considerable intersection between epilepsy, Alzheimer’s disease and cerebrovascular disease raising the possibility that better understanding of shared mechanisms in these conditions might help to ameliorate not just seizures, but also epileptogenesis and cognitive dysfunction. PMID:29506031

Combined Therapy of Iron Chelator and Antioxidant Completely Restores Brain Dysfunction Induced by Iron Toxicity

PubMed Central

Sripetchwandee, Jirapas; Pipatpiboon, Noppamas; Chattipakorn, Nipon; Chattipakorn, Siriporn

2014-01-01

Background Excessive iron accumulation leads to iron toxicity in the brain; however the underlying mechanism is unclear. We investigated the effects of iron overload induced by high iron-diet consumption on brain mitochondrial function, brain synaptic plasticity and learning and memory. Iron chelator (deferiprone) and antioxidant (n-acetyl cysteine) effects on iron-overload brains were also studied. Methodology Male Wistar rats were fed either normal diet or high iron-diet consumption for 12 weeks, after which rats in each diet group were treated with vehicle or deferiprone (50 mg/kg) or n-acetyl cysteine (100 mg/kg) or both for another 4 weeks. High iron-diet consumption caused brain iron accumulation, brain mitochondrial dysfunction, impaired brain synaptic plasticity and cognition, blood-brain-barrier breakdown, and brain apoptosis. Although both iron chelator and antioxidant attenuated these deleterious effects, combined therapy provided more robust results. Conclusion In conclusion, this is the first study demonstrating that combined iron chelator and anti-oxidant therapy completely restored brain function impaired by iron overload. PMID:24400127

The KEEPS-Cognitive and Affective Study: baseline associations between vascular risk factors and cognition.

PubMed

Wharton, Whitney; Gleason, Carey E; Dowling, N Maritza; Carlsson, Cynthia M; Brinton, Eliot A; Santoro, M Nanette; Neal-Perry, Genevieve; Taylor, Hugh; Naftolin, Frederick; Lobo, Rogerio A; Merriam, George; Manson, Joann E; Cedars, Marcelle I; Miller, Virginia M; Black, Dennis M; Budoff, Matthew; Hodis, Howard N; Harman, S Mitchell; Asthana, Sanjay

2014-01-01

Midlife vascular risk factors influence later cognitive decline and Alzheimer's disease (AD). The decrease in serum estradiol levels during menopause has been associated with cognitive impairment and increased vascular risk, such as high blood pressure (BP), which independently contributes to cognitive dysfunction and AD. We describe the extent to which vascular risk factors relate to cognition in healthy, middle-aged, recently postmenopausal women enrolled in the Kronos Early Estrogen Prevention Cognitive and Affective Study (KEEPS-Cog) at baseline. KEEPS-Cog is a double-blind, randomized, placebo-controlled, parallel group, clinical trial, investigating the efficacy of low-dose, transdermal 17β-estradiol and oral conjugated equine estrogen on cognition. All results are cross-sectional and represent baseline data only. Analyses confirm that the KEEPS-Cog cohort (n = 571) was middle aged (mean 52.7 years, range 42-59 years), healthy, and free of cognitive dysfunction. Higher systolic BP was weakly related to poorer performance in auditory working memory and attention (p = 0.004; adjusted for multiple comparisons p = 0.10). This relationship was not associated with endogenous hormone levels, and systolic BP was not related to any other cognitive domain. BP levels may be more sensitive than other vascular risk factors in detecting subtle differences in cognitive task performance in healthy, recently menopausal women. Lower BP early in menopause may affect cognitive domains known to be associated with AD.

The role of cognitive impairment in psychosocial functioning in remitted depression.

PubMed

Knight, Mattew J; Air, Tracy; Baune, Bernhard T

2018-08-01

Cognitive dysfunction is a prevalent and disabling symptom of Major Depressive Disorder (MDD), and is often retained in the remitted stage of illness. Emerging evidence suggests that cognitive impairment may be associated with dysfunction in a number of psychosocial domains (e.g., workplace productivity, social relationships). The current study explored the relationship between cognition and psychosocial functioning in remitted MDD and in healthy controls. Data were obtained from 182 participants of the Cognitive Function and Mood Study (CoFaM-S), a cross-sectional study of cognition, mood, and social cognition in mood disorders. Participants' (Remitted MDD n = 72, Healthy n = 110) cognition was assessed with a battery of cognitive tests including the Repeatable Battery for the Assessment of Neuropsychological Function (RBANS) and other standard measures of cognition (e.g., The Tower of London task). Psychosocial functioning was clinically evaluated with the Functioning Assessment Short Test (FAST). The results indicated that executive functioning was the strongest independent predictor of functioning in remitted MDD patients, whereas various cognitive domains predicted psychosocial functioning in healthy individuals. Psychosocial functioning was measured with a clinical interview, and was therefore reliant on clinicians' judgement of impairment, as opposed to more objective measures of functioning. These findings suggest that executive cognition plays an important role in functional recovery in remitted depression, and may be a crucial target in adjunctive treatment. Copyright © 2018 Elsevier B.V. All rights reserved.

NMDA receptor agonists reverse impaired psychomotor and cognitive functions associated with hippocampal Hbegf-deficiency in mice.

PubMed

Sasaki, Keita; Omotuyi, Olaposi Idowu; Ueda, Mutsumi; Shinohara, Kazuyuki; Ueda, Hiroshi

2015-12-04

Structural and functional changes of the hippocampus are correlated with psychiatric disorders and cognitive dysfunctions. Genetic deletion of heparin-binding epidermal growth factor-like growth factor (HB-EGF), which is predominantly expressed in cortex and hippocampus, also causes similar psychiatric and cognitive dysfunctions, accompanying down-regulated NMDA receptor signaling. However, little is known of such dysfunctions in hippocampus-specific Hbegf cKO mice. We successfully developed hippocampus-specific cKO mice by crossbreeding floxed Hbegf and Gng7-Cre knock-in mice, as Gng7 promoter-driven Cre is highly expressed in hippocampal neurons as well as striatal medium spiny neurons. In mice lacking hippocampus Hbegf gene, there was a decreased neurogenesis in the subgranular zone (SGZ) of the dentate gyrus as well as down-regulation of PSD-95/NMDA-receptor-NR1/NR2B subunits and related NMDA receptor signaling. Psychiatric, social-behavioral and cognitive abnormalities were also observed in hippocampal cKO mice. Interestingly, D-cycloserine and nefiracetam, positive allosteric modulators (PAMs) of NMDA receptor reversed the apparent reduction in NMDA receptor signaling and most behavioral abnormalities. Furthermore, decreased SGZ neurogenesis in hippocampal cKO mice was reversed by nefiracetam. The present study demonstrates that PAMs of NMDA receptor have pharmacotherapeutic potentials to reverse down-regulated NMDA receptor signaling, neuro-socio-cognitive abnormalities and decreased neurogenesis in hippocampal cKO mice.

Group versus individual cognitive treatment for Obsessive-Compulsive Disorder: changes in non-OCD symptoms and cognitions at post-treatment and one-year follow-up.

PubMed

Belloch, Amparo; Cabedo, Elena; Carrió, Carmen; Fernández-Alvarez, Héctor; García, Fernando; Larsson, Christina

2011-05-15

Current cognitive approaches postulate that obsessions and compulsions are caused and/or maintained by misinterpretations about their meaning. This assumption has led to the development of cognitive therapeutic (CT) procedures designed to challenge the dysfunctional appraisals and beliefs patients have about their obsessions. Nonetheless, few studies have compared the efficacy of individual and group CT in changing the dysfunctional cognitions that hypothetically underlie Obsessive-Compulsive Disorder (OCD). In this study, 44 OCD patients were assigned to individual (n=18) or group (n=24) CT. Sixteen completed the individual CT, and 22 completed the group CT. The effects of the two CT conditions on depression and worry tendencies were comparable. Individual treatment was more effective than group treatment in decreasing scores on dysfunctional beliefs (responsibility, overestimation of threat, and intolerance to uncertainty) and the use of suppression as a thought control strategy. The post-treatment changes were maintained one year later. The correlations between symptom improvement (OCD severity change) and belief changes were moderate: in the individual treatment the greatest associations were with beliefs about thoughts (importance and control), whereas in the group treatment the greatest associations were with beliefs related to anxiety in general (threat overestimation and intolerance to uncertainty). Copyright © 2010 Elsevier Ltd. All rights reserved.

Advances in the mechanisms and early warning indicators of the postoperative cognitive dysfunction after the extracorporeal circulation.

PubMed

Liu, Chao; Han, Jian-ge

2015-02-01

The high incidence of postoperative cognitive dysfunction (POCD) after extracorporeal circulation has seriously affected the prognosis and quality of life. Its mechanism may involve the inflammatory response and oxidative stress,the excessive phosphorylation of tau protein, the decreased blood volume and oxygen in the cerebral cortex. Appropriate early warning indicators of POCD after the extracorporeal circulation should be chosen to facilitate the cross validation of the results obtained different technical approaches and thus promote the early diagnosis and treatment of POCD.

Electrophysiological Studies of Autism: The Whisper of the Bang.

ERIC Educational Resources Information Center

Tanguay, Peter E.; Edwards, Rose Mary

1982-01-01

Although some have argued that the type of language and cognitive defects shown by autistic children almost certainly reflects forebrain dysfunctions, current studies point to the possibility that some autistic children may have dysfunction of neural systems in the brainstem. (Author)

Health Status and Performance of United States Air Force Airmen Following Mild Traumatic Brain Injury

DTIC Science & Technology

2010-09-01

adrenal insufficiency, hypopituitarism, hypothyroidism , growth- hormone deficiency and posterior pituitary dysfunction [53, 54, 56-60]. Growth...central hypothyroidism which can result in fatigue, apathy, decreased strength and cognitive dysfunction, symptoms commonly observed in PTSD [54

Role of Oxidative Stress in the Neurocognitive Dysfunction of Obstructive Sleep Apnea Syndrome

PubMed Central

Chen, Ping

2016-01-01

Obstructive sleep apnea syndrome (OSAS) is characterized by chronic nocturnal intermittent hypoxia and sleep fragmentations. Neurocognitive dysfunction, a significant and extraordinary complication of OSAS, influences patients' career, family, and social life and reduces quality of life to some extent. Previous researches revealed that repetitive hypoxia and reoxygenation caused mitochondria and endoplasmic reticulum dysfunction, overactivated NADPH oxidase, xanthine oxidase, and uncoupling nitric oxide synthase, induced an imbalance between prooxidants and antioxidants, and then got rise to a series of oxidative stress (OS) responses, such as protein oxidation, lipid peroxidation, and DNA oxidation along with inflammatory reaction. OS in brain could trigger neuron injury especially in the hippocampus and cerebral cortex regions. Those two regions are fairly susceptible to hypoxia and oxidative stress production which could consequently result in cognitive dysfunction. Apart from continuous positive airway pressure (CPAP), antioxidant may be a promising therapeutic method to improve partially reversible neurocognitive function. Understanding the role that OS played in the cognitive deficits is crucial for future research and therapeutic strategy development. In this paper, recent important literature concerning the relationship between oxidative stress and cognitive impairment in OSAS will be summarized and the results can provide a rewarding overview for future breakthrough in this field. PMID:27774119

Functional vascular contributions to cognitive impairment and dementia: mechanisms and consequences of cerebral autoregulatory dysfunction, endothelial impairment, and neurovascular uncoupling in aging

PubMed Central

Toth, Peter; Tarantini, Stefano; Csiszar, Anna

2017-01-01

Increasing evidence from epidemiological, clinical and experimental studies indicate that age-related cerebromicrovascular dysfunction and microcirculatory damage play critical roles in the pathogenesis of many types of dementia in the elderly, including Alzheimer’s disease. Understanding and targeting the age-related pathophysiological mechanisms that underlie vascular contributions to cognitive impairment and dementia (VCID) are expected to have a major role in preserving brain health in older individuals. Maintenance of cerebral perfusion, protecting the microcirculation from high pressure-induced damage and moment-to-moment adjustment of regional oxygen and nutrient supply to changes in demand are prerequisites for the prevention of cerebral ischemia and neuronal dysfunction. This overview discusses age-related alterations in three main regulatory paradigms involved in the regulation of cerebral blood flow (CBF): cerebral autoregulation/myogenic constriction, endothelium-dependent vasomotor function, and neurovascular coupling responses responsible for functional hyperemia. The pathophysiological consequences of cerebral microvascular dysregulation in aging are explored, including blood-brain barrier disruption, neuroinflammation, exacerbation of neurodegeneration, development of cerebral microhemorrhages, microvascular rarefaction, and ischemic neuronal dysfunction and damage. Due to the widespread attention that VCID has captured in recent years, the evidence for the causal role of cerebral microvascular dysregulation in cognitive decline is critically examined. PMID:27793855

Design and feasibility of a memory intervention with focus on self-management for cognitive impairment in epilepsy.

PubMed

Caller, Tracie A; Secore, Karen L; Ferguson, Robert J; Roth, Robert M; Alexandre, Faith P; Henegan, Patricia L; Harrington, Jessica J; Jobst, Barbara C

2015-03-01

The aim of this study was to assess the feasibility of a self-management intervention targeting cognitive dysfunction to improve quality of life and reduce memory-related disability in adults with epilepsy. The intervention incorporates (1) education on cognitive function in epilepsy, (2) self-awareness training, (3) compensatory strategies, and (4) application of these strategies in day-to-day life using problem-solving therapy. In addition to the behavioral modification, formal working memory training was conducted by utilizing a commercially available program in a subgroup of patients. Our findings suggest that a self-management intervention targeting cognitive dysfunction was feasible for delivery to a rural population with epilepsy, with 13 of 16 enrolled participants completing the 8-session program. Qualitative data indicate high satisfaction and subjective improvement in cognitive functioning in day-to-day life. These findings provide support for further evaluation of the efficacy of this intervention through a randomized controlled trial. Copyright © 2015 Elsevier Inc. All rights reserved.

Noradrenergic System in Down Syndrome and Alzheimer's Disease A Target for Therapy.

PubMed

Phillips, Cristy; Fahimi, Atoossa; Das, Devsmita; Mojabi, Fatemeh S; Ponnusamy, Ravikumar; Salehi, Ahmad

2016-01-01

Locus coeruleus (LC) neurons in the brainstem send extensive noradrenergic (NE)-ergic terminals to the majority of brain regions, particularly those involved in cognitive function. Both Alzheimer's disease (AD) and Down syndrome (DS) are characterized by similar pathology including significant LC degeneration and dysfunction of the NE-ergic system. Extensive loss of NE-ergic terminals has been linked to alterations in brain regions vital for cognition, mood, and executive function. While the mechanisms by which NE-ergic abnormalities contribute to cognitive dysfunction are not fully understood, emergent evidence suggests that rescue of NE-ergic system can attenuate neuropathology and cognitive decline in both AD and DS. Therapeutic strategies to enhance NE neurotransmission have undergone limited testing. Among those deployed to date are NE reuptake inhibitors, presynaptic α-adrenergic receptor antagonists, NE prodrugs, and β-adrenergic agonists. Here we examine alterations in the NE-ergic system in AD and DS and suggest that NE-ergic system rescue is a plausible treatment strategy for targeting cognitive decline in both disorders.

Do sedation and analgesia contribute to long-term cognitive dysfunction in critical care survivors?

PubMed

Fernandez-Gonzalo, S; Turon, M; De Haro, C; López-Aguilar, J; Jodar, M; Blanch, L

2018-03-01

Deep sedation during stay in the Intensive Care Unit (ICU) may have deleterious effects upon the clinical and cognitive outcomes of critically ill patients undergoing mechanical ventilation. Over the last decade a vast body of literature has been generated regarding different sedation strategies, with the aim of reducing the levels of sedation in critically ill patients. There has also been a growing interest in acute brain dysfunction, or delirium, in the ICU. However, the effect of sedation during ICU stay upon long-term cognitive deficits in ICU survivors remains unclear. Strategies for reducing sedation levels in the ICU do not seem to be associated with worse cognitive and psychological status among ICU survivors. Sedation strategy and management efforts therefore should seek to secure the best possible state in the mechanically ventilated patient and lower the prevalence of delirium, in order to prevent long-term cognitive alterations. Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

GABA Neuron Alterations, Cortical Circuit Dysfunction and Cognitive Deficits in Schizophrenia

PubMed Central

Gonzalez-Burgos, Guillermo; Fish, Kenneth N.; Lewis, David A.

2011-01-01

Schizophrenia is a brain disorder associated with cognitive deficits that severely affect the patients' capacity for daily functioning. Whereas our understanding of its pathophysiology is limited, postmortem studies suggest that schizophrenia is associated with deficits of GABA-mediated synaptic transmission. A major role of GABA-mediated transmission may be producing synchronized network oscillations which are currently hypothesized to be essential for normal cognitive function. Therefore, cognitive deficits in schizophrenia may result from a GABA synapse dysfunction that disturbs neural synchrony. Here, we highlight recent studies further suggesting alterations of GABA transmission and network oscillations in schizophrenia. We also review current models for the mechanisms of GABA-mediated synchronization of neural activity, focusing on parvalbumin-positive GABA neurons, which are altered in schizophrenia and whose function has been strongly linked to the production of neural synchrony. Alterations of GABA signaling that impair gamma oscillations and, as a result, cognitive function suggest paths for novel therapeutic interventions. PMID:21904685

Frontal Dysfunctions of Impulse Control – A Systematic Review in Borderline Personality Disorder and Attention-Deficit/Hyperactivity Disorder

PubMed Central

Sebastian, Alexandra; Jung, Patrick; Krause-Utz, Annegret; Lieb, Klaus; Schmahl, Christian; Tüscher, Oliver

2014-01-01

Disorders such as borderline personality disorder (BPD) or attention-deficit/hyperactivity disorder (ADHD) are characterized by impulsive behaviors. Impulsivity as used in clinical terms is very broadly defined and entails different categories including personality traits as well as different cognitive functions such as emotion regulation or interference resolution and impulse control. Impulse control as an executive function, however, is neither cognitively nor neurobehaviorally a unitary function. Recent findings from behavioral and cognitive neuroscience studies suggest related but dissociable components of impulse control along functional domains like selective attention, response selection, motivational control, and behavioral inhibition. In addition, behavioral and neural dissociations are seen for proactive vs. reactive inhibitory motor control. The prefrontal cortex with its sub-regions is the central structure in executing these impulse control functions. Based on these concepts of impulse control, neurobehavioral findings of studies in BPD and ADHD were reviewed and systematically compared. Overall, patients with BPD exhibited prefrontal dysfunctions across impulse control components rather in orbitofrontal, dorsomedial, and dorsolateral prefrontal regions, whereas patients with ADHD displayed disturbed activity mainly in ventrolateral and medial prefrontal regions. Prefrontal dysfunctions, however, varied depending on the impulse control component and from disorder to disorder. This suggests a dissociation of impulse control related frontal dysfunctions in BPD and ADHD, although only few studies are hitherto available to assess frontal dysfunctions along different impulse control components in direct comparison of these disorders. Yet, these findings might serve as a hypothesis for the future systematic assessment of impulse control components to understand differences and commonalities of prefrontal cortex dysfunction in impulsive disorders. PMID:25232313

Executive dysfunction, obsessive-compulsive symptoms, and attention deficit and hyperactivity disorder in Systemic Lupus Erythematosus: Evidence for basal ganglia dysfunction?

PubMed

Maciel, Ricardo Oliveira Horta; Ferreira, Gilda Aparecida; Akemy, Bárbara; Cardoso, Francisco

2016-01-15

Chorea is well described in a group of patients with Systemic Lupus Erythematosus (SLE). There is less information, however, on other movement disorders as well as non-motor neuropsychiatric features such as obsessive-compulsive symptoms (OCS), executive dysfunction and attention deficit and hyperactivity disorder (ADHD) in subjects with SLE. Fifty-four subjects with SLE underwent a battery of neuropsychiatric tests that included the Mini Mental State Examination, the Montreal Cognitive Assessment, the Frontal Assessment Battery (FAB), the FAS verbal and the categorical (animals) semantic fluency tests, the Obsessive and Compulsive Inventory - Revised, the Yale-Brown Obsessive and Compulsive Scale and Beck's Anxiety and Depression Scales. ADHD was diagnosed according to DSM-IV criteria. SLE disease activity and cumulative damage were evaluated according to the modified SLE Disease Activity Index 2000 (mSLEDAI-2K) and the SLICC/ACR, respectively. Six (11.1%) and 33 (61.1%) patients had cognitive impairment according to the MMSE and MoCA, respectively. Eleven (20.4%) had abnormal FAB scores, and 5 (9.3%) had lower semantic fluency scores than expected. The overall frequency of cognitive dysfunction was 72.2% (39 patients) and of neuropsychiatric SLE was 77.8% (42 patients). Two patients (3.7%) had movement disorders. Fifteen (27.8%) had OCS and 17 (31.5%) met diagnostic criteria for ADHD. ADHD and OCS correlated with higher disease activity, p=0.003 and 0.006, respectively. Higher cumulative damage correlated with lower FAB scores (p 0.026). Executive dysfunction, ADHD, OCS, and movement disorders are common in SLE. Our finding suggests that there is frequent basal ganglia dysfunction in SLE. Copyright © 2015 Elsevier B.V. All rights reserved.

Pathophysiology and Treatment of Memory Dysfunction after Traumatic Brain Injury

PubMed Central

Paterno, Rosalia; Folweiler, Kaitlin A.; Cohen, Akiva S.

2018-01-01

Memory is fundamental to everyday life, and cognitive impairments resulting from traumatic brain injury (TBI) have devastating effects on TBI survivors. A contributing component to memory impairments caused by TBI are alterations in the neural circuits associated with memory function. In this review, we aim to bring together experimental findings that characterize behavioral memory deficits and the underlying pathophysiology of memory-involved circuits after TBI. While there is little doubt that TBI causes memory and cognitive dysfunction, it is difficult to conclude which memory phase i.e., encoding, maintenance or retrieval is specifically altered by TBI. This is most likely due to variation in behavioral protocols and experimental models. Additionally we review a selection of experimental treatments that hold translational potential to mitigate memory dysfunction following injury. PMID:28500417

Profile of cognitive problems in schizophrenia and implications for vocational functioning.

PubMed

Tan, Bhing-Leet

2009-08-01

This literature review attempts to profile specific areas of cognition that have shown unique and consistent evidence of dysfunction among people with schizophrenia. In addition, their impact on vocational functioning is illustrated, so as to highlight the importance of managing these cognitive difficulties in vocational rehabilitation. Literature search was carried out on seven key cognitive domains identified by the National Institute of Mental Health in the USA. Their impact on vocational function was also reviewed. It is found that attention, declarative and working memory, reasoning, problem-solving and social cognition are areas of impairment that have great impact on vocational functioning. Attention and memory problems affect learning of new work tasks. Executive function is particularly crucial in determining supported and open employment outcomes, as executive dysfunction cannot be easily compensated. Lastly, social cognition plays a major role in determining the success of workplace social exchanges. Occupational therapists need to have a good understanding of the profile of cognitive problems among people with schizophrenia, in order to tailor our intervention according to their cognitive strengths and difficulties. Several cognitive remediation strategies and programs have been designed specifically for people with mental illness. Equipping ourselves with skills in conducting such programs will augment our expertise in vocational rehabilitation.

Translating advances in the molecular basis of schizophrenia into novel cognitive treatment strategies.

PubMed

O'Tuathaigh, Colm M P; Moran, Paula M; Zhen, Xuechu C; Waddington, John L

2017-10-01

The presence and severity of cognitive symptoms, including working memory, executive dysfunction and attentional impairment, contributes materially to functional impairment in schizophrenia. Cognitive symptoms have proved to be resistant to both first- and second-generation antipsychotic drugs. Efforts to develop a consensus set of cognitive domains that are both disrupted in schizophrenia and are amenable to cross-species validation (e.g. the National Institute of Mental Health Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia and Research Domain Criteria initiatives) are an important step towards standardization of outcome measures that can be used in preclinical testing of new drugs. While causative genetic mutations have not been identified, new technologies have identified novel genes as well as hitherto candidate genes previously implicated in the pathophysiology of schizophrenia and/or mechanisms of antipsychotic efficacy. This review comprises a selective summary of these developments, particularly phenotypic data arising from preclinical genetic models for cognitive dysfunction in schizophrenia, with the aim of indicating potential new directions for pro-cognitive therapeutics. Linked Articles This article is part of a themed section on Pharmacology of Cognition: a Panacea for Neuropsychiatric Disease? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.19/issuetoc. © 2017 The British Pharmacological Society.

The Need for Screening, Assessment, and Treatment for Cognitive Dysfunction in Multiple Sclerosis

PubMed Central

Benedict, Ralph H.B.; Gromisch, Elizabeth S.; DeLuca, John

2012-01-01

Cognitive dysfunction is observed in about half of people with multiple sclerosis (MS), and MS health-care professionals face the challenge of screening, assessing, and treating patients for cognitive problems. Considering the inconsistent or limited empirical evidence to assist in this task, a multidisciplinary consensus conference of MS experts, sponsored by the Consortium of Multiple Sclerosis Centers (CMSC), was held on September 24, 2010, to address these issues. Key articles from the literature on these topics were distributed prior to the meeting, and CMSC member professionals were surveyed on clinical practices related to screening, assessment, and treatment for cognitive problems. The purpose of the meeting was threefold: 1) to achieve a multidisciplinary perspective on practices for screening, monitoring, evaluating, and treating MS patients for cognitive problems; 2) to propose consensus candidate measures for screening and/or monitoring for cognitive problems in MS that neurologists or nurses might administer on a regular basis; and 3) to propose consensus treatment approaches from a multidisciplinary perspective. This article summarizes the conclusions of the conference participants and provides preliminary suggestions for screening and brief assessment. PMID:24453735

Can the REBT theory explain loneliness? Theoretical and clinical applications.

PubMed

Hyland, Philip; McGinty, Gráinne; Karatzias, Thanos; Murphy, Jamie; Vallières, Frédérique; McHugh Power, Joanna

2018-06-05

Loneliness is a common psychological experience affecting a significant minority of the general population. Loneliness may in part be related to the existence of dysfunctional cognitive evaluations. To date, however, loneliness has yet to be explicitly assessed within a cognitive-behavioural theoretical framework. The current study sought to determine the association between negative cognitions, within the context of Rational Emotive Behaviour Therapy (REBT), and the experience of loneliness. A multinational sample of university students (n = 397) completed self-report assessments of rational and irrational beliefs, and loneliness. Structural equation modelling results found that the REBT model of psychopathology, and the REBT model of psychological health, provided satisfactory representations of loneliness, explaining 36% and 23% of variance in loneliness, respectively. Several dysfunctional ("Demandingness", "Catastrophising" and "Self-Downing" beliefs) and functional ("Preferences" and "Self-Acceptance" beliefs) cognitions were directly and indirectly associated with loneliness. These results highlight that cognitions and loneliness are meaningfully related, and indicate that cognitive-behavioural models may be useful in understanding loneliness. More specifically, current results suggest that REBT may offer a viable psychotherapeutic approach to treating loneliness.

Cognitive Characteristics of Children with Genetic Syndromes

PubMed Central

Simon, Tony J.

2008-01-01

The cognitive profile of several different populations of children, each with a distinct neurogenetic disorder that has been described as fitting the pattern of a “nonverbal learning disorder”, is examined. In particular, this paper presents the view that a cognitive endophenotype, specified in terms of specific cognitive processes involving the spatial, temporal and attentional domains, can be used to generate an explanation of the neurocognitive foundation of the common impairments found in these disorders. Methods for evaluating cognitive impairments are first compared and contrasted and the concept of “nonverbal learning disorders” is described. The paper then examines data from experimental tests of spatiotemporal and executive cognitive function acquired from children with one of several disorders to determine whether such a cognitive endophenotype holds promise for moving from descriptions of to explanations for the impairments observed and whether prescriptions for therapeutic interventions might flow from such an account. Synopsis This paper presents the cognitive profile observed in children with one of several common genetic syndromes associated with “nonverbal learning disorders”. It introduces the concept of a cognitive endophenotype in order to help explain the similar pattern of impairments across the syndromes. It explores the explanation of diverse impairments in higher-order visual, spatial, temporal, numerical and executive cognitive competencies deriving from origins in more basic attentional and spatial cognitive dysfunctions. The importance of a developmental approach to understanding dysfunction is stressed. PMID:17562581

Dietary enrichment counteracts age-associated cognitive dysfunction in canines.

PubMed

Milgram, N W; Zicker, S C; Head, E; Muggenburg, B A; Murphey, H; Ikeda-Douglas, C J; Cotman, C W

2002-01-01

Advanced age is accompanied by cognitive decline indicative of central nervous system dysfunction. One possibly critical causal factor is oxidative stress. Accordingly, we studied the effects of dietary antioxidants and age in a canine model of aging that parallels the key features of cognitive decline and neuropathology in humans. Old and young animals were placed on either a standard control food, or a food enriched with a broad spectrum of antioxidants and mitochondrial enzymatic cofactors. After 6 months of treatment, the animals were tested on four increasingly difficult oddity discrimination learning problems. The old animals learned more slowly than the young, making significantly more errors. However, this age-associated decline was reduced in the animals fed the enriched food, particularly on the more difficult tasks. These results indicate that maintenance on foods fortified with complex mixtures of antioxidants can partially counteract the deleterious effects of aging on cognition. Copyright 2002 Elsevier Science Inc.

A cognitive neuroscience perspective on psychopathy: evidence for paralimbic system dysfunction.

PubMed

Kiehl, Kent A

2006-06-15

Psychopathy is a complex personality disorder that includes interpersonal and affective traits such as glibness, lack of empathy, guilt or remorse, shallow affect, and irresponsibility, and behavioral characteristics such as impulsivity, poor behavioral control, and promiscuity. Much is known about the assessment of psychopathy; however, relatively little is understood about the relevant brain disturbances. The present review integrates data from studies of behavioral and cognitive changes associated with focal brain lesions or insults and results from psychophysiology, cognitive psychology and cognitive and affective neuroscience in health and psychopathy. The review illustrates that the brain regions implicated in psychopathy include the orbital frontal cortex, insula, anterior and posterior cingulate, amygdala, parahippocampal gyrus, and anterior superior temporal gyrus. The relevant functional neuroanatomy of psychopathy thus includes limbic and paralimbic structures that may be collectively termed 'the paralimbic system'. The paralimbic system dysfunction model of psychopathy is discussed as it relates to the extant literature on psychopathy.

Cerebral Autoregulation in Hypertension and Ischemic Stroke: A Mini Review

PubMed Central

Shekhar, Shashank; Liu, Ruen; Travis, Olivia K; Roman, Richard J; Fan, Fan

2017-01-01

Aging and chronic hypertension are associated with dysfunction in vascular smooth muscle, endothelial cells, and neurovascular coupling. These dysfunctions induce impaired myogenic response and cerebral autoregulation, which diminish the protection of cerebral arterioles to the cerebral microcirculation from elevated pressure in hypertension. Chronic hypertension promotes cerebral focal ischemia in response to reductions in blood pressure that are often seen in sedentary elderly patients on antihypertensive therapy. Cerebral autoregulatory dysfunction evokes Blood-Brain Barrier (BBB) leakage, allowing the circulating inflammatory factors to infiltrate the brain to activate glia. The impaired cerebral autoregulation-induced inflammatory and ischemic injury could cause neuronal cell death and synaptic dysfunction which promote cognitive deficits. In this brief review, we summarize the pathogenesis and signaling mechanisms of cerebral autoregulation in hypertension and ischemic stroke-induced cognitive deficits, and discuss our new targets including 20-Hydroxyeicosatetraenoic acid (20-HETE), Gamma-Adducin (Add3) and Matrix Metalloproteinase-9 (MMP-9) that may contribute to the altered cerebral vascular function. PMID:29333537

Dreaming and cognition in patients with frontotemporal dysfunction.

PubMed

Paiva, Teresa; Bugalho, Paulo; Bentes, Carla

2011-12-01

Individuals with Parkinson's disease (PD) and temporal lobe epilepsy (TLE) have hallucinations and mild cognitive dysfunction. The objective of this work was to study dreams in PD and TLE patients using a common functional model of dream production involving the limbic and paralimbic structures. Dreams were characterised in early-stage PD (19 males) and TLE patients (52) with dream diaries classified by the Hall van de Castle system and were compared with matched controls. In PD, there were significant differences between patients' dreams and those of controls: animals, physical aggression, and a befriender were more common in patients, and aggressor and bodily misfortunes were less common. The dreams of patients with frontal dysfunction showed more aggressive features. TLE patients had lower recall than PD patients and a higher proportion of dreams involving family and familiar settings, lower proportions involving success, and a higher incidence of frontal dysfunction. The dreams of PD and TLE patients share important features. Copyright © 2011. Published by Elsevier Inc.

Zebrafish as a Model for Epilepsy-Induced Cognitive Dysfunction: A Pharmacological, Biochemical and Behavioral Approach

PubMed Central

Kundap, Uday P.; Kumari, Yatinesh; Othman, Iekhsan; Shaikh, Mohd. Farooq

2017-01-01

Epilepsy is a neuronal disorder allied with distinct neurological and behavioral alterations characterized by recurrent spontaneous epileptic seizures. Impairment of the cognitive performances such as learning and memory is frequently observed in epileptic patients. Anti-epileptic drugs (AEDs) are efficient to the majority of patients. However, 30% of this population seems to be refractory to the drug treatment. These patients are not seizure-free and frequently they show impaired cognitive functions. Unfortunately, as a side effect, some AEDs could contribute to such impairment. The major problem associated with conducting studies on epilepsy-related cognitive function is the lack of easy, rapid, specific and sensitive in vivo testing models. However, by using a number of different techniques and parameters in the zebrafish, we can incorporate the unique feature of specific disorder to study the molecular and behavior basis of this disease. In the view of current literature, the goal of the study was to develop a zebrafish model of epilepsy induced cognitive dysfunction. In this study, the effect of AEDs on locomotor activity and seizure-like behavior was tested against the pentylenetetrazole (PTZ) induced seizures in zebrafish and epilepsy associated cognitive dysfunction was determined using T-maze test followed by neurotransmitter estimation and gene expression analysis. It was observed that all the AEDs significantly reversed PTZ induced seizure in zebrafish, but had a negative impact on cognitive functions of zebrafish. AEDs were found to modulate neurotransmitter levels, especially GABA, glutamate, and acetylcholine and gene expression in the drug treated zebrafish brains. Therefore, combination of behavioral, neurochemical and genenetic information, makes this model a useful tool for future research and discovery of newer and safer AEDs. PMID:28824436

Executive functions: a discussion of the issues facing children with autism spectrum disorders and related disorders.

PubMed

Calhoun, James A

2006-02-01

The interest and attention devoted to executive functions has grown steadily in the last several decades. The concept and definitions of executive functions and their association with certain disorders such as autism spectrum disorders (ASD) and overall cognitive, social, emotional, and behavioral functioning are important knowledge areas for those working in education, health, and mental health-related fields. It is particularly important for providers to have an understanding of the basic issues related to assessment and remediation of executive dysfunction. This article briefly addresses the background, current definitions, research, and some intervention options associated with executive functions. The intent is to present a foundation for encouraging additional research on the issues relevant to this important topic.

Altered Resting State Functional Connectivity in Young Survivors of Acute Lymphoblastic Leukemia

PubMed Central

Kesler, Shelli R.; Gugel, Meike; Pritchard-Berman, Mika; Lee, Clement; Kutner, Emily; Hosseini, S.M. Hadi; Dahl, Gary; Lacayo, Norman

2014-01-01

Background Chemotherapy treatment for pediatric acute lymphoblastic leukemia (ALL) has been associated with long-term cognitive impairments in some patients. However, the neurobiologic mechanisms underlying these impairments, particularly in young survivors, are not well understood. This study aimed to examine intrinsic functional brain connectivity in pediatric ALL and its relationship with cognitive status. Procedure We obtained resting state functional magnetic resonance imaging (rsfMRI) and cognitive testing data from 15 ALL survivors age 8–15 years and 14 matched healthy children. The ALL group had a history of intrathecal chemotherapy treatment but were off-therapy for at least 6 months at the time of enrollment. We used seed-based analyses to compare intrinsic functional brain network connectivity between the groups. We also explored correlations between connectivity and cognitive performance, demographic, medical, and treatment variables. Results We demonstrated significantly reduced connectivity between bilateral hippocampus, left inferior occipital, left lingual gyrus, bilateral calcarine sulcus, and right amygdala in the ALL group compared to controls. The ALL group also showed regions of functional hyperconnectivity including right lingual gyrus, precuneus, bilateral superior occipital lobe, and right inferior occipital lobe. Functional hypoconnectivity was associated with reduced cognitive function as well as younger age at diagnosis in the ALL group. Conclusions This is the first study to demonstrate that intrinsic functional brain connectivity is disrupted in pediatric ALL following chemotherapy treatment. These results help explain cognitive dysfunction even when objective test performance is seemingly normal. Children diagnosed at a younger age may show increased vulnerability to altered functional brain connectivity. PMID:24619953

Improved Memory Function 12 Weeks after Bariatric Surgery

PubMed Central

Gunstad, John; Strain, Gladys; Devlin, Michael J.; Wing, Rena; Cohen, Ronald A.; Paul, Robert H.; Crosby, Ross D.; Mitchell, James E.

2010-01-01

Background There is growing evidence that obesity is associated with poor neurocognitive outcome. Bariatric surgery is an effective intervention for morbid obesity and improves many comorbid medical conditions that are associated with cognitive dysfunction. The effects of bariatric surgery on cognition are unknown. Methods Prospective study total of 150 individuals (109 bariatric surgery patients enrolled in the Longitudinal Assessment of Bariatric Surgery (LABS) project and 41 obese controls that did not undergo surgery) completed cognitive evaluation at baseline and 12 week follow-up. Demographic, medical, and psychosocial information was also collected to elucidate possible mechanisms of change. Results Many bariatric surgery patients exhibited impaired performance on cognitive testing at baseline (range from 4.6%–23.9%). However, surgery patients were no more likely to exhibit decline on two or more cognitive tests at 12-week follow-up than obese controls [12.84% vs. 23.26%; χ2 (1) = 2.51, p = .11]. Group comparisons using repeated measures MANOVA showed surgery patients had improved memory performance at 12 week follow-up [λ = .86, F(4, 147) = 5.88, p<.001], whereas obese controls actually declined. Regression analyses showed surgery patients without hypertension had better short delay recall at 12 weeks than those that did [β = 0.31, p = .005], though other demographic and medical variables were largely unrelated to test performance. Conclusion The current results suggest that cognitive impairment is common in bariatric surgery patients, though these deficits may be at least partly reversible. Future studies are needed to clarify underlying mechanisms, particularly longitudinal studies employing neuroimaging and blood markers. PMID:21145295

Cumulative exposure to lead and cognition in persons with Parkinson’s disease

PubMed Central

Weuve, Jennifer; Press, Daniel Z.; Grodstein, Francine; Wright, Robert O.; Hu, Howard; Weisskopf, Marc G.

2012-01-01

Background Dementia is an important consequence of Parkinson’s disease (PD), with few known modifiable risk factors. Cumulative exposure to lead, at levels experienced in the community, may exacerbate PD-related neural dysfunction, resulting in impaired cognition. Methods Among 101 persons with PD (“cases”) and, separately, 50 persons without PD (“controls”), we evaluated cumulative lead exposure, gauged via tibia and patella bone lead concentrations, in relation to cognitive function, assessed using a telephone battery developed and validated in a separate sample of PD patients. We also assessed the interaction between lead and case-control status. Results After multivariable adjustment, higher tibia bone lead concentration among PD cases was associated with worse performance on all of the individual telephone tests. In particular, tibia lead levels corresponded to significantly worse performance on a telephone analogue of the Mini-Mental State Examination and tests of working memory and attention. Moreover, higher tibia bone lead concentration was associated with significantly worse global composite score encompassing all the cognitive tests (P=0.04). The magnitude of association per standard deviation increment in tibia bone lead level was equivalent to the difference in global scores among controls in our study who were about seven years apart in age. The tibia lead-cognition association was notably stronger within cases than within controls (Pdifference=0.06). Patella bone lead concentration was not consistently associated with performance on the tests. Conclusions These data provide evidence suggesting that cumulative exposure to lead may result in worsened cognition among persons with PD. PMID:23143985

Further support for the role of dysfunctional attitudes in models of real-world functioning in schizophrenia.

PubMed

Horan, William P; Rassovsky, Yuri; Kern, Robert S; Lee, Junghee; Wynn, Jonathan K; Green, Michael F

2010-06-01

According to A.T. Beck and colleagues' cognitive formulation of poor functioning in schizophrenia, maladaptive cognitive appraisals play a key role in the expression and persistence of negative symptoms and associated real-world functioning deficits. They provided initial support for this model by showing that dysfunctional attitudes are elevated in schizophrenia and account for significant variance in negative symptoms and subjective quality of life. The current study used structural equation modeling to further evaluate the contribution of dysfunctional attitudes to outcome in schizophrenia. One hundred eleven outpatients and 67 healthy controls completed a Dysfunctional Attitudes Scale, and patients completed a competence measure of functional capacity, clinical ratings of negative symptoms, and interview-based ratings of real-world functioning. Patients reported higher defeatist performance beliefs than controls and these were significantly related to lower functional capacity, higher negative symptoms, and worse community functioning. Consistent with Beck and colleagues' formulation, modeling analyses indicated a significant indirect pathway from functional capacity-->dysfunctional attitudes-->negative symptoms-->real-world functioning. These findings support the value of dysfunctional attitudes for understanding the determinants of outcome in schizophrenia and suggest that therapeutic interventions targeting these attitudes may facilitate functional recovery. (c) 2009 Elsevier Ltd. All rights reserved.

Pituitary Dysfunction after Blast Traumatic Brain Injury: The UK BIOSAP Study

PubMed Central

Baxter, David; Sharp, David J; Feeney, Claire; Papadopoulou, Debbie; Ham, Timothy E; Jilka, Sagar; Hellyer, Peter J; Patel, Maneesh C; Bennett, Alexander N; Mistlin, Alan; McGilloway, Emer; Midwinter, Mark; Goldstone, Anthony P

2013-01-01

Objective Pituitary dysfunction is a recognized consequence of traumatic brain injury (TBI) that causes cognitive, psychological, and metabolic impairment. Hormone replacement offers a therapeutic opportunity. Blast TBI (bTBI) from improvised explosive devices is commonly seen in soldiers returning from recent conflicts. We investigated: (1) the prevalence and consequences of pituitary dysfunction following moderate to severe bTBI and (2) whether it is associated with particular patterns of brain injury. Methods Nineteen male soldiers with moderate to severe bTBI (median age = 28.3 years) and 39 male controls with moderate to severe nonblast TBI (nbTBI; median age = 32.3 years) underwent full dynamic endocrine assessment between 2 and 48 months after injury. In addition, soldiers had structural brain magnetic resonance imaging, including diffusion tensor imaging (DTI), and cognitive assessment. Results Six of 19 (32.0%) soldiers with bTBI, but only 1 of 39 (2.6%) nbTBI controls, had anterior pituitary dysfunction (p = 0.004). Two soldiers had hyperprolactinemia, 2 had growth hormone (GH) deficiency, 1 had adrenocorticotropic hormone (ACTH) deficiency, and 1 had combined GH/ACTH/gonadotrophin deficiency. DTI measures of white matter structure showed greater traumatic axonal injury in the cerebellum and corpus callosum in those soldiers with pituitary dysfunction than in those without. Soldiers with pituitary dysfunction after bTBI also had a higher prevalence of skull/facial fractures and worse cognitive function. Four soldiers (21.1%) commenced hormone replacement(s) for hypopituitarism. Interpretation We reveal a high prevalence of anterior pituitary dysfunction in soldiers suffering moderate to severe bTBI, which was more frequent than in a matched group of civilian moderate to severe nbTBI subjects. We recommend that all patients with moderate to severe bTBI should routinely have comprehensive assessment of endocrine function. Ann Neurol 2013;74:527–536 PMID:23794460

White matter and cognition: making the connection

PubMed Central

Fields, R. Douglas

2016-01-01

Whereas the cerebral cortex has long been regarded by neuroscientists as the major locus of cognitive function, the white matter of the brain is increasingly recognized as equally critical for cognition. White matter comprises half of the brain, has expanded more than gray matter in evolution, and forms an indispensable component of distributed neural networks that subserve neurobehavioral operations. White matter tracts mediate the essential connectivity by which human behavior is organized, working in concert with gray matter to enable the extraordinary repertoire of human cognitive capacities. In this review, we present evidence from behavioral neurology that white matter lesions regularly disturb cognition, consider the role of white matter in the physiology of distributed neural networks, develop the hypothesis that white matter dysfunction is relevant to neurodegenerative disorders, including Alzheimer's disease and the newly described entity chronic traumatic encephalopathy, and discuss emerging concepts regarding the prevention and treatment of cognitive dysfunction associated with white matter disorders. Investigation of the role of white matter in cognition has yielded many valuable insights and promises to expand understanding of normal brain structure and function, improve the treatment of many neurobehavioral disorders, and disclose new opportunities for research on many challenging problems facing medicine and society. PMID:27512019

Effects of stimulus salience on touchscreen serial reversal learning in a mouse model of fragile X syndrome

PubMed Central

Dickson, Price E.; Corkill, Beau; McKimm, Eric; Miller, Mellessa M.; Calton, Michele A.; Goldowitz, Daniel; Blaha, Charles D.; Mittleman, Guy

2013-01-01

Fragile X syndrome (FXS) is the most common inherited form of intellectual disability in males and the most common genetic cause of autism. Although executive dysfunction is consistently found in humans with FXS, evidence of executive dysfunction in Fmr1 KO mice, a mouse model of FXS, has been inconsistent. One possible explanation for this is that executive dysfunction in Fmr1 KO mice, similar to humans with FXS, is only evident when cognitive demands are high. Using touchscreen operant conditioning chambers, male Fmr1 KO mice and their male wildtype littermates were tested on the acquisition of a pairwise visual discrimination followed by four serial reversals of the response rule. We assessed reversal learning performance under two different conditions. In the first, the correct stimulus was salient and the incorrect stimulus was non-salient. In the second and more challenging condition, the incorrect stimulus was salient and the correct stimulus was non-salient; this increased cognitive load by introducing conflict between sensory-driven (i.e., bottom-up) and task-dependent (i.e., top-down) signals. Fmr1 KOs displayed two distinct impairments relative to wildtype littermates. First, Fmr1 KOs committed significantly more learning-type errors during the second reversal stage, but only under high cognitive load. Second, during the first reversal stage, Fmr1 KOs committed significantly more attempts to collect a reward during the timeout following an incorrect response. These findings indicate that Fmr1 KO mice display executive dysfunction that, in some cases, is only evident under high cognitive load. PMID:23747611

A role for Kalirin-7 in corticostriatal synaptic dysfunction in Huntington's disease

PubMed Central

Puigdellívol, Mar; Cherubini, Marta; Brito, Verónica; Giralt, Albert; Suelves, Núria; Ballesteros, Jesús; Zamora-Moratalla, Alfonsa; Martín, Eduardo D.; Eipper, Betty A.; Alberch, Jordi; Ginés, Silvia

2015-01-01

Cognitive dysfunction is an early clinical hallmark of Huntington's disease (HD) preceding the appearance of motor symptoms by several years. Neuronal dysfunction and altered corticostriatal connectivity have been postulated to be fundamental to explain these early disturbances. However, no treatments to attenuate cognitive changes have been successful: the reason may rely on the idea that the temporal sequence of pathological changes is as critical as the changes per se when new therapies are in development. To this aim, it becomes critical to use HD mouse models in which cognitive impairments appear prior to motor symptoms. In this study, we demonstrate procedural memory and motor learning deficits in two different HD mice and at ages preceding motor disturbances. These impairments are associated with altered corticostriatal long-term potentiation (LTP) and specific reduction of dendritic spine density and postsynaptic density (PSD)-95 and spinophilin-positive clusters in the cortex of HD mice. As a potential mechanism, we described an early decrease of Kalirin-7 (Kal7), a guanine-nucleotide exchange factor for Rho-like small GTPases critical to maintain excitatory synapse, in the cortex of HD mice. Supporting a role for Kal7 in HD synaptic deficits, exogenous expression of Kal7 restores the reduction of excitatory synapses in HD cortical cultures. Altogether, our results suggest that cortical dysfunction precedes striatal disturbances in HD and underlie early corticostriatal LTP and cognitive defects. Moreover, we identified diminished Kal7 as a key contributor to HD cortical alterations, placing Kal7 as a molecular target for future therapies aimed to restore corticostriatal function in HD. PMID:26464483

Inhibitory saccadic dysfunction is associated with cerebellar injury in multiple sclerosis.

PubMed

Kolbe, Scott C; Kilpatrick, Trevor J; Mitchell, Peter J; White, Owen; Egan, Gary F; Fielding, Joanne

2014-05-01

Cognitive dysfunction is common in patients with multiple sclerosis (MS). Saccadic eye movement paradigms such as antisaccades (AS) can sensitively interrogate cognitive function, in particular, the executive and attentional processes of response selection and inhibition. Although we have previously demonstrated significant deficits in the generation of AS in MS patients, the neuropathological changes underlying these deficits were not elucidated. In this study, 24 patients with relapsing-remitting MS underwent testing using an AS paradigm. Rank correlation and multiple regression analyses were subsequently used to determine whether AS errors in these patients were associated with: (i) neurological and radiological abnormalities, as measured by standard clinical techniques, (ii) cognitive dysfunction, and (iii) regionally specific cerebral white and gray-matter damage. Although AS error rates in MS patients did not correlate with clinical disability (using the Expanded Disability Status Score), T2 lesion load or brain parenchymal fraction, AS error rate did correlate with performance on the Paced Auditory Serial Addition Task and the Symbol Digit Modalities Test, neuropsychological tests commonly used in MS. Further, voxel-wise regression analyses revealed associations between AS errors and reduced fractional anisotropy throughout most of the cerebellum, and increased mean diffusivity in the cerebellar vermis. Region-wise regression analyses confirmed that AS errors also correlated with gray-matter atrophy in the cerebellum right VI subregion. These results support the use of the AS paradigm as a marker for cognitive dysfunction in MS and implicate structural and microstructural changes to the cerebellum as a contributing mechanism for AS deficits in these patients. Copyright © 2013 Wiley Periodicals, Inc.

Controlled randomized clinical trial of spirituality integrated psychotherapy, cognitive-behavioral therapy and medication intervention on depressive symptoms and dysfunctional attitudes in patients with dysthymic disorder.

PubMed

Ebrahimi, Amrollah; Neshatdoost, Hamid Taher; Mousavi, Seyed Ghafur; Asadollahi, Ghorban Ali; Nasiri, Hamid

2013-01-01

Due to the controversy over efficacy of cognitive-behavioral therapy for chronic depression, recently, there has been an increasingly tendency toward therapeutic methods based on the cultural and spiritual approaches. The aim of this research was to compare efficacy of spiritual integrated psychotherapy (SIPT) and cognitive-behavioral therapy (CBT) on the intensity of depression symptoms and dysfunctional attitudes of patients with dysthymic disorder. This study had a mixed qualitative and quantitative design. In the first phase, SIPT model was prepared and, in the second phase, a double-blind random clinical trial was performed. Sixty-two patients with dysthymic disorder were selected from several centers include Nour and Alzahra Medical Center, Counseling Centers of Isfahan University of Medical Sciences and Goldis in Isfahan. The participants were randomly assigned to three experimental groups and one control group. The first group received 8 sessions treatment of SIPT, second groups also had 8 sessions of cognitive-behavioral therapy, which was specific to dysthymic disorder and third group were under antidepressant treatment. Beck depression inventory and dysfunctional attitudes scale were used to evaluate all the participants in four measurement stages. The data were analyzed using MANCOVA repeated measure method. The results revealed that SIPT had more efficacy than medication based on both scales (P < 0.01); however, it was not different from CBT. SIPT was more effective on the modification of dysfunctional attitudes compared with CBT and medication (P < 0.05). These findings supported the efficacy of psychotherapy enriched with cultural capacities and religious teachings.

Affective dysfunction in a mouse model of Rett syndrome: Therapeutic effects of environmental stimulation and physical activity.

PubMed

Kondo, Mari A; Gray, Laura J; Pelka, Gregory J; Leang, Sook-Kwan; Christodoulou, John; Tam, Patrick P L; Hannan, Anthony J

2016-02-01

Rett syndrome (RTT) is a neurodevelopmental disorder associated with mutations in the X-linked gene encoding methyl-CpG-binding protein 2 (MeCP2) and consequent dysregulation of brain maturation. Patients suffer from a range of debilitating physical symptoms, however, behavioral and emotional symptoms also severely affect their quality of life. Here, we present previously unreported and clinically relevant affective dysfunction in the female heterozygous Mecp2(tm1Tam) mouse model of RTT (129sv and C57BL6 mixed background). The affective dysfunction and aberrant anxiety-related behavior of the Mecp2(+/-) mice were found to be reversible with environmental enrichment (EE) from 4 weeks of age. The effect of exercise alone (via wheel running) was also explored, providing the first evidence that increased voluntary physical activity in an animal model of RTT is beneficial for some phenotypes. Mecp2(+/-) mutants displayed elevated corticosterone despite decreased Crh expression, demonstrating hypothalamic-pituitary-adrenal axis dysregulation. EE of Mecp2(+/-) mice normalized basal serum corticosterone and hippocampal BDNF protein levels. The enrichment-induced rescue appears independent of the transcriptional regulation of the MeCP2 targets Bdnf exon 4 and Crh. These findings provide new insight into the neurodevelopmental role of MeCP2 and pathogenesis of RTT, in particular the affective dysfunction. The positive outcomes of environmental stimulation and physical exercise have implications for the development of therapies targeting the affective symptoms, as well as behavioral and cognitive dimensions, of this devastating neurodevelopmental disorder. © 2015 Wiley Periodicals, Inc.

Effects of task-irrelevant emotional stimuli on working memory processes in mild cognitive impairment.

PubMed

Berger, Christoph; Erbe, Anna-Katharina; Ehlers, Inga; Marx, Ivo; Hauenstein, Karlheinz; Teipel, Stefan

2015-01-01

Research suggests generally impaired cognitive control functions in working memory (WM) processes in amnestic mild cognitive impairment (MCI) and incipient Alzheimer's disease (AD). Little is known how emotional salience of task-irrelevant stimuli may modulate cognitive control of WM performance and neurofunctional activation in MCI and AD individuals. We investigated the impact of emotional task-irrelevant visual stimuli on cortical activation during verbal WM. Twelve AD/MCI individuals and 12 age-matched healthy individuals performed a verbal WM (nback-) task with task-irrelevant emotionally neutral and emotionally negative background pictures during fMRI measurement. AD/MCI individuals showed decreased WM performance compared with controls; both AD/MCI and control groups reacted slower during presentation of negative pictures, regardless of WM difficulty. The AD/MCI group showed increased activation in the left hemispheric prefrontal network, higher amygdala and less cerebellar activation with increasing WM task difficulty compared to healthy controls. Correlation analysis between neurofunctional activation and WM performance revealed a negative correlation between task sensitivity and activation in the dorsal anterior cingulum for the healthy controls but not for the AD/MCI group. Our data suggest compensatory activation in prefrontal cortex and amygdala, but also dysfunctional inhibition of distracting information in the AD/MCI group during higher WM task difficulty. Additionally, attentional processes affecting the correlation between WM performance and neurofunctional activation seem to be different between incipient AD and healthy aging.

Functional and Structural Benefits Induced by Omega-3 Polyunsaturated Fatty Acids During Aging

PubMed Central

Cutuli, Debora

2017-01-01

Background Omega-3 polyunsaturated fatty acids (n-3 PUFA) are structural components of the brain and are indispensable for neuronal membrane synthesis. Along with decline in cognition, decreased synaptic density and neuronal loss, normal aging is accompanied by a reduction in n-3 PUFA concentration in the brain in both humans and rodents. Recently, many clinical and experimental studies have demonstrated the importance of n-3 PUFA in counteracting neurodegeneration and age-related dysfunctions. Methods Methods: This review will focus on the neuroprotective effects of n-3 PUFA on cognitive impairment, neuroinflammation and neurodegeneration during normal aging. Multiple pathways of n-3 PUFA preventive action will be examined. Results Namely, n-3 PUFA have been shown to increase the levels of several signaling factors involved in synaptic plasticity, thus leading to the increase of dendritic spines and synapses as well as the enhancement of hippocampal neurogenesis even at old age. In elderly subjects n-3 PUFA exert anti-inflammatory effects associated with improved cognitive functions. Interestingly, growing evidence highlights n-3 PUFA efficacy in preventing the loss of both gray and white matter volume and integrity. Conclusion This review shows that n-3 PUFA are essential for a successful aging and appear as ideal cognitive enhancers to be implemented in nutritional interventions for the promotion of healthy aging. PMID:27306037

Application and validation of the barrow neurological institute screen for higher cerebral functions in a control population and in patient groups commonly seen in neurorehabilitation.

PubMed

Hofgren, Caisa; Esbjörnsson, Eva; Aniansson, Hans; Sunnerhagen, Katharina Stibrant

2007-09-01

To determine whether the Barrow Neurological Institute Screen for Higher Cerebral Functions (BNIS) can differentiate brain-dysfunctional patients from controls. A case-control study. A total of 92 controls and 120 patients from a neuro-rehabilitation clinic with a diagnosis of: right and left hemisphere stroke, traumatic brain injury, Parkinson's disease or anoxic brain damage. The BNIS has a maximum total score of 50 points, < 47 indicates cognitive dysfunction. Group comparisons and exploration of variables influencing the BNIS total score were made. A significant difference was found between the control group and the total patient group for the BNIS total score and for the subscales (p < 0.0005). Sensitivity was 88% and specificity 78%. Presence of disease and educational level had the greatest influence on the results of the BNIS. Patients with Parkinson's disease were shown to be the least cognitively affected and those with anoxic brain damage the most affected. The BNIS has potential value as a screening instrument for cognitive functions and is sufficiently sensitive to differentiate brain-dysfunctional patients from a control population. It appears to be applicable in a neurological rehabilitation setting, and can be used early in the process, giving a baseline cognitive functional level.

Human recombinant erythropoietin reduces sensorimotor dysfunction and cognitive impairment in rat models of chronic kidney disease.

PubMed

Reza-Zaldívar, E E; Sandoval-Avila, S; Gutiérrez-Mercado, Y K; Vázquez-Méndez, E; Canales-Aguirre, A A; Esquivel-Solís, H; Gómez-Pinedo, U; Márquez-Aguirre, A L

2017-11-10

Chronic kidney disease (CKD) can cause anaemia and neurological disorders. Recombinant human erythropoietin (rHuEPO) is used to manage anaemia in CKD. However, there is little evidence on the effects of rHuEPO on behaviour and cognitive function in CKD. This study aimed to evaluate the impact of rHuEPO in sensorimotor and cognitive functions in a CKD model. Male Wistar rats were randomly assigned to 4 groups: control and CKD, with and without rHuEPO treatment (1050 IU per kg body weight, once weekly for 4 weeks). The Morris water maze, open field, and adhesive removal tests were performed simultaneously to kidney damage induction and treatment. Markers of anaemia and renal function were measured at the end of the study. Treatment with rHuEPO reduced kidney damage and corrected anaemia in rats with CKD. We observed reduced sensorimotor dysfunction in animals with CKD and treated with rHuEPO. These rats also completed the water maze test in a shorter time than the control groups. rHuEPO reduces kidney damage, corrects anemia, and reduces sensorimotor and cognitive dysfunction in animals with CKD. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Treatment of Cognitive Impairment in Multiple Sclerosis

PubMed Central

Pierson, Susan H.; Griffith, Nathan

2006-01-01

Cognitive impairment in multiple sclerosis is an increasingly recognized entity. This article reviews the cognitive impairment of multiple sclerosis, its prevalence, its relationship to different types of multiple sclerosis, and its contribution to long-term functional prognosis. The discussion also focuses on the key elements of cognitive dysfunction in multiple sclerosis which distinguish it from other forms of cognitive impairment. Therapeutic interventions potentially effective for the cognitive impairment of multiple sclerosis are reviewed including the effects of disease modifying therapies and the use of physical and cognitive interventions. PMID:16720960

'Whose atlas I use, his song I sing?' - The impact of anatomical atlases on fiber tract contributions to cognitive deficits after stroke.

PubMed

de Haan, Bianca; Karnath, Hans-Otto

2017-12-01

Nowadays, different anatomical atlases exist for the anatomical interpretation of the results from neuroimaging and lesion analysis studies that investigate the contribution of white matter fiber tract integrity to cognitive (dys)function. A major problem with the use of different atlases in different studies, however, is that the anatomical interpretation of neuroimaging and lesion analysis results might vary as a function of the atlas used. This issue might be particularly prominent in studies that investigate the contribution of white matter fiber tract integrity to cognitive (dys)function. We used a single large-sample dataset of right brain damaged stroke patients with and without cognitive deficit (here: spatial neglect) to systematically compare the influence of three different, widely-used white matter fiber tract atlases (1 histology-based atlas and 2 DTI tractography-based atlases) on conclusions concerning the involvement of white matter fiber tracts in the pathogenesis of cognitive dysfunction. We both calculated the overlap between the statistical lesion analysis results and each long association fiber tract (topological analyses) and performed logistic regressions on the extent of fiber tract damage in each individual for each long association white matter fiber tract (hodological analyses). For the topological analyses, our results suggest that studies that use tractography-based atlases are more likely to conclude that white matter integrity is critical for a cognitive (dys)function than studies that use a histology-based atlas. The DTI tractography-based atlases classified approximately 10 times as many voxels of the statistical map as being located in a long association white matter fiber tract than the histology-based atlas. For hodological analyses on the other hand, we observed that the conclusions concerning the overall importance of long association fiber tract integrity to cognitive function do not necessarily depend on the white matter atlas used, but conclusions may vary as a function of atlas used at the level of individual fiber tracts. Moreover, these analyses revealed that hodological studies that express the individual extent of injury to each fiber tract as a binomial variable are more likely to conclude that white matter integrity is critical for a cognitive function than studies that express the individual extent of injury to each fiber tract as a continuous variable. Copyright © 2017 Elsevier Inc. All rights reserved.

Highly water pressurized brown rice improves cognitive dysfunction in senescence-accelerated mouse prone 8 and reduces amyloid beta in the brain.

PubMed

Okuda, Michiaki; Fujita, Yuki; Katsube, Takuya; Tabata, Hiromasa; Yoshino, Katsumi; Hashimoto, Michio; Sugimoto, Hachiro

2018-03-27

Alzheimer's disease (AD) is the most common form of dementia and the number of AD patients continues to increase worldwide. Components of the germ layer and bran of Brown rice (BR) help maintain good health and prevent AD. Because the germ layer and bran absorb little water and are very hard and difficult to cook, they are often removed during processing. To solve these problems, in this study, we tried to use a high-pressure (HP) technique. We produced the highly water pressurized brown rice (HPBR) by pressurizing BR at 600 MPa, and then we fed it to an AD mouse model, senescence-accelerated mouse prone 8, to investigate the therapeutic effects of HPBR on cognitive dysfunction by Y-maze spatial memory test. HP treatment increased the water absorbency of BR without nutrient loss. HPBR ameliorated cognitive dysfunction and reduced the levels of amyloid-β, which is a major protein responsible for AD, in the brain. These results suggest that HPBR is effective for preventing AD.

Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy: a randomized, double-blind, placebo-controlled trial

PubMed Central

Brown, Paul D.; Pugh, Stephanie; Laack, Nadia N.; Wefel, Jeffrey S.; Khuntia, Deepak; Meyers, Christina; Choucair, Ali; Fox, Sherry; Suh, John H.; Roberge, David; Kavadi, Vivek; Bentzen, Soren M.; Mehta, Minesh P.; Watkins-Bruner, Deborah

2013-01-01

Background To determine the protective effects of memantine on cognitive function in patients receiving whole-brain radiotherapy (WBRT). Methods Adult patients with brain metastases received WBRT and were randomized to receive placebo or memantine (20 mg/d), within 3 days of initiating radiotherapy for 24 weeks. Serial standardized tests of cognitive function were performed. Results Of 554 patients who were accrued, 508 were eligible. Grade 3 or 4 toxicities and study compliance were similar in the 2 arms. There was less decline in delayed recall in the memantine arm at 24 weeks (P = .059), but the difference was not statistically significant, possibly because there were only 149 analyzable patients at 24 weeks, resulting in only 35% statistical power. The memantine arm had significantly longer time to cognitive decline (hazard ratio 0.78, 95% confidence interval 0.62–0.99, P = .01); the probability of cognitive function failure at 24 weeks was 53.8% in the memantine arm and 64.9% in the placebo arm. Superior results were seen in the memantine arm for executive function at 8 (P = .008) and 16 weeks (P = .0041) and for processing speed (P = .0137) and delayed recognition (P = .0149) at 24 weeks. Conclusions Memantine was well tolerated and had a toxicity profile very similar to placebo. Although there was less decline in the primary endpoint of delayed recall at 24 weeks, this lacked statistical significance possibly due to significant patient loss. Overall, patients treated with memantine had better cognitive function over time; specifically, memantine delayed time to cognitive decline and reduced the rate of decline in memory, executive function, and processing speed in patients receiving WBRT. RTOG 0614, ClinicalTrials.gov number CT00566852. PMID:23956241

Association of Social Support and Family Environment with Cognitive Function in Peritoneal Dialysis Patients.

PubMed

Wang, Qin; Yang, Zhi-Kai; Sun, Xiu-Mei; Du, Yun; Song, Yi-Fan; Ren, Ye-Ping; Dong, Jie

♦ BACKGROUND: Cognitive impairment (CI) is a common phenomenon and predictive of high mortality in peritoneal dialysis (PD) patients. This study aimed to analyze the association of social support and family environment with cognitive function in PD patients. ♦ METHODS: This is a cross-sectional study of PD patients from Peking University First Hospital and the Second Affiliated Hospital of Harbin Medical University. Global cognitive function was measured using the Modified Mini-Mental State Examination (3MS), executive function was measured by the A and B trail-making tests, and other cognitive functions were measured by the Repeatable Battery for the Assessment of Neuropsychological Status. Social support was measured with the Social Support Scale developed by Xiaoshuiyuan and family environment was measured with the Chinese Version of the Family Environment Scale (FES-CV). ♦ RESULTS: The prevalence of CI and executive dysfunction among the 173 patients in the study was, respectively, 16.8% and 26.3%. Logistic regression found that higher global social support (odds ratio [OR] = 1.09, 1.01 - 1.17, p = 0.027) and subjective social support predicted higher prevalence of CI (OR = 1.13, 1.02 - 1.25, p = 0.022), adjusting for covariates. Analyses of the FES-CV dimensions found that greater independence was significantly associated with better immediate memory and delayed memory. Moreover, higher scores on achievement orientation were significantly associated with poorer language skills. ♦ CONCLUSIONS: Our findings indicate that social support is negatively associated with the cognitive function of PD patients and that some dimensions of the family environment are significantly associated with several domains of cognitive function. Copyright © 2017 International Society for Peritoneal Dialysis.

Δ9-Tetrahydrocannabinol decreases willingness to exert cognitive effort in male rats

PubMed Central

Silveira, Mason M.; Adams, Wendy K.; Morena, Maria; Hill, Matthew N.; Winstanley, Catharine A.

2017-01-01

Background Acceptance of cannabis use is growing. However, prolonged use is associated with diminished psychosocial outcomes, potentially mediated by drug-induced cognitive impairments. Δ9-Tetrahydrocannabinol (THC) is the main psychoactive ingredient in cannabis, yet other phytocannabinoids in the plant, such as cannabidiol (CBD), have unique properties. Given that CBD can modulate the undesirable effects of THC, therapeutic agents, such as nabiximols, contain higher CBD:THC ratios than illicit marijuana. We tested the hypothesis that THC impairs a relevant cognitive function for long-term success, namely willingness to exert cognitive effort for greater rewards, and that CBD could attenuate such decision-making impairments. Methods Male Long–Evans rats (n = 29) performing the rat cognitive effort task (rCET) received acute THC and CBD, independently and concurrently, in addition to other cannabinoids. Rats chose between 2 options differing in reward magnitude, but also in the cognitive effort (attentional load) required to obtain them. Results We found that THC decreased choice of hard trials without impairing the animals’ ability to accurately complete them. Strikingly, this impairment was correlated with CB1 receptor density in the medial prefrontal cortex — an area previously implicated in effortful decision-making. In contrast, CBD did not affect choice. Coadministration of 1:1 CBD:THC matching that in nabiximols modestly attenuated the deleterious effects of THC in “slacker” rats. Limitations Only male rats were investigated, and the THC/CBD coadministration experiment was carried out in a subset of individuals. Conclusion These findings confirm that THC, but not CBD, selectively impairs decision-making involving cognitive effort costs. However, coadministration of CBD only partially ameliorates such THC-induced dysfunction. PMID:28245177

Association of plasma ghrelin levels and ghrelin rs4684677 polymorphism with mild cognitive impairment in type 2 diabetic patients

PubMed Central

Huang, Rong; Han, Jing; Tian, Sai; Cai, Rongrong; Sun, Jie; Shen, Yanjue; Wang, Shaohua

2017-01-01

Background and aims People with insulin resistance and type 2 diabetes mellitus (T2DM) are at increased risks of cognitive impairment. We aimed to investigate the association of plasma ghrelin levels and ghrelin rs4684677 polymorphism with mild cognitive impairment (MCI) in T2DM patients. Results In addition to elevated glycosylated hemoglobin (HbA1c), fasting blood glucose (FBG) and homeostasis model assessment of insulin resistance (HOMA-IR), T2DM patients with MCI had decreased plasma ghrelin levels compared with their healthy-cognition subjects (all p < 0.05). Further logistic regression analysis showed that ghrelin level was one of independent factors for MCI in T2DM patients (p < 0.05). Moreover, partial correlation analysis demonstrated that ghrelin levels were positively associated with the scores of Montreal Cognitive Assessment (r = 0.196, p = 0.041) and Auditory Verbal Learning Test-delayed recall (r = 0.197, p = 0.040) after adjustment for HbA1c, FBG and HOMA-IR, wherein the latter represented episodic memory functions. No significant differences were found for the distributions of genotype and allele of ghrelin rs4684677 polymorphism between MCI and control group. Materials and methods A total of 218 T2DM patients, with 112 patients who satisfied the MCI diagnostic criteria and 106 who exhibited healthy cognition, were enrolled in this study. Demographic characteristics, clinical variables and cognitive performances were extensively assessed. Plasma ghrelin levels and ghrelin rs4684677 polymorphism were also determined. Conclusions Our results suggest that decreased ghrelin levels are associated with MCI, especially with episodic memory dysfunction in T2DM populations. PMID:28146431

Postoperative cognitive dysfunction and its relationship to cognitive reserve in elderly total joint replacement patients.

PubMed

Scott, J E; Mathias, J L; Kneebone, A C; Krishnan, J

2017-06-01

Whether total joint replacement (TJR) patients are susceptible to postoperative cognitive dysfunction (POCD) remains unclear due to inconsistencies in research methodologies. Moreover, cognitive reserve may moderate the development of POCD after TJR, but has not been investigated in this context. The current study investigated POCD after TJR, and its relationship with cognitive reserve, using a more rigorous methodology than has previously been utilized. Fifty-three older adults (aged 50+) scheduled for TJR were assessed pre and post surgery (6 months). Forty-five healthy controls matched for age, gender, and premorbid IQ were re-assessed after an equivalent interval. Cognition, cognitive reserve, and physical and mental health were all measured. Standardized regression-based methods were used to assess cognitive changes, while controlling for the confounding effect of repeated cognitive testing. TJR patients only demonstrated a significant decline in Trail Making Test Part B (TMT B) performance, compared to controls. Cognitive reserve only predicted change in TMT B scores among a subset of TJR patients. Specifically, patients who showed the most improvement pre to post surgery had significantly higher reserve than those who showed the greatest decline. The current study provides limited evidence of POCD after TJR when examined using a rigorous methodology, which controlled for practice effects. Cognitive reserve only predicted performance within a subset of the TJR sample. However, the role of reserve in more cognitively compromised patients remains to be determined.

Italian neurologists' perception on cognitive symptoms in major depressive disorder.

PubMed

Neri, G; Serrati, C; Zolo, P; Cataldo, N; Ripellino, C

2016-09-01

The assessment of cognition is an important part of major depressive disorder (MDD) evaluation and a crucial issue is the physicians' perception of cognitive dysfunction in MDD that remains nowadays a little known matter. The present study aims at investigating the understanding of neurologists' perception about cognitive dysfunction in MDD. An on-line survey addressed to 85 Italian neurologists in the period between May and June 2015 was performed. The questionnaire comprised three sections: the first section collecting information on neurologists' socio-demographic profile, the second investigating cognitive symptoms relevance in relation with different aspects and the third one explicitly focusing on cognitive symptoms in MDD. Cognitive symptoms are considered most significant among DSM-5 symptoms to define the presence of a Major Depressive Episode in a MDD, to improve antidepressant therapy adherence, patients' functionality and concurrent neurological condition, once resolved. Furthermore, an incongruity came to light from this survey: the neurologists considered cognitive symptoms a not relevant aspect to choose the antidepressant treatment in comparison with the other DSM-5 symptoms on one side, but they declared the opposite in the third part of the questionnaire focused on cognitive symptoms. Cognitive symptoms appeared to be a relevant aspect in MDD and neurologists have a clear understanding of this issue. Nevertheless, the discrepancy between neurologists' perception on cognitive symptoms and the antidepressant treatment highlights the feeling of an unmet need that could be filled increasing the awareness of existing drugs with pro-cognitive effects.

Toward an Integration of Psychologic, Social, and Biologic Factors in Depression: Effects on Outcome and Course of Cognitive Therapy.

ERIC Educational Resources Information Center

Simons, Anne D.; And Others

1995-01-01

Integrates key variables from three major domains (cognition, stress, and psychobiology) that are typically studied separately. Dysfunctional attitudes, negative life events, or sleep electroencephalogram were assessed in 53 outpatients before treatment with cognitive therapy. Results are discussed in terms of the promise of integrative research.…

Indulgent thinking? Ecological momentary assessment of overweight and healthy-weight participants' cognitions and emotions.

PubMed

Boh, Bastiaan; Jansen, Anita; Clijsters, Ineke; Nederkoorn, Chantal; Lemmens, Lotte H J M; Spanakis, Gerasimos; Roefs, Anne

2016-12-01

Cognitions and emotions are considered important determinants of eating behaviour in cognitive behavioural models of obesity. Ecological data on these determinants is still limited. The present study investigated cognitions and emotions of overweight (n = 57) and healthy-weight (n = 43) participants via Ecological Momentary Assessment. It was found that eating-related cognitions mainly focused on desire and taste. Unexpectedly, dysfunctional cognitions (i.e., thoughts that may promote overeating) did not occur more often for overweight participants in almost all cases. So, the present EMA study provides no evidence for a role of dysfunctional cognitions in obesity-promoting eating behaviour when assessing eating-related cognitions immediately prior to eating events using a free-text format assessment. Right before eating events, participants mostly reported feeling calm/relaxed and cheerful/happy. Overweight participants scored higher on negative emotions, both at eating events and non-eating moments, than did healthy-weight participants. In addition, scores on standard questionnaires assessing emotional eating were positively associated with negative emotions reported at both eating and non-eating moments. As such, negative emotions, as assessed in the present study, do not seem to be specific triggers for food consumption. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cognitive Function | Science Inventory | US EPA

EPA Pesticide Factsheets

Because chemicals can adversely affect cognitive function in humans, considerable effort has been made to characterize their effects using animal models. Information from such models will be necessary to: evaluate whether chemicals identified as potentially neurotoxic by screening methods actually do affect cognitive function; identify and characterize the mechanisms or pathways by which effects at these targets lead to cognitive dysfunction; address issues of susceptibility and variability, which require understanding the compensations and interactions that only a whole organism can engage; and improve our understanding of the neurobiological underpinnings of cognitive function.This chapter has several purposes. First, it provides working definitions of cognitive functions, such as learning, memory and attention, in terms frequently used by behavioral toxicologists. It is important to have a common vocabulary to assess methods used in this area of research. Second, it presents an overview of some of the procedures commonly used in behavioral toxicology to assess the effects of chemicals on cognitive function in animals. It should be noted that this overview is not intended to be comprehensive or complete, but is intended to illustrate specific points by discussing examples. Finally, this chapter discusses some critical experimental and conceptual variables that are important for studies on chemical-induced cognitive dysfunction, and touches on the potential p

An association of cognitive impairment with diabetes and retinopathy in end stage renal disease patients under peritoneal dialysis.

PubMed

Liao, Jin-Lan; Xiong, Zu-Ying; Yang, Zhi-Kai; Hao, Li; Liu, Gui-Ling; Ren, Ye-Ping; Wang, Qin; Duan, Li-Ping; Zheng, Zhao-Xia; Dong, Jie

2017-01-01

Diabetes and retinopathy have been considered as risk factors of cognitive impairment (CI) in previous studies. We investigated both of these two factors and their relationship with global and specific cognitive functions in end stage renal disease patients under peritoneal dialysis (PD). In this multicenter cross-sectional study, 424 clinically stable patients were enrolled from 5 PD units, who performed PD for at least three months and completed fundoscopy examination if they had diabetes. Global cognitive function was measured using the Modified Mini-Mental State Examination (3MS), Trail-Making Test forms A and B for executive function, and subtests of the Battery for the Assessment of Neuropsychological Status for immediate and delayed memory, visuospatial skills, and language ability. PD Patients with DM and Retinopathy had significantly higher prevalence of CI, executive dysfunction, impaired immediate memory and visuospatial skill, compared with patients in non-DM group. By multivariate logistic regression analyses, DM and retinopathy rather than DM only were significantly associated with increased risk for CI, executive dysfunction, impaired immediate memory and visuospatial skill, odds ratios(ORs) and 95% confidence intervals were 2.09[1.11,3.92], 2.89[1.55,5.37], 2.16 [1.15,4.06] and 2.37[1.32,4.22], respectively (all P < 0.05). Diabetic PD patients with retinopathy were at two times risk for overall cognitive impairment, executive dysfunction, impaired immediate memory and visuospatial skill as compared to non-diabetic PD patients.

Role of GSK-3β in isoflurane-induced neuroinflammation and cognitive dysfunction in aged rats.

PubMed

Li, Shi-yong; Chen, Xin; Chen, Ye-ling; Tan, Lei; Zhao, Yi-lin; Wang, Jin-tao; Xiang, Qiang; Luo, Ai-lin

2013-08-01

This study investigated the role of glycogen synthase kinase-3β (GSK-3β) in isoflurane-induced neuroinflammation and cognitive dysfunction in aged rats. The hippocampi were dissected from aged rats which had been intraperitoneally administered lithium chloride (LiCl, 100 mg/kg) and then exposed to 1.4% isoflurane for 6 h. The expression of GSK-3β was detected by Western blotting. The mRNA and protein expression levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 were measured by real-time PCR and enzyme-linked immunosorbent assay (ELISA), respectively. Morris water maze was employed to detect spatial memory ability of rats. The results revealed that the level of GSK-3β was upregulated after isofurane exposure. Real-time PCR analysis demonstrated that isoflurane anesthesia increased mRNA levels of TNF-α, IL-1β and IL-6, which was consistent with the ELISA results. However, these changes were reversed by prophylactic LiCl, a non-selective inhibitor of GSK-3β. Additionally, we discovered that LiCl alleviated isoflurane-induced cognitive impairment in aged rats. Furthermore, the role of GSK-3β in isoflurae-induced neuroinflammation and cognitive dysfunction was associated with acetylation of NF-κB p65 (Lys310). In conclusion, these results suggested that GSK-3β is associated with isoflurane-induced upregulation of proinflammatory cytokines and cognitive disorder in aged rats.

Dysfunctional attitudes and poor problem solving skills predict hopelessness in major depression.

PubMed

Cannon, B; Mulroy, R; Otto, M W; Rosenbaum, J F; Fava, M; Nierenberg, A A

1999-09-01

Hopelessness is a significant predictor of suicidality, but not all depressed patients feel hopeless. If clinicians can predict hopelessness, they may be able to identify those patients at risk of suicide and focus interventions on factors associated with hopelessness. In this study, we examined potential predictors of hopelessness in a sample of depressed outpatients. In this study, we examined potential demographic, diagnostic, and symptom predictors of hopelessness in a sample of 138 medication-free outpatients (73 women and 65 men) with a primary diagnosis of major depression. The significance of predictors was evaluated in both simple and multiple regression analyses. Consistent with previous studies, we found no significant associations between demographic and diagnostic variables and greater hopelessness. Hopelessness was significantly associated with greater depression severity, poor problem solving abilities as assessed by the Problem Solving Inventory, and each of two measures of dysfunctional cognitions (the Dysfunctional Attitudes Scale and the Cognitions Questionnaire). In a stepwise multiple regression equation, however, only dysfunctional cognitions and poor problem solving offered non-redundant prediction of hopelessness scores, and accounted for 20% of the variance in these scores. This study is based on depressed patients entering into an outpatient treatment protocol. All analyses were correlational in nature, and no causal links can be concluded. Our findings, identifying clinical correlates of hopelessness, provide clinicians with potential additional targets for assessment and treatment of suicidal risk. In particular, clinical attention to dysfunctional attitudes and problem solving skills may be important for further reduction of hopelessness and perhaps suicidal risk.

Impairment of cognitive functioning during Sunitinib or Sorafenib treatment in cancer patients: a cross sectional study

PubMed Central

2014-01-01

Background Impairment of cognitive functioning has been reported in several studies in patients treated with chemotherapy. So far, no studies have been published on the effects of the vascular endothelial growth factor receptor (VEGFR) inhibitors on cognitive functioning. We investigated the objective and subjective cognitive function of patients during treatment with VEGFR tyrosine kinase inhibitors (VEGFR TKI). Methods Three groups of participants, matched on age, sex and education, were enrolled; 1. metastatic renal cell cancer (mRCC) or GIST patients treated with sunitinib or sorafenib (VEGFR TKI patients n = 30); 2. patients with mRCC not receiving systemic treatment (patient controls n = 20); 3. healthy controls (n = 30). Sixteen neuropsychological tests examining the main cognitive domains (intelligence, memory, attention and concentration, executive functions and abstract reasoning) were administered by a neuropsychologist. Four questionnaires were used to assess subjective cognitive complaints, mood, fatigue and psychological wellbeing. Results No significant differences in mean age, sex distribution, education level or IQ were found between the three groups. Both patient groups performed significantly worse on the cognitive domains Learning & Memory and Executive Functions (Response Generation and Problem Solving) compared to healthy controls. However only the VEGFR TKI patients showed impairments on the Executive subdomain Response Generation. Effect sizes of cognitive dysfunction in patients using VEGFR TKI were larger on the domains Learning & Memory and Executive Functions, compared to patient controls. Both patients groups performed on the domain Attention & Concentration the same as the healthy controls. Longer duration of treatment on VEGFR TKI was associated with a worse score on Working Memory tasks. Conclusions Our data suggest that treatment with VEGFR TKI has a negative impact on cognitive functioning, specifically on Learning & Memory, and Executive Functioning. We propose that patients who are treated with VEGFR TKI are monitored and informed for possible signs or symptoms associated with cognitive impairment. Trial registration ClinicalTrials.gov Identifier: NCT01246843. PMID:24661373

2q11.2 microdeletions: linking DNA structural variation to brain dysfunction and schizophrenia

PubMed Central

Karayiorgou, Maria; Simon, Tony J.; Gogos, Joseph A.

2010-01-01

Recent studies are beginning to paint a clear and consistent picture of the impairments in psychological and cognitive competencies that are associated with microdeletions in chromosome 22q11.2. These studies have highlighted a strong link between this genetic lesion and schizophrenia. Parallel studies in humans and animal models are starting to uncover the complex genetic and neural substrates altered by the microdeletion. In addition to offering a deeper understanding of the effects of this genetic lesion, these findings may guide analysis of other copy-number variants associated with cognitive dysfunction and psychiatric disorders. PMID:20485365

IgLON5-Associated Encephalitis With Atypical Brain Magnetic Resonance Imaging and Cerebrospinal Fluid Changes.

PubMed

Montagna, Massimiliano; Amir, Rizvana; De Volder, Ilse; Lammens, Martin; Huyskens, Jef; Willekens, Barbara

2018-01-01

IgLON5-associated encephalitis is a syndrome with different clinical presentations consisting of sleep dysfunction, bulbar dysfunction, chorea, and progressive supranuclear palsy-like symptoms whereas dysautonomy and cognitive decline usually appear in later stages of the disease. We report a case of a patient with IgLON5-associated encephalitis presenting with rapidly progressive cognitive decline and atypical inflammatory lesions on brain magnetic resonance imaging, oligoclonal bands on cerebrospinal fluid, anti-IgLON5 antibodies exclusively of the IgG1 class, and a fierce inflammatory reaction on brain biopsy, who responded favorably to immunotherapy.

Antibodies and the brain: antiribosomal P protein antibody and the clinical effects in patients with systemic lupus erythematosus.

PubMed

González, Alfonso; Massardo, Loreto

2018-06-01

Analysis of antiribosomal P protein autoantibodies (anti-P) pathogenicity in diffuse brain manifestations of neuropsychiatric lupus, emphasizing cognitive dysfunction and the recently emerged role of cross-reacting neuronal surface P antigen (NSPA) in α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and N-Methyl-D-Aspartate receptor glutamatergic transmission. Circulating anti-P antibodies associate with executive planning dysfunction and attention impairments in lupus patients and perturb glutamatergic transmission through NSPA in mice hippocampus, translating into impaired synaptic plasticity and spatial memory. Planning impairment impacts quality of life. In addition to the known association with lupus psychosis, new clinical and experimental evidence reveal a pathogenic role of anti-P antibodies in cognitive dysfunction, mechanistically explained by the anti-P interaction with NSPA as a target involved in glutamatergic synaptic plasticity.

ALS and Frontotemporal Dysfunction: A Review

PubMed Central

Achi, Eugene Y.; Rudnicki, Stacy A.

2012-01-01

Though once believed to be a disease that was limited to the motor system, it is now apparent that amyotrophic lateral sclerosis (ALS) may be associated with cognitive changes in some patients. Changes are consistent with frontotemporal dysfunction, and may range from mild abnormalities only recognized with formal neuropsychological testing, to profound frontotemporal dementia (FTD). Executive function, behavior, and language are the most likely areas to be involved. Screening helpful in detecting abnormalities includes verbal or categorical fluency, behavioral inventories filled out by the caregiver, and evaluation for the presence of depression and pseudobulbar affect. Patients with cognitive dysfunction have shortened survival and may be less compliant with recommendations regarding use of feeding tubes and noninvasive ventilation. Evolving knowledge of genetic and pathological links between ALS and FTD has allowed us to better understand the overlapping spectrum of ALS and FTD. PMID:22919484

Family functionality: a study of Brazilian institutionalized elderly individuals.

PubMed

de Oliveira, Simone Camargo; Pavarini, Sofia Cristina Iost; Orlandi, Fabiana de Souza; de Mendiondo, Marisa Silvana Zazzeta

2014-01-01

This study presents an analysis of a potential association between family functionality and the variables of gender, length of institutionalization, family composition, depressive symptoms, and cognitive disorders in elderly individuals living in Long-Term Care Facilities (LTCF) in a city in the interior of São Paulo, Brazil. This is a quantitative, cross-sectional study with a descriptive-correlational design. A total of 107 institutionalized elderly individuals were interviewed. Data were analyzed through raw and adjusted Logistic Regression. The results indicate that most elderly individuals experience family dysfunction, 57% present a high level of family dysfunction, 21% present moderate family dysfunction and 22% present good family functionality. There was a statistical association between the Family APGAR and the variables of length of institutionalization, depressive symptoms, family composition and cognitive disorders. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

A prospective controlled investigation of the cognitive effects of amateur boxing.

PubMed Central

Butler, R J; Forsythe, W I; Beverly, D W; Adams, L M

1993-01-01

Eighty six amateur boxers underwent a series of neuropsychological assessments on three occasions--pre bout, immediate post bout and follow up within two years; 31 water polo players and 47 rugby union players acted as controls. The neuropsychological tests were selected as being sensitive to subtle cognitive dysfunction and formed part of a battery of other neurological and ophthalmic assessments. No evidence of neuropsychological dysfunction due to boxing was found, either following a bout or a series of bouts at follow up. None of a range of parameters including number of previous contests, recovery from an earlier bout, number of head blows received during a bout and number of bouts between initial assessment and follow up, were found to be related to changes in cognitive functioning. PMID:8410002

Brain Fog

MedlinePlus

... Always report changes in cognition/memory and mood (depression, anxiety). • Make sure your physician knows about all the prescription and OTC medications you are taking. Especially in patients over 65-70 years of age, a major cause of cognitive dysfunction can be side effects of ...

Understanding Dysfunctional and Functional Family Behaviors for the At-Risk Adolescent.

ERIC Educational Resources Information Center

Martin, Don; Martin, Maggie

2000-01-01

At-risk adolescents and their impact on families and society, as well as characteristics of both healthy and maladaptive families, are discussed. Cognitive distortions of dysfunctional adolescents and their effect on family members, along with methods for intervention and creating more healthy environments, are delineated from a systemic…

Environmental enteric dysfunction and growth failure/stunting in global child health

USDA-ARS?s Scientific Manuscript database

Approximately 25% of the world's children aged <5 years have stunted growth, which is associated with increased mortality, cognitive dysfunction, and loss of productivity. Reducing by 40% the number of stunted children is a global target for 2030. The pathogenesis of stunting is poorly understood. P...

Adaptive Inferential Feedback Partner Training for Depression: A Pilot Study

ERIC Educational Resources Information Center

Dobkin, Roseanne DeFronzo; Allen, Lesley A.; Alloy, Lauren B.; Menza, Matthew; Gara, Michael A.; Panzarella, Catherine

2007-01-01

Adaptive inferential feedback (AIF) partner training is a cognitive technique that teaches the friends and family members of depressed patients to respond to the patients' dysfunctional thoughts in a targeted manner. These dysfunctional attributions, which AIF addresses, are a common residual feature of depression amongst remitted patients, and…

Selective decline of neurotrophin and neurotrophin receptor genes within CA1 pyramidal neurons and hippocampus proper: Correlation with cognitive performance and neuropathology in mild cognitive impairment and Alzheimer's disease.

PubMed

Ginsberg, Stephen D; Malek-Ahmadi, Michael H; Alldred, Melissa J; Che, Shaoli; Elarova, Irina; Chen, Yinghua; Jeanneteau, Freddy; Kranz, Thorsten M; Chao, Moses V; Counts, Scott E; Mufson, Elliott J

2017-09-09

Hippocampal CA1 pyramidal neurons, a major component of the medial temporal lobe memory circuit, are selectively vulnerable during the progression of Alzheimer's disease (AD). The cellular mechanism(s) underlying degeneration of these neurons and the relationship to cognitive performance remains largely undefined. Here, we profiled neurotrophin and neurotrophin receptor gene expression within microdissected CA1 neurons along with regional hippocampal dissections from subjects who died with a clinical diagnosis of no cognitive impairment (NCI), mild cognitive impairment (MCI), or AD using laser capture microdissection (LCM), custom-designed microarray analysis, and qPCR of CA1 subregional dissections. Gene expression levels were correlated with cognitive test scores and AD neuropathology criteria. We found a significant downregulation of several neurotrophin genes (e.g., Gdnf, Ngfb, and Ntf4) in CA1 pyramidal neurons in MCI compared to NCI and AD subjects. In addition, the neurotrophin receptor transcripts TrkB and TrkC were decreased in MCI and AD compared to NCI. Regional hippocampal dissections also revealed select neurotrophic gene dysfunction providing evidence for vulnerability within the hippocampus proper during the progression of dementia. Downregulation of several neurotrophins of the NGF family and cognate neurotrophin receptor (TrkA, TrkB, and TrkC) genes correlated with antemortem cognitive measures including the Mini-Mental State Exam (MMSE), a composite global cognitive score (GCS), and Episodic, Semantic, and Working Memory, Perceptual Speed, and Visuospatial domains. Significant correlations were found between select neurotrophic expression downregulation and neuritic plaques (NPs) and neurofibrillary tangles (NFTs), but not diffuse plaques (DPs). These data suggest that dysfunction of neurotrophin signaling complexes have profound negative sequelae within vulnerable hippocampal cell types, which play a role in mnemonic and executive dysfunction during the progression of AD. © 2017 Wiley Periodicals, Inc.

Impaired affective and cognitive theory of mind and behavioural change in amyotrophic lateral sclerosis.

PubMed

van der Hulst, Egberdina-Józefa; Bak, Thomas H; Abrahams, Sharon

2015-11-01

Executive and behavioural changes are well-recognised in classical amyotrophic lateral sclerosis (ALS), indicating a subclinical behavioural-variant frontotemporal dementia (bvFTD) in some patients. Social cognitive deficits in ALS have been recently described and an impairment was identified on a simple Theory of Mind (ToM) test, which assesses the judgement of the preference of another through direction of eye gaze. The present study further delineated this deficit, by distinguishing between Affective and Cognitive subcomponents, and determining the relationship to behavioural change, levels of empathy and self-awareness. The Cognitive-Affective Judgement of Preference Test was administered to 33 patients with ALS and 26 controls. Furthermore, a comprehensive neuropsychological battery and detailed behavioural assessment, with measures of empathy and awareness, were included. Patients with ALS showed a significant impairment in Affective ToM only when compared with healthy controls, with a deficit in 36% of patients; 12% showed an isolated Affective ToM deficit while 24% showed more generic ToM dysfunction. A Cognitive ToM deficit was found in 27% of patients, with 3% showing an isolated Cognitive ToM deficit. The patients with ALS showed reduced empathy (Fantasy scale) and increased behavioural dysfunction with high levels of apathy. In addition, patients with either an Affective and/or Cognitive ToM deficit exhibited poor self-awareness of their performance and abnormalities on verbal fluency, while those with an Affective ToM deficit also displayed higher levels of apathy and a naming deficit. Dysfunctional ToM is a prominent feature of the cognitive profile of ALS. This specific difficulty in identifying and distinguishing the feelings and thoughts of another from a self-perspective may underpin the social behavioural abnormalities present in some patients with ALS, manifest as apathy and loss of awareness. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Diffusion-Tensor Imaging Findings and Cognitive Function Following Hospitalized Mixed-Mechanism Mild Traumatic Brain Injury: A Systematic Review and Meta-Analysis.

PubMed

Oehr, Lucy; Anderson, Jacqueline

2017-11-01

To undertake a systematic review and meta-analysis of the relationship between microstructural damage and cognitive function after hospitalized mixed-mechanism (HMM) mild traumatic brain injury (mTBI). PsycInfo, EMBASE, and MEDLINE were used to find relevant empirical articles published between January 2002 and January 2016. Studies that examined the specific relationship between diffusion tensor imaging (DTI) and cognitive test performance were included. The final sample comprised previously medically and psychiatrically healthy adults with HMM mTBI. Specific data were extracted including mTBI definitional criteria, descriptive statistics, outcome measures, and specific results of associations between DTI metrics and cognitive test performance. Of the 248 original articles retrieved and reviewed, 8 studies met all inclusion criteria and were included in the meta-analysis. The meta-analysis revealed statistically significant associations between reduced white matter integrity and poor performance on measures of attention (fractional anisotropy [FA]: d=.413, P<.001; mean diffusivity [MD]: d=-.407, P=.001), memory (FA: d=.347, P<.001; MD: d=-.568, P<.001), and executive function (FA: d=.246, P<.05), which persisted beyond 1 month postinjury. The findings from the meta-analysis provide clear support for an association between in vivo markers of underlying neuropathology and cognitive function after mTBI. Furthermore, these results demonstrate clearly for the first time that in vivo markers of structural neuropathology are associated with cognitive dysfunction within the domains of attention, memory, and executive function. These findings provide an avenue for future research to examine the causal relationship between mTBI-related neuropathology and cognitive dysfunction. Furthermore, they have important implications for clinical management of patients with mTBI because they provide a more comprehensive understanding of factors that are associated with cognitive dysfunction after mTBI. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Prevalence and Pattern of Executive Dysfunction in School Age Children with Congenital Heart Disease

PubMed Central

Sanz, Jacqueline H.; Berl, Madison M.; Armour, Anna C.; Wang, Jichuan; Cheng, Yao I.; Donofrio, Mary T.

2016-01-01

Objective Executive Function, a set of cognitive skills important to social and academic outcomes, is a specific area of cognitive weakness in children with congenital heart disease (CHD). We evaluated the prevalence and profile of executive dysfunction in a heterogeneous sample of school aged children with CHD, examined whether children with executive dysfunction are receiving school services and support, and identified risk factors for executive dysfunction at school age. Design 91 school aged patients completed questionnaires, including the Behavior Rating Inventory of Executive Function (BRIEF) and a medical history questionnaire. An age and gender matched control sample was drawn from a normativedatabase. Results CHD patients had a higher rate of parent reported executive dysfunction (OR=4.37, p<0.0001), especially for working memory (OR=8.22, p<0.0001) and flexibility (OR=8.05, p<0.0001). Those with executive dysfunction were not more likely to be receiving school services (p>0.05). Gender, premature birth (≤37 weeks), and CHD with aortic obstruction were predictive of executive dysfunction, especially for behavior regulation skills. Conclusions School aged children with CHD have an increased prevalence of executive dysfunction, especially problems with working memory and flexibility, and are underserved by the school system. The increased risk for executive dysfunction in those with CHD and prematurity or CHD with aortic obstruction suggests an etiology of delayed brain development in the fetal and neonatal periods, while male gender may increase susceptibility to brain injury. This study highlights the need for regular neurodevelopmental follow up in children with CHD, and a need to better understand mechanisms that contribute to adverse neurodevelopmental outcomes. PMID:27863079

Prevalence and pattern of executive dysfunction in school age children with congenital heart disease.

PubMed

Sanz, Jacqueline H; Berl, Madison M; Armour, Anna C; Wang, Jichuan; Cheng, Yao I; Donofrio, Mary T

2017-03-01

Executive function, a set of cognitive skills important to social and academic outcomes, is a specific area of cognitive weakness in children with congenital heart disease (CHD). We evaluated the prevalence and profile of executive dysfunction in a heterogeneous sample of school aged children with CHD, examined whether children with executive dysfunction are receiving school services and support, and identified risk factors for executive dysfunction at school age. Ninety-one school aged patients completed questionnaires, including the Behavior Rating Inventory of Executive Function (BRIEF) and a medical history questionnaire. An age- and gender- matched control sample was drawn from a normative database. Children with CHD had a higher rate of parent reported executive dysfunction (OR = 4.37, P < .0001), especially for working memory (OR = 8.22, P < .0001) and flexibility (OR = 8.05, P < .0001). Those with executive dysfunction were not more likely to be receiving school services (P > .05). Gender, premature birth (≤37 weeks), and CHD with aortic obstruction were predictive of executive dysfunction, especially for behavior regulation skills. School aged children with CHD have an increased prevalence of executive dysfunction, especially problems with working memory and flexibility, and are underserved by the school system. The increased risk for executive dysfunction in those with CHD and prematurity or CHD with aortic obstruction suggests an etiology of delayed brain development in the fetal and neonatal periods, while male gender may increase susceptibility to brain injury. This study highlights the need for regular neurodevelopmental follow up in children with CHD, and a need to better understand mechanisms that contribute to adverse neurodevelopmental outcomes. © 2016 Wiley Periodicals, Inc.

Functional brain imaging of cognitive dysfunction in Parkinson's disease.

PubMed

Hirano, Shigeki; Shinotoh, Hitoshi; Eidelberg, David

2012-10-01

Multiple factors are involved in the development of cognitive impairment in Parkinson's disease (PD) and related disorders. Notably, several underlying factors, such as monoaminergic dysfunction, Lewy body pathology, Alzheimer disease-like pathology and cerebrovascular disease are implied in the PD pathophysiology of cognitive impairment. The mesocortical dopaminergic system is associated with executive functions which are frequently affected in PD and are influenced by local levodopa concentration, dopamine metabolism and baseline performance status. The ventral striatum and frontal cortex are associated with impulse control disorders reported in PD patients treated with dopamine replacement therapy. Cholinergic impairment in PD plays a cardinal role in the development of dementia. Acetylcholinesterase positron emission tomography demonstrates that posterior brain areas are related to cognitive decline in PD patients. Amyloid radiotracer illustrates that patients with PD with severe cognitive impairment were prone to accompanied cortical amyloid deposition. Metabolism/perfusion change associated with cognitive impairment in PD, so-called PD related cognitive pattern, is characterised by reduced frontoparietal activity and is an effective way to differentiate and monitor cognitive function of individual PD patients. Cognitive impairment in PD cannot be explained by a single mechanism and is entangled by multiple factors. Imaging studies can unravel each pathological domain, further shed light on the interrelation between different pathomechanisms, not only in PD but also in other dementia related disorders, and thereby integrate its interpretation to apply to therapeutics in individual patients.

Burden of Systolic and Diastolic Left Ventricular Dysfunction among Hispanics in the United States: Insights from the Echocardiographic Study of Latinos (ECHO-SOL)

PubMed Central

Mehta, Hardik; Armstrong, Anderson; Swett, Katrina; Shah, Sanjiv J.; Allison, Matthew A.; Hurwitz, Barry; Bangdiwala, Shrikant; Dadhania, Rupal; Kitzman, Dalane W.; Arguelles, William; Lima, Joao; Youngblood, Marston; Schneiderman, Neil; Daviglus, Martha L.; Spevack, Daniel; Talavera, Greg A.; Raisinghani, Ajit; Kaplan, Robert; Rodriguez, Carlos J.

2016-01-01

Background Population-based estimates of cardiac dysfunction and clinical heart failure (HF) remain undefined among Hispanics/Latino adults. Methods and Results Participants of Hispanic/Latino origin across the US, aged 45–74 years were enrolled into the Echocardiographic Study of Latinos (ECHO-SOL) and underwent a comprehensive echocardiography exam to define left ventricular systolic dysfunction (LVSD) and left ventricular diastolic dysfunction (LVDD). Clinical HF was defined according to self-report; and those with cardiac dysfunction but without clinical HF were characterized as having subclinical or unrecognized cardiac dysfunction. Of 1,818 ECHO-SOL participants (mean age 56.4 years; 42.6% male) , 49.7% had LVSD and/or LVDD. LVSD prevalence was 3.6%, while LVDD was detected in 50.3%. Participants with LVSD were more likely to be males and current smokers (all p<0.05). Female sex, hypertension, diabetes, higher body-mass index and renal dysfunction were more common among those with LVDD (all p<0.05). In age-sex adjusted models, individuals of Central American and Cuban backgrounds were almost two-fold more likely to have LVDD compared to those of Mexican backgrounds. Prevalence of clinical HF with LVSD (HF with reduced EF) was 7.3%; prevalence of clinical HF with LVDD (HF with preserved EF) was 3.6%. 96.1% of the cardiac dysfunction seen was subclinical or unrecognized. Compared to those with clinical cardiac dysfunction, prevalent coronary heart disease was the only factor independently associated with subclinical or unrecognized cardiac dysfunction (odds ratio: 0.1; 95% confidence interval: 0.1–0.4). Conclusions Among Hispanics/Latinos, most cardiac dysfunction is subclinical or unrecognized, with a high prevalence of diastolic dysfunction. This identifies a high-risk population for the development of clinical HF. PMID:27048764

The effects of participation in leisure activities on neuropsychiatric symptoms of persons with cognitive impairment: a cross-sectional study.

PubMed

Chiu, Yi-Chen; Huang, Chien-Ying; Kolanowski, Ann M; Huang, Hsiu-Li; Shyu, Yeaing Lotus; Lee, Shu-Hwa; Lin, Ching-Rong; Hsu, Wen-Chuin

2013-10-01

People with cognitive impairment have been shown to engage in few structured activities. During periods of unoccupied time or boredom, these patients most likely manifest neuropsychiatric symptoms. The purposes of this study were to (1) describe the leisure-activity indicators (variety in leisure activities, appraisal of each activity's restorative function, and leisure dysfunction, i.e. failure to appreciate the importance of restorative aspects of leisure activity), of community-dwelling older Taiwanese adults with cognitive impairment, and (2) explore the relationships between these indicators and neuropsychiatric symptoms in this population. Cross-sectional. Memory disorder and geriatric psychiatric clinics of two hospitals in northern Taiwan. Patient-family caregiver dyads (N=60). Patients' dementia severity, based on Clinical Dementia Rating scores, was 0.5-2.0. Family caregivers completed the Chinese Neuropsychiatric Inventory to assess patients' behavioral problems and the Restorative Activity Questionnaire to assess patients' participation in leisure activities, restorative experience, and leisure dysfunction. On average, patients participated in approximately five individual leisure activities, but very few group leisure activities. The top three leisure activities were watching TV, taking a walk, and talking to relatives and friends. The leisure activities in which participants least commonly engaged were fishing, attending cultural exhibitions, and chess/card playing. All leisure-activity indicators were significantly correlated with disease stage, global cognitive function, and neuropsychiatric symptoms. Two leisure-activity indicators (leisure dysfunction and restorative experiences) were significantly correlated with depressive symptoms. Only leisure dysfunction significantly and consistently predicted neuropsychiatric symptoms. These results can be used by home health or community health nurses to design tailored leisure-activity plans for improving the care quality of patients with cognitive impairment. Health professionals can develop leisure-education programmes to emphasize the value of leisure pursuit and to modify attitudes toward participating in leisure activities. Finally, parks and recreational agencies may re-examine their services and facilities to meet the increasing needs of this population. Copyright © 2013 Elsevier Ltd. All rights reserved.

Objective measurement of daytime napping, cognitive dysfunction and subjective sleepiness in Parkinson's disease.

PubMed

Bolitho, Samuel J; Naismith, Sharon L; Salahuddin, Pierre; Terpening, Zoe; Grunstein, Ron R; Lewis, Simon J G

2013-01-01

Sleep-wake disturbances and concomitant cognitive dysfunction in Parkinson's disease (PD) contribute significantly to morbidity in patients and their carers. Subjectively reported daytime sleep disturbance is observed in over half of all patients with PD and has been linked to executive cognitive dysfunction. The current study used daytime actigraphy, a novel objective measure of napping and related this to neuropsychological performance in a sample of PD patients and healthy, age and gender-matched controls. Furthermore this study aimed to identify patients with PD who may benefit from pharmacologic and behavioural intervention to improve these symptoms. Eighty-five PD patients and 21 healthy, age-matched controls completed 14 days of wrist actigraphy within two weeks of neuropsychological testing. Objective napping measures were derived from actigraphy using a standardised protocol and subjective daytime sleepiness was recorded by the previously validated Epworth Sleepiness Scale. Patients with PD had a 225% increase in the mean nap time per day (minutes) as recorded by actigraphy compared to age matched controls (39.2 ± 35.2 vs. 11.5 ± 11.0 minutes respectively, p < 0.001). Significantly, differences in napping duration between patients, as recorded by actigraphy were not distinguished by their ratings on the subjective measurement of excessive daytime sleepiness. Finally, those patients with excessive daytime napping showed greater cognitive deficits in the domains of attention, semantic verbal fluency and processing speed. This study confirms increased levels of napping in PD, a finding that is concordant with subjective reports. However, subjective self-report measures of excessive daytime sleepiness do not robustly identify excessive napping in PD. Fronto-subcortical cognitive dysfunction was observed in those patients who napped excessively. Furthermore, this study suggests that daytime actigraphy, a non-invasive and inexpensive objective measure of daytime sleep, can identify patients with PD who may benefit from pharmacologic and behavioural interventions to improve these symptoms.

Objective Measurement of Daytime Napping, Cognitive Dysfunction and Subjective Sleepiness in Parkinson’s Disease

PubMed Central

Bolitho, Samuel J.; Naismith, Sharon L.; Salahuddin, Pierre; Terpening, Zoe; Grunstein, Ron R.; Lewis, Simon J. G.

2013-01-01

Introduction Sleep-wake disturbances and concomitant cognitive dysfunction in Parkinson’s disease (PD) contribute significantly to morbidity in patients and their carers. Subjectively reported daytime sleep disturbance is observed in over half of all patients with PD and has been linked to executive cognitive dysfunction. The current study used daytime actigraphy, a novel objective measure of napping and related this to neuropsychological performance in a sample of PD patients and healthy, age and gender-matched controls. Furthermore this study aimed to identify patients with PD who may benefit from pharmacologic and behavioural intervention to improve these symptoms. Methods Eighty-five PD patients and 21 healthy, age-matched controls completed 14 days of wrist actigraphy within two weeks of neuropsychological testing. Objective napping measures were derived from actigraphy using a standardised protocol and subjective daytime sleepiness was recorded by the previously validated Epworth Sleepiness Scale. Results Patients with PD had a 225% increase in the mean nap time per day (minutes) as recorded by actigraphy compared to age matched controls (39.2 ± 35.2 vs. 11.5 ± 11.0 minutes respectively, p < 0.001). Significantly, differences in napping duration between patients, as recorded by actigraphy were not distinguished by their ratings on the subjective measurement of excessive daytime sleepiness. Finally, those patients with excessive daytime napping showed greater cognitive deficits in the domains of attention, semantic verbal fluency and processing speed. Conclusion This study confirms increased levels of napping in PD, a finding that is concordant with subjective reports. However, subjective self-report measures of excessive daytime sleepiness do not robustly identify excessive napping in PD. Fronto-subcortical cognitive dysfunction was observed in those patients who napped excessively. Furthermore, this study suggests that daytime actigraphy, a non-invasive and inexpensive objective measure of daytime sleep, can identify patients with PD who may benefit from pharmacologic and behavioural interventions to improve these symptoms. PMID:24278399

White matter lesions and brain atrophy in systemic lupus erythematosus patients: correlation to cognitive dysfunction in a cohort of systemic lupus erythematosus patients using different definition models for neuropsychiatric systemic lupus erythematosus.

PubMed

Cannerfelt, B; Nystedt, J; Jönsen, A; Lätt, J; van Westen, D; Lilja, A; Bengtsson, A; Nilsson, P; Mårtensson, J; Sundgren, P C

2018-06-01

Aim The aim of this study was to evaluate the extent of white matter lesions, atrophy of the hippocampus and corpus callosum, and their correlation with cognitive dysfunction (CD), in patients diagnosed with systemic lupus erythematosus (SLE). Methods Seventy SLE patients and 25 healthy individuals (HIs) were included in the study. To evaluate the different SLE and neuropsychiatric SLE (NPSLE) definition schemes, patients were grouped both according to the American College of Rheumatology (ACR) definition, as well as the more stringent ACR-Systemic Lupus International Collaborating Clinics definition. Patients and HIs underwent a 3 Tesla brain MRI and a standardized neuropsychological test. MRI data were evaluated for number and volume of white matter lesions and atrophy of the hippocampus and corpus callosum. Differences between groups and subgroups were evaluated for significance. Number and volume of white matter lesions and atrophy of the hippocampus and corpus callosum were correlated to cognitive dysfunction. Results The total volume of white matter lesions was significantly larger in SLE patients compared to HIs ( p = 0.004). However, no significant differences were seen between the different SLE subgroups. Atrophy of the bilateral hippocampus was significantly more pronounced in patients with NPSLE compared to those with non-NPSLE (right: p = 0.010; left p = 0.023). Significant negative correlations between cognitive test scores on verbal memory and number and volume of white matter lesions were present. Conclusion SLE patients have a significantly larger volume of white matter lesions on MRI compared to HIs and the degree of white matter lesion volume correlates to cognitive dysfunction, specifically to verbal memory. No significant differences in the number or volume of white matter lesions were identified between subgroups of SLE patients regardless of the definition model used.

Dysfunctional metacognition and drive for thinness in typical and atypical anorexia nervosa.

PubMed

Davenport, Emily; Rushford, Nola; Soon, Siew; McDermott, Cressida

2015-01-01

Anorexia nervosa is complex and difficult to treat. In cognitive therapies the focus has been on cognitive content rather than process. Process-oriented therapies may modify the higher level cognitive processes of metacognition, reported as dysfunctional in adult anorexia nervosa. Their association with clinical features of anorexia nervosa, however, is unclear. With reclassification of anorexia nervosa by DSM-5 into typical and atypical groups, comparability of metacognition and drive for thinness across groups and relationships within groups is also unclear. Main objectives were to determine whether metacognitive factors differ across typical and atypical anorexia nervosa and a non-clinical community sample, and to explore a process model by determining whether drive for thinness is concurrently predicted by metacognitive factors. Women receiving treatment for anorexia nervosa (n = 119) and non-clinical community participants (n = 100), aged between 18 and 46 years, completed the Eating Disorders Inventory (3(rd) Edition) and Metacognitions Questionnaire (Brief Version). Body Mass Index (BMI) of 18.5 kg/m(2) differentiated between typical (n = 75) and atypical (n = 44) anorexia nervosa. Multivariate analyses of variance and regression analyses were conducted. Metacognitive profiles were similar in both typical and atypical anorexia nervosa and confirmed as more dysfunctional than in the non-clinical group. Drive for thinness was concurrently predicted in the typical patients by the metacognitive factors, positive beliefs about worry, and need to control thoughts; in the atypical patients by negative beliefs about worry and, inversely, by cognitive self-consciousness, and in the non-clinical group by cognitive self-consciousness. Despite having a healthier weight, the atypical group was as severely affected by dysfunctional metacognitions and drive for thinness as the typical group. Because metacognition concurrently predicted drive for thinness in both groups, a role for process-oriented therapy in adults is suggested. Implications are discussed.

Intermittent Fasting Pretreatment Prevents Cognitive Impairment in a Rat Model of Chronic Cerebral Hypoperfusion.

PubMed

Hu, Yuan; Yang, Ying; Zhang, Miao; Deng, Min; Zhang, Jun-Jian

2017-07-01

Background: Whether intermittent fasting (IF) pretreatment can prevent vascular cognitive dysfunction remains unknown to our knowledge. Objective: We investigated the effects and underlying mechanisms of IF pretreatment on cognitive dysfunction in a permanent 2-vessel occlusion (2VO) vascular dementia rat model. Methods: Male Wistar rats weighing 200 g were subjected to either IF or ad libitum feeding for 12 wk before 2VO surgery. Rats in the IF protocol underwent alternative-day feed deprivation (FD). Memory of the animals was assessed by using the Morris water maze (MWM) and the novel object recognition (NOR) test 6 wk after the surgery. After behavioral testing, malondialdehyde and glutathione concentrations, superoxide dismutase (SOD) activity, gene expression of antioxidative enzymes, inflammatory protein concentrations, and microglia density were determined in the hippocampus of rats. Results: 2-vessel occlusion operation ad libitum (2VO-AL) rats had significantly longer escape latencies on day 4 of the training phase and spent a lower percentage of time in the target quadrant (25% compared with 38% and 41%) in the MWM, and had lower discrimination ratios (47% compared with 65% and 67%) in the NOR test than 2-vessel operation and alternate-day feed deprivation (2VO-FD) and sham operation ad libitum (Sham-AL) rats, respectively ( P < 0.05). This indicates that IF helps to prevent vascular cognitive deficits. 2VO-AL rats also had higher malondialdehyde (3.54 compared with 2.15 and 1.66 nmol/mg protein) and lower glutathione concentrations (53.25 compared with 66.41 and 91.71 nmol/mg protein), lower SOD activity (100.1 compared with 133.3 and 138.5 U/mg protein), lower gene expression of antioxidative enzymes, higher expression of inflammatory proteins, and higher microglia density in the hippocampus than 2VO-FD and Sham-AL rats, respectively ( P < 0.05). This suggests that IF has antioxidative and anti-inflammatory effects. Conclusions: IF pretreatment provided sustained neuroprotection in a rat model of vascular dementia. These effects were associated with reduced oxidative stress and neuroinflammation. © 2017 American Society for Nutrition.

70. Cortisol Response to Psychosocial Stress and Working Memory Performance in Schizophrenia

PubMed Central

Reed, Alexandra; Lake, Jessica; Hamilton, Holly; Bachman, Peter; Clayson, Peter; Miller, Gregory; Subotnik, Kenneth; Nuechterlein, Keith; Yee, Cindy

2017-01-01

Abstract Background: Working memory (WM) deficits are part of the constellation of cognitive impairments associated with schizophrenia (SZ). Although WM efficiency may be especially important for patients functioning within academic and employment settings, much of the research on WM in SZ neglects the social context of cognitive performance and fails to consider the extent to which stress may contribute to cognitive dysfunction. This is a crucial oversight considering growing evidence that high levels of cortisol disrupt WM in healthy individuals. Stress may be especially detrimental to cognitive functions in patients who often demonstrate HPA dysregulation including high basal cortisol and attenuated cortisol responses to acute stressors. Methods: The present study examined effects of a laboratory psychosocial stress task, the Trier Social Stress Test (TSST), on WM performance in patients with SZ (n = 87) and healthy comparison subjects (HCs; n = 68). Each participant completed an n-back task before and after the TSST. Salivary cortisol samples collected at baseline, post-TSST, and recovery were available from participants with chronic SZ (n = 23, mean illness duration = 11.21, SD = 6.79 years), first-episode SZ (n = 43, mean illness duration = 0.78, SD = 0.85 years), and HCs (n = 51). Results: As predicted, the TSST disrupted performance accuracy during the WM task, but only in SZ. Post-TSST cortisol levels were positively correlated with sensitivity to detect match trials and overall accuracy on n-back performance in chronic patients but not in first episode patients or in healthy participants. Total cortisol response in chronic patients, summarized as area under the curve, accounted for approximately 26% of the variance in WM accuracy after stress. Conclusion: Results replicate findings of blunted cortisol reactivity in SZ and extend prior work by connecting cortisol stress response to specific changes in WM performance in a chronic sample. Findings are consistent with the hypothesis that flexible HPA functioning may moderate WM dysfunction in chronic SZ.

Biomarkers Associated with Cognitive Impairment in Treated Cancer Patients: Potential Predisposition and Risk Factors

PubMed Central

Castel, Hélène; Denouel, Angeline; Lange, Marie; Tonon, Marie-Christine; Dubois, Martine; Joly, Florence

2017-01-01

Purpose: Cognitive impairment in cancer patients induced, at least in part, by treatment are frequently observed and likely have negative impacts on patient quality of life. Such cognitive dysfunctions can affect attention, executive functions, and memory and processing speed, can persist after treatment, and their exact causes remain unclear. The aim of this review was to create an inventory and analysis of clinical studies evaluating biological markers and risk factors for cognitive decline in cancer patients before, during, or after therapy. The ultimate objectives were to identify robust markers and to determine what further research is required to develop original biological markers to enable prevention or adapted treatment management of patients at risk. Method: This review was guided by the PRISMA statement and included a search strategy focused on three components: “cognition disorders,” “predictive factors”/“biological markers,” and “neoplasms,” searched in PubMed since 2005, with exclusion criteria concerning brain tumors, brain therapy, and imaging or animal studies. Results: Twenty-three studies meeting the criteria were analyzed. Potential associations/correlations were identified between cognitive impairments and specific circulating factors, cerebral spinal fluid constituents, and genetic polymorphisms at baseline, during, and at the end of treatment in cancer populations. The most significant results were associations between cognitive dysfunctions and genetic polymorphisms, including APOE-4 and COMT-Val; increased plasma levels of the pro-inflammatory cytokine, IL-6; anemia; and hemoglobin levels during chemotherapy. Plasma levels of specific hormones of the hypothalamo-pituitary-adrenal axis are also modified by treatment. Discussion: It is recognized in the field of cancer cognition that cancer and comorbidities, as well as chemotherapy and hormone therapy, can cause persistent cognitive dysfunction. A number of biological circulating factors and genetic polymorphisms, can predispose to the development of cognitive disorders. However, many predictive factors remain unproven and discordant findings are frequently reported, warranting additional clinical and preclinical longitudinal cohort studies, with goals of better characterization of potential biomarkers and identification of patient populations at risk and/or particularly deleterious treatments. Research should focus on prevention and personalized cancer management, to improve the daily lives, autonomy, and return to work of patients. PMID:28377717

Cognitive Contributions to Freezing of Gait in Parkinson Disease: Implications for Physical Rehabilitation

PubMed Central

King, Laurie A.; Cohen, Rajal G.; Horak, Fay B.

2016-01-01

People with Parkinson disease (PD) who show freezing of gait also have dysfunction in cognitive domains that interact with mobility. Specifically, freezing of gait is associated with executive dysfunction involving response inhibition, divided attention or switching attention, and visuospatial function. The neural control impairments leading to freezing of gait have recently been attributed to higher-level, executive and attentional cortical processes involved in coordinating posture and gait rather than to lower-level, sensorimotor impairments. To date, rehabilitation for freezing of gait primarily has focused on compensatory mobility training to overcome freezing events, such as sensory cueing and voluntary step planning. Recently, a few interventions have focused on restitutive, rather than compensatory, therapy. Given the documented impairments in executive function specific to patients with PD who freeze and increasing evidence of overlap between cognitive and motor function, incorporating cognitive challenges with mobility training may have important benefits for patients with freezing of gait. Thus, a novel theoretical framework is proposed for exercise interventions that jointly address both the specific cognitive and mobility challenges of people with PD who freeze. PMID:26381808

Cognitive Contributions to Freezing of Gait in Parkinson Disease: Implications for Physical Rehabilitation.

PubMed

Peterson, Daniel S; King, Laurie A; Cohen, Rajal G; Horak, Fay B

2016-05-01

People with Parkinson disease (PD) who show freezing of gait also have dysfunction in cognitive domains that interact with mobility. Specifically, freezing of gait is associated with executive dysfunction involving response inhibition, divided attention or switching attention, and visuospatial function. The neural control impairments leading to freezing of gait have recently been attributed to higher-level, executive and attentional cortical processes involved in coordinating posture and gait rather than to lower-level, sensorimotor impairments. To date, rehabilitation for freezing of gait primarily has focused on compensatory mobility training to overcome freezing events, such as sensory cueing and voluntary step planning. Recently, a few interventions have focused on restitutive, rather than compensatory, therapy. Given the documented impairments in executive function specific to patients with PD who freeze and increasing evidence of overlap between cognitive and motor function, incorporating cognitive challenges with mobility training may have important benefits for patients with freezing of gait. Thus, a novel theoretical framework is proposed for exercise interventions that jointly address both the specific cognitive and mobility challenges of people with PD who freeze. © 2016 American Physical Therapy Association.

Cognitive control dysfunction in workers exposed to manganese-containing welding fume.

PubMed

Al-Lozi, Amal; Nielsen, Susan Searles; Hershey, Tamara; Birke, Angela; Checkoway, Harvey; Criswell, Susan R; Racette, Brad A

2017-02-01

Chronic exposure to manganese (Mn) is a health concern in occupations such as welding because of well-established motor effects due to basal ganglia dysfunction. We hypothesized that cognitive control (the ability to monitor, manipulate, and regulate ongoing cognitive demands) would also be affected by chronic Mn exposure. We examined the relationship between Mn exposure and cognitive control performance in 95 workers with varying intensity and duration (median 15.5 years) of exposure to welding fume. We performed linear regression to assess the association between exposure to Mn-containing welding fume and cognitive control tasks. Overall performance was inversely related to intensity of welding exposure (P = 0.009) and was driven by the Two-Back and Letter Number Sequencing tests that assess working memory (both P = 0.02). Occupational exposure to Mn-containing welding fume may be associated with poorer working memory performance, and workers may benefit from practices that reduce exposure intensity. Am. J. Ind. Med. 60:181-188, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Neuropsychological study of amyotrophic lateral sclerosis and parkinsonism-dementia complex in Kii peninsula, Japan

PubMed Central

2014-01-01

Background The Kii peninsula of Japan is one of the foci of amyotrophic lateral sclerosis and parkinsonism-dementia complex (ALS/PDC) in the world. The purpose of this study is to clarify the neuropsychological features of the patients with ALS/PDC of the Kii peninsula (Kii ALS/PDC). Methods The medical interview was done on 13 patients with Kii ALS/PDC, 12 patients with Alzheimer’s disease, 10 patients with progressive supranuclear palsy, 10 patients with frontotemporal lobar degeneration and 10 patients with dementia with Lewy bodies. These patients and their carer/spouse were asked to report any history of abulia-apathy, hallucination, personality change and other variety of symptoms. Patients also underwent brain magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT), and neuropsychological tests comprising the Mini Mental State Examination, Raven’s Colored Progressive Matrices, verbal fluency, and Paired-Associate Word Learning Test and some of them were assessed with the Frontal Assessment Battery (FAB). Results All patients with Kii ALS/PDC had cognitive dysfunction including abulia-apathy, bradyphrenia, hallucination, decrease of extraversion, disorientation, and delayed reaction time. Brain MRI showed atrophy of the frontal and/or temporal lobes, and SPECT revealed a decrease in cerebral blood flow of the frontal and/or temporal lobes in all patients with Kii ALS/PDC. Disorientation, difficulty in word recall, delayed reaction time, and low FAB score were recognized in Kii ALS/PDC patients with cognitive dysfunction. Conclusions The core neuropsychological features of the patients with Kii ALS/PDC were characterized by marked abulia-apathy, bradyphrenia, and hallucination. PMID:25041813

Predictors of functional dependency after stroke in Nigeria.

PubMed

Ojagbemi, Akin; Owolabi, Mayowa

2013-11-01

The factors impacting poststroke functional dependency have not been adequately explored in sub-Saharan Africa. This study examined the risk factors for functional dependency in a group of Nigerian African stroke survivors. One hundred twenty-eight stroke survivors attending a tertiary general hospital in southwestern Nigeria were consecutively recruited and assessed for functional dependency using the modified Rankin Scale (mRS). Stroke was diagnosed according to the World Health Organization criteria. Candidate independent variables assessed included the demographic and clinical characteristics of survivors, cognitive dysfunction, and a diagnosis of major depressive disorder. Variables with significant relationship to functional dependency were entered into a logistic regression model to identify factors that were predictive of functional dependency among the stroke survivors. In all, 60.9% of the stroke survivors were functionally dependent (mRS scores≥3), with mean±SD mRS scores of 2.71±1.01. Female sex (P=.003; odds ratio [OR] 3.08; 95% confidence interval [CI] 1.47-6.44), global cognitive dysfunction (P=.002; OR 5.04; 95% CI 1.79-14.16), and major depressive disorder (P<.0001; OR 3.06; 95% CI 1.92-4.87) were strongly associated with functional dependency in univariate analysis. Major depressive disorder was an independent predictor of functional dependency in multivariate analysis (P<.0001; OR 6.89; 95% CI 2.55-18.6; R2=0.19). Depression, female sex, and cognitive dysfunction were strongly associated with poorer functioning after stroke. Interventions aimed at depression and cognitive dysfunction after stroke may improve functional independence in stroke survivors. Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Ketamine Corrects Stress-Induced Cognitive Dysfunction through JAK2/STAT3 Signaling in the Orbitofrontal Cortex

PubMed Central

Patton, Michael S; Lodge, Daniel J; Morilak, David A; Girotti, Milena

2017-01-01

Deficits in cognitive flexibility are prominent in stress-related psychiatric disorders, including depression. Ketamine has rapid antidepressant efficacy, but it is unknown if ketamine improves cognitive symptoms. In rats, 2 weeks chronic intermittent cold (CIC) stress impairs reversal learning, a form of cognitive flexibility mediated by the orbitofrontal cortex (OFC) that we have used previously to model cognitive dysfunction in depression. We have shown that activating JAK2/STAT3 signaling in the OFC rescued the CIC stress-induced reversal learning deficit. Thus, in the present study we determined whether ketamine also corrects the stress-induced reversal learning deficit, and if JAK2/STAT3 signaling is involved in this effect. A single injection of ketamine (10 mg/kg, i.p.) 24 h prior to testing rescued the CIC stress-induced reversal learning deficit. CIC stress decreased JAK2 phosphorylation in the OFC, and ketamine restored pJAK2 levels within 2 h post injection. The JAK2 inhibitor AG490 given systemically or into the OFC at the time of ketamine injection prevented its beneficial effect on reversal learning. We then tested the role of JAK2/STAT3 in ketamine-induced plasticity in the OFC. Ketamine depressed local field potentials evoked in the OFC by excitatory thalamic afferent stimulation, and this was prevented by JAK2 inhibition in the OFC. Further, in both the OFC and primary cortical neurons in culture, ketamine increased expression of the neural plasticity-related protein Arc, and this was prevented by JAK2 inhibition. These results suggest that the JAK2/STAT3 signaling pathway is a novel mechanism by which ketamine exerts its therapeutic effects on stress-induced cognitive dysfunction in the OFC. PMID:27748739

Cognitive processes and attitudes in bipolar disorder: a study into personality, dysfunctional attitudes and attention bias in patients with bipolar disorder and their relatives.

PubMed

Jabben, Nienke; Arts, Baer; Jongen, Ellen M M; Smulders, Fren T Y; van Os, Jim; Krabbendam, Lydia

2012-12-20

Research in cognitive processes and attitudes in bipolar disorder is scarce and has provided mixed findings, possibly due to differences in current mood state. It is unclear whether alterations in cognitive processes and attitudes are only related to the depressive mood states of bipolar patients or also represent a vulnerability marker for the development of future (depressive) episodes. This was investigated in the current study. Both implicit (attentional bias for emotional words) and explicit (dysfunctional attitudes and personality characteristics) measures of cognitive processes and attitudes were assessed in 77 bipolar patients with varying levels of depressive symptoms (depressed=17, euthymic n=60), their healthy first-degree relatives (n=39) and a healthy control group (n=61). Analyses of variance were used to investigate differences between groups. Mildly depressed patients with bipolar disorder demonstrated an attentional bias away from positive emotional words and showed increased dysfunctional attitudes and higher levels of neuroticism. Euthymic patients were largely comparable to healthy controls and only differed from controls in higher levels of neuroticism. Relatives were similar to controls on all measures, although they significantly differed from bipolar patients in displaying less neuroticism and more extraversion. No firm conclusions regarding causality can be drawn from the associations that were found between cognitive processes and attitudes and the evolution of mood symptoms in bipolar disorder. Alterations in cognitive processes and attitudes in bipolar patients appear to be mostly related to the expression of mood symptomatology rather than to the vulnerability for bipolar disorder. Copyright © 2012 Elsevier B.V. All rights reserved.

Spatial working memory impairment in primary onset middle-age type 2 diabetes mellitus: An ethology and BOLD-fMRI study.

PubMed

Huang, Ran-Ran; Jia, Bao-Hui; Xie, Lei; Ma, Shu-Hua; Yin, Jing-Jing; Sun, Zong-Bo; Le, Hong-Bo; Xu, Wen-Can; Huang, Jin-Zhuang; Luo, Dong-Xue

2016-01-01

To explore mild cognitive dysfunction and/or spatial working memory impairment in patients with primary onset middle-age type 2 diabetes mellitus (T2DM] using ethology (behavior tests) and blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI). Eighteen primary onset T2DM patients and 18 matched subjects with normal blood glucose levels were all tested using the Montreal cognitive assessment scale test, the Wechsler Memory Scale Chinese-revised test, and scanned using BOLD-fMRI (1.5T, EPI sequence) while performing the n-back task to find the activation intensity of some cognition-related areas. The ethology results showed that T2DM patients had a mild cognitive impairment and memory dysfunction (P < 0.05). The fMRI scan identified a neural network consisting of bilateral dorsolateral prefrontal cortex (DLPFC), bilateral premotor area (PreMA), bilateral parietal lobe (PA), and anterior cingulate cortex (ACC) / supplementary motor area (SMA) that was activated during the n-back task, with right hemisphere dominance. However, only the right PA and ACC/SMA showed a load effect via quantitative analysis in the T2DM group; the activation intensity of most working memory-related brain areas for the T2DM group were lower than for the control group under three memory loads. Furthermore, we found that the activation intensity of some cognition-related areas, including the right insular lobe, left caudate nucleus, and bilateral hippocampus/parahippocampal gyrus were lower than the control group under the memory loads. Diabetes-related brain damage of primary onset middle-age T2DM patients with right DLPFC-posterior parietal lobe and parahippocampal gyrus default network causes impairment of spatial working memory and mild cognitive dysfunction. © 2015 Wiley Periodicals, Inc.

Ginsenoside Ameliorates Cognitive Dysfunction in Type 2 Diabetic Goto-Kakizaki Rats.

PubMed

Tian, Zhiyan; Ren, Ning; Wang, Jinghua; Zhang, Danhong; Zhou, Yuying

2018-06-10

BACKGROUND Ginsenoside is the major bioactive component of ginseng, which has been proven to be a neuroprotective drug. The aim of this study was to evaluate the therapeutic effect of ginsenoside in a diabetic Goto-Kakizaki (GK) rat model. MATERIAL AND METHODS Twenty GK rats were randomly divided into a diabetic model (DM) group (n=10) and a ginsenoside + DM group (n=10); Wistar rats with the same age and body weight were used as the control (CON) group (n=10). Food and water intake, body weight, and blood fasting plasma glucose were measured. The Morris water maze test was used to detect learning and memory functions of the rats. Superoxide dismutase (SOD), malondialdehyde (MDA), and inflammatory cytokines (TNF-α, IL-1β, and IL-6) in the hippocampus were analyzed after ginsenoside treatment. RESULTS The blood glucose, body weight, Morris correlation index, SOD, MDA, and other test results were increased in the diabetic rats. Ginsenoside ameliorated diabetic cognitive decline. CONCLUSIONS The possible mechanism was related to inhibiting brain oxidative/nitrosative damage and affecting the expression of the cytokines IL-1β, IL-6, and TNF-α.

Cycle Checkpoint Abnormalities during Dementia: A Plausible Association with the Loss of Protection against Oxidative Stress in Alzheimer’s Disease

PubMed Central

Katsel, Pavel; Tan, Weilun; Fam, Peter; Purohit, Dushyant P.; Haroutunian, Vahram

2013-01-01

Background Increasing evidence suggests an association between neuronal cell cycle (CCL) events and the processes that underlie neurodegeneration in Alzheimer’s disease (AD). Elevated levels of oxidative stress markers and mitochondrial dysfunction are also among early events in AD. Recent studies have reported the role of CCL checkpoint proteins and tumor suppressors, such as ATM and p53 in the control of glycolysis and oxidative metabolism in cancer, but their involvement in AD remains uncertain. Methods and Findings In this postmortem study, we measured gene expression levels of eight CCL checkpoint proteins in the superior temporal cortex (STC) of persons with varying severities of AD dementia and compare them to those of cognitively normal controls. To assess whether the CCL changes associated with cognitive impairment in AD are specific to dementia, gene expression of the same proteins was also measured in STC of persons with schizophrenia (SZ), which is also characterized by mitochondrial dysfunction. The expression of CCL-checkpoint and DNA damage response genes: MDM4, ATM and ATR was strongly upregulated and associated with progression of dementia (cognitive dementia rating, CDR), appearing as early as questionable or mild dementia (CDRs 0.5–1). In addition to gene expression changes, the downstream target of ATM-p53 signaling - TIGAR, a p53-inducible protein, the activation of which can regulate energy metabolism and protect against oxidative stress was progressively decreased as severity of dementia evolved, but it was unaffected in subjects with SZ. In contrast to AD, different CCL checkpoint proteins, which include p53, CHEK1 and BRCA1 were significantly downregulated in SZ. Conclusions These results support the activation of an ATM signaling and DNA damage response network during the progression of AD dementia, while the progressive decrease in the levels of TIGAR suggests loss of protection initiated by ATM-p53 signaling against intensifying oxidative stress in AD. PMID:23861893

Epigenetic determinants of space radiation-induced cognitive dysfunction

PubMed Central

Acharya, Munjal M.; Baddour, Al Anoud D.; Kawashita, Takumi; Allen, Barrett D.; Syage, Amber R.; Nguyen, Thuan H.; Yoon, Nicole; Giedzinski, Erich; Yu, Liping; Parihar, Vipan K.; Baulch, Janet E.

2017-01-01

Among the dangers to astronauts engaging in deep space missions such as a Mars expedition is exposure to radiations that put them at risk for severe cognitive dysfunction. These radiation-induced cognitive impairments are accompanied by functional and structural changes including oxidative stress, neuroinflammation, and degradation of neuronal architecture. The molecular mechanisms that dictate CNS function are multifaceted and it is unclear how irradiation induces persistent alterations in the brain. Among those determinants of cognitive function are neuroepigenetic mechanisms that translate radiation responses into altered gene expression and cellular phenotype. In this study, we have demonstrated a correlation between epigenetic aberrations and adverse effects of space relevant irradiation on cognition. In cognitively impaired irradiated mice we observed increased 5-methylcytosine and 5-hydroxymethylcytosine levels in the hippocampus that coincided with increased levels of the DNA methylating enzymes DNMT3a, TET1 and TET3. By inhibiting methylation using 5-iodotubercidin, we demonstrated amelioration of the epigenetic effects of irradiation. In addition to protecting against those molecular effects of irradiation, 5-iodotubercidin restored behavioral performance to that of unirradiated animals. The findings of this study establish the possibility that neuroepigenetic mechanisms significantly contribute to the functional and structural changes that affect the irradiated brain and cognition. PMID:28220892

Insulin resistance is associated with cognition among HIV-1-infected patients: the Hawaii Aging With HIV cohort.

PubMed

Valcour, Victor G; Sacktor, Ned C; Paul, Robert H; Watters, Michael R; Selnes, Ola A; Shiramizu, Bruce T; Williams, Andrew E; Shikuma, Cecilia M

2006-12-01

To determine if insulin resistance (IR) is associated with lower cognitive performance among HIV-1-infected adults and to determine if advanced age magnifies risk. Cross-sectional analysis within the Hawaii Aging With HIV Cohort. We calculated the homeostasis model assessment of insulin resistance (HOMA-IR) among 145 cohort participants. Values were compared to concurrent neuropsychological test performance and cognitive diagnoses. Hypertension, body mass index (BMI), and non-Caucasian self-identity were directly related to insulin resistance (IR); however, age, CD4 lymphocyte count, and rates of treatment with HAART were not. In logistic regression analyses and stratifying cognition status on a 3-tiered scale (normal, minor cognitive motor disorder (MCMD), and HIV-associated dementia (HAD)), we identified an increased risk of meeting a higher diagnostic category as HOMA-IR increased (OR, 1.12; 95% CI: 1.003 to 1.242 per unit of HOMA-IR, P = 0.044). In linear regression models and among nondiabetic participants, an increasing degree of IR was associated with lower performance on neuropsychological summary scores. IR is associated with cognitive dysfunction in this contemporary HIV-1 cohort enriched with older individuals. Metabolic dysfunction may contribute to the multifactorial pathogenesis of cognitive impairment in the era of HAART.

Amelioration of Metabolic Syndrome-Associated Cognitive Impairments in Mice via a Reduction in Dietary Fat Content or Infusion of Non-Diabetic Plasma

PubMed Central

Johnson, Lance A.; Zuloaga, Kristen L.; Kugelman, Tara L.; Mader, Kevin S.; Morré, Jeff T.; Zuloaga, Damian G.; Weber, Sydney; Marzulla, Tessa; Mulford, Amelia; Button, Dana; Lindner, Jonathan R.; Alkayed, Nabil J.; Stevens, Jan F.; Raber, Jacob

2015-01-01

Obesity, metabolic syndrome (MetS) and type 2 diabetes (T2D) are associated with decreased cognitive function. While weight loss and T2D remission result in improvements in metabolism and vascular function, it is less clear if these benefits extend to cognitive performance. Here, we highlight the malleable nature of MetS-associated cognitive dysfunction using a mouse model of high fat diet (HFD)-induced MetS. While learning and memory was generally unaffected in mice with type 1 diabetes (T1D), multiple cognitive impairments were associated with MetS, including deficits in novel object recognition, cued fear memory, and spatial learning and memory. However, a brief reduction in dietary fat content in chronic HFD-fed mice led to a complete rescue of cognitive function. Cerebral blood volume (CBV), a measure of vascular perfusion, was decreased during MetS, was associated with long term memory, and recovered following the intervention. Finally, repeated infusion of plasma collected from age-matched, low fat diet-fed mice improved memory in HFD mice, and was associated with a distinct metabolic profile. Thus, the cognitive dysfunction accompanying MetS appears to be amenable to treatment, related to cerebrovascular function, and mitigated by systemic factors. PMID:26870815

Bergamot Polyphenolic Fraction Supplementation Improves Cognitive Functioning in Schizophrenia: Data From an 8-Week, Open-Label Pilot Study.

PubMed

Bruno, Antonio; Pandolfo, Gianluca; Crucitti, Manuela; Cedro, Clemente; Zoccali, Rocco Antonio; Muscatello, Maria Rosaria Anna

2017-08-01

Novel treatment strategies for cognitive dysfunctions may prevent long-term disability in patients with schizophrenia, and polyphenolic compounds might be a promising strategy. Bergamot (Citrus bergamia), a citrus fruit characterized by a high amount of flavonoids and flavonoid glycosides, may represent a potential nutraceutical approach to cognitive dysfunction. The present study was aimed to explore the efficacy of bergamot polyphenolic fraction (BPF) supplementation on cognitive/executive functioning in a sample of patients with schizophrenia receiving second-generation antipsychotics. Twenty outpatients treated with second-generation antipsychotics assumed BPF at an oral daily dose of 1000 mg/d for 8 weeks. Brief Psychiatric Rating Scale, Wisconsin Card Sorting Test (WCST), Verbal Fluency Task-Controlled Oral Word Association Test, and Stroop Color-Word Test were administered. At end point, (week 8) BPF supplementation significantly improved WCST "perseverative errors" (P = 0.004) and semantic fluency test (P = 0.004). Moreover, a trend for other cognitive variable (WCST "categories," phonemic fluency, and Stroop Color-Word Test) improvement was observed. The findings provide evidence that BPF administration may be proposed as a potential supplementation strategy to improve cognitive outcome in schizophrenia. Further clinical trials with adequately powered and well-designed methodology are needed to better explore the BPF effectiveness on cognitive impairments in patients with schizophrenia.

Mechanisms of radiotherapy-associated cognitive disability in patients with brain tumours.

PubMed

Makale, Milan T; McDonald, Carrie R; Hattangadi-Gluth, Jona A; Kesari, Santosh

2017-01-01

Standard treatment of primary and metastatic brain tumours includes high-dose megavoltage-range radiation to the cranial vault. About half of patients survive >6 months, and many attain long-term control or cure. However, 50-90% of survivors exhibit disabling cognitive dysfunction. The radiation-associated cognitive syndrome is poorly understood and has no effective prevention or long-term treatment. Attention has primarily focused on mechanisms of disability that appear at 6 months to 1 year after radiotherapy. However, recent studies show that CNS alterations and dysfunction develop much earlier following radiation exposure. This finding has prompted the hypothesis that subtle early forms of radiation-induced CNS damage could drive chronic pathophysiological processes that lead to permanent cognitive decline. This Review presents evidence of acute radiation-triggered CNS inflammation, injury to neuronal lineages, accessory cells and their progenitors, and loss of supporting structure integrity. Moreover, injury-related processes initiated soon after irradiation could synergistically alter the signalling microenvironment in progenitor cell niches in the brain and the hippocampus, which is a structure critical to memory and cognition. Progenitor cell niche degradation could cause progressive neuronal loss and cognitive disability. The concluding discussion addresses future directions and potential early treatments that might reverse degenerative processes before they can cause permanent cognitive disability.

Dysfunctional Relationship Beliefs in Parent-Late Adolescent Relationship and Conflict Resolution Behaviors

ERIC Educational Resources Information Center

Hamamci, Zeynep

2007-01-01

The purpose of this study is to investigate the role of dysfunctional relationships beliefs on both the perceptions of their relationships with the parents and conflict resolution behaviors of late adolescence. The sample was consisted of 372 Turkish university students (248 women and 124 men). Interpersonal Cognitive Distortions Scale,…

Evaluation of Planning Dysfunction in Attention Deficit Hyperactivity Disorder and Autistic Spectrum Disorders Using the Zoo Map Task

ERIC Educational Resources Information Center

Salcedo-Marin, M. D.; Moreno-Granados, J. M.; Ruiz-Veguilla, M.; Ferrin, M.

2013-01-01

Attention-Deficit-Hyperactivity-Disorders (ADHD) and Autistic-Spectrum-Disorders (ASD) share overlapping clinical and cognitive features that may confuse the diagnosis. Evaluation of executive problems and planning dysfunction may aid the clinical diagnostic process and help disentangle the neurobiological process underlying these conditions. This…

Digital Dysfunctions in Primary School: A Pilot Study

ERIC Educational Resources Information Center

Thorvaldsen, Steinar; Egeberg, Gunstein; Pettersen, Geir Olaf; Vavik, Lars

2011-01-01

Learning often involves complex cognitive and motorical processes, and while most learners cope adequately with these challenges there are always some that struggle. When new kinds of knowledge are introduced there is a possibility that some learners will find this new knowledge hard to acquire, and thus manifest a dysfunction. Today the new…

Lactoferrin and lysozyme to reduce environmental enteric dysfunction and stunting in Malawian children: Study protocol for a randomized controlled trial

USDA-ARS?s Scientific Manuscript database

Chronic childhood malnutrition, as manifested by stunted linear growth, remains a persistent barrier to optimal child growth and societal development. Environmental enteric dysfunction (EED) is a significant underlying factor in the causal pathway to stunting, delayed cognitive development, and ulti...

GPS for the English Classroom: Understanding Executive Dysfunction in Secondary Students with Autism

ERIC Educational Resources Information Center

Azano, Amy; Tuckwiller, Elizabeth D.

2011-01-01

This article identifies instructional strategies that capitalize on the cognitive strengths of students with ASD by exploring the executive dysfunction theory of ASD. The authors focus on the middle/secondary English classroom where students are often in inclusive settings with a general education teacher. (Contains 1 table and 2 figures.)

Mechanisms of change in cognitive therapy for major depressive disorder in the community mental health setting.

PubMed

Crits-Christoph, Paul; Gallop, Robert; Diehl, Caroline K; Yin, Seohyun; Gibbons, Mary Beth Connolly

2017-06-01

This study examined the relation of change in theory-relevant cognitive variables to depressive symptom change over the course of cognitive therapy, as well as the specificity of change mechanisms to cognitive therapy as compared with dynamic therapy. There were 237 adult outpatients who were randomized to either cognitive (n = 119) or dynamic (n = 118) therapy for major depressive disorder in a community mental health setting. Assessments of compensatory skills (Ways of Responding Community Version and Self-Report Version), dysfunctional attitudes (Dysfunctional Attitudes Scale), and depressogenic schemas (Psychological Distance Scaling Task) were obtained at baseline and months 1, 2, and 5 following baseline. Primary outcome was measured using the Hamilton Rating Scale for Depression. Across both therapy conditions, change in all 3 cognitive domains was associated with concurrent change in depressive symptoms. After controlling for other cognitive variables, increased interconnectedness of the positive achievement-related schema was significantly associated with concurrent symptom change in cognitive (rp = .26, p < .001) but not dynamic therapy (rp = .08, p = .29). Increases in positive compensatory skills were associated with subsequent change in depressive symptoms in cognitive therapy (rp = -.36, p = .003), but not in dynamic therapy (rp = .11, p = .386). Results provide support for the compensatory skills model of cognitive therapy (CT) within a community mental health setting. Additional research is necessary to understand other possible mechanisms of change in CT in the community setting. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Epigenetic Contributions to Cognitive Aging: Disentangling Mindspan and Lifespan

ERIC Educational Resources Information Center

Spiegel, Amy M.; Sewal, Angila S.; Rapp, Peter R.

2014-01-01

Epigenetic modifications of chromatin structure provide a mechanistic interface for gene-environment interactions that impact the individualization of health trajectories across the lifespan. A growing body of research indicates that dysfunctional epigenetic regulation contributes to poor cognitive outcomes among aged populations. Here we review…

Cognitive functioning in bilateral perisylvian polymicrogyria (BPP): clinical and radiological correlations.

PubMed

Jansen, An C; Leonard, Gabriel; Bastos, Alexandre C; Esposito-Festen, Josée E; Tampieri, Donatella; Watkins, Kate; Andermann, Frederick; Andermann, Eva

2005-05-01

Bilateral perisylvian polymicrogyria (BPP) is a malformation of cortical development, frequently associated with severe dysarthria or anarthria. BPP patients are therefore often labeled as severely retarded, but a detailed neuropsychological profile has not been reported to date. In a series of 14 patients, we demonstrated that only a minority had extremely low intelligence, and that some aspects of cognitive function correlated with the extent of the cortical disorganization. Early age at seizure onset correlated positively with Performance IQ scores (P<0.05) and negatively with the extent of the lesion (P<0.01), reflecting that patients with more severe BPP are more likely to have early seizure onset, resulting in greater interference with ongoing cognitive development. Receptive and expressive language skills were found to be equally poor. Frontal lobe function and memory abilities were relatively well preserved, suggesting that the observed cognitive profiles were related, at least in part, to specific areas of cortical dysfunction and not only to global dysfunction.

Visuo-motor and cognitive procedural learning in children with basal ganglia pathology.

PubMed

Mayor-Dubois, C; Maeder, P; Zesiger, P; Roulet-Perez, E

2010-06-01

We investigated procedural learning in 18 children with basal ganglia (BG) lesions or dysfunctions of various aetiologies, using a visuo-motor learning test, the Serial Reaction Time (SRT) task, and a cognitive learning test, the Probabilistic Classification Learning (PCL) task. We compared patients with early (<1 year old, n=9), later onset (>6 years old, n=7) or progressive disorder (idiopathic dystonia, n=2). All patients showed deficits in both visuo-motor and cognitive domains, except those with idiopathic dystonia, who displayed preserved classification learning skills. Impairments seem to be independent from the age of onset of pathology. As far as we know, this study is the first to investigate motor and cognitive procedural learning in children with BG damage. Procedural impairments were documented whatever the aetiology of the BG damage/dysfunction and time of pathology onset, thus supporting the claim of very early skill learning development and lack of plasticity in case of damage. Copyright 2010 Elsevier Ltd. All rights reserved.

Cognitive patterns in relation to biomarkers of cerebrovascular disease and vascular risk factors.

PubMed

Miralbell, Júlia; López-Cancio, Elena; López-Oloriz, Jorge; Arenillas, Juan Francisco; Barrios, Maite; Soriano-Raya, Juan José; Galán, Amparo; Cáceres, Cynthia; Alzamora, Maite; Pera, Guillem; Toran, Pere; Dávalos, Antoni; Mataró, Maria

2013-01-01

Risk factors for vascular cognitive impairment (VCI) are the same as traditional risk factors for cerebrovascular disease (CVD). Early identification of subjects at higher risk of VCI is important for the development of effective preventive strategies. In addition to traditional vascular risk factors (VRF), circulating biomarkers have emerged as potential tools for early diagnoses, as they could provide in vivo measures of the underlying pathophysiology. While VRF have been consistently linked to a VCI profile (i.e., deficits in executive functions and processing speed), the cognitive correlates of CVD biomarkers remain unclear. In this population-based study, the aim was to study and compare cognitive patterns in relation to VRF and circulating biomarkers of CVD. The Barcelona-AsIA Neuropsychology Study included 747 subjects older than 50, without a prior history of stroke or coronary disease and with a moderate to high vascular risk (mean age, 66 years; 34.1% women). Three cognitive domains were derived from factoral analysis: visuospatial skills/speed, verbal memory and verbal fluency. Multiple linear regression was used to assess relationships between cognitive performance (multiple domains) and a panel of circulating biomarkers, including indicators of inflammation, C-reactive protein (CRP) and resistin, endothelial dysfunction, asymmetric dimethylarginine (ADMA), thrombosis, plasminogen activator inhibitor 1 (PAI-1), as well as traditional VRF, metabolic syndrome and insulin resistance (homeostatic model assessment for insulin resistance index). Analyses were adjusted for age, gender, years of education and depressive symptoms. Traditional VRF were related to lower performance in verbal fluency, insulin resistance accounted for lower performance in visuospatial skills/speed and the metabolic syndrome predicted lower performance in both cognitive domains. From the biomarkers of CVD, CRP was negatively related to verbal fluency performance and increasing ADMA levels were associated with lower performance in verbal memory. Resistin and PAI-1 did not relate to cognitive function performance. Vascular risk factors, and markers of inflammation and endothelial dysfunction predicted lower performance in several cognitive domains. Specifically, cognitive functions associated with CRP are typically affected in VCI and overlap those related to VRF. ADMA indicated a dissociation in the cognitive profile involving verbal memory. These findings suggest that inflammation and endothelial dysfunction might play a role in the predementia cognitive impairment stages. Copyright © 2013 S. Karger AG, Basel.

Urine Metabonomics Reveals Early Biomarkers in Diabetic Cognitive Dysfunction.

PubMed

Song, Lili; Zhuang, Pengwei; Lin, Mengya; Kang, Mingqin; Liu, Hongyue; Zhang, Yuping; Yang, Zhen; Chen, Yunlong; Zhang, Yanjun

2017-09-01

Recently, increasing attention has been paid to diabetic encephalopathy, which is a frequent diabetic complication and affects nearly 30% of diabetics. Because cognitive dysfunction from diabetic encephalopathy might develop into irreversible dementia, early diagnosis and detection of this disease is of great significance for its prevention and treatment. This study is to investigate the early specific metabolites biomarkers in urine prior to the onset of diabetic cognitive dysfunction (DCD) by using metabolomics technology. An ultra-high performance liquid-chromatography-quadrupole time-of-flight-mass spectrometry (UPLC-Q/TOF-MS) platform was used to analyze the urine samples from diabetic mice that were associated with mild cognitive impairment (MCI) and nonassociated with MCI in the stage of diabetes (prior to the onset of DCD). We then screened and validated the early biomarkers using OPLS-DA model and support vector machine (SVM) method. Following multivariate statistical and integration analysis, we found that seven metabolites could be accepted as early biomarkers of DCD, and the SVM results showed that the prediction accuracy is as high as 91.66%. The identities of four biomarkers were determined by mass spectrometry. The identified biomarkers were largely involved in nicotinate and nicotinamide metabolism, glutathione metabolism, tryptophan metabolism, and sphingolipid metabolism. The present study first revealed reliable biomarkers for early diagnosis of DCD. It provides new insight and strategy for the early diagnosis and treatment of DCD.

A Single Bout of High-Intensity Interval Training Reduces Awareness of Subsequent Hypoglycemia in Patients With Type 1 Diabetes.

PubMed

Rooijackers, Hanne M; Wiegers, Evita C; van der Graaf, Marinette; Thijssen, Dick H; Kessels, Roy P C; Tack, Cees J; de Galan, Bastiaan E

2017-07-01

High-intensity interval training (HIIT) has gained increasing popularity in patients with diabetes. HIIT acutely increases plasma lactate levels. This may be important, since the administration of lactate during hypoglycemia suppresses symptoms and counterregulation while preserving cognitive function. We tested the hypothesis that, in the short term, HIIT reduces awareness of hypoglycemia and attenuates hypoglycemia-induced cognitive dysfunction. In a randomized crossover trial, patients with type 1 diabetes and normal awareness of hypoglycemia (NAH), patients with impaired awareness of hypoglycemia (IAH), and healthy participants ( n = 10 per group) underwent a hyperinsulinemic-hypoglycemic (2.6 mmol/L) clamp, either after a HIIT session or after seated rest. Compared with rest, HIIT reduced symptoms of hypoglycemia in patients with NAH but not in healthy participants or patients with IAH. HIIT attenuated hypoglycemia-induced cognitive dysfunction, which was mainly driven by changes in the NAH subgroup. HIIT suppressed cortisol and growth hormone responses, but not catecholamine responses to hypoglycemia. The present findings demonstrate that a single HIIT session rapidly reduces awareness of subsequent hypoglycemia in patients with type 1 diabetes and NAH, but does not in patients with IAH, and attenuates hypoglycemia-induced cognitive dysfunction. The role of exercise-induced lactate in mediating these effects, potentially serving as an alternative fuel for the brain, should be further explored. © 2017 by the American Diabetes Association.

A Computational Model of Major Depression: the Role of Glutamate Dysfunction on Cingulo-Frontal Network Dynamics

PubMed Central

Ramirez-Mahaluf, Juan P.; Roxin, Alexander; Mayberg, Helen S.; Compte, Albert

2017-01-01

Abstract Major depression disease (MDD) is associated with the dysfunction of multinode brain networks. However, converging evidence implicates the reciprocal interaction between midline limbic regions (typified by the ventral anterior cingulate cortex, vACC) and the dorso-lateral prefrontal cortex (dlPFC), reflecting interactions between emotions and cognition. Furthermore, growing evidence suggests a role for abnormal glutamate metabolism in the vACC, while serotonergic treatments (selective serotonin reuptake inhibitor, SSRI) effective for many patients implicate the serotonin system. Currently, no mechanistic framework describes how network dynamics, glutamate, and serotonin interact to explain MDD symptoms and treatments. Here, we built a biophysical computational model of 2 areas (vACC and dlPFC) that can switch between emotional and cognitive processing. MDD networks were simulated by slowing glutamate decay in vACC and demonstrated sustained vACC activation. This hyperactivity was not suppressed by concurrent dlPFC activation and interfered with expected dlPFC responses to cognitive signals, mimicking cognitive dysfunction seen in MDD. Simulation of clinical treatments (SSRI or deep brain stimulation) counteracted this aberrant vACC activity. Theta and beta/gamma oscillations correlated with network function, representing markers of switch-like operation in the network. The model shows how glutamate dysregulation can cause aberrant brain dynamics, respond to treatments, and be reflected in EEG rhythms as biomarkers of MDD. PMID:26514163

Cognitive findings after transient global amnesia: role of prefrontal cortex.

PubMed

Le Pira, Francesco; Giuffrida, Salvatore; Maci, Tiziana; Reggio, Ester; Zappalà, Giuseppe; Perciavalle, Vincenzo

2005-01-01

The aim of this study is to verify, after recovery, the presence of specific patterns of cognitive dysfunctions in Transient Global Amnesia (TGA). Fourteen patients with the diagnosis of TGA were submitted to a battery of neuropsychological tests and compared to a matched control group. We found significant qualitative and quantitative differences between TGA patients and controls in the California Verbal Learning Test (CLVT) and Rey-Osterrieth Complex Figure Test. Our data support the presence of selective cognitive dysfunctions after the clinical recovery. Moreover, for Verbal Fluency, Digit Span Backward, and Number of Clusters in the CVLT short-term memory test, the relation resulted as positively related with the temporal interval from the TGA episode. Reduction of categorical learning, attention, and qualitative alterations of spatial strategy seem to postulate a planning defect due to a prefrontal impairment.

Smoking in Schizophrenia: an Updated Review.

PubMed

Šagud, Marina; Vuksan-Ćusa, Bjanka; Jakšić, Nenad; Mihaljević-Peleš, Alma; Rojnić Kuzman, Martina; Pivac, Nela

2018-06-01

Patients with schizophrenia continue to have the highest rate of both smoking and heavy nicotine dependence. The interaction between smoking and schizophrenia is complex. There is evidence of the shared genetic background. Recent preclinical and clinical research has further investigated self-medication hypothesis, given that nicotine might alleviate cortical dysfunction. While prior research indicated some favorable effects of smoking on cognitive performance, particulatly on attention/vigilance, recent studies did not confirm those findings. Lower severity of negative symptoms in smokers was not confirmed across studies. Cigarette smoking decreases clozapine and olanzapine concentrations. There is no consistent evidence of favorable effects of nicotine on symptoms in schizophrenia, but the evidence of detrimental effects of smoking on general health is highly consistent. Smoking cessation should be a priority in patients with schizophrenia.

Dissociation of decision making under ambiguity and decision making under risk in breast cancer patients receiving adjuvant chemotherapy: a neuropsychological study.

PubMed

Chen, Xingui; Zhu, Chunyan; Li, Jingjing; Qiu, Linlin; Zhang, Long; Yu, Fengqiong; Ye, Rong; Zhang, Jingjie; Wang, Kai

2013-10-02

There is evidence that women with breast cancer show a cognitive impairment after having undergone chemotherapy treatment; this cognitive impairment may result in behavioral deficits. However, the neural mechanism of this cognitive impairment remains unclear. The present study investigated the neural basis of the cognitive impairment caused by chemotherapy treatment by exploring the decision-making function of the executive subcomponents under ambiguity and risk in breast cancer survivors. Participants included breast cancer patients who had undergone chemotherapy (CT, N=63) or patients who did not undergo chemotherapy (non-CT, N=62), as well as matched healthy controls (HC, N=61). All participants were examined using the Iowa Gambling Task (IGT) to assess their decision-making under ambiguity, the Game of Dice Task (GDT) to assess their decision-making under risk and neuropsychological background tests. Our results indicated that during the IGT test, the chemotherapy-treated breast cancer patients selected from the disadvantageous decks with a higher frequency than the non-treated breast cancer patients or healthy controls, whereas all three groups performed at the same level when performing the GDT. The CT group demonstrated significantly lower scores in several cognitive tasks, including attention, memory, executive functions and cognitive processing, when compared with the other two groups. In addition, within the CT group, significant correlations were found between the IGT performance and information processing, as well as with working memory. This study demonstrated that breast cancer survivors treated with chemotherapy may have selective reductions in IGT performance but unimpaired GDT performance and that these deficits may result from dysfunctions in the limbic loop rather than in the dorsolateral prefrontal loop. © 2013 Elsevier B.V. All rights reserved.

Orthopedic Surgery and Post-Operative Cognitive Decline in Idiopathic Parkinson’s Disease: Considerations from a Pilot Study

PubMed Central

Price, Catherine C.; Levy, Shellie-Anne; Tanner, Jared; Garvan, Cyndi; Ward, Jade; Akbar, Farheen; Bowers, Dawn; Rice, Mark; Okun, Michael

2016-01-01

BACKGROUND Post-operative cognitive dysfunction (POCD) demarks cognitive decline after major surgery but has been studied to date in “healthy” adults. Although individuals with neurodegenerative disorders such as Parkinson’s disease (PD) commonly undergo elective surgery, these individuals have yet to be prospectively followed despite hypotheses of increased POCD risk. OBJECTIVE To conduct a pilot study examining cognitive change pre-post elective orthopedic surgery for PD relative to surgery and non-surgery peers. METHODS A prospective one-year longitudinal design. No-dementia idiopathic PD individuals were actively recruited along with non-PD “healthy” controls (HC) undergoing knee replacement surgery. Non-surgical PD and HC controls were also recruited. Attention/processing speed, inhibitory function, memory recall, animal (semantic) fluency, and motor speed were assessed at baseline (pre-surgery), three-weeks, three-months, and one-year post- orthopedic surgery. Reliable change methods examined individual changes for PD individuals relative to control surgery and control non-surgery peers. RESULTS Over two years we screened 152 older adult surgery or non-surgery candidates with 19 of these individuals having a diagnosis of PD. Final participants included 8 PD (5 surgery, 3 non-surgery), 47 Control Surgery, and 21 Control Non-Surgery. Eighty percent (4 of the 5) PD surgery declined greater than 1.645 standard deviations from their baseline performance on measures assessing processing speed and inhibitory function. This was not observed for the non-surgery PD individuals. CONCLUSION This prospective pilot study demonstrated rationale and feasibility for examining cognitive decline in at-risk neurodegenerative populations. We discuss recruitment and design challenges for examining post-operative cognitive decline in neurodegenerative samples. PMID:26683785

Assessment of Olfactory Function in MAPT-Associated Neurodegenerative Disease Reveals Odor-Identification Irreproducibility as a Non-Disease-Specific, General Characteristic of Olfactory Dysfunction.

PubMed

Markopoulou, Katerina; Chase, Bruce A; Robowski, Piotr; Strongosky, Audrey; Narożańska, Ewa; Sitek, Emilia J; Berdynski, Mariusz; Barcikowska, Maria; Baker, Matt C; Rademakers, Rosa; Sławek, Jarosław; Klein, Christine; Hückelheim, Katja; Kasten, Meike; Wszolek, Zbigniew K

2016-01-01

Olfactory dysfunction is associated with normal aging, multiple neurodegenerative disorders, including Parkinson's disease, Lewy body disease and Alzheimer's disease, and other diseases such as diabetes, sleep apnea and the autoimmune disease myasthenia gravis. The wide spectrum of neurodegenerative disorders associated with olfactory dysfunction suggests different, potentially overlapping, underlying pathophysiologies. Studying olfactory dysfunction in presymptomatic carriers of mutations known to cause familial parkinsonism provides unique opportunities to understand the role of genetic factors, delineate the salient characteristics of the onset of olfactory dysfunction, and understand when it starts relative to motor and cognitive symptoms. We evaluated olfactory dysfunction in 28 carriers of two MAPT mutations (p.N279K, p.P301L), which cause frontotemporal dementia with parkinsonism, using the University of Pennsylvania Smell Identification Test. Olfactory dysfunction in carriers does not appear to be allele specific, but is strongly age-dependent and precedes symptomatic onset. Severe olfactory dysfunction, however, is not a fully penetrant trait at the time of symptom onset. Principal component analysis revealed that olfactory dysfunction is not odor-class specific, even though individual odor responses cluster kindred members according to genetic and disease status. Strikingly, carriers with incipient olfactory dysfunction show poor inter-test consistency among the sets of odors identified incorrectly in successive replicate tests, even before severe olfactory dysfunction appears. Furthermore, when 78 individuals without neurodegenerative disease and 14 individuals with sporadic Parkinson's disease were evaluated twice at a one-year interval using the Brief Smell Identification Test, the majority also showed inconsistency in the sets of odors they identified incorrectly, independent of age and cognitive status. While these findings may reflect the limitations of these tests used and the sample sizes, olfactory dysfunction appears to be associated with the inability to identify odors reliably and consistently, not with the loss of an ability to identify specific odors. Irreproducibility in odor identification appears to be a non-disease-specific, general feature of olfactory dysfunction that is accelerated or accentuated in neurodegenerative disease. It may reflect a fundamental organizational principle of the olfactory system, which is more "error-prone" than other sensory systems.

Current Paranoid Thinking in Patients With Delusions: The Presence of Cognitive-Affective Biases

PubMed Central

Freeman, Daniel

2013-01-01

Background: There has been renewed interest in the influence of affect on psychosis. Psychological research on persecutory delusions ascribes a prominent role to cognitive processes related to negative affect: anxiety leads to the anticipation of threat within paranoia; depressive negative ideas about the self create a sense of vulnerability in which paranoid thoughts flourish; and self-consciousness enhances feelings of the self as a target. The objective of this study was to examine such affective processes in relation to state paranoia in patients with delusions. Methods: 130 patients with delusions in the context of a nonaffective psychosis diagnosis (predominately schizophrenia) were assessed for contemporaneous levels of persecutory ideation on 5 visual analog scales. Measures were taken of anxiety, depression, threat anticipation, interpretation of ambiguity, self-focus, and negative ideas about the self. Results: Of the patients, 85% report paranoid thinking at testing. Symptoms of anxiety and depression were highly prevalent. Current paranoid thinking was associated with anxiety, depression, greater anticipation of threat events, negative interpretations of ambiguous events, a self-focused cognitive style, and negative ideas about the self. Conclusions: The study provides a clear demonstration that a range of emotion-related cognitive biases, each of which could plausibly maintain delusions, are associated with current paranoid thinking in patients with psychosis. We identified biases both in the contents of cognition and in the processing of information. Links between affect and psychosis are central to the understanding of schizophrenia. We conclude that treatment of emotional dysfunction should lead to reductions in current psychotic experiences. PMID:23223342

Cognitive training plus a comprehensive psychosocial programme (OPUS) versus the comprehensive psychosocial programme alone for patients with first-episode schizophrenia (the NEUROCOM trial): a study protocol for a centrally randomised, observer-blinded multi-centre clinical trial.

PubMed

Vesterager, Lone; Christensen, Torben Ø; Olsen, Birthe B; Krarup, Gertrud; Forchhammer, Hysse B; Melau, Marianne; Gluud, Christian; Nordentoft, Merete

2011-02-09

Up to 85% of patients with schizophrenia demonstrate cognitive dysfunction in at least one domain. Cognitive dysfunction plays a major role in functional outcome. It is hypothesized that addition of cognitive training to a comprehensive psychosocial programme (OPUS) enhances both cognitive and everyday functional capacity of patients more than the comprehensive psychosocial programme alone. The NEUROCOM trial examines the effect on cognitive functioning and everyday functional capacity of patients with schizophrenia of a 16-week manualised programme of individual cognitive training integrated in a comprehensive psychosocial programme versus the comprehensive psychosocial programme alone. The cognitive training consists of four modules focusing on attention, executive functioning, learning, and memory. Cognitive training involves computer-assisted training tasks as well as practical everyday tasks and calendar training. It takes place twice a week, and every other week the patient and trainer engage in a dialogue on the patient's cognitive difficulties, motivational goals, and progress in competence level. Cognitive training relies on errorless learning principles, scaffolding, and verbalisation in its effort to improve cognitive abilities and teach patients how to apply compensation strategies as well as structured problem solving techniques. At 16-week post-training and at ten-months follow-up, assessments are conducted to investigate immediate outcome and possible long-term effects of cognitive training. We conduct blinded assessments of cognition, everyday functional capacity and associations with the labour market, symptom severity, and self-esteem. Results from four-month and ten-month follow-ups have the potential of reliably providing documentation of the long-term effect of CT for patients with schizophrenia. Clinicaltrials.gov NCT00472862.

Cognitive Function Among Obstructive Sleep Apnea Patients in North East Malaysia.

PubMed

Yusop, Che Yusfarina Che; Mohamad, Irfan; Mohammad, Wan Mohd Zahiruddin Wan; Abdullah, Baharudin

2017-01-01

Obstructive sleep apnea patients may develop deficits in the cognitive domains of attention, concentration, executive function, verbal and visuospatial memory, constructional abilities, and psychomotor functioning. As cognitive performance will improve with the treatment, early screening for cognitive dysfunction should be done to prevent further deterioration. We aim to evaluate the cognitive function of obstructive sleep apnea patients by using the 'Mini Mental State Examination'. This was a cross sectional study to evaluate the cognitive function of moderate and severe obstructive sleep apnea patients with age ranged from 18 to 60 old who attended our sleep clinic. These patients were confirmed to have moderate and severe obstructive sleep apnea by Type 1 polysomnography (attended full overnight study). The age, gender and ethnicity were noted and other relevant data such as weight, height, body mass index and apnea and hypopnoea index were recorded accordingly. The cognitive function was evaluated using validated Malay version of Mini Mental State Examination which measured 5 areas of cognitive functions comprising orientation, registration, attention and calculation, word recall and language abilities, and visuospatial. A total of 38 patients participated in this study. All 19 patients of moderate group and 14 patients of severe group had normal cognitive function while only 5 patients in severe group had mild cognitive function impairment. There was a statistically significant difference between the moderate group and severe group on cognitive performance (p value = 0.042). Severe obstructive sleep apnea patients may have impaired cognitive function. Mini Mental State Examination is useful in the screening of cognitive function of obstructive sleep apnea patients but in normal score, more sophisticated test batteries are required as it is unable to identify in 'very minimal' or 'extremely severe' cognitive dysfunction. Copyright © 2017 National Medical Association. Published by Elsevier Inc. All rights reserved.

Insulin dysfunction and Tau pathology.

PubMed

El Khoury, Noura B; Gratuze, Maud; Papon, Marie-Amélie; Bretteville, Alexis; Planel, Emmanuel

2014-01-01

The neuropathological hallmarks of Alzheimer's disease (AD) include senile plaques of β-amyloid (Aβ) peptides (a cleavage product of the Amyloid Precursor Protein, or APP) and neurofibrillary tangles (NFT) of hyperphosphorylated Tau protein assembled in paired helical filaments (PHF). NFT pathology is important since it correlates with the degree of cognitive impairment in AD. Only a small proportion of AD is due to genetic variants, whereas the large majority of cases (~99%) is late onset and sporadic in origin. The cause of sporadic AD is likely to be multifactorial, with external factors interacting with biological or genetic susceptibilities to accelerate the manifestation of the disease. Insulin dysfunction, manifested by diabetes mellitus (DM) might be such factor, as there is extensive data from epidemiological studies suggesting that DM is associated with an increased relative risk for AD. Type 1 diabetes (T1DM) and type 2 diabetes (T2DM) are known to affect multiple cognitive functions in patients. In this context, understanding the effects of diabetes on Tau pathogenesis is important since Tau pathology show a strong relationship to dementia in AD, and to memory loss in normal aging and mild cognitive impairment. Here, we reviewed preclinical studies that link insulin dysfunction to Tau protein pathogenesis, one of the major pathological hallmarks of AD. We found more than 30 studies reporting Tau phosphorylation in a mouse or rat model of insulin dysfunction. We also payed attention to potential sources of artifacts, such as hypothermia and anesthesia, that were demonstrated to results in Tau hyperphosphorylation and could major confounding experimental factors. We found that very few studies reported the temperature of the animals, and only a handful did not use anesthesia. Overall, most published studies showed that insulin dysfunction can promote Tau hyperphosphorylation and pathology, both directly and indirectly, through hypothermia.

Insulin dysfunction and Tau pathology

PubMed Central

El Khoury, Noura B.; Gratuze, Maud; Papon, Marie-Amélie; Bretteville, Alexis; Planel, Emmanuel

2013-01-01

The neuropathological hallmarks of Alzheimer's disease (AD) include senile plaques of β-amyloid (Aβ) peptides (a cleavage product of the Amyloid Precursor Protein, or APP) and neurofibrillary tangles (NFT) of hyperphosphorylated Tau protein assembled in paired helical filaments (PHF). NFT pathology is important since it correlates with the degree of cognitive impairment in AD. Only a small proportion of AD is due to genetic variants, whereas the large majority of cases (~99%) is late onset and sporadic in origin. The cause of sporadic AD is likely to be multifactorial, with external factors interacting with biological or genetic susceptibilities to accelerate the manifestation of the disease. Insulin dysfunction, manifested by diabetes mellitus (DM) might be such factor, as there is extensive data from epidemiological studies suggesting that DM is associated with an increased relative risk for AD. Type 1 diabetes (T1DM) and type 2 diabetes (T2DM) are known to affect multiple cognitive functions in patients. In this context, understanding the effects of diabetes on Tau pathogenesis is important since Tau pathology show a strong relationship to dementia in AD, and to memory loss in normal aging and mild cognitive impairment. Here, we reviewed preclinical studies that link insulin dysfunction to Tau protein pathogenesis, one of the major pathological hallmarks of AD. We found more than 30 studies reporting Tau phosphorylation in a mouse or rat model of insulin dysfunction. We also payed attention to potential sources of artifacts, such as hypothermia and anesthesia, that were demonstrated to results in Tau hyperphosphorylation and could major confounding experimental factors. We found that very few studies reported the temperature of the animals, and only a handful did not use anesthesia. Overall, most published studies showed that insulin dysfunction can promote Tau hyperphosphorylation and pathology, both directly and indirectly, through hypothermia. PMID:24574966

[New diagnostic approach can improve treatment of whiplash injuries. Functional magnetic resonance tomography makes visualization of the injuries possible].

PubMed

Bergholm, Ulla; Johansson, Bengt H

2003-11-20

Patients suffering from chronic pain and dysfunction after acceleration/deceleration trauma to the cervical spine often present reliability problems. This is partly due to inadequate possibilities of diagnosing of the soft tissue structures in this area. A new diagnostic method--functional magnetic resonance imaging (fMRI) has made it possible to detect injuries in ligaments and capsules at the craniocervical junction. Not only do these structures stabilize the head during rotation movements, but they also contain receptors of the central nervous system, and thus have the most important function in position perception (i.e. proprioception) and movement control. The late onset of symptoms in this patient group can now be explained by the functional stenosis of the spinal cord and brainstem due to scar formation around the dens axis after injury. Modern neurophysiology can now explain the background of the generalized and complex picture of chronic pain and muscular and cognitive dysfunction. This new knowledge has prepared the way for more specific therapy in patients suffering from craniocervical instability symptoms and pain from disks and facet joints in the cervical spine after whiplash trauma.

Is language impairment more common than executive dysfunction in amyotrophic lateral sclerosis?

PubMed

Taylor, Lorna J; Brown, Richard G; Tsermentseli, Stella; Al-Chalabi, Ammar; Shaw, Christopher E; Ellis, Catherine M; Leigh, P Nigel; Goldstein, Laura H

2013-05-01

Systematic explorations of language abilities in patients with amyotrophic lateral sclerosis (ALS) are lacking in the context of wider cognitive change. Neuropsychological assessment data were obtained from 51 patients with ALS and 35 healthy controls matched for age, gender and IQ. Composite scores were derived for the domains of language and executive functioning. Domain impairment was defined as a composite score ≤5th centile relative to the control mean. Cognitive impairment was also classified using recently published consensus criteria. The patients with ALS were impaired on language and executive composite scores. Language domain impairment was found in 43% of patients with ALS, and executive domain impairment in 31%. Standardised language and executive composite scores correlated in the ALS group (r=0.68, p<0.001). Multiple regression analyses indicated that scores on the executive composite accounted for 44% of the variance in language composite scores. Language impairments are at least as prevalent as executive dysfunction in ALS. While the two domains are strongly associated, executive dysfunction does not fully account for the profile of language impairments observed, further highlighting the heterogeneity of cognitive impairment in non-demented patients with ALS.

Effect of Urtica dioica on memory dysfunction and hypoalgesia in an experimental model of diabetic neuropathy.

PubMed

Patel, Sita Sharan; Udayabanu, M

2013-09-27

Diabetic neuropathy is considered as a disease of the peripheral nervous system, but recent evidences suggest the involvement of central nervous system as well. In this study we evaluated the effect of Urtica dioica (UD) extract against memory dysfunction and hypoalgesia on a mouse model of streptozotocin (STZ) induced diabetic neuropathy. STZ (50 mg/kg, i.p. consecutively for 5 days) was used to induce diabetes, followed by treatment with the UD extract (50 mg/kg, oral) and rosiglitazone (5 mg/kg, oral) for 8 weeks. Cognitive functions were evaluated using Morris water maze and passive avoidance step through task. Pain thresholds were measured using thermal, mechanical and chemical induced hyperalgesia. We observed that chronic diabetes resulted in a decline in circulating insulin level, elevated blood glucose, reduced body weight, increased water intake, cognitive impairment and hypoalgesia. UD significantly reduced the blood glucose and polydypsia, as well as improved the body weight, insulin level, cognition and insensate neuropathy. In conclusion, UD showed results comparable to rosiglitazone in reversing the long standing diabetes induced complications such as central and peripheral neuronal dysfunction. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Extracorporeal life support for critical enterovirus 71 rhombencephalomyelitis: long-term neurologic follow-up.

PubMed

Lee, Hsiu-Fen; Chi, Ching-Shiang; Jan, Sheng-Ling; Fu, Yun-Ching; Huang, Fang-Liang; Chen, Po-Yen; Wang, Chung-Chi; Wei, Hao-Ji

2012-04-01

Enterovirus 71 rhombencephalomyelitis with cardiopulmonary dysfunction has become an endemic problem in Taiwan since an epidemic outbreak in 1998. Such cases frequently involve significant morbidity and mortality. From October 2000-June 2008, we collected 10 consecutive patients diagnosed with enterovirus 71 rhombencephalomyelitis complicated by left heart failure, with or without pulmonary edema, and surviving more than 3 months after receiving extracorporeal life support. Follow-up neurologic outcomes were analyzed prospectively. The median duration of neurologic follow-up was 7 years and 2 months. Significant morbidities included bulbar dysfunction, respiratory failure, and flaccid quadriparesis. Eight patients exhibited bulbar dysfunction, and feeding tubes could be removed from four patients (median, 15.5 months). Respiratory failure was observed in seven patients. Three patients were gradually withdrawn from their tracheostomy tube (median period, 30 months). Intelligence tests revealed four patients with normal cognitive function, one with borderline cognitive function, and one with mild mental retardation. Four were bedridden survivors. Extracorporeal life support for critical enterovirus 71 rhombencephalomyelitis demonstrated decreased neurologic sequelae during long-term follow-up, allowing for decannulation of feeding and tracheostomy tubes, and resulting in improved cognitive function. Copyright © 2012 Elsevier Inc. All rights reserved.

Differential General Anesthetic Effects on Microglial Cytokine Expression

PubMed Central

Ye, Xuefei; Lian, Qingquan; Eckenhoff, Maryellen F.; Eckenhoff, Roderic G.; Pan, Jonathan Z.

2013-01-01

Post-operative cognitive dysfunction has been widely observed, especially in older patients. An association of post-operative cognitive dysfunction with the neurodegenerative diseases, such as Alzheimer's disease, has been suggested. Neuroinflammation contributes to Alzheimer pathology, through elevated pro-inflammatory cytokines and microglial activation in the CNS leading to neuronal damage, synaptic disruption and ultimately cognitive dysfunction. We compare the effects of three different, clinically-used, anesthetics on microglial activation with, and without, the prototypical inflammatory trigger, lipopolysaccharide (LPS). Microglial BV-2 cell cultures were first exposed to isoflurane, sevoflurane (each at 2 concentrations) or propofol for 6 h, and cytokine levels measured in lysates and media. The same experiments were repeated after 1 h LPS pre-treatment. We found; 1) anesthetics alone have either no or only a small effect on cytokine expression; 2) LPS provoked a large increase in microglia cytokine expression; 3) the inhaled anesthetics either had no effect on LPS-evoked responses or enhanced it; 4) propofol nearly eliminated the LPS pro-inflammatory cytokine response and improved cell survival as reflected by lactate dehydrogenase release. These data suggest that propofol may be a preferred anesthetic when it is desirable to minimize neuroinflammation. PMID:23382826

Depressive disorders: Processes leading to neurogeneration and potential novel treatments.

PubMed

Brown, Gregory M; McIntyre, Roger S; Rosenblat, Joshua; Hardeland, Rüdiger

2018-01-03

Mood disorders are wide spread with estimates that one in seven of the population are affected at some time in their life (Kessler et al., 2012). Many of those affected with severe depressive disorders have cognitive deficits which may progress to frank neurodegeneration. There are several peripheral markers shown by patients who have cognitive deficits that could represent causative factors and could potentially serve as guides to the prevention or even treatment of neurodegeneration. Circadian rhythm misalignment, immune dysfunction and oxidative stress are key pathologic processes implicated in neurodegeneration and cognitive dysfunction in depressive disorders. Novel treatments targeting these pathways may therefore potentially improve patient outcomes whereby the primary mechanism of action is outside of the monoaminergic system. Moreover, targeting immune dysfunction, oxidative stress and circadian rhythm misalignment (rather than primarily the monoaminergic system) may hold promise for truly disease modifying treatments that may prevent neurodegeneration rather than simply alleviating symptoms with no curative intent. Further research is required to more comprehensively understand the contributions of these pathways to the pathophysiology of depressive disorders to allow for disease modifying treatments to be discovered. Copyright © 2017 Elsevier Inc. All rights reserved.

Cognitive dysfunction in patients with brain metastases: influences on caregiver resilience and coping.

PubMed

Saria, Marlon Garzo; Courchesne, Natasia; Evangelista, Lorraine; Carter, Joshua; MacManus, Daniel A; Gorman, Mary Kay; Nyamathi, Adeline M; Phillips, Linda R; Piccioni, David; Kesari, Santosh; Maliski, Sally

2017-04-01

Neurologic deficits that may be manifested as cognitive impairment contribute to the challenges faced by caregivers of patients with brain metastases. To better address their needs, we examined how caregivers respond to these challenges and explore the relationship between the patient's cognitive impairment and caregiver resilience and coping. We conducted a descriptive, cross-sectional study using self-reported data from 56 caregivers of patients with brain metastases. Study participants from a comprehensive cancer center were asked to complete a series of instruments that measured their perception of the patient's cognitive dysfunction (revised memory and behavior problems checklist, RMBC), their own personal resilience (Resilience Scale, RS), and their utilization of a broad range of coping responses (COPE inventory and Emotional-Approach Coping scale). Caregivers reported that memory-related problems occurred more frequently in the patients they cared for compared to depression and disruptive behavior (mean scores 3.52 vs 2.34 vs. 1.32, respectively). Coping strategies most frequently used by caregivers were acceptance (3.28), planning (3.08), and positive reinterpretation and growth (2.95). Most caregivers scored moderate to high on the RS (77%). The coping strategy acceptance correlated significantly with the memory and disruptive behavior subscales of the RMBC. Given the protective effect of problem-focused coping and the high rate of caregivers utilizing less effective coping strategies in instances of worsening cognitive dysfunction, healthcare professionals need to systematically assess the coping strategies of caregivers and deliver a more personalized approach to enhance effective coping among caregivers of patients with brain metastases.

Got worms? Perinatal exposure to helminths prevents persistent immune sensitization and cognitive dysfunction induced by early-life infection.

PubMed

Williamson, Lauren L; McKenney, Erin A; Holzknecht, Zoie E; Belliveau, Christine; Rawls, John F; Poulton, Susan; Parker, William; Bilbo, Staci D

2016-01-01

The incidence of autoimmune and inflammatory diseases has risen dramatically in post-industrial societies. "Biome depletion" - loss of commensal microbial and multicellular organisms such as helminths (intestinal worms) that profoundly modulate the immune system - may contribute to these increases. Hyperimmune-associated disorders also affect the brain, especially neurodevelopment, and increasing evidence links early-life infection to cognitive and neurodevelopmental disorders. We have demonstrated previously that rats infected with bacteria as newborns display life-long vulnerabilities to cognitive dysfunction, a vulnerability that is specifically linked to long-term hypersensitivity of microglial cell function, the resident immune cells of the brain. Here, we demonstrate that helminth colonization of pregnant dams attenuated the exaggerated brain cytokine response of their offspring to bacterial infection, and that combined with post-weaning colonization of offspring with helminths (consistent with their mothers treatment) completely prevented enduring microglial sensitization and cognitive dysfunction in adulthood. Importantly, helminths had no overt impact on adaptive immune cell subsets, whereas exaggerated innate inflammatory responses in splenic macrophages were prevented. Finally, helminths altered the effect of neonatal infection on the gut microbiome; neonatal infection with Escherichia coli caused a shift from genera within the Actinobacteria and Tenericutes phyla to genera in the Bacteroidetes phylum in rats not colonized with helminths, but helminths attenuated this effect. In sum, these data point toward an inter-relatedness of various components of the biome, and suggest potential mechanisms by which this helminth might exert therapeutic benefits in the treatment of neuroinflammatory and cognitive disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

Patient Reported Cognitive Limitations in Brain Tumor Survivors

DTIC Science & Technology

2006-01-01

seizures may also have a negative impact on cognitive function. Common side effects can include sedation , language dysfunction, psychomotor slowing...treatment exposure [40]. Also, when compared to collateral data collected from nursing staff regarding patient symptoms and functioning (e.g...Moen J, Fougner B, Borchgrevink PC, and Kaasa S. 2002. Self-reports are not related to objective assessments of cognitive function and sedation in

Specific Features of Executive Dysfunction in Alzheimer-Type Mild Dementia Based on Computerized Cambridge Neuropsychological Test Automated Battery (CANTAB) Test Results.

PubMed

Kuzmickienė, Jurgita; Kaubrys, Gintaras

2016-10-08

BACKGROUND The primary manifestation of Alzheimer's disease (AD) is decline in memory. Dysexecutive symptoms have tremendous impact on functional activities and quality of life. Data regarding frontal-executive dysfunction in mild AD are controversial. The aim of this study was to assess the presence and specific features of executive dysfunction in mild AD based on Cambridge Neuropsychological Test Automated Battery (CANTAB) results. MATERIAL AND METHODS Fifty newly diagnosed, treatment-naïve, mild, late-onset AD patients (MMSE ≥20, AD group) and 25 control subjects (CG group) were recruited in this prospective, cross-sectional study. The CANTAB tests CRT, SOC, PAL, SWM were used for in-depth cognitive assessment. Comparisons were performed using the t test or Mann-Whitney U test, as appropriate. Correlations were evaluated by Pearson r or Spearman R. Statistical significance was set at p<0.05. RESULTS AD and CG groups did not differ according to age, education, gender, or depression. Few differences were found between groups in the SOC test for performance measures: Mean moves (minimum 3 moves): AD (Rank Sum=2227), CG (Rank Sum=623), p<0.001. However, all SOC test time measures differed significantly between groups: SOC Mean subsequent thinking time (4 moves): AD (Rank Sum=2406), CG (Rank Sum=444), p<0.001. Correlations were weak between executive function (SOC) and episodic/working memory (PAL, SWM) (R=0.01-0.38) or attention/psychomotor speed (CRT) (R=0.02-0.37). CONCLUSIONS Frontal-executive functions are impaired in mild AD patients. Executive dysfunction is highly prominent in time measures, but minimal in performance measures. Executive disorders do not correlate with a decline in episodic and working memory or psychomotor speed in mild AD.

Electrophysiological correlates of word recognition memory process in patients with ischemic left ventricular dysfunction.

PubMed

Giovannelli, Fabio; Simoni, David; Gavazzi, Gioele; Giganti, Fiorenza; Olivotto, Iacopo; Cincotta, Massimo; Pratesi, Alessandra; Baldasseroni, Samuele; Viggiano, Maria Pia

2016-09-01

The relationship between left ventricular ejection fraction (LVEF) and cognitive performance in patients with coronary artery disease without overt heart failure is still under debate. In this study we combine behavioral measures and event-related potentials (ERPs) to verify whether electrophysiological correlates of recognition memory (old/new effect) are modulated differently as a function of LVEF. Twenty-three male patients (12 without [LVEF>55%] and 11 with [LVEF<40%] left ventricular dysfunction), and a Mini Mental State Examination score >25 were enrolled. ERPs were recorded while participants performed an old/new visual word recognition task. A late positive ERP component between 350 and 550ms was differentially modulated in the two groups: a clear old/new effect (enhanced mean amplitude for old respect to new items) was observed in patients without LVEF dysfunction; whereas patients with overt LVEF dysfunction did not show such effect. In contrast, no significant differences emerged for behavioral performance and neuropsychological evaluations. These data suggest that ERPs may reveal functional brain abnormalities that are not observed at behavioral level. Detecting sub-clinical measures of cognitive decline may contribute to set appropriate treatments and to monitor asymptomatic or mildly symptomatic patients with LVEF dysfunction. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

CD40-CD40 Ligand Pathway is a Major Component of Acute Neuroinflammation and Contributes to Long-term Cognitive Dysfunction after Sepsis.

PubMed

Michels, Monique; Danieslki, Lucinéia Gainski; Vieira, Andriele; Florentino, Drielly; Dall'Igna, Dhébora; Galant, Letícia; Sonai, Beatriz; Vuolo, Francieli; Mina, Franciele; Pescador, Bruna; Dominguini, Diogo; Barichello, Tatiana; Quevedo, João; Dal-Pizzol, Felipe; Petronilho, Fabrícia

2015-03-26

Sepsis-associated encephalopathy (SAE) is associated with an increased rate of morbidity and mortality. It is not understood what the exact mechanism is for the brain dysfunction that occurs in septic patients, but brain inflammation and oxidative stress are a possible theory. Such events can occur through the alteration of molecules that perpetuate the inflammatory response. Thus, it is possible to postulate that CD40 may be involved in this process. The aim of this work is to evaluate the role of CD40-CD40L pathway activation in brain dysfunction associated with sepsis in an animal model. Microglia activation induces the upregulation of CD40-CD40L, both in vitro and in vivo. The inhibition of microglia activation decreases levels of CD40-CD40L in the brain and decreases brain inflammation, oxidative damage and blood brain barrier dysfunction. Despite this, anti-CD40 treatment does not improve mortality in this model. However, it is able to improve long-term cognitive impairment in sepsis survivors. In conclusion, there is a major involvement of the CD40-CD40L signaling pathway in long-term brain dysfunction in an animal model of sepsis.

CD40–CD40 Ligand Pathway Is a Major Component of Acute Neuroinflammation and Contributes to Long-term Cognitive Dysfunction after Sepsis

PubMed Central

Michels, Monique; Danieslki, Lucinéia Gainski; Vieira, Andriele; Florentino, Drielly; Dall’Igna, Dhébora; Galant, Letícia; Sonai, Beatriz; Vuolo, Francieli; Mina, Franciele; Pescador, Bruna; Dominguini, Diogo; Barichello, Tatiana; Quevedo, João; Dal-Pizzol, Felipe; Petronilho, Fabrícia

2015-01-01

Sepsis-associated encephalopathy (SAE) is associated with an increased rate of morbidity and mortality. It is not understood what the exact mechanism is for the brain dysfunction that occurs in septic patients, but brain inflammation and oxidative stress are a possible theory. Such events can occur through the alteration of molecules that perpetuate the inflammatory response. Thus, it is possible to postulate that CD40 may be involved in this process. The aim of this work is to evaluate the role of CD40–CD40L pathway activation in brain dysfunction associated with sepsis in an animal model. Microglia activation induces the upregulation of CD40–CD40L, both in vitro and in vivo. The inhibition of microglia activation decreases levels of CD40–CD40L in the brain and decreases brain inflammation, oxidative damage and blood brain barrier dysfunction. Despite this, anti-CD40 treatment does not improve mortality in this model. However, it is able to improve long-term cognitive impairment in sepsis survivors. In conclusion, there is a major involvement of the CD40–CD40L signaling pathway in long-term brain dysfunction in an animal model of sepsis. PMID:25822797

Locating Dyslexic Performance: Text, Identity and Creativity

ERIC Educational Resources Information Center

Leveroy, Deborah

2013-01-01

Historically, dyslexia research has focused on the literacy aspects of dyslexia on children, and more recent definitions of dyslexia have included the cognitive processing aspects of verbal language, memory and organisation. However, these neuro-cognitive accounts largely conceptualise dyslexia as a neurological dysfunction, with only a small body…

Presleep thoughts and dysfunctional beliefs in subjects of insomnia with or without depression: Implications for cognitive behavior therapy for insomnia in Indian context

PubMed Central

Gupta, Ravi

2016-01-01

Background: Presleep thoughts may vary between patients of insomnia with or without depression. They are important for cognitive behavior therapy for insomnia (CBT-I), but they have never been systemically examined in Indian population. Materials and Methods: Patients with insomnia (>1 month) who were willing to undergo CBT-I were included in this study after obtaining informed consent. They were requested to fill a sleep diary and return after 15 days. At the time of intake, diagnosis of depression and anxiety disorders was made according to Diagnostic and Statistical Manual - IV-Text Revision. They were encouraged to provide information regarding presleep thoughts through open-ended and then, close-ended questions. Dysfunctional attitudes and beliefs about sleep were assessed with Hindi version of “dysfunctional beliefs and attitudes scale-brief version”. Hindi version of “insomnia severity index” was used to assess the severity of insomnia. Subjects were divided into two-groups - insomnia without depression (I) and insomnia with major depressive disorder (I-MDD+). Statistical Analysis: It was done with the help of SPSS v 21.0. Descriptive statistics was calculated. Proportions between groups were tested with Chi-square analysis and categorical variables were compared using independent sample t-test. Results: This study included a total of 63 subjects, out of which 60% were women. Mean age of the whole group was 41.7 ± 11.8 years. About 40% of all the subjects were diagnosed as having I-MDD+. Forty-one percent of the subjects had clinically significant anxiety. Both groups - I and I-MDD+ had comparable proportion of female subjects (χ2 = 0.002; P = 0.96) and there was no difference regarding precipitating factors for insomnia (χ2 = 0.97; P = 0.61). They were also comparable with regards to sleep-related measures, themes of presleep thoughts, and dysfunctional beliefs and attitudes about sleep and insomnia severity. Major themes of presleep thoughts included family issues and health issues. Only a small proportion had recurrent thoughts related to insomnia and its consequences. Conclusion: Insomnia is a co-morbid illness with depression and it needs to be separately addressed during therapy. CBT-I should include the element of problem-solving technique, especially when we are dealing with the Indian population. PMID:26985109

Cognitive enhancement treatments for bipolar disorder: A systematic review and methodological recommendations.

PubMed

Miskowiak, Kamilla W; Carvalho, André F; Vieta, Eduard; Kessing, Lars V

2016-10-01

Cognitive dysfunction is an emerging treatment target in bipolar disorder (BD). Several trials have assessed the efficacy of novel pharmacological and psychological treatments on cognition in BD but the findings are contradictory and unclear. A systematic search following the PRISMA guidelines was conducted on PubMed and PsychInfo. Eligible articles reported randomized, controlled or open-label trials investigating pharmacological or psychological treatments targeting cognitive dysfunction in BD. The quality of the identified randomized controlled trials (RCTs) was evaluated with the Cochrane Collaboration's Risk of Bias tool. We identified 19 eligible studies of which 13 were RCTs and six were open-label or non-randomized studies. The findings regarding efficacy on cognition were overall disappointing or preliminary, possibly due to several methodological challenges. For the RCTs, the risk of bias was high in nine cases, unclear in one case and low in three cases. Key reasons for the high risk of bias were lack of details on the randomization process, suboptimal handling of missing data and lack of a priori priority between cognition outcomes. Other challenges were the lack of consensus on whether and how to screen for cognitive impairment and on how to assess efficacy on cognition. In conclusion, methodological problems are likely to impede the success rates of cognition trials in BD. We recommend adherence to the CONSORT guidelines for RCTs, screening for cognitive impairment before inclusion of trial participants and selection of one primary cognition outcome. Future implementation of a 'neurocircuitry-based' biomarker model to evaluate neural target engagement is warranted. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Improvement of postoperative cognitive dysfunction and attention network function of patients with ischemic cerebrovascular disease via dexmedetomidine.

PubMed

Zhang, Jingchao; Wang, Guoliang; Zhang, Fangxiang; Zhao, Qian

2018-03-01

The protective effect of dexmedetomidine on cognitive dysfunction and decreased attention network function of patients with ischemic cerebrovascular disease after stenting was investigated. Fifty-eight patients with ischemic cerebrovascular disease undergoing stenting in Guizhou Provincial People's Hospital were selected and randomly divided into control group (n=29) and dexmedetomidine group (n=29). The dexmedetomidine group was treated with dexmedetomidine before induced anesthesia, while the control group was given the same dose of normal saline; and the normal volunteers of the same age were selected as the normal group (n=29). At 3 days after operation, the levels of serum S100B and nerve growth factor (NGF) in each group were detected using the enzyme-linked immunosorbent assay, and the level of brain-derived neurotrophic factor (BDNF) was detected via western blotting. Montreal cognitive assessment (MoCA) and attention network test (ANT) were performed. Moreover, the cognitive function and attention network function, and the effects of dexmedetomidine on cognitive function and attention network function were evaluated. The concentrations of serum S100B and NGF in dexmedetomidine group was lower than those in control group (P<0.01). The results of western blotting showed that the levels of serum BDNF in control group and dexmedetomidine group were significantly lower than that in normal group (P<0.01), and it was higher in dexmedetomidine group than that in control group (P<0.01). Besides, both MoCA and ANT results revealed that the visual space and executive function scores, attention scores, delayed memory scores, targeted network efficiency and executive control network efficiency in dexmedetomidine group were obviously higher than those in control group (P<0.01). The cognitive function and attention network function of patients with ischemic cerebrovascular disease have a certain degree of damage, and the preoperative administration of dexmedetomidine can effectively improve the patient's cognitive dysfunction and attention network function after operation.

Evidence of the impact of systemic inflammation on neuroinflammation from a non-bacterial endotoxin animal model.

PubMed

Huang, Chunxia; Irwin, Michael Garnet; Wong, Gordon Tin Chun; Chang, Raymond Chuen Chung

2018-05-17

Systemic inflammation induces neuroinflammation and cellular changes such as tau phosphorylation to impair cognitive function, including learning and memory. This study uses a single model, laparotomy without any pathogen, to characterize these changes and their responses to anti-inflammatory treatment in the intermediate term. In a two-part experiment, wild-type C57BL/6N mice (male, 3 month old, 25 ± 2 g) were subjected to sevoflurane anesthesia alone or to a laparotomy. Cognitive performance, systemic and neuroinflammatory responses, and tau phosphorylation were evaluated on postoperative days (POD) 1, 3, and 14. The effect of perioperative ibuprofen intervention (60 mg/kg) on these changes was then assessed. Mice in the laparotomy group displayed memory impairment up to POD 14 with initial high levels of inflammatory cytokines in the liver, frontal cortex (IL-1β, IL-6, and TNF-α), and hippocampus (IL-1β and IL-8). On POD 14, although most circulating and resident cytokine levels returned to normal, a significant number of microglia and astrocytes remained activated in the frontal cortex and microglia in the hippocampus, as well as abnormal tau phosphorylation in these two brain regions. Perioperative ibuprofen improved cognitive performance, attenuated systemic inflammation and glial activation, and suppressed the abnormal tau phosphorylation both in the frontal cortex and hippocampus. Our results suggest that (1) cognitive dysfunction is associated with an unbalanced pro-inflammatory and anti-inflammatory response, tauopathy, and gliosis; (2) cognitive dysfunction, gliosis, and tauopathy following laparotomy can persist well beyond the immediate postoperative period; and (3) anti-inflammatory drugs can act rapidly to attenuate inflammatory responses in the brain and negatively modulate neuropathological changes to improve cognition. These findings may have implications for the duration of therapeutic strategies aimed at curtaining cognitive dysfunction following surgery.