Long-term Ameliorative Effects of the Antidepressant Fluoxetine Exposure on Cognitive Deficits in 3 × TgAD Mice.

PubMed

Jin, Li; Gao, Li-Feng; Sun, Dong-Sheng; Wu, Hao; Wang, Qun; Ke, Dan; Lei, Hao; Wang, Jian-Zhi; Liu, Gong-Ping

2017-08-01

Fluoxetine, a selective serotonin reuptake inhibitor, is neuroprotective; therefore, it has been applied to treat some neurodegenerative disorders. For instance, chronic fluoxetine exposure has short-term effects on Alzheimer's disease (AD). However, the long-term ameliorative effects of fluoxetine exposure on AD have not been reported. In the present study, 6-month-old 3 × TgAD mice were treated with fluoxetine for 15 days, and then the influence of fluoxetine was detected at 20 days after the drug withdrawal. We found that chronic fluoxetine treatment ameliorated cognitive deficits of 3 × TgAD mice and increased the volume of the hippocampal CA1 and dentate gyrus (DG) with increased neuron number and dendritic spine density. Meanwhile, fluoxetine exposure also stimulated the long-term potentiation (LTP) in hippocampal DG. The synaptic-related protein expression increased via activation of the cyclic AMP response element binding (CREB) protein/brain-derived neurotrophic factor (BDNF) signaling pathway induced by fluoxetine exposure. Lastly, we found that fluoxetine treatment decreased beta-amyloid (Aβ) levels. These results further certified that fluoxetine may be a potent effective drug for AD.

Withdrawal From Chronic Nicotine Reduces Thyroid Hormone Levels and Levothyroxine Treatment Ameliorates Nicotine Withdrawal-Induced Deficits in Hippocampus-Dependent Learning in C57BL/6J Mice

PubMed Central

Leach, Prescott T.; Holliday, Erica; Kutlu, Munir G.

2015-01-01

Introduction: Cigarette smoking alters a variety of endocrine systems including thyroid hormones. Altered thyroid hormone signaling may lead to a subclinical or overt hypothyroid condition that could contribute to nicotine withdrawal-related symptoms, such as cognitive deficits. Thus, normalizing thyroid hormone levels may represent a novel therapeutic target for ameliorating nicotine withdrawal-associated cognitive deficits. Methods: The current studies conducted an analysis of serum thyroid hormone levels after chronic and withdrawal from chronic nicotine treatment in C57BL/6J mice using an enzyme-linked immunosorbent assay. The present studies also evaluated the effect of synthetic thyroid hormone (levothyroxine) on contextual and cued memory. Results: The current studies found that nicotine withdrawal reduces secreted thyroid hormone levels by 9% in C57BL/6J mice. Further, supplemental thyroid hormone not only enhanced memory in naïve animals, but also ameliorated deficits in hippocampus-dependent learning associated with nicotine withdrawal. Conclusions: These results suggest that smokers attempting to quit should be monitored closely for changes in thyroid function. If successfully treated, normalization of thyroid hormone levels may ameliorate some deficits associated with nicotine withdrawal and this may lead to higher rates of successful abstinence. PMID:25358661

Selenomethionine ameliorates cognitive decline, reduces tau hyperphosphorylation, and reverses synaptic deficit in the triple transgenic mouse model of Alzheimer's disease.

PubMed

Song, Guoli; Zhang, Zhonghao; Wen, Lei; Chen, Chen; Shi, Qingxue; Zhang, Yu; Ni, Jiazuan; Liu, Qiong

2014-01-01

Disruption of the intracellular balance between free radicals and the antioxidant system is a prominent and early feature in the neuropathology of Alzheimer's disease (AD). Selenium, a vital trace element with known antioxidant potential, has been reported to provide neuroprotection through resisting oxidative damage but its therapeutic effect on AD remains to be investigated. The objective of our study was to investigate the potential of selenomethionine (Se-Met), an organic form of selenium, in the treatment of cognitive dysfunction and neuropathology of triple transgenic AD (3 × Tg-AD) mice. 3 × Tg-AD mice, which were four months old, were treated with Se-Met for 3 months and demonstrated significant improvements in cognitive deficit along with an increased selenium level compared with the untreated control mice. Se-Met treatment significantly reduced the level of total tau and phosphorylated tau, mitigated the decrease of synaptic proteins including synaptophysin and postsynaptic density protein 95 in the hippocampus and cortex of the 3 × Tg-AD mice. Meanwhile, glial activation in AD mice was inhibited and the level of reduced glutathione was increased in the treated mice compared with control mice. Additionally, the expression and activity of glycogen synthase kinase 3β and protein phosphatase 2A, two important enzymes involved in tau phosphorylation, were markedly decreased and increased respectively by Se-Met treatment. Thus Se-Met improves cognitive deficit in a murine model of AD, which is associated with reduction in tau expression and hyperphosphorylation, amelioration of inflammation, and restoration of synaptic proteins and antioxidants. This study provides a novel therapeutic approach for the prevention of AD.

Glucose-Dependent Insulinotropic Polypeptide Ameliorates Mild Traumatic Brain Injury-Induced Cognitive and Sensorimotor Deficits and Neuroinflammation in Rats

PubMed Central

Yu, Yu-Wen; Hsieh, Tsung-Hsun; Chen, Kai-Yun; Wu, John Chung-Che; Hoffer, Barry J.; Greig, Nigel H.; Li, Yazhou; Lai, Jing-Huei; Chang, Cheng-Fu; Lin, Jia-Wei; Chen, Yu-Hsin

2016-01-01

Abstract Mild traumatic brain injury (mTBI) is a major public health issue, representing 75–90% of all cases of TBI. In clinical settings, mTBI, which is defined as a Glascow Coma Scale (GCS) score of 13–15, can lead to various physical, cognitive, emotional, and psychological-related symptoms. To date, there are no pharmaceutical-based therapies to manage the development of the pathological deficits associated with mTBI. In this study, the neurotrophic and neuroprotective properties of glucose-dependent insulinotropic polypeptide (GIP), an incretin similar to glucagon-like peptide-1 (GLP-1), was investigated after its steady-state subcutaneous administration, focusing on behavior after mTBI in an in vivo animal model. The mTBI rat model was generated by a mild controlled cortical impact (mCCI) and used to evaluate the therapeutic potential of GIP. We used the Morris water maze and novel object recognition tests, which are tasks for spatial and recognition memory, respectively, to identify the putative therapeutic effects of GIP on cognitive function. Further, beam walking and the adhesive removal tests were used to evaluate locomotor activity and somatosensory functions in rats with and without GIP administration after mCCI lesion. Lastly, we used immunohistochemical (IHC) staining and Western blot analyses to evaluate the inflammatory markers, glial fibrillary acidic protein (GFAP), amyloid-β precursor protein (APP), and bone marrow tyrosine kinase gene in chromosome X (BMX) in animals with mTBI. GIP was well tolerated and ameliorated mTBI-induced memory impairments, poor balance, and sensorimotor deficits after initiation in the post-injury period. In addition, GIP mitigated mTBI-induced neuroinflammatory changes on GFAP, APP, and BMX protein levels. These findings suggest GIP has significant benefits in managing mTBI-related symptoms and represents a novel strategy for mTBI treatment. PMID:26972789

Glucose-Dependent Insulinotropic Polypeptide Ameliorates Mild Traumatic Brain Injury-Induced Cognitive and Sensorimotor Deficits and Neuroinflammation in Rats.

PubMed

Yu, Yu-Wen; Hsieh, Tsung-Hsun; Chen, Kai-Yun; Wu, John Chung-Che; Hoffer, Barry J; Greig, Nigel H; Li, Yazhou; Lai, Jing-Huei; Chang, Cheng-Fu; Lin, Jia-Wei; Chen, Yu-Hsin; Yang, Liang-Yo; Chiang, Yung-Hsiao

2016-11-15

Mild traumatic brain injury (mTBI) is a major public health issue, representing 75-90% of all cases of TBI. In clinical settings, mTBI, which is defined as a Glascow Coma Scale (GCS) score of 13-15, can lead to various physical, cognitive, emotional, and psychological-related symptoms. To date, there are no pharmaceutical-based therapies to manage the development of the pathological deficits associated with mTBI. In this study, the neurotrophic and neuroprotective properties of glucose-dependent insulinotropic polypeptide (GIP), an incretin similar to glucagon-like peptide-1 (GLP-1), was investigated after its steady-state subcutaneous administration, focusing on behavior after mTBI in an in vivo animal model. The mTBI rat model was generated by a mild controlled cortical impact (mCCI) and used to evaluate the therapeutic potential of GIP. We used the Morris water maze and novel object recognition tests, which are tasks for spatial and recognition memory, respectively, to identify the putative therapeutic effects of GIP on cognitive function. Further, beam walking and the adhesive removal tests were used to evaluate locomotor activity and somatosensory functions in rats with and without GIP administration after mCCI lesion. Lastly, we used immunohistochemical (IHC) staining and Western blot analyses to evaluate the inflammatory markers, glial fibrillary acidic protein (GFAP), amyloid-β precursor protein (APP), and bone marrow tyrosine kinase gene in chromosome X (BMX) in animals with mTBI. GIP was well tolerated and ameliorated mTBI-induced memory impairments, poor balance, and sensorimotor deficits after initiation in the post-injury period. In addition, GIP mitigated mTBI-induced neuroinflammatory changes on GFAP, APP, and BMX protein levels. These findings suggest GIP has significant benefits in managing mTBI-related symptoms and represents a novel strategy for mTBI treatment.

Enriched environment ameliorates depression-induced cognitive deficits and restores abnormal hippocampal synaptic plasticity.

PubMed

Mahati, K; Bhagya, V; Christofer, T; Sneha, A; Shankaranarayana Rao, B S

2016-10-01

Severe depression compromises structural and functional integrity of the brain and results in impaired learning and memory, maladaptive synaptic plasticity as well as degenerative changes in the hippocampus and amygdala. The precise mechanisms underlying cognitive dysfunctions in depression remain largely unknown. On the other hand, enriched environment (EE) offers beneficial effects on cognitive functions, synaptic plasticity in the hippocampus. However, the effect of EE on endogenous depression associated cognitive dysfunction has not been explored. Accordingly, we have attempted to address this issue by investigating behavioural, structural and synaptic plasticity mechanisms in an animal model of endogenous depression after exposure to enriched environment. Our results demonstrate that depression is associated with impaired spatial learning and enhanced anxiety-like behaviour which is correlated with hypotrophy of the dentate gyrus and amygdalar hypertrophy. We also observed a gross reduction in the hippocampal long-term potentiation (LTP). We report a complete behavioural recovery with reduced indices of anhedonia and behavioural despair, reduced anxiety-like behaviour and improved spatial learning along with a complete restoration of dentate gyrus and amygdalar volumes in depressive rats subjected to EE. Enrichment also facilitated CA3-Schaffer collateral LTP. Our study convincingly proves that depression-induces learning deficits and impairs hippocampal synaptic plasticity. It also highlights the role of environmental stimuli in restoring depression-induced cognitive deficits which might prove vital in outlining more effective strategies to treat major depressive disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

Cognitive deficits caused by prefrontal cortical and hippocampal neural disinhibition.

PubMed

Bast, Tobias; Pezze, Marie; McGarrity, Stephanie

2017-10-01

contributes to clinically relevant cognitive deficits, and we consider pharmacological strategies for ameliorating cognitive deficits by rebalancing disinhibition-induced aberrant neural activity. 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.

Animal model of dementia induced by entorhinal synaptic damage and partial restoration of cognitive deficits by BDNF and carnitine.

PubMed

Ando, Susumu; Kobayashi, Satoru; Waki, Hatsue; Kon, Kazuo; Fukui, Fumiko; Tadenuma, Tomoko; Iwamoto, Machiko; Takeda, Yasuo; Izumiyama, Naotaka; Watanabe, Kazutada; Nakamura, Hiroaki

2002-11-01

A rat dementia model with cognitive deficits was generated by synapse-specific lesions using botulinum neurotoxin (BoNTx) type B in the entorhinal cortex. To detect cognitive deficits, different tasks were needed depending upon the age of the model animals. Impaired learning and memory with lesions were observed in adult rats using the Hebb-Williams maze, AKON-1 maze and a continuous alternation task in T-maze. Cognitive deficits in lesioned aged rats were detected by a continuous alternation and delayed non-matching-to-sample tasks in T-maze. Adenovirus-mediated BDNF gene expression enhanced neuronal plasticity, as revealed by behavioral tests and LTP formation. Chronic administration of carnitine over time pre- and post-lesions seemed to partially ameliorate the cognitive deficits caused by the synaptic lesion. The carnitine-accelerated recovery from synaptic damage was observed by electron microscopy. These results demonstrate that the BoNTx-lesioned rat can be used as a model for dementia and that cognitive deficits can be alleviated in part by BDNF gene transfer or carnitine administration. Copyright 2002 Wiley-Liss, Inc.

Diet-Induced Cognitive Deficits: The Role of Fat and Sugar, Potential Mechanisms and Nutritional Interventions

PubMed Central

Beilharz, Jessica E.; Maniam, Jayanthi; Morris, Margaret J.

2015-01-01

It is of vital importance to understand how the foods which are making us fat also act to impair cognition. In this review, we compare the effects of acute and chronic exposure to high-energy diets on cognition and examine the relative contributions of fat (saturated and polyunsaturated) and sugar to these deficits. Hippocampal-dependent memory appears to be particularly vulnerable to the effects of high-energy diets and these deficits can occur rapidly and prior to weight gain. More chronic diet exposure seems necessary however to impair other sorts of memory. Many potential mechanisms have been proposed to underlie diet-induced cognitive decline and we will focus on inflammation and the neurotrophic factor, brain-derived neurotrophic factor (BDNF). Finally, given supplementation of diets with omega-3 and curcumin has been shown to have positive effects on cognitive function in healthy ageing humans and in disease states, we will discuss how these nutritional interventions may attenuate diet-induced cognitive decline. We hope this approach will provide important insights into the causes of diet-induced cognitive deficits, and inform the development of novel therapeutics to prevent or ameliorate such memory impairments. PMID:26274972

Diet-Induced Cognitive Deficits: The Role of Fat and Sugar, Potential Mechanisms and Nutritional Interventions.

PubMed

Beilharz, Jessica E; Maniam, Jayanthi; Morris, Margaret J

2015-08-12

It is of vital importance to understand how the foods which are making us fat also act to impair cognition. In this review, we compare the effects of acute and chronic exposure to high-energy diets on cognition and examine the relative contributions of fat (saturated and polyunsaturated) and sugar to these deficits. Hippocampal-dependent memory appears to be particularly vulnerable to the effects of high-energy diets and these deficits can occur rapidly and prior to weight gain. More chronic diet exposure seems necessary however to impair other sorts of memory. Many potential mechanisms have been proposed to underlie diet-induced cognitive decline and we will focus on inflammation and the neurotrophic factor, brain-derived neurotrophic factor (BDNF). Finally, given supplementation of diets with omega-3 and curcumin has been shown to have positive effects on cognitive function in healthy ageing humans and in disease states, we will discuss how these nutritional interventions may attenuate diet-induced cognitive decline. We hope this approach will provide important insights into the causes of diet-induced cognitive deficits, and inform the development of novel therapeutics to prevent or ameliorate such memory impairments.

Biflorin Ameliorates Memory Impairments Induced by Cholinergic Blockade in Mice

PubMed Central

Jeon, Se Jin; Kim, Boseong; Ryu, Byeol; Kim, Eunji; Lee, Sunhee; Jang, Dae Sik; Ryu, Jong Hoon

2017-01-01

To examine the effect of biflorin, a component of Syzygium aromaticum, on memory deficit, we introduced a scopolamine-induced cognitive deficit mouse model. A single administration of biflorin increased latency time in the passive avoidance task, ameliorated alternation behavior in the Y-maze, and increased exploration time in the Morris water maze task, indicating the improvement of cognitive behaviors against cholinergic dysfunction. The biflorin-induced reverse of latency in the scopolamine-treated group was attenuated by MK-801, an NMDA receptor antagonist. Biflorin also enhanced cognitive function in a naïve mouse model. To understand the mechanism of biflorin for memory amelioration, we performed Western blot. Biflorin increased the activation of protein kinase C-ζ and its downstream signaling molecules in the hippocampus. These results suggest that biflorin ameliorates drug-induced memory impairment by modulation of protein kinase C-ζ signaling in mice, implying that biflorin could function as a possible therapeutic agent for the treatment of cognitive problems. PMID:27829270

Bacopa monnieri ameliorates memory deficits in olfactory bulbectomized mice: possible involvement of glutamatergic and cholinergic systems.

PubMed

Le, Xoan Thi; Pham, Hang Thi Nguyet; Do, Phuong Thi; Fujiwara, Hironori; Tanaka, Ken; Li, Feng; Van Nguyen, Tai; Nguyen, Khoi Minh; Matsumoto, Kinzo

2013-10-01

This study investigated the effects of alcoholic extract of Bacopa monnieri (L.) Wettst. (BM) on cognitive deficits using olfactory bulbectomized (OBX) mice and the underlying molecular mechanisms of its action. OBX mice were treated daily with BM (50 mg/kg, p.o.) or a reference drug, tacrine (2.5 mg/kg, i.p.), 1 week before and continuously 3 days after OBX. Cognitive performance of the animals was analyzed by the novel object recognition test, modified Y maze test, and fear conditioning test. Brain tissues of OBX animals were used for neurochemical and immunohistochemical studies. OBX impaired non-spatial short-term memory, spatial working memory, and long-term fair memory. BM administration ameliorated these memory disturbances. The effect of BM on short-term memory deficits was abolished by a muscarinic receptor antagonist, scopolamine. OBX downregulated phosphorylation of synaptic plasticity-related signaling proteins: NR1 subunit of N-methyl-D-aspartate receptor, glutamate receptor 1 (GluR1), and calmodulin-dependent kinase II but not cyclic AMP-responsive element binding protein (CREB), and reduced brain-derived neurotrophic factor (BDNF) mRNA in the hippocampus. OBX also reduced choline acetyltransferase in the hippocampus and cholinergic neurons in the medial septum, and enlarged the size of lateral ventricle. BM administration reversed these OBX-induced neurochemical and histological alterations, except the decrease of GluR1 phosphorylation, and enhanced CREB phosphorylation. Moreover, BM treatment inhibited ex vivo activity of acetylcholinesterase in the brain. These results indicate that BM treatment ameliorates OBX-induced cognition dysfunction via a mechanism involving enhancement of synaptic plasticity-related signaling and BDNF transcription and protection of cholinergic systems from OBX-induced neuronal damage.

Edaravone injection ameliorates cognitive deficits in rat model of Alzheimer's disease.

PubMed

Yang, Rui; Wang, Qingjun; Li, Fang; Li, Jian; Liu, Xuewen

2015-11-01

Oxidative stress plays important role in the pathogenesis of Alzheimer's disease (AD). Edaravone is a potent free radical scavenger that exerts antioxidant effects. Therefore, in this study we aimed to investigate neuroprotective effects of edaravone for AD. Wistar rats were randomly divided into three groups (n = 15): control group, model group, and treatment group, which were injected with phosphate buffered saline, Aβ1-40, and Aβ1-40 together with 5 mg/kg edaravone, respectively, into the right hippocampal dentate gyrus. Spatial learning and memory of the rats were examined by Morris water maze test. 4-Hydroxynonenal (4-HNE) level in rat hippocampus was analyzed by immunohistochemistry. Acetylcholinesterase (AChE) and choline acetylase (ChAT) activities were assayed by commercial kits. We found that edaravone ameliorated spatial learning and memory deficits in the rats. 4-HNE level in the hippocampus as well as AChE and ChAT activities in the hippocampus was significantly lower in treatment group than in model group. In conclusion, edaravone may be developed as a novel agent for the treatment of AD for improving cholinergic system and protecting neurons from oxidative toxicity.

Cognitive Deficits in Schizophrenia: Focus on Neuronal Nicotinic Acetylcholine Receptors and Smoking

PubMed Central

Lasalde-Dominicci, Jose

2015-01-01

Patients with schizophrenia present with deficits in specific areas of cognition. These are quantifiable by neuropsychological testing and can be clinically observable as negative signs. Concomitantly, they self-administer nicotine in the form of cigarette smoking. Nicotine dependence is more prevalent in this patient population when compared to other psychiatric conditions or to non-mentally ill people. The target for nicotine is the neuronal nicotinic acetylcholine receptor (nAChR). There is ample evidence that these receptors are involved in normal cognitive operations within the brain. This review describes neuronal nAChR structure and function, focusing on both cholinergic agonist-induced nAChR desensitization and nAChR up-regulation. The several mechanisms proposed for the nAChR up-regulation are examined in detail. Desensitization and up-regulation of nAChRs may be relevant to the physiopathology of schizophrenia. The participation of several subtypes of neuronal nAChRs in the cognitive processing of non-mentally ill persons and schizophrenic patients is reviewed. The role of smoking is then examined as a possible cognitive remediator in this psychiatric condition. Finally, pharmacological strategies focused on neuronal nAChRs are discussed as possible therapeutic avenues that may ameliorate the cognitive deficits of schizophrenia. PMID:17554626

N-Acetylcysteine improves mitochondrial function and ameliorates behavioral deficits in the R6/1 mouse model of Huntington's disease

PubMed Central

Wright, D J; Renoir, T; Smith, Z M; Frazier, A E; Francis, P S; Thorburn, D R; McGee, S L; Hannan, A J; Gray, L J

2015-01-01

Huntington's disease (HD) is a neurodegenerative disorder, involving psychiatric, cognitive and motor symptoms, caused by a CAG-repeat expansion encoding an extended polyglutamine tract in the huntingtin protein. Oxidative stress and excitotoxicity have previously been implicated in the pathogenesis of HD. We hypothesized that N-acetylcysteine (NAC) may reduce both excitotoxicity and oxidative stress through its actions on glutamate reuptake and antioxidant capacity. The R6/1 transgenic mouse model of HD was used to investigate the effects of NAC on HD pathology. It was found that chronic NAC administration delayed the onset and progression of motor deficits in R6/1 mice, while having an antidepressant-like effect on both R6/1 and wild-type mice. A deficit in the astrocytic glutamate transporter protein, GLT-1, was found in R6/1 mice. However, this deficit was not ameliorated by NAC, implying that the therapeutic effect of NAC is not due to rescue of the GLT-1 deficit and associated glutamate-induced excitotoxicity. Assessment of mitochondrial function in the striatum and cortex revealed that R6/1 mice show reduced mitochondrial respiratory capacity specific to the striatum. This deficit was rescued by chronic treatment with NAC. There was a selective increase in markers of oxidative damage in mitochondria, which was rescued by NAC. In conclusion, NAC is able to delay the onset of motor deficits in the R6/1 model of Huntington's disease and it may do so by ameliorating mitochondrial dysfunction. Thus, NAC shows promise as a potential therapeutic agent in HD. Furthermore, our data suggest that NAC may also have broader antidepressant efficacy. PMID:25562842

Curcumin attenuates inflammatory response and cognitive deficits in experimental model of chronic epilepsy.

PubMed

Kaur, Harpreet; Patro, Ishan; Tikoo, Kulbhushan; Sandhir, Rajat

2015-10-01

Evidence suggests that glial cells play a critical role in inflammation in chronic epilepsy, contributing to perpetuation of seizures and cognitive dysfunctions. The present study was designed to evaluate the beneficial effect of curcumin, a polyphenol with pleiotropic properties, on cognitive deficits and inflammation in chronic epilepsy. Kindled model of epilepsy was induced by administering sub-convulsive dose of pentylenetetrazole (PTZ) at 40 mg/kg, i.p. every alternative day for 30 days to Wistar rats. The animals were assessed for cognitive deficits by Morris water maze and inflammatory response in terms of microglial and astrocyte activation. PTZ treated animals had increased escape latency suggesting impaired cognitive functions. Further, an increased expression of astrocyte (GFAP) and microglial (Iba-1) activation markers were observed in terms of mRNA and protein levels in the PTZ treated animals. Concomitantly, mRNA and protein levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and chemokine (MCP-1) were increased in hippocampus and cortex. Immunoreactivity to anti-GFAP and anti-Iba-1 antibodies was also enhanced in hippocampus and cortex suggesting gliosis in PTZ treated animals. However, curcumin administration at a dose of 100 mg/kg to PTZ animals prevented cognitive deficits. A significant decrease in pro-inflammatory cytokines and chemokine expression was observed in hippocampus and cortex of PTZ treated rats supplemented with curcumin. In addition, curcumin also attenuated increased expression of GFAP and Iba-1 in animals with PTZ induced chronic epilepsy. Moreover, immunohistochemical analysis also showed significant reduction in number of activated glial cells on curcumin administration to PTZ treated animals. Taken together, these findings suggest that curcumin is effective in attenuating glial activation and ameliorates cognitive deficits in chronic epilepsy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Huperzine A Ameliorates Cognitive Deficits in Streptozotocin-Induced Diabetic Rats

PubMed Central

Mao, Xiao-Yuan; Cao, Dan-Feng; Li, Xi; Yin, Ji-Ye; Wang, Zhi-Bin; Zhang, Ying; Mao, Chen-Xue; Zhou, Hong-Hao; Liu, Zhao-Qian

2014-01-01

The present study was designed to probe the effects of Huperzine A (HupA) on diabetes-associated cognitive decline (DACD) using a streptozotocin (STZ)-injected rat model. Diabetic rats were treated with HupA (0.05 and 0.1 mg/kg) for seven weeks. Memory functions were evaluated by the water maze test. Nissl staining was selected for detecting neuronal loss. Protein and mRNA levels of brain-derived neurotrophic factor (BDNF) were analyzed by ELISA and real-time PCR, respectively. The activities of choline acetylase (ChAT), Acetylcholinesterase (AChE), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), NF-κB p65 unit, TNF-α, IL-1β, IL-6 and caspase-3 were measured using corresponding kits. After seven weeks, diabetic rats exhibited remarkable reductions in: body weight, percentage of time spent in target quadrant, number of times crossing the platform, ChAT and BDNF levels, SOD, GSH-Px and CAT accompanied with increases in neuronal damage, plasma glucose levels, escape latency, mean path length, AChE, MDA level as well as CAT, NF-κB p65 unit, TNF-α, IL-1β, IL-6 and caspase-3 in cerebral cortex and hippocampus. Supplementation with HupA significantly and dose-dependently reversed the corresponding values in diabetes. It is concluded that HupA ameliorates DACD via modulating BDNF, oxidative stress, inflammation and apoptosis. PMID:24857910

Methylthioninium chloride reverses cognitive deficits induced by scopolamine: comparison with rivastigmine.

PubMed

Deiana, Serena; Harrington, Charles R; Wischik, Claude M; Riedel, Gernot

2009-01-01

The cholinergic system is involved in cognition as well as in age-related cognitive decline and Alzheimer disease (AD). Cholinergic enhancers ameliorate AD symptoms and represent the main current therapy for AD. MTC (Methylthioninium chloride), an antioxidant with metabolism-enhancing properties may be a novel candidate with pro-cognitive capacities. This study was performed: (1) to assess the pro-cognitive efficacy of MTC and establish its dose-response; (2) to compare the efficacy of MTC with rivastigmine and (3) to determine the potential for combination therapy by co-administration of MTC and rivastigmine. Spatial cognition of female NMRI mice was tested in a reference memory water maze task. Subjects received intra-peritoneal injections of scopolamine (0.5 mg/kg) followed by vehicle, and/or MTC and/or rivastigmine (0.15-4 mg/kg MTC; 0.1-0.5 mg/kg rivastigmine) in mono or combination treatment. Scopolamine treatment prevented spatial learning in NMRI female mice and the deficit was reversed by both rivastigmine and MTC in a dose-dependent manner. Mono-therapy with high doses of rivastigmine (>0.5 mg/kg) caused severe side effects but MTC was safe up to 4 mg/kg. Co-administration of sub-effective doses of both drugs acted synergistically in reversing learning deficits and scopolamine-induced memory impairments. In our model, MTC reversed the spatial learning impairment. When combined with the ChEI rivastigmine, the effect of MTC appeared to be amplified indicating that combination therapy could potentially improve not only symptoms but also contribute beneficially to neuronal metabolism by minimising side effects at lower doses.

Beta-hydroxy-beta-methylbutyrate (HMB) ameliorates age-related deficits in water maze performance, especially in male rats.

PubMed

Kougias, Daniel G; Hankosky, Emily R; Gulley, Joshua M; Juraska, Janice M

2017-03-01

Beta-hydroxy-beta-methylbutyrate (HMB) is commonly supplemented to maintain muscle in elderly and clinical populations and has potential as a nootropic. Previously, we have shown that in both male and female rats, long-term HMB supplementation prevents age-related dendritic shrinkage within the medial prefrontal cortex (mPFC) and improves cognitive flexibility and working memory performance that are both age- and sex-specific. In this study, we further explore the cognitive effects by assessing visuospatial learning and memory with the Morris water maze. Female rats were ovariectomized at 11months of age to model human menopause. At 12months of age, male and female rats received relatively short- or long-term (1- or 7-month) dietary HMB (450mg/kg/dose) supplementation twice a day prior to testing. Spatial reference learning and memory was assessed across four days in the water maze with four trials daily and a probe trial on the last day. Consistent with previous work, there were age-related deficits in water maze performance in both sexes. However, these deficits were ameliorated in HMB-treated males during training and in both sexes during probe trial performance. Thus, HMB supplementation prevented the age-related decrement in water maze performance, especially in male rats. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of environmental enrichment on behavioral and spatial cognitive deficits in morphine-dependent and -withdrawn rats.

PubMed

Hammami-Abrand Abadi, Arezoo; Miladi-Gorji, Hossein

2017-02-01

This study was designed to examine the effect of environmental enrichment during morphine dependence and withdrawal on morphine-induced behavioral and spatial cognitive disorders in morphine-withdrawn rats. Adult male Wistar rats (190 ± 20 g) were injected with bi-daily doses (10 mg/kg, 12 h intervals) of morphine for 14 days. Rats were reared in SE or EE during the development of dependence on morphine and withdrawal. Then, rats were tested for spatial learning and memory (the water maze), spontaneous withdrawal signs, and grooming behavior. We found that the EE blocked chronic morphine-induced partial impairments of spatial memory retention. Moreover, the EE diminished the occurrence of spontaneous morphine withdrawal signs as mild and the self-grooming behavior. Our findings showed that EE ameliorates chronic morphine-induced partial deficits of spatial cognition, obsessive-like behavior, and the overall severity of the morphine withdrawal. Thus, environmental enrichment may be a potential therapeutic strategy for spatial memory and behavioral deficits in morphine-dependent individuals.

Do cognitive deficits predict negative emotionality and aggression in schizophrenia?

PubMed

Ahmed, Anthony O; Richardson, Jenae; Buckner, Alex; Romanoff, Sabrina; Feder, Michelle; Oragunye, Njideka; Ilnicki, Andriana; Bhat, Ishrat; Hoptman, Matthew J; Lindenmayer, Jean-Pierre

2018-01-01

Schizophrenia is associated with an elevated risk of aggression. Cognitive deficits have been associated with inpatient aggression and future violence. The relationship between cognitive deficits and violent behavior has however been inconsistent across studies. In addition, studies have failed to inform how cognitive deficits may contribute to aggression in schizophrenia. The current study examined the association of cognitive deficits with schizophrenia-related aggression and violent offending. It also explored the putative mediating role of negative emotionality on the impact of cognitive deficits on aggression. People with schizophrenia and schizoaffective disorder (N = 78) were recruited from a state hospital. Participants were classified based on their history of violent offending. Participants completed measures of cognition, symptoms, and aggression. Deficits in working memory, reasoning/problem-solving, and verbal learning were the most prioritized for the prediction of violent offender status. Violent offenders demonstrated greater impairments in most cognitive domains especially working memory and verbal learning. Offenders also demonstrated greater negative emotionality, excitement/agitation, and incidents of verbal and physical aggression. Negative emotionality and excitement/agitation fully transmitted the effect of cognitive deficits on impulsive aggression in meditational models. Cognitive deficits increase the risk of impulsive aggression in schizophrenia via inefficient regulation of negative affective states. Copyright © 2017 Elsevier B.V. All rights reserved.

[Neurocognitive deficit and social cognition in schizophrenia].

PubMed

Rychkova, O V; Gurevich, G L

2012-01-01

To study the association between neurocognitive deficit and impairment of social cognition in schizophrenia, we assessed 30 patients and 30 healthy people (controls) using clinical, psychometric and psychological tests. Based on the results obtained in the study, authors could single out a specific block of impairment which was not associated with perceptive and gnostic deficits. The data confirmed the significant contribution of deficit neurodynamic and regulatory parameters in the impairment of social cognition in schizophrenia.

A Multiple Deficit Model of Reading Disability and Attention-Deficit/Hyperactivity Disorder: Searching for Shared Cognitive Deficits

ERIC Educational Resources Information Center

McGrath, Lauren M.; Pennington, Bruce F.; Shanahan, Michelle A.; Santerre-Lemmon, Laura E.; Barnard, Holly D.; Willcutt, Erik G.; DeFries, John C.; Olson, Richard K.

2011-01-01

Background: This study tests a multiple cognitive deficit model of reading disability (RD), attention-deficit/hyperactivity disorder (ADHD), and their comorbidity. Methods: A structural equation model (SEM) of multiple cognitive risk factors and symptom outcome variables was constructed. The model included phonological awareness as a unique…

Agmatine for combined treatment of epilepsy, depression and cognitive impairment in chronic epileptic animals.

PubMed

Singh, Tanveer; Bagga, Neetu; Kaur, Anureet; Kaur, Navjot; Gawande, Dinesh Yugraj; Goel, Rajesh Kumar

2017-08-01

Epilepsy is fourth most common neurological disorders associated with depression and cognitive deficits. As per present scenario, none of the antiseizure drugs have been reported successful to have ameliorative effect on epilepsy associated depression and cognitive deficits. Thus, the study was envisioned to assess an ameliorative potential of agmatine on epilepsy and its efficacy and safety for management of associated depression and cognitive deficits. The animals were made epileptic employing pentylenetetrazole (35mg/kg i.p. every 48±2h) kindling model of epilepsy and subsequently were treated with vehicle, valproic acid (300mg/kg/day i.p.) and agmatine (2.5, 5, and 10mg/kg)/day/i.p. for 15days. Except naïve, all the groups were challenged with same pentylenetetrazole dose as employed during kindling on days 5, 10, and 15 to evaluate seizure severity. Two hours after seizure severity test, tail suspension test and passive shock avoidance paradigm was employed to evaluate depression and cognitive behavior respectively. Results suggested that epileptic animals were significantly associated with depression and cognitive impairment. Chronic valproate treatment significantly reduced seizure severity, but was found unable to mitigate depression and cognitive deficits. However, agmatine treatment dose dependently ameliorated seizure severity as well as associated depression and cognitive deficits. On 15th day, animals were euthanized and pertinent neurochemical estimations were carried out in cortical and hippocampal areas of the mice brain. Thus, study concluded that agmatine ameliorated seizure severity, depression and cognitive impairment in epileptic animals, possibly via restoring glutamate-GABA neurotransmission and serotonin synthesis with decreased nitrosative stress. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Glycogen synthase kinase-3 inhibitors reverse deficits in long-term potentiation and cognition in Fragile X mice

PubMed Central

Franklin, Aimee V.; King, Margaret K.; Palomo, Valle; Martinez, Ana; McMahon, Lori L.; Jope, Richard S.

2013-01-01

Background Identifying feasible therapeutic interventions is crucial for ameliorating the intellectual disability and other afflictions of Fragile X Syndrome (FXS), the most common inherited cause of intellectual disability and autism. Hippocampal glycogen synthase kinase-3 (GSK3) is hyperactive in the mouse model of FXS (FX mice), and hyperactive GSK3 promotes locomotor hyperactivity and audiogenic seizure susceptibility in FX mice, raising the possibility that specific GSK3 inhibitors may improve cognitive processes. Methods We tested if specific GSK3 inhibitors improve deficits in N-methyl-D-aspartate receptor (NMDAR)-dependent long term potentiation (LTP) at medial perforant path synapses onto dentate granule cells (MPP-DGC) and dentate gyrus-dependent cognitive behavioral tasks. Results GSK3 inhibitors completely rescued deficits in LTP at MPP-DGC synapses in FX mice. Furthermore, synaptosomes from the dentate gyrus of FX mice displayed decreased inhibitory serine-phosphorylation of GSK3β compared with wild-type littermates. The potential therapeutic utility of GSK3 inhibitors was further tested on dentate gyrus-dependent congnitive behaviors. In vivo administration of GSK3 inhibitors completely reversed impairments in several cognitive tasks in FX mice, including novel object detection, coordinate and categorical spatial processing, and temporal ordering for visual objects. Conclusions These findings establish that synaptic plasticity and cognitive deficits in FX mice can be improved by intervention with inhibitors of GSK3, which may prove therapeutically beneficial in FXS. PMID:24041505

Comparison of the effect of three licorice varieties on cognitive improvement via an amelioration of neuroinflammation in lipopolysaccharide-induced mice.

PubMed

Cho, Min Ji; Kim, Ji Hyun; Park, Chan Hum; Lee, Ah Young; Shin, Yu Su; Lee, Jeong Hoon; Park, Chun Geun; Cho, Eun Ju

2018-06-01

Neuroinflammation plays critical role in neurodegenerative disorders, such as Alzheimer's disease (AD). We investigated the effect of three licorice varieties, Glycyrhiza uralensis , G. glabra , and Shinwongam (SW) on a mouse model of inflammation-induced memory and cognitive deficit. C57BL/6 mice were injected with lipopolysaccharide (LPS; 2.5 mg/kg, intraperitoneally) and orally administrated G. uralensis , G. glabra , and SW extract (150 mg/kg/day). SW, a new species of licorice in Korea, was combined with G. uralensis and G. glabra . Behavioral tests, including the T-maze, novel object recognition and Morris water maze, were carried out to assess learning and memory. In addition, the expressions of inflammation-related proteins in brain tissue were measured by western blotting. There was a significant decrease in spatial and objective recognition memory in LPS-induced cognitive impairment group, as measured by the T-maze and novel object recognition test; however, the administration of licorice ameliorated these deficits. In addition, licorice-treated groups exhibited improved learning and memory ability in the Morris water maze. Furthermore, LPS-injected mice had up-regulated pro-inflammatory proteins, such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2, interleukin-6, via activation of toll like receptor 4 (TLR4) and nuclear factor-kappa B (NFκB) pathways in the brain. However, these were attenuated by following administration of the three licorice varieties. Interestingly, the SW-administered group showed greater inhibition of iNOS and TLR4 when compared with the other licorice varieties. Furthermore, there was a significant increase in the expression of brain-derived neurotrophic factor (BDNF) in the brain of LPS-induced cognitively impaired mice that were administered licorice, with the greatest effect following SW treatment. The three licorice varieties ameliorated the inflammation-induced cognitive dysfunction by down

Gypenosides ameliorate memory deficits in MPTP-lesioned mouse model of Parkinson's disease treated with L-DOPA.

PubMed

Zhao, Ting Ting; Kim, Kyung Sook; Shin, Keon Sung; Park, Hyun Jin; Kim, Hyun Jeong; Lee, Kyung Eun; Lee, Myung Koo

2017-09-06

Previous studies have revealed that gypenosides (GPS) improve the symptoms of anxiety disorders in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned rat model of Parkinson's disease (PD). The present study aimed to investigate the effects of GPS on memory deficits in an MPTP-lesioned mouse model of PD treated with L-3,4-dihydroxyphenylalanine (L-DOPA). MPTP (30 mg/kg/day, 5 days)-lesioned mice were treated with GPS (50 mg/kg) and/or L-DOPA (10 and 25 mg/kg) for 21 days. After the final treatments, behavioral changes were assessed in all mice using passive avoidance and elevated plus-maze tests. We then evaluated the biochemical influences of GPS treatment on levels of tyrosine hydroxylase (TH), dopamine, N-methyl-D-aspartate (NMDA) receptors, extracellular signal-regulated kinase (ERK1/2), and cyclic AMP-response element binding protein (CREB) phosphorylation. MPTP-lesioned mice exhibited deficits associated with habit learning and spatial memory, which were further aggravated by treatment with L-DOPA (25 mg/kg). However, treatment with GPS (50 mg/kg) ameliorated memory deficits. Treatment with GPS (50 mg/kg) also improved L-DOPA (25 mg/kg)-treated MPTP lesion-induced decreases in retention latency on the passive avoidance test, as well as levels of TH-immunopositive cells and dopamine in the substantia nigra and striatum. GPS treatment also attenuated increases in retention transfer latency on the elevated plus-maze test and in NMDA receptor expression, as well as decreases in the phosphorylation of ERK1/2 and CREB in the hippocampus. Treatment with L-DOPA (10 mg/kg) also ameliorated deficits in habit learning and spatial memory in MPTP-lesioned mice, and this effect was further enhanced by treatment with GPS (50 mg/kg). GPS ameliorate deficits in habit learning and spatial memory by modulating the dopaminergic neuronal and N-methyl-D-aspartate receptor-mediated signaling systems in MPTP-lesioned mice treated with L-DOPA. GPS may serve as an adjuvant

Common Cognitive Deficits in Children with Attention-Deficit/Hyperactivity Disorder and Autism: Working Memory and Visual-Motor Integration

ERIC Educational Resources Information Center

Englund, Julia A.; Decker, Scott L.; Allen, Ryan A.; Roberts, Alycia M.

2014-01-01

Cognitive deficits in working memory (WM) are characteristic features of Attention-Deficit/Hyperactivity Disorder (ADHD) and autism. However, few studies have investigated cognitive deficits using a wide range of cognitive measures. We compared children with ADHD ("n" = 49) and autism ("n" = 33) with a demographically matched…

Oculomotor Performance Identifies Underlying Cognitive Deficits in Attention-Deficit/Hyperactivity Disorder

ERIC Educational Resources Information Center

Loe, Irene M.; Feldman, Heidi M.; Yasui, Enami; Luna, Beatriz

2009-01-01

The evaluation of the cognitive control in children with attention-deficit hyperactivity disorder through the use of oculomotor tests reveal that this group showed susceptibility to peripheral distractors and deficits in response inhibition. All subjects were found to have intact sensorimotor function and working memory.

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.

Cognitive Deficits and Positively Biased Self-Perceptions in Children with ADHD

PubMed Central

McQuade, Julia D.; Tomb, Meghan; Hoza, Betsy; Waschbusch, Daniel A.; Hurt, Elizabeth A.; Vaughn, Aaron J.

2011-01-01

This study examined the relation between cognitive deficits and positive bias in a sample of 272 children with and without Attention Deficit Hyperactivity Disorder (ADHD; 7–12 years old). Results indicated that children with ADHD with and without biased self-perceptions exhibit differences in specific cognitive deficits (executive processes, working memory, broad attention, and cognitive fluency) compared to each other and to control children. Further, specific cognitive deficits emerged as partial mediators of the relation between ADHD diagnostic status and positive bias. Interestingly, some differences in results emerged based on the domain considered (academic, social, behavioral competence). Results lend initial support to the role of cognitive deficits in the positive bias of some children with ADHD. Implications for future research and intervention are discussed. PMID:20820902

Electroacupuncture ameliorates cognitive impairment through inhibition of NF-κB-mediated neuronal cell apoptosis in cerebral ischemia-reperfusion injured rats.

PubMed

Feng, Xiaodong; Yang, Shanli; Liu, Jiao; Huang, Jia; Peng, Jun; Lin, Jiumao; Tao, Jing; Chen, Lidian

2013-05-01

Cognitive impairment is a serious mental deficit following stroke that severely affects the quality of life of stroke survivors. Nuclear factor‑κB (NF-κB)-mediated neuronal cell apoptosis is involved in the development of post-stroke cognitive impairment; therefore, it has become a promising target for the treatment of impaired cognition. Acupuncture at the Baihui (DU20) and Shenting (DU24) acupoints is commonly used in China to clinically treat post‑stroke cognitive impairment; however, the precise mechanism of its action is largely unknown. In the present study, we evaluated the therapeutic efficacy of electroacupuncture against post-stroke cognitive impairment and investigated the underlying molecular mechanisms using a rat model of focal cerebral ischemia-reperfusion (I/R) injury. Electroacupuncture at Baihui and Shenting was identified to significantly ameliorate neurological deficits and reduce cerebral infarct volume. Additionally, electroacupuncture improved learning and memory ability in cerebral I/R injured rats, demonstrating its therapeutic efficacy against post-stroke cognitive impairment. Furthermore, electroacupuncture significantly suppressed the I/R-induced activation of NF-κB signaling in ischemic cerebral tissues. The inhibitory effect of electroacupuncture on NF-κB activation led to the inhibition of cerebral cell apoptosis. Finally, electroacupuncture markedly downregulated the expression of pro-apoptotic Bax and Fas, two critical downstream target genes of the NF-κB pathway. Collectively, our findings suggest that inhibition of NF-κB‑mediated neuronal cell apoptosis may be one mechanism via which electroacupuncture at Baihui and Shenting exerts a therapeutic effect on post-stroke cognitive impairment.

Cognitive deficits in Korean women treated with chemotherapy for breast cancer.

PubMed

Jung, Mi Sook; Cimprich, Bernadine

2014-01-01

Cognitive deficits have been reported as detrimental side effects in chemotherapy-treated breast cancer patients and survivors. Korean women treated for breast cancer may experience unrecognized cognitive deficits related to their treatment. However, no research has examined cognitive test performance in chemotherapy-treated Korean breast cancer survivors. The objectives of this study were 2-fold: (1) to examine differences in occurrence and severity of cognitive deficits in Korean women treated with adjuvant chemotherapy for breast cancer as compared with a control group of women without breast cancer and (2) to examine the relationship of selected demographic and cultural factors with cognitive test performance. Sixty-four Korean women, 32 women treated for localized breast cancer and 32 healthy controls, were enrolled. Breast cancer participants were assessed with established cognitive measures within 4 months after chemotherapy, and healthy controls, within 6 months after negative screening mammography. The breast cancer group showed a significantly higher occurrence and greater severity of cognitive deficits than controls did. Importantly, older age, less education, greater collectivist tendency, and greater childrearing burden were reliably associated with poorer attention and working memory test performance. Cognitive deficits were found in chemotherapy-treated Korean women with moderate to large effect sizes compared with controls. Cultural characteristics contributed to worse cognitive performance. Healthcare providers should recognize that Korean women may be highly vulnerable to cognitive deficits. Cultural factors also need to be considered when assessing cognitive function and designing therapeutic interventions to counteract negative cognitive outcomes.

Subjective deficits of attention, cognition and depression in patients with narcolepsy.

PubMed

Zamarian, Laura; Högl, Birgit; Delazer, Margarete; Hingerl, Katharina; Gabelia, David; Mitterling, Thomas; Brandauer, Elisabeth; Frauscher, Birgit

2015-01-01

Patients with narcolepsy often complain about attention deficits in everyday situations. In comparison with these subjective complaints, deficits in objective testing are subtler. The present study assessed the relationships between subjective complaints, objectively measured cognitive performance, disease-related variables, and mood. A total of 51 patients with narcolepsy and 35 healthy controls responded to questionnaires regarding subjectively perceived attention deficits, sleepiness, anxiety and depression. Moreover, they performed an extensive neuropsychological assessment tapping into attention, executive functions, and memory. Patients rated their level of attention in everyday situations to be relatively poor. In an objective assessment of cognitive functioning, they showed only slight attention and executive function deficits. The subjective ratings of attention deficits significantly correlated with ratings of momentary sleepiness, anxiety, and depression, but not with objectively measured cognitive performance. Momentary sleepiness and depression predicted almost 39% of the variance in the ratings of subjectively perceived attention deficits. The present study showed that sleepiness and depression, more than objective cognitive deficits, might play a role in the subjectively perceived attention deficits of patients with narcolepsy. The results suggested that when counselling and treating patients with narcolepsy, clinicians should pay attention to potential depression because subjective cognitive complaints may not relate to objective cognitive impairments. Copyright © 2014 Elsevier B.V. All rights reserved.

A multiple deficit model of reading disability and attention-deficit/hyperactivity disorder: searching for shared cognitive deficits.

PubMed

McGrath, Lauren M; Pennington, Bruce F; Shanahan, Michelle A; Santerre-Lemmon, Laura E; Barnard, Holly D; Willcutt, Erik G; Defries, John C; Olson, Richard K

2011-05-01

This study tests a multiple cognitive deficit model of reading disability (RD), attention-deficit/hyperactivity disorder (ADHD), and their comorbidity. A structural equation model (SEM) of multiple cognitive risk factors and symptom outcome variables was constructed. The model included phonological awareness as a unique predictor of RD and response inhibition as a unique predictor of ADHD. Processing speed, naming speed, and verbal working memory were modeled as potential shared cognitive deficits. Model fit indices from the SEM indicated satisfactory fit. Closer inspection of the path weights revealed that processing speed was the only cognitive variable with significant unique relationships to RD and ADHD dimensions, particularly inattention. Moreover, the significant correlation between reading and inattention was reduced to non-significance when processing speed was included in the model, suggesting that processing speed primarily accounted for the phenotypic correlation (or comorbidity) between reading and inattention. This study illustrates the power of a multiple deficit approach to complex developmental disorders and psychopathologies, particularly for exploring comorbidities. The theoretical role of processing speed in the developmental pathways of RD and ADHD and directions for future research are discussed. © 2010 The Authors. Journal of Child Psychology and Psychiatry © 2010 Association for Child and Adolescent Mental Health.

Arctigenin isolated from the seeds of Arctium lappa ameliorates memory deficits in mice.

PubMed

Lee, In-Ah; Joh, Eun-Ha; Kim, Dong-Hyun

2011-09-01

The seeds of Arctium lappa L. (AL, family Asteraceae), the main constituents of which are arctiin and arctigenin, have been used as an herbal medicine or functional food to treat inflammatory diseases. These main constituents were shown to inhibit acetylcholinesterase (AChE) activity. Arctigenin more potently inhibited AChE activity than arctiin. Arctigenin at doses of 30 and 60 mg/kg (p. o.) potently reversed scopolamine-induced memory deficits by 62 % and 73 %, respectively, in a passive avoidance test. This finding is comparable with that of tacrine (10 mg/kg p. o.). Arctigenin also significantly reversed scopolamine-induced memory deficits in the Y-maze and Morris water maze tests. On the basis of these findings, arctigenin may ameliorate memory deficits by inhibiting AChE. © Georg Thieme Verlag KG Stuttgart · New York.

Maslinic acid ameliorates NMDA receptor blockade-induced schizophrenia-like behaviors in mice.

PubMed

Jeon, Se Jin; Kim, Eunji; Lee, Jin Su; Oh, Hee Kyong; Zhang, Jiabao; Kwon, Yubeen; Jang, Dae Sik; Ryu, Jong Hoon

2017-11-01

Schizophrenia is a chronic psychotic disorder characterized by positive, negative, and cognitive symptoms. Primary treatments for schizophrenia relieve the positive symptoms but are less effective against the negative and cognitive symptoms. In the present study, we investigated whether maslinic acid, isolated from Syzygium aromaticum (clove), can ameliorate schizophrenia-like behaviors in mice induced by MK-801, an N-methyl-d-aspartate (NMDA) receptor antagonist. After maslinic acid treatment in the MK-801 model, we examined the behavioral alteration and signaling pathways in the prefrontal cortex. Mice were treated with maslinic acid (30 mg/kg), and their behaviors were evaluated through an array of behavioral tests. The effects of maslinic acid were also examined in the signaling pathways in the prefrontal cortex. A single administration of maslinic acid blocked the MK-801-induced hyperlocomotion and reversed the MK-801-induced sensorimotor gating deficit in the acoustic startle response test. In the social novelty preference test, maslinic acid ameliorated the social behavior deficits induced by MK-801. The MK-801-induced attention and recognition memory impairments were also alleviated by a single administration of maslinic acid. Furthermore, maslinic acid normalized the phosphorylation levels of Akt-GSK-3β and ERK-CREB in the prefrontal cortex. Overall, maslinic acid ameliorated the schizophrenia-like symptoms induced by MK-801, and these effects may be partly mediated through Akt-GSK-3β and ERK-CREB activation. These findings suggest that maslinic acid could be a candidate for the treatment of several symptoms of schizophrenia, including positive symptoms, sensorimotor gating disruption, social interaction deficits, and cognitive impairments. Copyright © 2017 Elsevier Ltd. All rights reserved.

Uncovering the Neural Bases of Cognitive and Affective Empathy Deficits in Alzheimer's Disease and the Behavioral-Variant of Frontotemporal Dementia.

PubMed

Dermody, Nadene; Wong, Stephanie; Ahmed, Rebekah; Piguet, Olivier; Hodges, John R; Irish, Muireann

2016-05-30

Loss of empathy is a core presenting feature of the behavioral-variant of frontotemporal dementia (bvFTD), resulting in socioemotional difficulties and behavioral transgressions. In contrast, interpersonal functioning remains relatively intact in Alzheimer's disease (AD), despite marked cognitive decline. The neural substrates mediating these patterns of loss and sparing in social functioning remain unclear, yet are relevant for our understanding of the social brain. We investigated cognitive versus affective aspects of empathy using the Interpersonal Reactivity Index (IRI) in 25 AD and 24 bvFTD patients and contrasted their performance with 22 age- and education-matched controls. Cognitive empathy was comparably compromised in AD and bvFTD, whereas affective empathy was impaired exclusively in bvFTD. While controlling for overall cognitive dysfunction ameliorated perspective-taking deficits in AD, empathy loss persisted across cognitive and affective domains in bvFTD. Voxel-based morphometry analyses revealed divergent neural substrates of empathy loss in each patient group. Perspective-taking deficits correlated with predominantly left-sided temporoparietal atrophy in AD, whereas widespread bilateral frontoinsular, temporal, parietal, and occipital atrophy was implicated in bvFTD. Reduced empathic concern in bvFTD was associated with atrophy in the left orbitofrontal, inferior frontal, and insular cortices, and the bilateral mid-cingulate gyrus. Our findings suggest that social cognitive deficits in AD arise largely as a consequence of global cognitive dysfunction, rather than a loss of empathy per se. In contrast, loss of empathy in bvFTD reflects the deterioration of a distributed network of frontoinsular and temporal structures that appear crucial for monitoring and processing social information.

Cognitive Behavioral Therapies in older adults with depression and cognitive deficits: a systematic review.

PubMed

Simon, Sharon Sanz; Cordás, Táki Athanássios; Bottino, Cássio M C

2015-03-01

The objective of this study is to investigate the effectiveness of cognitive behavioral therapies (CBTs) in improving depressive symptoms, disability, and cognition in older adults with depression and cognitive deficits. It was performed a systematic search for articles published between 1994 and February 2014 in the MEDLINE/Pubmed, PsycINFO, and SCIELO. The studies should have provided information about benefits after CBTs to older adults with depression and cognitive deficits. Cognitive behavioral therapy focused on problem solving is the main approach studied, having better effectiveness than supportive therapy in randomized clinical trials. Significant improvements in mood and disability were consistent, although evidence of changes in cognitive measures is controversial, less studied, and limited. Nevertheless, improvements in executive functions, processing speed, and changes in patients' perspectives of problem solving skills, such as generating alternatives and decision-making, were described. Also, it would be necessary that future studies more often evaluate cognitive status of depressed elders, as well as cognitive changes after psychotherapy. It should be emphasized that there is a lack of studies in this field, and more approaches in CBTs need to be investigated to this population. Older adults with depression and cognitive deficits can benefit from CBTs. Improvements in mood and disability are more consistent than changes in cognition, which are little studied after CBTs. It is necessary more studies in the field, as well as, to investigate more approaches in CBTs to older adults with depression and cognitive deficits. Copyright © 2014 John Wiley & Sons, Ltd.

Apigenin Ameliorates Post-Stroke Cognitive Deficits in Rats Through Histone Acetylation-Mediated Neurochemical Alterations.

PubMed

Tu, Fengxia; Pang, Qiongyi; Huang, Tingting; Zhao, Yun; Liu, Meixia; Chen, Xiang

2017-08-19

BACKGROUND To identify the effect of apigenin on cognitive deficits of rats after cerebral ischemia and reperfusion injury, and to investigate the potential molecular mechanisms. MATERIAL AND METHODS The rats were given sodium butyrate (NaB) or apigenin (20 or 40 mg/kg) for 28 days. Cognition was investigated by the Morris water maze (MWM) test. On day 28, the rats were euthanized and their hippocampal brain regions were used to identify biochemical and neurochemical alterations. The content of histone deacetylase (HDAC) was measured by enzyme-linked immunosorbent assay (ELISA). Western blot analysis was performed to determine the levels of BDNF, phosphorylated cAMP response element-binding protein (pCREB), acetylated H3, and acetylated H4. The mRNA expressions of brain-derived neurotrophic factor (BDNF) and synapsin-I (Syn-I) were examined by polymerase chain reaction (PCR). RESULTS The rats with chronic administration of apigenin (20 and 40 mg/kg) showed better performance in the MWM task than the model rats; there was no significant difference between the apigenin-treated and NaB-treated rats. At the higher apigenin dose of 40 mg/kg, the HDAC content was decreased, the BDNF level was markedly increased, and acetylated H3 and acetylated H4 expressions and Syn-I expressions in the hippocampus was upregulated compared with the model group. Apigenin at 20 mg/kg did not show reversal of the neurochemical alterations. CONCLUSIONS The improvement effect of apigenin on cognitive impairments after cerebral ischemia and reperfusion injury may involve multiple mechanisms, such as the inhibition of HDAC, induction of BDNF and Syn-I expression, and regulation of histone acetylation.

Adjunctive Pregnenolone Ameliorates the Cognitive Deficits in Recent-Onset Schizophrenia: An 8-Week, Randomized, Double-Blind, Placebo-Controlled Trial.

PubMed

Kreinin, Anatoly; Bawakny, Nisham; Ritsner, Michael S

This study aimed to examine the effect of add-on treatment with the neurosteroid pregnenolone (PREG) on neurocognitive dysfunctions of patients with recent-onset schizophrenia (SZ) and schizoaffective disorder (SA). Sixty out- and inpatients that met DSM-IV criteria for SZ/SA were randomized to an 8-week, double-blind, randomized, placebo-controlled, 2-center trial. Participants received either pregnenolone (50 mg/d) or placebo added on to antipsychotic medications. Computerized Cambridge Automated Neuropsychological Test Battery measures were administered at baseline and after 4 and 8 weeks of treatment. ANOVA and paired t- or z-tests were applied to examine between- and within-group differences over time. Compared to placebo, adjunctive PREG significantly reduced the deficits in visual attention measured with the Matching to Sample Visual Search task (p=0.002), with moderate effect sizes (d=0.42). In addition, a significant improvement was observed from baseline to end-of-study with respect to the visual (p=0.008) and sustained attention (Rapid Visual Information Processing, p=0.038) deficits, and executive functions (Stockings of Cambridge, p=0.049; Spatial Working Memory, p<0.001) among patients receiving PREG but not among those receiving placebo (all p's>0.05). This beneficial effect of PREG was independent of the type of antipsychotic agents, gender, age, education, and illness duration. Pregnenolone augmentation demonstrated significant amelioration of the visual attention deficit in recent-onset SZ/SA. Long-term, large-scale studies are required to obtain greater statistical significance and more confident clinical generalization.

Cognitive Deficits in Breast Cancer Survivors After Chemotherapy and Hormonal Therapy.

PubMed

Frank, Jennifer Sandson; Vance, David E; Triebel, Kristen L; Meneses, Karen M

2015-12-01

Adjuvant treatments, specifically chemotherapy and hormonal therapy, have dramatically increased breast cancer survival, resulting in increased attention to the residual effects of treatment. Breast cancer survivors (BCS) frequently report that cognitive deficits are a particular source of distress, interfering with many aspects of quality of life. The literature on neuropsychological performance measures in BCS supports the reality of subtle cognitive deficits after both chemotherapy and hormonal therapy. This premise is supported by recent imaging studies, which reveal anatomical changes after chemotherapy as well as changes in patterns of neural activation while performing cognitive tasks. This review suggests that, even when performance on neuropsychological performance measures is within normal limits, BCS may be using increased cognitive resources in the face of reduced cognitive reserve. Potential interventions for cognitive deficits after adjuvant therapy include prescriptions for healthy living, pharmacotherapy, complementary therapy, and cognitive remediation therapy directed toward specific cognitive deficits or a combination of several strategies.

GLYX-13 (rapastinel) ameliorates subchronic phencyclidine- and ketamine-induced declarative memory deficits in mice

PubMed Central

Rajagopal, Lakshmi; Burgdorf, Jeffrey S.; Moskal, Joseph R.; Meltzer, Herbert Y.

2016-01-01

GLYX-13 (rapastinel), a tetrapeptide (Thr-Pro-Pro-Thr-amide), has been reported to have fast acting antidepressant properties in man based upon its N-methyl-d-aspartate receptor (NMDAR) glycine site functional partial agonism. Ketamine, a non-competitive NMDAR antagonist, also reported to have fast acting antidepressant properties, produces cognitive impairment in rodents and man, whereas rapastinel has been reported to have cognitive enhancing properties in rodents, without impairing cognition in man, albeit clinical testing has been limited. The goal of this study was to compare the cognitive impairing effects of rapastinel and ketamine in novel object recognition (NOR), a measure of declarative memory, in male C57BL/6J mice treated with phencyclidine (PCP), another NMDAR noncompetitive antagonist known to severely impair cognition, in both rodents and man. C57BL/6J mice given a single dose or subchronic ketamine (30 mg/kg. i.p.) showed acute or persistent deficits in NOR, respectively. Acute i.v. rapastinel (1.0 mg/kg), did not induce NOR deficit. Pre-treatment with rapastinel significantly prevented acute ketamine-induced NOR deficit. Rapastinel (1.0 mg/kg, but not 0.3 mg/kg, iv) significantly reversed both subchronic ketamine- and subchronic PCP-induced NOR deficits. Rapastinel also potentiated the atypical antipsychotic drug with antidepressant properties, lurasidone, to restore NOR in subchronic ketamine-treated mice. These findings indicate that rapastinel, unlike ketamine, does not induce a declarative memory deficit in mice, and can prevent or reverse the ketamine-induced NOR deficit. Further study is required to determine if these differences translate during clinical use of ketamine and rapastinel as fast acting antidepressant drugs and if rapastinel could have non-ionotropic effects as an add-on therapy with antipsychotic/antidepressant medications. PMID:26632337

Inhibition of inflammation by astaxanthin alleviates cognition deficits in diabetic mice.

PubMed

Zhou, Xiaoyan; Zhang, Fang; Hu, Xiaotong; Chen, Jing; Wen, Xiangru; Sun, Ying; Liu, Yonghai; Tang, Renxian; Zheng, Kuiyang; Song, Yuanjian

2015-11-01

Neurons in the hippocampal and cortical functional regions are more susceptible to damage induced by hyperglycemia, which can result in severe spatial learning and memory impairment. Neuroprotection ameliorates cognitive impairment induced by hyperglycemia in diabetic encephalopathy (DE). Astaxanthin has been widely studied in diabetes mellitus and diabetic complications due to its hypoglycemic, antioxidant and anti-apoptotic effects. However, whether astaxanthin can alleviate cognition deficits induced by DE and its precise mechanisms remain undetermined. In this study, DE was induced by streptozotocin (STZ, 150 mg/kg) in ICR mice. We observed the effect of astaxanthin on cognition and investigated its potential mechanisms in DE mice. Results showed that astaxanthin treatment significantly decreased the latency and enhanced the distance and time spent in the target quadrant in the Morris water maze test. Furthermore, neuronal survival was significantly increased in the hippocampal CA3 region and the frontal cortex following treatment with astaxanthin. Meanwhile, immunoblotting was used to observe the nuclear translocation of nuclear factor-kappaB (NF-κB) p65 and the expression of tumor necrosis factor-α (TNF-α) in the hippocampus and frontal cortex. The results indicated that astaxanthin could inhibit NF-κB nuclear translocation and downregulate TNF-α expression in the hippocampus and frontal cortex. Overall, the present study implied that astaxanthin could improve cognition by protecting neurons against inflammation injury potentially through inhibiting the nuclear translocation of NF-κB and down-regulating TNF-α. Copyright © 2015. Published by Elsevier Inc.

Cognitive Deficits in Schizophrenia: Understanding the Biological Correlates and Remediation Strategies

PubMed Central

Tripathi, Adarsh; Shukla, Rashmi

2018-01-01

Cognitive deficits are one of the core symptoms of schizophrenia that evolve during the course of schizophrenia, after being originated even before the onset of illness. Existing pharmacological and biological treatment modalities fall short to meet the needs to improve the cognitive symptoms; hence, various cognitive remediation strategies have been adopted to address these deficits. Research evidences suggest that cognitive remediation measures improve the functioning, limit disability bettering the quality of life. The functional outcomes of cognitive remediation in schizophrenia are resultant of neurobiological changes in specific brain areas. Recent years witnessed significant innovations in cognitive remediation strategies in schizophrenia. This comprehensive review highlights the biological correlates of cognitive deficits in schizophrenia and the remedial measures with evidence base. PMID:29397662

Cognitive deficits in individuals with methamphetamine use disorder: A meta-analysis.

PubMed

Potvin, Stéphane; Pelletier, Julie; Grot, Stéphanie; Hébert, Catherine; Barr, Alasdair M; Lecomte, Tania

2018-05-01

Methamphetamine has long been considered as a neurotoxic substance causing cognitive deficits. Recently, however, the magnitude and the clinical significance of the cognitive effects associated with methamphetamine use disorder (MUD) have been debated. To help clarify this controversy, we performed a meta-analysis of the cognitive deficits associated with MUD. A literature search yielded 44 studies that assessed cognitive dysfunction in 1592 subjects with MUD and 1820 healthy controls. Effect size estimates were calculated using the Comprehensive Meta-Analysis, for the following 12 cognitive domains: attention, executive functions, impulsivity/reward processing, social cognition, speed of processing, verbal fluency/language, verbal learning and memory, visual learning and memory, visuo-spatial abilities and working memory. Findings revealed moderate impairment across most cognitive domains, including attention, executive functions, language/verbal fluency, verbal learning and memory, visual memory and working memory. Deficits in impulsivity/reward processing and social cognition were more prominent, whereas visual learning and visuo-spatial abilities were relatively spared cognitive domains. A publication bias was observed. These results show that MUD is associated with broad cognitive deficits that are in the same range as those associated with alcohol and cocaine use disorder, as recently shown by way of meta-analysis. The prominent effects of MUD on social cognition and impulsivity/reward processing are based on a small number of studies, and as such, these results will need to be replicated. The functional consequences (social and occupational) of the cognitive deficits of methamphetamine will also need to be determined. Copyright © 2018 Elsevier Ltd. All rights reserved.

Cognitive Deficits and Positively Biased Self-Perceptions in Children with ADHD

ERIC Educational Resources Information Center

McQuade, Julia D.; Tomb, Meghan; Hoza, Betsy; Waschbusch, Daniel A.; Hurt, Elizabeth A.; Vaughn, Aaron J.

2011-01-01

This study examined the relation between cognitive deficits and positive bias in a sample of 272 children with and without Attention Deficit Hyperactivity Disorder (ADHD; 7-12 years old). Results indicated that children with ADHD with and without biased self-perceptions exhibit differences in specific cognitive deficits (executive processes,…

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

Cognitive deficits in heart failure: Re-cognition of vulnerability as a strange new world.

PubMed

Sloan, Rebecca S; Pressler, Susan J

2009-01-01

Patients with chronic heart failure (HF) have impairment in memory, psychomotor speed, and executive function. The aim of this study was to describe how individuals with HF and cognitive deficits manage self-care in their daily lives. Using an interpretive phenomenology method, HF patients completed unstructured face-to-face interviews about their ability to manage complex health regimens and maintain their health-related quality of life. Analysis of data was aided by use of Atlas.ti computer software. The sample consisted of 12 patients (10 men; aged 43-81 years) who had previously undergone neuropsychological testing and were found to have deficits in 3 or more cognitive domains. Patients confirmed that they followed the advice of healthcare providers by adherence to medication regimens, dietary sodium restrictions, and HF self-care. One overarching theme was identified: "Re-cognition of Vulnerability: A Strange New World." This theme was further differentiated into 3 components: (1) not recognizing cognitive deficits; (2) recognizing cognitive deficits, described as (a) never could remember anything, (b) just old age, (c) HF-related change, and (d) making normal accommodations; and (3) recognizing vulnerability, explained by perception of (a) cognitive, (b) physical, and (c) social vulnerabilities, as well as perception of (d) the nearness of death. Although the study was designed to focus on the cognitive changes in HF patients, it was difficult to separate cognitive, physical, and social challenges. These changes are most useful when taken as a constellation. Healthcare professionals can use the knowledge to identify problems and interventions for HF patients.

Juvenile treatment with a novel mGluR2 agonist/mGluR3 antagonist compound, LY395756, reverses learning deficits and cognitive flexibility impairments in adults in a neurodevelopmental model of schizophrenia.

PubMed

Li, Meng-Lin; Gulchina, Yelena; Monaco, Sarah A; Xing, Bo; Ferguson, Brielle R; Li, Yan-Chun; Li, Feng; Hu, Xi-Quan; Gao, Wen-Jun

2017-04-01

Schizophrenia (SCZ) is a neurodevelopmental psychiatric disorder, in which cognitive function becomes disrupted at early stages of the disease. Although the mechanisms underlying cognitive impairments remain unclear, N-methyl-D-aspartate receptors (NMDAR) hypofunctioning in the prefrontal cortex (PFC) has been implicated. Moreover, cognitive symptoms in SCZ are usually unresponsive to treatment with current antipsychotics and by onset, disruption of the dopamine system, not NMDAR hypofunctioning, dominates the symptoms. Therefore, treating cognitive deficits at an early stage is a realistic approach. In this study, we tested whether an early treatment targeting mGluR2 would be effective in ameliorating cognitive impairments in the methylazoxymethanol acetate (MAM) model of SCZ. We investigated the effects of an mGluR2 agonist/mGluR3 antagonist, LY395756 (LY39), on the NMDAR expression and function in juveniles, as well as cognitive deficits in adult rats after juvenile treatment. We found that gestational MAM exposure induced a significant decrease in total protein levels of the NMDAR subunit, NR2B, and a significant increase of pNR2BTyr1472 in the juvenile rat PFC. Treatment with LY39 in juvenile MAM-exposed rats effectively recovered the disrupted NMDAR expression. Furthermore, a subchronic LY39 treatment in juvenile MAM-exposed rats also alleviated the learning deficits and cognitive flexibility impairments when tested with a cross-maze based set-shifting task in adults. Therefore, our study demonstrates that targeting dysfunctional NMDARs with an mGluR2 agonist during the early stage of SCZ could be an effective strategy in preventing the development and progression in addition to ameliorating cognitive impairments of SCZ. Copyright © 2017 Elsevier Inc. All rights reserved.

Cognitive Control Deficits Associated with Antisocial Personality Disorder and Psychopathy

PubMed Central

Zeier, Joshua D.; Baskin-Sommers, Arielle R.; Newman, Joseph P.; Racer, Kristina Hiatt

2011-01-01

Antisociality has been linked to a variety of executive functioning deficits, including poor cognitive control. Surprisingly, cognitive control deficits are rarely found in psychopathic individuals, despite their notoriously severe and persistent antisocial behavior. In fact, primary (low-anxious) psychopathic individuals display superior performance on cognitive control-type tasks under certain circumstances. To clarify these seemingly contradictory findings, we administered a response competition (i.e. flanker) task to incarcerated offenders, who were assessed for Antisocial Personality Disorder (APD) symptoms and psychopathy. As hypothesized, APD related to poorer accuracy, especially on incongruent trials. Contrary to expectation, however, the same pattern of results was found in psychopathy. Additional analyses indicated that these effects of APD and psychopathy were associated with overlapping variance. The findings suggest that psychopathy and APD symptoms are both associated with deficits in cognitive control, and that this deficit relates to general antisociality as opposed to a specific antisocial syndrome. PMID:22452754

Cognitive control deficits associated with antisocial personality disorder and psychopathy.

PubMed

Zeier, Joshua D; Baskin-Sommers, Arielle R; Hiatt Racer, Kristina D; Newman, Joseph P

2012-07-01

Antisociality has been linked to a variety of executive functioning deficits, including poor cognitive control. Surprisingly, cognitive control deficits are rarely found in psychopathic individuals, despite their notoriously severe and persistent antisocial behavior. In fact, primary (low-anxious) psychopathic individuals display superior performance on cognitive control-type tasks under certain circumstances. To clarify these seemingly contradictory findings, we administered a response competition (i.e., flanker) task to incarcerated offenders, who were assessed for Antisocial Personality Disorder (APD) symptoms and psychopathy. As hypothesized, APD related to poorer accuracy, especially on incongruent trials. Contrary to expectation, however, the same pattern of results was found in psychopathy. Additional analyses indicated that these effects of APD and psychopathy were associated with overlapping variance. The findings suggest that psychopathy and APD symptoms are both associated with deficits in cognitive control, and that this deficit relates to general antisociality as opposed to a specific antisocial syndrome. PsycINFO Database Record (c) 2012 APA, all rights reserved.

Acteoside and Isoacteoside Protect Amyloid β Peptide Induced Cytotoxicity, Cognitive Deficit and Neurochemical Disturbances In Vitro and In Vivo

PubMed Central

Shiao, Young-Ji; Su, Muh-Hwan; Lin, Hang-Ching; Wu, Chi-Rei

2017-01-01

Acteoside and isoacteoside, two phenylethanoid glycosides, coexist in some plants. This study investigates the memory-improving and cytoprotective effects of acteoside and isoacteoside in amyloid β peptide 1-42 (Aβ 1-42)-infused rats and Aβ 1-42-treated SH-SY5Y cells. It further elucidates the role of amyloid cascade and central neuronal function in these effects. Acteoside and isoacteoside ameliorated cognitive deficits, decreased amyloid deposition, and reversed central cholinergic dysfunction that were caused by Aβ 1-42 in rats. Acteoside and isoacteoside further decreased extracellular Aβ 1-40 production and restored the cell viability that was decreased by Aβ 1-42 in SH-SY5Y cells. Acteoside and isoacteoside also promoted Aβ 1-40 degradation and inhibited Aβ 1-42 oligomerization in vitro. However, the memory-improving and cytoprotective effects of isoacteoside exceeded those of acteoside. Isoacteoside promoted exploratory behavior and restored cortical and hippocampal dopamine levels, but acteoside did not. We suggest that acteoside and isoacteoside ameliorated the cognitive dysfunction that was caused by Aβ 1-42 by blocking amyloid deposition via preventing amyloid oligomerization, and reversing central neuronal function via counteracting amyloid cytotoxicity. PMID:28441758

Speech Deficits in Serious mental Illness: A Cognitive Resource Issue?

PubMed Central

Cohen, Alex S.; McGovern, Jessica E.; Dinzeo, Thomas J.; Covington, Michael A.

2014-01-01

Speech deficits, notably those involved in psychomotor retardation, blunted affect, alogia and poverty of content of speech, are pronounced in a wide range of serious mental illnesses (e.g., schizophrenia, unipolar depression, bipolar disorders). The present project evaluated the degree to which these deficits manifest as a function of cognitive resource limitations. We examined natural speech from 52 patients meeting criteria for serious mental illnesses (i.e., severe functional deficits with a concomitant diagnosis of schizophrenia, unipolar and/or bipolar affective disorders) and 30 non-psychiatric controls using a range of objective, computer-based measures tapping speech production (“alogia”), variability (“blunted vocal affect”) and content (“poverty of content of speech”). Subjects produced natural speech during a baseline condition and while engaging in an experimentally-manipulated cognitively-effortful task. For correlational analysis, cognitive ability was measured using a standardized battery. Generally speaking, speech deficits did not differ as a function of SMI diagnosis. However, every speech production and content measure was significantly abnormal in SMI versus control groups. Speech variability measures generally did not differ between groups. For both patients and controls as a group, speech during the cognitively-effortful task was sparser and less rich in content. Relative to controls, patients were abnormal under cognitive load with respect only to average pause length. Correlations between the speech variables and cognitive ability were only significant for this same variable: average pause length. Results suggest that certain speech deficits, notably involving pause length, may manifest as a function of cognitive resource limitations. Implications for treatment, research and assessment are discussed. PMID:25464920

Novel 5-HT5A receptor antagonists ameliorate scopolamine-induced working memory deficit in mice and reference memory impairment in aged rats.

PubMed

Yamazaki, Mayako; Okabe, Mayuko; Yamamoto, Noriyuki; Yarimizu, Junko; Harada, Katsuya

2015-03-01

Despite the human 5-HT5A receptor being cloned in 1994, the biological function of this receptor has not been extensively characterized due to a lack of specific ligands. We recently reported that the selective 5-HT5A receptor antagonist ASP5736 ameliorated cognitive impairment in several animal models of schizophrenia. Given that areas of the brain with high levels of 5-HT5A receptor expression, such as the hippocampus and cerebral cortex, have important functions in cognition and memory, we evaluated the chemically diverse, potent and brain-penetrating 5-HT5A receptor antagonists ASP5736, AS2030680, and AS2674723 in rodent models of cognitive dysfunction associated with dementia. Each of these compounds exhibited a high affinity for recombinant 5-HT5A receptors that was comparable to that of the non-selective ligand of this receptor, lysergic acid diethylamide (LSD). Although each compound had a low affinity for other receptors, 5-HT5A was the only receptor for which all three compounds had a high affinity. Each of the three compounds ameliorated scopolamine-induced working memory deficit in mice and improved reference memory impairment in aged rats at similar doses. Further, ASP5736 decreased the binding of LSD to 5-HT5A receptors in the olfactory bulb of rats in a dose-dependent manner and occupied 15%-50% of brain 5-HT5A receptors at behaviorally effective doses. These results indicate that the 5-HT5A receptor is involved in learning and memory and that treatment with 5-HT5A receptor antagonists might be broadly effective for cognitive impairment associated with not only schizophrenia but also dementia. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Cognitive Deficits as a Mediator of Poor Occupational Function in Remitted Major Depressive Disorder Patients

PubMed Central

Woo, Young Sup; Rosenblat, Joshua D.; Kakar, Ron; Bahk, Won-Myong; McIntyre, Roger S.

2016-01-01

Cognitive deficits in major depressive disorder (MDD) patients have been described in numerous studies. However, few reports have aimed to describe cognitive deficits in the remitted state of MDD and the mediational effect of cognitive deficits on occupational outcome. The aim of the current review is to synthesize the literature on the mediating and moderating effects of specific domains of cognition on occupational impairment among people with remitted MDD. In addition, predictors of cognitive deficits found to be vocationally important will be examined. Upon examination of the extant literature, attention, executive function and verbal memory are areas of consistent impairment in remitted MDD patients. Cognitive domains shown to have considerable impact on vocational functioning include deficits in memory, attention, learning and executive function. Factors that adversely affect cognitive function related to occupational accommodation include higher age, late age at onset, residual depressive symptoms, history of melancholic/psychotic depression, and physical/psychiatric comorbidity, whereas higher levels of education showed a protective effect against cognitive deficit. Cognitive deficits are a principal mediator of occupational impairment in remitted MDD patients. Therapeutic interventions specifically targeting cognitive deficits in MDD are needed, even in the remitted state, to improve functional recovery, especially in patients who have a higher risk of cognitive deficit. PMID:26792035

Choline Ameliorates Deficits in Balance Caused by Acute Neonatal Ethanol Exposure.

PubMed

Bearer, Cynthia F; Wellmann, Kristen A; Tang, Ningfeng; He, Min; Mooney, Sandra M

2015-08-01

Fetal alcohol spectrum disorder (FASD) is estimated to occur in 1 % of all live births. The developing cerebellum is vulnerable to the toxic effects of alcohol. People with FASD have cerebellar hypoplasia and developmental deficits associated with cerebellar injury. Choline is an essential nutrient, but many diets in the USA are choline deficient. In rats, choline given with or following alcohol exposure reduces many alcohol-induced neurobehavioral deficits but not those associated with cerebellar function. Our objective was to determine if choline supplementation prior to alcohol exposure would ameliorate the impact of ethanol on a cerebellar-associated behavioral test in mice. Pregnant C57Bl6/J mice were maintained on a choline-deficient diet from embryonic day 4.5. On postnatal day 1 (P1), pups were assigned to one of eight treatment groups: choline (C) or saline (S) pre-treatment from P1 to P5, ethanol (6 g/kg) or Intralipid(®) on P5, C and or S post-treatment from P6 to P20. On P30, balance and coordination were tested using the dowel crossing test. Overall, there was a significant effect of treatment and females crossed longer distances than males. Ethanol exposure significantly reduced the total distance crossed. Choline pre-treatment increased the distance crossed by males, and both pre- and post-treatment with choline significantly increased total distance crossed for females and males. There was no effect of choline on Intralipid®-exposed animals. This is the first study to show that choline ameliorates ethanol-induced effects on balance and coordination when given before ethanol exposure. Choline fortification of common foodstuffs may reduce the effects of alcohol.

CHOLINE AMELIORATES DEFICITS IN BALANCE CAUSED BY ACUTE NEONATAL ETHANOL EXPOSURE

PubMed Central

Bearer, Cynthia F.; Wellmann, Kristen A.; Tang, Ningfeng; He, Min; Mooney, Sandra M.

2015-01-01

Fetal alcohol spectrum disorder (FASD) is estimated to occur in 1% of all live births. The developing cerebellum is vulnerable to the toxic effects of alcohol. People with FASD have cerebellar hypoplasia and developmental deficits associated with cerebellar injury. Choline is an essential nutrient but many diets in the USA are choline deficient. In rats, choline given with or following alcohol exposure reduces many alcohol-induced neurobehavioral deficits, but not those associated with cerebellar function. Our objective was to determine if choline supplementation prior to alcohol exposure would ameliorate the impact of ethanol on a cerebellar-associated behavioral test in mice. Pregnant C57Bl6/J mice were maintained on a choline deficient diet from embryonic day 4.5. On postnatal day 1 (P1), pups were assigned to one of 8 treatment groups: choline (C) or saline (S) pre-treatment from P1-5, ethanol (6 g/kg) or Intralipid® on P5, C or S post-treatment from P6-20. On P30, balance and coordination were tested using the dowel crossing test. Overall, there was a significant effect of treatment and females crossed longer distances than males. Ethanol exposure significantly reduced the total distance crossed. Choline pre-treatment increased the distance crossed by males, and both pre- and post-treatment with choline significantly increased total distance crossed for females and males. There was no effect of choline on Intralipid®-exposed animals. This is the first study to show that choline ameliorates ethanol-induced effects on balance and coordination when given before ethanol exposure. Choline fortification of common foodstuffs may reduce the effects of alcohol. PMID:26085462

A novel phosphodiesterase-5 Inhibitor: Yonkenafil modulates neurogenesis, gliosis to improve cognitive function and ameliorates amyloid burden in an APP/PS1 transgenic mice model.

PubMed

Zhu, Lei; Yang, Jing-yu; Xue, Xue; Dong, Ying-xu; Liu, Yang; Miao, Feng-rong; Wang, Yong-feng; Xue, Hong; Wu, Chun-fu

2015-09-01

In Alzheimer's disease (AD), activated microglia invade and surround β-amyloid plaques, possibly contributing to the aggregation of amyloid β (Aβ), which affect the survival of neurons and lead to memory loss. Phosphodiesterase-5 (PDE-5) inhibitors have recently been shown a potential therapeutic effect on AD. In this study, the effects of yonkenafil (yonk), a novel PDE-5 inhibitor, on cognitive behaviors as well as the pathological features in transgenic AD mice were investigated. Seven-month-old APP/PS1 transgenic mice were treated with yonk (2, 6, or 18 mg/kg, intraperitoneal injection (i.p.)) or sildenafil (sild) (6 mg/kg, i.p.) daily for 3 months and then behavioral tests were performed. The results demonstrated that yonk improved nesting-building ability, ameliorated working memory deficits in the Y-maze tasks, and significantly improved learning and memory function in the Morris water maze (MWM) tasks. In addition, yonk reduced the area of Aβ plaques, and inhibited over-activation of microglia and astrocytes. Furthermore, yonk increased neurogenesis in the dentate granule brain region of APP/PS1 mice, indicated by increased BrdU(+)/NeuN(+) and BrdU(+)/DCX(+) cells compared to vehicle-treated transgenic mice. These results suggest that yonk could rescue cognitive deficits by ameliorated amyloid burden through regulating APP processing, inhibited the over-activation of microglia and astrocytes as well as restored neurogenesis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Cognitive Neuroscience of Attention Deficit Hyperactivity Disorder: Current Status and Working Hypotheses

ERIC Educational Resources Information Center

Vaidya, Chandan J.; Stollstorff, Melanie

2008-01-01

Cognitive neuroscience studies of Attention Deficit Hyperactivity Disorder (ADHD) suggest multiple loci of pathology with respect to both cognitive domains and neural circuitry. Cognitive deficits extend beyond executive functioning to include spatial, temporal, and lower-level "nonexecutive" functions. Atypical functional anatomy extends beyond…

Speech deficits in serious mental illness: a cognitive resource issue?

PubMed

Cohen, Alex S; McGovern, Jessica E; Dinzeo, Thomas J; Covington, Michael A

2014-12-01

Speech deficits, notably those involved in psychomotor retardation, blunted affect, alogia and poverty of content of speech, are pronounced in a wide range of serious mental illnesses (e.g., schizophrenia, unipolar depression, bipolar disorders). The present project evaluated the degree to which these deficits manifest as a function of cognitive resource limitations. We examined natural speech from 52 patients meeting criteria for serious mental illnesses (i.e., severe functional deficits with a concomitant diagnosis of schizophrenia, unipolar and/or bipolar affective disorders) and 30 non-psychiatric controls using a range of objective, computer-based measures tapping speech production ("alogia"), variability ("blunted vocal affect") and content ("poverty of content of speech"). Subjects produced natural speech during a baseline condition and while engaging in an experimentally-manipulated cognitively-effortful task. For correlational analysis, cognitive ability was measured using a standardized battery. Generally speaking, speech deficits did not differ as a function of SMI diagnosis. However, every speech production and content measure was significantly abnormal in SMI versus control groups. Speech variability measures generally did not differ between groups. For both patients and controls as a group, speech during the cognitively-effortful task was sparser and less rich in content. Relative to controls, patients were abnormal under cognitive load with respect only to average pause length. Correlations between the speech variables and cognitive ability were only significant for this same variable: average pause length. Results suggest that certain speech deficits, notably involving pause length, may manifest as a function of cognitive resource limitations. Implications for treatment, research and assessment are discussed. Copyright © 2014 Elsevier B.V. All rights reserved.

Perceived Cognitive Deficits in a Sample of Persons Living With Multiple Sclerosis.

PubMed

Henneghan, Ashley; Stuifbergen, Alexa; Becker, Heather; Kullberg, Vicki; Gloris, Nicole

2017-10-01

The aims of this study were to describe the nature and diversity of perceived cognitive deficits using the Perceived Deficits Questionnaire (PDQ), to assess the reliability of the PDQ, and to explore self-reported predictors of PDQ scores in a large community-based sample of persons with multiple sclerosis (MS). Persons with MS enrolled in a randomized controlled trial provided demographic data and completed the PDQ along with measures of cognitive and memory strategies, cognitive abilities, self-efficacy, and depressive symptoms and neuropsychological tests. Most of the 183 participants were non-Hispanic white women, approximately 49 years old, and diagnosed with MS 12.5 years prior. The most frequent cognitive complaints regarded trouble remembering telephone numbers, mind drifting, and forgetting why one came into a room. The PDQ scores were significantly related to self-rated cognitive abilities, depressive symptoms, self-efficacy, and use of cognitive strategies, but not to scores on neuropsychological performance tests. When controlling for other variables, self-rated cognitive abilities was the strongest, significant predictor of perceived cognitive deficits. Persons with MS most frequently experience deficits related to short-term memory and attention. The PDQ total is a reliable measure of perceived cognitive deficits in persons with MS, is feasible for use by nurses in clinical settings-can be administered in approximately 5 minutes, and is easily scored.

Individually modifiable risk factors to ameliorate cognitive aging: a systematic review and meta-analysis

PubMed Central

Lehert, Philippe; Villaseca, Paulina; Hogervorst, Eef; Maki, Pauline M.; Henderson, Victor W.

2016-01-01

A number of health and lifestyle factors are thought to contribute to cognitive decline associated with age but cannot be easily modified by the individual patient. We identified 12 individually-modifiable interventions that can be implemented during midlife or later with the potential to ameliorate cognitive aging. For 10 of these, we used PubMed databases for a systematic review of long-duration (at least six months), randomized controlled trials in midlife and older adults without dementia or mild cognitive impairment with objective measures of neuropsychological performance. Using network meta-analysis, we performed a quantitative synthesis for global cognition (primary outcome) and episodic memory (secondary outcome). Of 1038 publications identified by our search strategy, 24 eligible trials were included in the network meta-analysis. Results suggested that the Mediterranean diet supplemented by olive oil and tai chi exercise may improve global cognition, and the Mediterranean diet plus olive oil and soy isoflavone supplements may improve memory. Effect sizes were no more than small (standardized mean differences 0.11 to 0.22). Cognitive training may have cognitive benefit as well. Most individually modifiable risk factors have not yet been adequately studied. We conclude that some interventions that can be self-initiated by healthy midlife and older adults may ameliorate cognitive aging. PMID:26361790

Individually modifiable risk factors to ameliorate cognitive aging: a systematic review and meta-analysis.

PubMed

Lehert, P; Villaseca, P; Hogervorst, E; Maki, P M; Henderson, V W

2015-10-01

A number of health and lifestyle factors are thought to contribute to cognitive decline associated with age but cannot be easily modified by the individual patient. We identified 12 individually modifiable interventions that can be implemented during midlife or later with the potential to ameliorate cognitive aging. For ten of these, we used PubMed databases for a systematic review of long-duration (at least 6 months), randomized, controlled trials in midlife and older adults without dementia or mild cognitive impairment with objective measures of neuropsychological performance. Using network meta-analysis, we performed a quantitative synthesis for global cognition (primary outcome) and episodic memory (secondary outcome). Of 1038 publications identified by our search strategy, 24 eligible trials were included in the network meta-analysis. Results suggested that the Mediterranean diet supplemented by olive oil and tai chi exercise may improve global cognition, and the Mediterranean diet plus olive oil and soy isoflavone supplements may improve memory. Effect sizes were no more than small (standardized mean differences 0.11-0.22). Cognitive training may have cognitive benefit as well. Most individually modifiable risk factors have not yet been adequately studied. We conclude that some interventions that can be self-initiated by healthy midlife and older adults may ameliorate cognitive aging.

Persistent cognitive and dopamine transporter deficits in abstinent methamphetamine users.

PubMed

McCann, Una D; Kuwabara, Hiroto; Kumar, Anil; Palermo, Michael; Abbey, Rubyna; Brasic, James; Ye, Weiguo; Alexander, Mohab; Dannals, Robert F; Wong, Dean F; Ricaurte, George A

2008-02-01

Studies in abstinent methamphetamine (METH) users have demonstrated reductions in brain dopamine transporter (DAT) binding potential (BP), as well as cognitive and motor deficits, but it is not yet clear whether cognitive deficits and brain DAT reductions fully reverse with sustained abstinence, or whether behavioral deficits in METH users are related to dopamine (DA) deficits. This study was conducted to further investigate potential persistent psychomotor deficits secondary to METH abuse, and their relationship to brain DAT availability, as measured using quantitative PET methods with [(11)C]WIN 35428. Twenty-two abstinent METH users and 17 healthy non-METH using controls underwent psychometric testing to test the hypothesis that METH users would demonstrate selective deficits in neuropsychiatric domains known to involve DA neurons (e.g., working memory, executive function, motor function). A subset of subjects also underwent PET scanning with [(11)C]WIN 35428. METH users were found to have modest deficits in short-term memory, executive function, and manual dexterity. Exploratory correlational analyses revealed that deficits in memory, but not those in executive or motor function, were associated with decreases in striatal DAT BP. These results suggest a possible relationship between DAT BP and memory deficits in abstinent METH users, and lend support to the notion that METH produces lasting effects on central DA neurons in humans. As METH can also produce toxic effects on serotonin (5-HT) neurons, further study is needed to address the potential role of brain 5-HT depletion in cognitive deficits in abstinent METH users. (c) 2007 Wiley-Liss, Inc.

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

Neuroprotective role of Ginkgo biloba against cognitive deficits associated with Bisphenol A exposure: An animal model study.

PubMed

El Tabaa, Manar Mohammed; Sokkar, Samia Salem; Ramadan, Ehab Sayed; Abd El Salam, Inas Zakria; Zaid, Anis

2017-09-01

Our study aimed to elucidate to what extent Ginkgo biloba (Gb) can protect rats from cognitive deficits induced by exposure to Bisphenol A (BPA) at high dose. Therefore, sixty male Wistar rats were randomly divided into four groups of 15 animals in each group: Vehicle group, Gb-control group, BPA-exposed group and Gb pre-treated group. All administrations were given daily by an oral gavage once a day for eight weeks. Cognitive function was assessed using Morris water maze; Y-maze and Novel object recognition tasks. Additionally, hippocampal levels of DA, NE and 5-HT were measured. BPA-induced oxidative stress was evaluated by determining SOD activity, NO and MDA levels in rat hippocampus as well as level of circulating adiponectin. Moreover, histopathological changes in CA3 region of rat hippocampus and immunohistochemical expression of NF-κB and Caspase-3 were investigated. We found that Gb pretreatment significantly improved cognitive performance; may be via increasing hippocampal levels of estrogen-dependent biogenic amines. At the same time, Gb could strictly control BPA-induced oxidative stress by improving SOD activity and adiponectin level with decrease in NO and MDA levels. Lastly, Gb alleviated the histopathological injuries induced by BPA and inhibited NF-κB and caspase-3 activation. In conclusion, our results suggested that Gb has potential to ameliorate BPA-induced hippocampal neuronal damage and subsequent cognitive deficits through mechanisms involving its ability to enhance the release of biogenic amines as well as its antioxidant and adiponectin pro-secretory effects. Copyright © 2017 Elsevier Ltd. All rights reserved.

Deficits in cognition and synaptic plasticity in a mouse model of Down syndrome ameliorated by GABAB receptor antagonists

PubMed Central

Kleschevnikov, A.M.; Belichenko, P.V.; Faizi, M.; Jacobs, L.F.; Htun, K.; Shamloo, M.; Mobley, W.C.

2012-01-01

Cognitive impairment in Down syndrome (DS) is characterized by deficient learning and memory. Mouse genetic models of DS exhibit impaired cognition in hippocampally mediated behavioral tasks and reduced synaptic plasticity of hippocampal pathways. Enhanced efficiency of GABAergic neurotransmission was implicated in those changes. We have recently shown that signaling through postsynaptic GABAB receptors is significantly increased in the dentate gyrus (DG) of Ts65Dn mice, a genetic model of DS. Here we examined a role for GABAB receptors in cognitive deficits in DS by defining the effect of selective GABAB receptor antagonists on behavior and synaptic plasticity of adult Ts65Dn mice. Treatment with the GABAB receptor antagonist CGP55845 restored memory of Ts65Dn mice in the novel place recognition, novel object recognition and contextual fear conditioning tasks, but did not affect locomotion and performance in T-maze. The treatment increased hippocampal levels of brain-derived neurotrophic factor (BDNF), equally in 2N and Ts65Dn mice. In hippocampal slices, treatment with the GABAB receptor antagonists CGP55845 or CGP52432 enhanced long-term potentiation (LTP) in the Ts65Dn DG. The enhancement of LTP was accompanied by an increase in the NMDA receptor-mediated component of the tetanus-evoked responses. These findings are evidence for a contribution of GABAB receptors to changes in hippocampal-based cognition in the Ts65Dn mouse. The ability to rescue cognitive performance through treatment with selective GABAB receptor antagonists motivates studies to further explore the therapeutic potential of these compounds in people with DS. PMID:22764230

[Epigenetic research of cognitive deficit in schizophrenia: some methodological considerations].

PubMed

Lezheiko, T V; Alfimova, M V

To highlights the problems of assessing cognitive deficits in schizophrenia, relevant to the epigenetic, as well as a wide range of other approaches to the search for biological bases of cognition. The literature on the weaknesses in the evaluation of cognitive functions in patients with schizophrenia are summarized and discussed. The analysis is illustrated by our experience in developing a cognitive battery and a sample to examine relationships between DNA methylation in blood cells and cognitive deficits in schizophrenia. It has been shown that to assess cognitive deficits in patients and to reduce the influence of confounders in epigenetic analysis it is necessary (1) to use a battery with the existing co-normative data in the target population, which allows to evaluate representativeness of control and patients included in the study sample, (2) to verify the theoretically driven battery structure using normative population and a cohort of patients, (3) to balance groups of cases and controls on the number, age and sex, for which an individual matching of cases and controls is best suited, (4) to conduct an additional statistical analysis controlling for education and smoking.

Ameliorating effects of preadolescent aniracetam treatment on prenatal ethanol-induced impairment in AMPA receptor activity.

PubMed

Wijayawardhane, Nayana; Shonesy, Brian C; Vaithianathan, Thirumalini; Pandiella, Noemi; Vaglenova, Julia; Breese, Charles R; Dityatev, Alexander; Suppiramaniam, Vishnu

2008-01-01

Ethanol-induced damage in the developing hippocampus may result in cognitive deficits such as those observed in fetal alcohol spectrum disorder (FASD). Cognitive deficits in FASD are partially mediated by alterations in glutamatergic synaptic transmission. Recently, we reported that synaptic transmission mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) is impaired following fetal ethanol exposure. This finding led us to develop a rational approach for the treatment of alcohol-related cognitive deficits using aniracetam, an allosteric AMPAR modulator. In the present study, 28 to 34-day-old rats exposed to ethanol in utero were treated with aniracetam, and subsequently exhibited persistent improvement in mEPSC amplitude, frequency, and decay time. Furthermore, these animals expressed positive changes in synaptic single channel properties, suggesting that aniracetam ameliorates prenatal ethanol-induced deficits through modifications at the single channel level. Specifically, single channel open probability, conductance, mean open and closed times, and the number and burst duration were positively affected. Our findings emphasize the utility of compounds which slow the rate of deactivation and desensitization of AMPARs such as aniracetam.

Glycogen synthase kinase-3 inhibitors: Rescuers of cognitive impairments

PubMed Central

King, Margaret K.; Pardo, Marta; Cheng, Yuyan; Downey, Kimberlee; Jope, Richard S.; Beurel, Eléonore

2013-01-01

Impairment of cognitive processes is a devastating outcome of many diseases, injuries, and drugs affecting the central nervous system (CNS). Most often, very little can be done by available therapeutic interventions to improve cognitive functions. Here we review evidence that inhibition of glycogen synthase kinase-3 (GSK3) ameliorates cognitive deficits in a wide variety of animal models of CNS diseases, including Alzheimer's disease, Fragile X syndrome, Down syndrome, Parkinson's disease, spinocerebellar ataxia type 1, traumatic brain injury, and others. GSK3 inhibitors also improve cognition following impairments caused by therapeutic interventions, such as cranial irradiation for brain tumors. These findings demonstrate that GSK3 inhibitors are able to ameliorate cognitive impairments caused by a diverse array of diseases, injury, and treatments. The improvements in impaired cognition instilled by administration of GSK3 inhibitors appear to involve a variety of different mechanisms, such as supporting long-term potentiation and diminishing long-term depression, promotion of neurogenesis, reduction of inflammation, and increasing a number of neuroprotective mechanisms. The potential for GSK3 inhibitors to repair cognitive deficits associated with many conditions warrants further investigation of their potential for therapeutic interventions, particularly considering the current dearth of treatments available to reduce loss of cognitive functions. PMID:23916593

Deficits in Social Cognition: An Unveiled Signature of Multiple Sclerosis.

PubMed

Chalah, Moussa A; Ayache, Samar S

2017-03-01

Multiple sclerosis (MS) is a chronic progressive inflammatory disease of the central nervous system, representing the primary cause of non-traumatic disability in young adults. Cognitive dysfunction can affect patients at any time during the disease process and might alter the six core functional domains. Social cognition is a multi-component construct that includes the theory of mind, empathy and social perception of emotions from facial, bodily and vocal cues. Deficits in this cognitive faculty might have a drastic impact on interpersonal relationships and quality of life (QoL). Although exhaustive data exist for non-social cognitive functions in MS, only a little attention has been paid for social cognition. The objectives of the present work are to reappraise the definition and anatomy of social cognition and evaluate the integrity of this domain across MS studies. We will put special emphasis on neuropsychological and neuroimaging studies concerning social cognitive performance in MS. Studies were selected in conformity with PRISMA guidelines. We looked for computerized databases (PubMed, Medline, and Scopus) that index peer-reviewed journals to identify published reports in English and French languages that mention social cognition and multiple sclerosis, regardless of publication year. We combined keywords as follows: (facial emotion or facial expression or emotional facial expressions or theory of mind or social cognition or empathy or affective prosody) AND multiple sclerosis AND (MRI or functional MRI or positron emission tomography or functional imaging or structural imaging). We also scanned references from articles aiming to get additional relevant studies. In total, 26 studies matched the abovementioned criteria (26 neuropsychological studies including five neuroimaging studies). Available data support the presence of social cognitive deficits even at early stages of MS. The increase in disease burden along with the "multiple disconnection syndrome

Psychosocial support and cognitive deficits in adults with schizophrenia.

PubMed

Dalagdi, Aikaterini; Arvaniti, Aikaterini; Papatriantafyllou, John; Xenitidis, Kiriakos; Samakouri, Maria; Livaditis, Miltos

2014-08-01

In recent decades there has been an increasing interest in cognitive deficits in schizophrenia. However, only a few studies have examined the impact of psychosocial support on the prevention of cognitive deterioration in patients who suffer from schizophrenia. The aims of the present study are: (1) to confirm the presence of cognitive deficits among patients with schizophrenia; (2) to explore any correlations between such deficits and a range of clinical and/or demographic characteristics of the patients; and (3) to investigate any association between cognitive deficits and psychosocial support. A total of 118 patients with schizophrenia (the patient group) and 102 healthy volunteers (the control group) had a cognitive assessment using a battery of neuropsychological tests. The patients were allocated to one of the following groups: (1) patients under routine outpatient follow-up; or (2) patients receiving or having recently received intensive psychosocial support, in addition to follow-up. This included daily participation in vocational and recreational activities provided by dedicated mental health day centers. The findings of the neuropsychological testing of individuals in all groups were compared, after controlling for clinical or demographic factors. The scores in the neuropsychological tests were lower overall in the patients group compared to healthy volunteers. Within the patients group, those receiving/having received psychosocial support had higher scores compared to those on routine follow-up alone. There were no significant differences between patients currently receiving psychosocial support and those having received it in the past. Lower education, age and illness duration (but not severity of positive or negative symptoms) were factors associated with lower test scores. The study provides some evidence that psychosocial support may be beneficial for the cognitive functioning of patients with schizophrenia and this benefit may be a lasting one. �

Swertisin ameliorates pre-pulse inhibition deficits and cognitive impairment induced by MK-801 in mice.

PubMed

Oh, Hee Kyong; Jeon, Se Jin; Lee, Sunhee; Lee, Hyung Eun; Kim, Eunji; Park, Se Jin; Kim, Ha Neul; Jung, Won Yong; Cheong, Jae Hoon; Jang, Dae Sik; Ryu, Jong Hoon

2017-02-01

Swertisin, a plant-derived C-glucosylflavone, is known to have antidiabetic, anti-inflammatory and antioxidant effects. In the present study, we investigated in mice the effects of swertisin on glutamatergic dysfunction induced by dizocilpine (MK-801), a non-competitive N-methyl-D-aspartate receptor antagonist. In the Acoustic Startle Response test, their MK-801-induced (given 0.2 mg/kg i.p.) pre-pulse inhibition deficit was significantly attenuated by the administration of swertisin (30 mg/kg p.o.). In the Novel Object Recognition Test, the recognition memory impairments that were induced by MK-801 (0.2 mg/kg, given i.p.) were also reversed by administration of swertisin (30 mg/kg p.o.). In addition, swertisin normalized the MK-801-induced elevation of phosphorylation levels of Akt and GSK-3β signaling molecules in the prefrontal cortex. These results indicated that swertisin may be useful in managing the symptoms of schizophrenia, including sensorimotor gating disruption and cognitive impairment, and that these behavioral outcomes may be related to Akt-GSK-3β signaling in the prefrontal cortex.

Protective effect of stilbenes containing extract-fraction from Cajanus cajan L. on Abeta(25-35)-induced cognitive deficits in mice.

PubMed

Ruan, Can-Jun; Si, Jian-Yong; Zhang, Li; Chen, Di-Hua; Du, Guan-Hua; Su, Lan

2009-12-25

Cajanus cajan (L.) is a traditional Chinese herb medicine which contains a lot of potential active components. In the present study, we identified the effects of the stilbenes containing extract-fraction from C. cajan L. (sECC) on Abeta(25-35)-induced cognitive deficits, oxidative stress and cholinergic dysfunction in mice. Mice were treated with sECC (100 and 200mg/kg/d) for 1-week, and then received a single intracerebroventricular (i.c.v.) injection of Abeta(25-35) (5mug/mice). Behavioral changes and neuron apoptosis in mice were evaluated using Morris water maze and TUNEL tests. Furthermore, superoxide dismutase (SOD), choline acetyl transferase (ChAT) and acetylcholine esterase (AchE) activity in hippocampus and cortex were analyzed by spectrophotometric method. The data showed that consumption of sECC (200mg/kg) significantly ameliorated the cognitive deficits and neuron apoptosis caused by i.c.v. injection of Abeta(25-35). At the same time, the decreased SOD and ChAT activity in hippocampus and cortex were markedly increased by sECC (200mg/kg). sECC has no effect on AchE activity in hippocampus and cortex. These findings suggest that sECC may be a potential candidate for the development of therapeutic agents to manage cognitive impairment associated with Alzheimer's disease (AD) through increasing the activity of ChAT and anti-oxidative mechanism.

Selective activation of α7 nicotinic acetylcholine receptor by PHA-543613 improves Aβ25-35-mediated cognitive deficits in mice.

PubMed

Sadigh-Eteghad, S; Talebi, M; Mahmoudi, J; Babri, S; Shanehbandi, D

2015-07-09

Agonists of α7 nicotinic acetylcholine receptors (nAChRs) are currently being considered as therapeutic approaches for managing cognitive deficits in Alzheimer's disease (AD). Present study was designed to evaluate the effect of α7 nAChR selective activation by PHA-543613 (PHA) on beta-amyloid (Aβ)25-35-mediated cognitive deficits in mice. For this purpose, PHA (1mg/kg, i.p.), a selective α7 nAChR agonist, and galantamine (Gal) (3mg/kg, s.c.), an acetylcholine-esterase inhibitor (AChEI) effects on α7 nAChR were tested in Aβ25-35-received (intracerebroventricular, 10 nmol) mice model of AD. Methyllycaconitine (MLA) (1mg/kg, i.p.), a α7 nAChR antagonist, was used for receptor blockage effects evaluation. Working and reference memory in animals was assessed by the Morris water maze (MWM) task. The mRNA and protein levels of α7 subunit were analyzed by real-time PCR and Western blotting, respectively. PHA and Gal, ameliorate Aβ-impaired working and reference memory. However, Gal had less effect than PHA in this regard. Pretreatment with MLA reverses both Gal and PHA effects in MWM. PHA and Gal treatment prevent Aβ-induced α7 subunit protein reduction, but Gal has lesser effect than PHA. This effect blocked by pretreatment with MLA. In neither the pretreatment nor treatment group, the mRNA levels of nAChR α7 subunit were significantly changed. Therefore, α7 nAChR activation, reduces Aβ-induced cognitive deficits and increases the α7 protein level and subsequent neuron survival. However, blockage of receptor, increases Aβ toxicity and cognitive impairment and reduces the α7 nAChR protein level and flowing neuroprotection. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

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

PubMed Central

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

2016-01-01

Background 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. Methods 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. Results 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. Conclusions The observed ameliorative effects of NSO make it a promising agent against moto-cognitive dysfunction and cerebelo-hippocampal alterations induced by cannabis. PMID:27904421

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.

Evidence for distinct cognitive deficits after focal cerebellar lesions.

PubMed

Gottwald, B; Wilde, B; Mihajlovic, Z; Mehdorn, H M

2004-11-01

Anatomical evidence and lesion studies, as well as functional magnetic resonance imaging (fMRI) studies, indicate that the cerebellum contributes to higher cognitive functions. Cerebellar posterior lateral regions seem to be relevant for cognition, while vermal lesions seem to be associated with changes in affect. However, the results remain controversial. Deficits of patients are sometimes still attributed to motor impairment. We present data from a detailed neuropsychological examination of 21 patients with cerebellar lesions due to tumour or haematoma, and 21 controls matched for age, sex, and years of education. Patients showed deficits in executive function, and in attentional processes such as working memory and divided attention. Further analysis revealed that patients with right-sided lesions were in general more impaired than those with left-sided lesions. Those hypotheses that suggest that lesions of the right cerebellar hemisphere lead to verbal deficits, while those of the left lead to non-verbal deficits, have in part been confirmed. The generally greater impairment of those patients with a right-sided lesion has been interpreted as resulting from the connection of the right cerebellum to the left cerebral hemisphere, which is dominant for language functions and crucial for right hand movements. Motor impairment was correlated with less than half of the cognitive measures, with no stronger tendency for correlation with cognitive tests that require motor responses discernible. The results are discussed on the basis of an assumption that the cerebellum has a predicting and preparing function, indicating that cerebellar lesions lead to a "dysmetria of thought."

Profile of cognitive deficits and associations with depressive symptoms and intelligence in chronic early-onset schizophrenia patients.

PubMed

Jepsen, Jens Richardt Møllegaard; Fagerlund, Birgitte; Pagsberg, Anne Katrine; Christensen, Anne Marie Raaberg; Nordentoft, Merete; Mortensen, Erik Lykke

2013-10-01

Cognitive deficits in several domains have been demonstrated in early-onset schizophrenia patients but their profile and relation to depressive symptoms and intelligence need further characterization. The purpose was to characterize the profile of cognitive deficits in chronic, early-onset schizophrenia patients, assess the potential associations with depressive symptom severity, and examine whether cognitive deficits within several domains reflect intelligence impairments. This study compared attention, visual-construction, aspects of visual and verbal memory, and executive functions in chronic, early-onset schizophrenia patients (mean age = 20.7 years) (N = 18) and healthy controls (N = 38). Schizophrenia diagnoses were established at the time of the patients' first clinical presentation during childhood or adolescence and were confirmed five years later. In the chronic phase of early-onset schizophrenia, significant deficits were observed in all specific cognitive functions. The profile of cognitive deficits was jagged, and visual-construction, attention, and one aspect of verbal memory (verbal stories recall) were differentially impaired. Deficits of visual recall, visual recognition, and executive functions were accounted for by deficits in intelligence, while this was not the case for deficits of verbal recall of stories or attention. No significant associations were observed between the severity of cognitive deficits and that of depressive symptoms. Chronic, early-onset schizophrenia is characterized by a broad and jagged profile of cognitive deficits. Deficits of attention and verbal recall of stories appear not to be accounted for by deficits in intelligence, and the severity of cognitive deficits seems independent from that of depressive symptoms. © 2013 The Scandinavian Psychological Associations.

Gray matter morphological anomalies in the cerebellar vermis in first-episode schizophrenia patients with cognitive deficits.

PubMed

Wang, Jingjuan; Zhou, Li; Cui, Chunlei; Liu, Zhening; Lu, Jie

2017-11-22

Cognitive deficits are a core feature of early schizophrenia. However, the pathological foundations underlying cognitive deficits are still unknown. The present study examined the association between gray matter density and cognitive deficits in first-episode schizophrenia. Structural magnetic resonance imaging of the brain was performed in 34 first-episode schizophrenia patients and 21 healthy controls. Patients were divided into two subgroups according to working memory task performance. The three groups were well matched for age, gender, and education, and the two patient groups were also further matched for diagnosis, duration of illness, and antipsychotic treatment. Voxel-based morphometric analysis was performed to estimate changes in gray matter density in first-episode schizophrenia patients with cognitive deficits. The relationships between gray matter density and clinical outcomes were explored. Patients with cognitive deficits were found to have reduced gray matter density in the vermis and tonsil of cerebellum compared with patients without cognitive deficits and healthy controls, decreased gray matter density in left supplementary motor area, bilateral precentral gyrus compared with patients without cognitive deficits. Classifier results showed GMD in cerebellar vermis tonsil cluster could differentiate SZ-CD from controls, left supplementary motor area cluster could differentiate SZ-CD from SZ-NCD. Gray matter density values of the cerebellar vermis cluster in patients groups were positively correlated with cognitive severity. Decreased gray matter density in the vermis and tonsil of cerebellum may underlie early psychosis and serve as a candidate biomarker for schizophrenia with cognitive deficits.

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.

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

Effect of Treating Anxiety Disorders on Cognitive Deficits and Behaviors Associated with Attention Deficit Hyperactivity Disorder: A Preliminary Study.

PubMed

Denis, Isabelle; Guay, Marie-Claude; Foldes-Busque, Guillaume; BenAmor, Leila

2016-06-01

Twenty-five percent of children with ADHD also have an anxiety disorder (AD). As per Quay and in light of Barkley's model, anxiety may have a protective effect on cognitive deficits and behaviors associated with ADHD. This study aimed to evaluate the effect of treating AD on cognitive deficits and behaviors associated with ADHD in children with both disorders. Twenty-four children with ADHD and AD were divided into two groups: treatment for AD, and wait list. Participants were assessed at pre-treatment, post-treatment, and 6-month follow-up with the ADIS-C, the CBCL, and neuropsychological measures. The results revealed a significant improvement in automatic response inhibition and flexibility, and a decrease in inattention/hyperactivity behaviors following the treatment for AD. No significant differences were observed in motor response inhibition, working memory, or attention deficits. The results do not seem to support Quay's hypothesis: treating AD did not exacerbate cognitive deficits and behaviors associated with ADHD in our sample.

Escitalopram Ameliorates Tau Hyperphosphorylation and Spatial Memory Deficits Induced by Protein Kinase A Activation in Sprague Dawley Rats.

PubMed

Ren, Qing-Guo; Wang, Yan-Juan; Gong, Wei-Gang; Xu, Lin; Zhang, Zhi-Jun

2015-01-01

Here, we investigated the effect of escitalopram pretreatment on protein kinase A (PKA)-induced tau hyperphosphorylation and spatial memory deficits in rats using western blot and behavioral tests, respectively. We demonstrated that escitalopram effectively ameliorated tau hyperphosphorylation and the spatial memory deficits induced by PKA activation. We measured the total and activity-dependent Ser9-phosphorylated levels of glycogen synthase kinase (GSK)-3β in hippocampal extracts. No significant change in the total level of GSK-3β was observed between the different groups. However, compared with forskolin injection alone, pretreatment with escitalopram increased the level of Ser9-phosphorylated GSK-3β. We also demonstrated that escitalopram increased Akt phosphorylation at Ser473 (the active form of Akt). Furthermore, we identified other important kinases and phosphatases, such as protein phosphatase 2A, extracellular signal-regulated kinases 1 and 2, and MAP kinase kinase-1/2, that have previously been reported to play a crucial role in tau phosphorylation; however, we did not detect any significant change in the activation of these kinases or phosphatases in our study. We unexpectedly demonstrated that forskolin caused anxiety-like behavior in rats, and pretreatment with escitalopram did not significantly ameliorate the anxiety-like behavior induced by forskolin. These data provide the first evidence that escitalopram ameliorates forskolin-induced tau hyperphosphorylation and spatial memory impairment in rats; these effects do not occur via the anti-anxiety activity of escitalopram but may involve the Akt/GSK-3β signaling pathway.

A cog in cognition: how the alpha 7 nicotinic acetylcholine receptor is geared towards improving cognitive deficits.

PubMed

Leiser, Steven C; Bowlby, Mark R; Comery, Thomas A; Dunlop, John

2009-06-01

Cognition, memory, and attention and arousal have been linked to nicotinic acetylcholine receptors (nAChRs). Thus it is not surprising that nAChRs have been strongly implicated as therapeutic targets for treating cognitive deficits in disorders such as schizophrenia and Alzheimer's disease (AD). In particular the alpha7 (alpha7) nAChR has been closely linked with normalization of P50 auditory evoked potential (AEP) gating deficits, and to a lesser extent improvements in pre-pulse inhibition (PPI) of the acoustic startle response. These two brain phenomena can be considered as pre-attentive, occurring while sensory information is being processed, and are important endophenotypes in schizophrenia with deficits likely contributing to the cognitive fragmentation associated with the disease. In addition alpha7 nAChRs have been implicated in attention, in particular under high attentional demand, and in more demanding working memory tasks such as long delays in delayed matching tasks. Efficacy of alpha7 nAChR agonists across a range of cognitive processes ranging from pre-attentive to attentive states and working and recognition memory provides a solid basis for their pro-cognitive effects. This review will focus on the recent work highlighting the role of alpha7 in cognition and cognitive processes.

A specific cognitive deficit within semantic cognition across a multi-generational family

PubMed Central

Briscoe, Josie; Chilvers, Rebecca; Baldeweg, Torsten; Skuse, David

2012-01-01

We report a study of eight members of a single family (aged 8–72 years), who all show a specific deficit in linking semantic knowledge to language. All affected members of the family had high levels of overall intelligence; however, they had profound difficulties in prose and sentence recall, listening comprehension and naming. The behavioural deficit was remarkably consistent across affected family members. Structural neuroimaging data revealed grey matter abnormalities in the left infero-temporal cortex and fusiform gyri: brain areas that have been associated with integrative semantics. This family demonstrates, to our knowledge, the first example of a heritable, highly specific abnormality affecting the interface between language and cognition in humans and has important implications for our understanding of the genetic basis of cognition. PMID:22719041

BDNF (brain-derived neurotrophic factor) serum levels in schizophrenic patients with cognitive deficits

NASA Astrophysics Data System (ADS)

Utami, N.; Effendy, E.; Amin, M. M.

2018-03-01

Schizophrenia is a complex neurodevelopmental disorder with cognitive impairment as the main part. BDNF regulates aspects of developmental plasticity in the brain and is involved in cognitive function. Cognitive functions include capabilities such as attention, executive functioning, assessing, monitoring and evaluating. The aim of the study was to know the BDNF levels in schizophrenic patients with cognitive deficits. The study was held in October 2016 - March 2017, and was the first in Indonesia, especially in North Sumatra. The study was approved by the medical ethics committee of the University of North Sumatera. The study is descriptive based on a retrospective method with cross-sectional approach. The subject is 40 male schizophrenia. Cognitive deficits were assessed by MoCA-Ina. BDNF serum levels were analyzed using the quantitative sandwich enzyme immunoassay. The average MoCA-Ina score is 21.03±5.21. This suggests that there is a cognitive function deficit in schizophrenic patients. The mean serum BDNF level was 26629±6762. MoCA-Ina scores in schizophrenic patients <26 who experienced a deficit of 77.5% and serum BDNF levels with normal values ranging from 6.186 to 42.580pg/ml.

Citalopram restores short-term memory deficit and non-cognitive behaviors in APP/PS1 mice while halting the advance of Alzheimer's disease-like pathology.

PubMed

Zhang, Qin; Yang, Chen; Liu, Tianyao; Liu, Liang; Li, Fen; Cai, Yulong; Lv, Keyi; Li, Xin; Gao, Junwei; Sun, Dayu; Xu, Haiwei; Yang, Qingwu; Fan, Xiaotang

2018-03-15

Alzheimer's disease (AD) is the most common cause of dementia. In addition to cognitive impairments, deficits in non-cognitive behaviors are also common neurological sequelae in AD. Here, we show that complex behavioral deficits in 7-month-old APPswe/PSEN1dE9 (APP/PS1) mice include impairments in object recognition, deficient social interaction, increased depression and buried marbles. Citalopram, one of the selective serotonin reuptake inhibitors (SSRIs), ameliorated the amyloid deposition in AD patients and transgenic animal models. After treatment for 4 weeks, citalopram rescued the deficits in short-term memory, sociability and depression in these mice. Further immunohistochemical analysis showed chronic citalopram treatment significantly attenuated β-amyloid deposition and microglial activation in the brains of APP/PS1 mice as demonstrated previously. Parvalbumin (PV) interneurons, which are the primary cellular subtype of GABAergic neurons and considered indispensable for short-term memory and social interaction, also contributed to the progress of depression. Additionally, we found the citalopram could significantly increase the PV-positive neurons in the cortex of APP/PS1 mice without alteration in the hippocampus, which might contribute to the improvement of behavioral performance. Our findings suggest that citalopram might be a potential candidate for the early treatment of AD. Copyright © 2017 Elsevier Ltd. All rights reserved.

Social Cognition Deficits: Current Position and Future Directions for Neuropsychological Interventions in Cerebrovascular Disease.

PubMed

Njomboro, Progress

2017-01-01

Neuropsychological assessments of cognitive dysfunction in cerebrovascular illness commonly target basic cognitive functions involving aspects of memory, attention, language, praxis, and number processing. Here, I highlight the clinical importance of often-neglected social cognition functions. These functions recruit a widely distributed neural network, making them vulnerable in most cerebrovascular diseases. Sociocognitive deficits underlie most of the problematic social conduct observed in patients and are associated with more negative clinical outcomes (compared to nonsocial cognitive deficits). In clinical settings, social cognition deficits are normally gleaned from collateral information from caregivers or from indirect inferences made from patients' performance on standard nonsocial cognitive tests. Information from these sources is however inadequate. I discuss key social cognition functions, focusing initially on deficits in emotion perception and theory of mind, two areas that have gained sizeable attention in neuroscientific research, and then extend the discussion into relatively new, less covered but crucial functions involving empathic behaviour, social awareness, social judgements, and social decision making. These functions are frequently impaired following neurological change. At present, a wide range of psychometrically robust social cognition tests is available, and this review also makes the case for their inclusion in neuropsychological assessments.

Social Cognition Deficits: Current Position and Future Directions for Neuropsychological Interventions in Cerebrovascular Disease

PubMed Central

2017-01-01

Neuropsychological assessments of cognitive dysfunction in cerebrovascular illness commonly target basic cognitive functions involving aspects of memory, attention, language, praxis, and number processing. Here, I highlight the clinical importance of often-neglected social cognition functions. These functions recruit a widely distributed neural network, making them vulnerable in most cerebrovascular diseases. Sociocognitive deficits underlie most of the problematic social conduct observed in patients and are associated with more negative clinical outcomes (compared to nonsocial cognitive deficits). In clinical settings, social cognition deficits are normally gleaned from collateral information from caregivers or from indirect inferences made from patients' performance on standard nonsocial cognitive tests. Information from these sources is however inadequate. I discuss key social cognition functions, focusing initially on deficits in emotion perception and theory of mind, two areas that have gained sizeable attention in neuroscientific research, and then extend the discussion into relatively new, less covered but crucial functions involving empathic behaviour, social awareness, social judgements, and social decision making. These functions are frequently impaired following neurological change. At present, a wide range of psychometrically robust social cognition tests is available, and this review also makes the case for their inclusion in neuropsychological assessments. PMID:28729755

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.

Deficits in social cognition and response flexibility in pediatric bipolar disorder.

PubMed

McClure, Erin B; Treland, Julia E; Snow, Joseph; Schmajuk, Mariana; Dickstein, Daniel P; Towbin, Kenneth E; Charney, Dennis S; Pine, Daniel S; Leibenluft, Ellen

2005-09-01

Little is known about neuropsychological and social-cognitive function in patients with pediatric bipolar disorder. Identification of specific deficits and strengths that characterize pediatric bipolar disorder would facilitate advances in diagnosis, treatment, and research on pathophysiology. The purpose of this study was to test the hypothesis that youths with bipolar disorder would perform more poorly than matched healthy comparison subjects on measures of social cognition, motor inhibition, and response flexibility. Forty outpatients with pediatric bipolar disorder and 22 comparison subjects (no differences in age, gender, and IQ) completed measures of social cognition (the pragmatic judgment subtest of the Comprehensive Assessment of Spoken Language, facial expression recognition subtests of the Diagnostic Analysis of Nonverbal Accuracy Scale, the oral expression subtest of the Test of Language Competence), inhibition and response flexibility (stop and stop-change tasks), and motor inhibition (continuous performance tasks). Pediatric bipolar disorder patients performed more poorly than comparison subjects on social-cognitive measures (pragmatic judgment of language, facial expression recognition) and on a task requiring response flexibility. These deficits were present in euthymic patients. Differences between patients and comparison subjects could not be attributed to comorbid attention deficit hyperactivity disorder. Findings of impaired social cognition and response flexibility in youths with pediatric bipolar disorder suggest continuity between pediatric bipolar disorder and adult bipolar disorder. These findings provide a foundation for neurocognitive research designed to identify the neural mechanisms underlying these deficits.

Blast traumatic brain injury induced cognitive deficits are attenuated by pre- or post-injury treatment with the glucagon-like peptide-1 receptor agonist, exendin-4

PubMed Central

Tweedie, David; Rachmany, Lital; Rubovitch, Vardit; Li, Yazhou; Holloway, Harold W.; Lehrmann, Elin; Zhang, Yongqing; Becker, Kevin G.; Perez, Evelyn; Hoffer, Barry J.; Pick, Chaim G.; Greig, Nigel H.

2015-01-01

Background Blast traumatic brain injury (B-TBI) affects military and civilian personnel. Presently there are no approved drugs for blast brain injury. Methods Exendin-4, administered subcutaneously, was evaluated as a pre-treatment (48 hours) and post-injury treatment (2 hours) on neurodegeneration, behaviors and gene expressions in a murine open field model of blast injury. Results B-TBI induced neurodegeneration, changes in cognition and genes expressions linked to dementia disorders. Exendin-4, administered pre- or post-injury ameliorated B-TBI-induced neurodegeneration at 72 hours, memory deficits from days 7–14 and attenuated genes regulated by blast at day 14 post-injury. Conclusions The present data suggest shared pathological processes between concussive and B-TBI, with endpoints amenable to beneficial therapeutic manipulation by exendin-4. B-TBI-induced dementia-related gene pathways and cognitive deficits in mice somewhat parallel epidemiological studies of Barnes and co-workers who identified a greater risk in US military veterans who experienced diverse TBIs, for dementia in later life. PMID:26327236

Meta-analysis of social cognition in attention-deficit/hyperactivity disorder (ADHD): comparison with healthy controls and autistic spectrum disorder.

PubMed

Bora, E; Pantelis, C

2016-03-01

Impairment in social cognition is an established finding in autism spectrum disorders (ASD). Emerging evidence suggests that attention-deficit/hyperactivity disorder (ADHD) might be also associated with deficits in theory of mind (ToM) and emotion recognition. However, there are inconsistent findings, and it has been debatable whether such deficits persist beyond childhood and how similar social cognitive deficits are in ADHD v. ASD. We conducted a meta-analysis of social cognition, including emotion recognition and ToM, studies in ADHD compared with healthy controls and ASD. The current meta-analysis involved 44 studies comparing ADHD (n = 1999) with healthy controls (n = 1725) and 17 studies comparing ADHD (n = 772) with ASD (n = 710). Facial and vocal emotion recognition (d = 0.40-0.44) and ToM (d = 0.43) abilities were significantly impaired in ADHD. The most robust facial emotion recognition deficits were evident in anger and fear. Social cognitive deficits were either very subtle (emotion recognition) or non-significant (ToM) in adults with ADHD. Deficits in social cognition, especially ToM, were significantly more pronounced in ASD compared with ADHD. General cognitive impairment has contributed to social cognitive deficits in ADHD. Performance of individuals with ADHD on social cognition lies intermediate between ASD and healthy controls. However, developmental trajectories of social cognition probably differ between ADHD and ASD as social cognitive deficits in ADHD might be improving with age in most individuals. There is a need for studies investigating a potential subtype of ADHD with persistent social cognitive deficits and exploring longitudinal changes in social cognition during development.

Cognitive Ameliorating Effect of Acanthopanax koreanum Against Scopolamine-Induced Memory Impairment in Mice.

PubMed

Lee, Sunhee; Park, Ho Jae; Jeon, Se Jin; Kim, Eunji; Lee, Hyung Eun; Kim, Haneul; Kwon, Yubeen; Zhang, Jiabao; Jung, In Ho; Ryu, Jong Hoon

2017-03-01

Acanthopanax koreanum Nakai (Araliaceae) is one of the most widely cultivated medicinal plants in Jeju Island, Korea, and the roots and stem bark of A. koreanum have been traditionally used as a tonic agent for general weakness. However, the use of A. koreanum for general weakness observed in the elderly, including those with declined cognitive function, has not been intensively investigated. This study was performed to investigate the effect of the ethanol extract of A. koreanum (EEAK) on cholinergic blockade-induced memory impairment in mice. To evaluate the ameliorating effects of EEAK against scopolamine-induced memory impairment, mice were orally administered EEAK (25, 50, 100, or 200 mg/kg), and several behavioral tasks, including a passive avoidance task, the Y-maze, and a novel object recognition task, were employed. Besides, western blot analysis was conducted to examine whether EEAK affected memory-associated signaling molecules, such as protein kinase B (Akt), Ca 2+ /calmodulin-dependent protein kinase II (CaMKII), and cAMP response element-binding protein (CREB). The administration of EEAK (100 or 200 mg/kg, p.o.) significantly ameliorated the scopolamine-induced cognitive impairment in the passive avoidance task, the Y-maze, and the novel object recognition task. The phosphorylation levels of both Akt and CaMKII were significantly increased by approximately two-fold compared with the control group because of the administration of EEAK (100 or 200 mg/kg) (p < 0.05). Moreover, the phosphorylation level of CREB was also significantly increased compared with the control group by the administration of EEAK (200 mg/kg) (p < 0.05). The present study suggests that EEAK ameliorates the cognitive dysfunction induced by the cholinergic blockade, in part, via several memory-associated signaling molecules and may hold therapeutic potential against cognitive dysfunction, such as that presented in neurodegenerative diseases, for example, Alzheimer

Ameliorative effects of amide derivatives of 1,3,4-thiadiazoles on scopolamine induced cognitive dysfunction.

PubMed

Kulshreshtha, Akanksha; Piplani, Poonam

2016-10-21

The present study reports the effect of amide derivatives of 1,3,4-thiadizoles on scopolamine induced deficit cholinergic neurotransmission and oxidative stress serving as promising leads for the therapeutics of cognitive dysfunction. Fourteen compounds (2c-8d) have been synthesised and evaluated against behavioural alterations using step down passive avoidance protocol and morris water maze and at a dose of 0.5 mg/kg with reference to the standard, Rivastigmine. All the synthesised compounds were evaluated for their in vitro acetylcholinesterase (AChE) inhibition at five different concentrations using mice brain homogenate as the source of the enzyme. Biochemical estimation of markers of oxidative stress (lipid peroxidation, superoxide dismutase, glutathione, plasma nitrite, catalase) has also been carried out to assess the role of synthesised molecules on the oxidative damage induced by scopolamine. The compounds 5c, 6c and 8c displayed appreciable activity with an IC50 value of 3 μM, 3.033 μM and 2.743 μM, respectively towards acetylcholinesterase inhibition. These compounds also decreased scopolamine induced oxidative stress, thus serving as promising leads for the amelioration of oxidative stress induced cognitive decline. The molecular docking study performed to predict the binding mode of the compounds also suggested that these compounds bind appreciably with the amino acids present in the active site of recombinant human acetylcholinesterase (rhAChE). The results indicated that these compounds could be further traversed as inhibitors of AChE and oxidative stress for the treatment of cognitive dysfunction. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

The AT{sub 1} Receptor Antagonist, L-158,809, Prevents or Ameliorates Fractionated Whole-Brain Irradiation-Induced Cognitive Impairment

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

Robbins, Mike E.; Brain Tumor Center of Excellence, Wake Forest University School of Medicine, Winston-Salem, NC; Payne, Valerie B.S.

2009-02-01

Purpose: We hypothesized that administration of the angiotensin type 1 (AT1) receptor antagonist, L-158,809, to young adult male rats would prevent or ameliorate fractionated whole-brain irradiation (WBI)-induced cognitive impairment. Materials and Methods: Groups of 80 young adult male Fischer 344 x Brown Norway (F344xBN) rats, 12-14 weeks old, received either: (1) fractionated WBI; 40 Gy of {gamma} rays in 4 weeks, 2 fractions/week, (2) sham-irradiation; (3) WBI plus L-158,809 (20 mg/L drinking water) starting 3 days prior, during, and for 14, 28, or 54 weeks postirradiation; and (4) sham-irradiation plus L-158,809 for 14, 28, or 54 weeks postirradiation. An additionalmore » group of rats (n = 20) received L-158,809 before, during, and for 5 weeks postirradiation, after which they received normal drinking water up to 28 weeks postirradiation. Results: Administration of L-158,809 before, during, and for 28 or 54 weeks after fractionated WBI prevented or ameliorated the radiation-induced cognitive impairment observed 26 and 52 weeks postirradiation. Moreover, giving L-158,809 before, during, and for only 5 weeks postirradiation ameliorated the significant cognitive impairment observed 26 weeks postirradiation. These radiation-induced cognitive impairments occurred without any changes in brain metabolites or gross histologic changes assessed at 28 and 54 weeks postirradiation, respectively. Conclusions: Administering L-158,809 before, during, and after fractionated WBI can prevent or ameliorate the chronic, progressive, cognitive impairment observed in rats at 26 and 52 weeks postirradiation. These findings offer the promise of improving the quality of life for brain tumor patients.« less

Levothyroxine replacement therapy with vitamin E supplementation prevents oxidative stress and cognitive deficit in experimental hypothyroidism.

PubMed

Pan, Tianrong; Zhong, Mingkui; Zhong, Xing; Zhang, Yanqing; Zhu, Defa

2013-04-01

Hypothyroidism has a variety of adverse effects on cognitive function. The treatment of levothyroxine alone cannot restore cognitive defects of hypothyroid patients. Antioxidant vitamin E supplementation could be useful in disturbances which are associated with oxidative stress and could effectively slow the progression of Alzheimer disease. Thus, the purpose of this study was to evaluate oxidative stress status of the serum and hippocampus in hypothyroidism and to examine the effects of levothyroxine replacement therapy with vitamin E supplementation on cognitive deficit. Sprague-Dawley rats were randomly divided into five groups: control group, PTU group, PTU + Vit E group, PTU + L-T4 group, and PTU + L-T4 + Vit E group. Serum and hippocampus malondialdehyde (MDA) levels were determined using the thiobarbituric-acid reactive substances method. Serum and hippocampus superoxide dismutase (SOD) levels were determined by measuring its ability to inhibit the photoreduction of nitroblue tetrazolium. Learning and memory was assessed by Morris water maze test. In the present study, we found that the rats of PTU + Vit E group spent less time to find the platform on days 2, 3, 4, and 5 than the PTU group. Moreover, the rats of PTU + L-T4 + Vit E group spent less time to find the platform on days 4 and 5 than the PTU + L-T4 group. The time spent in the target quadrants was measured in the probe test and no difference was observed in all groups. Oxidative damage has been observed in the serum and hippocampus of hypothyroidism rat. SOD levels of serum and hippocampus tissue were significantly increased and MDA levels were significantly decreased in the PTU + Vit E and PTU + L-T4 + Vit E groups than the PTU and PTU + L-T4 groups. Therefore, these findings indicate that levothyroxine replacement therapy with vitamin E supplementation may ameliorate cognitive deficit in PTU-induced hypothyroidism through the decrease of oxidative stress status.

Diet-induced obesity attenuates endotoxin-induced cognitive deficits.

PubMed

Setti, Sharay E; Littlefield, Alyssa M; Johnson, Samantha W; Kohman, Rachel A

2015-03-15

Activation of the immune system can impair cognitive function, particularly on hippocampus dependent tasks. Several factors such as normal aging and prenatal experiences can modify the severity of these cognitive deficits. One additional factor that may modulate the behavioral response to immune activation is obesity. Prior work has shown that obesity alters the activity of the immune system. Whether diet-induced obesity (DIO) influences the cognitive deficits associated with inflammation is currently unknown. The present study explored whether DIO alters the behavioral response to the bacterial endotoxin, lipopolysaccharide (LPS). Female C57BL/6J mice were fed a high-fat (60% fat) or control diet (10% fat) for a total of five months. After consuming their respective diets for four months, mice received an LPS or saline injection and were assessed for alterations in spatial learning. One month later, mice received a second injection of LPS or saline and tissue samples were collected to assess the inflammatory response within the periphery and central nervous system. Results showed that LPS administration impaired spatial learning in the control diet mice, but had no effect in DIO mice. This lack of a cognitive deficit in the DIO female mice is likely due to a blunted inflammatory response within the brain. While cytokine production within the periphery (i.e., plasma, adipose, and spleen) was similar between the DIO and control mice, the DIO mice failed to show an increase in IL-6 and CD74 in the brain following LPS administration. Collectively, these data indicate that DIO can reduce aspects of the neuroinflammatory response as well as blunt the behavioral reaction to an immune challenge. Copyright © 2014 Elsevier Inc. All rights reserved.

Replenishment of microRNA-188-5p restores the synaptic and cognitive deficits in 5XFAD Mouse Model of Alzheimer's Disease.

PubMed

Lee, Kihwan; Kim, Hyunju; An, Kyongman; Kwon, Oh-Bin; Park, Sungjun; Cha, Jin Hee; Kim, Myoung-Hwan; Lee, Yoontae; Kim, Joung-Hun; Cho, Kwangwook; Kim, Hye-Sun

2016-10-06

MicroRNAs have emerged as key factors in development, neurogenesis and synaptic functions in the central nervous system. In the present study, we investigated a pathophysiological significance of microRNA-188-5p (miR-188-5p) in Alzheimer's disease (AD). We found that oligomeric Aβ 1-42 treatment diminished miR-188-5p expression in primary hippocampal neuron cultures and that miR-188-5p rescued the Aβ 1-42 -mediated synapse elimination and synaptic dysfunctions. Moreover, the impairments in cognitive function and synaptic transmission observed in 7-month-old five familial AD (5XFAD) transgenic mice, were ameliorated via viral-mediated expression of miR-188-5p. miR-188-5p expression was down-regulated in the brain tissues from AD patients and 5XFAD mice. The addition of miR-188-5p rescued the reduction in dendritic spine density in the primary hippocampal neurons treated with oligomeric Aβ 1-42 and cultured from 5XFAD mice. The reduction in the frequency of mEPSCs was also restored by addition of miR-188-5p. The impairments in basal fEPSPs and cognition observed in 7-month-old 5XFAD mice were ameliorated via the viral-mediated expression of miR-188-5p in the hippocampus. Furthermore, we found that miR-188 expression is CREB-dependent. Taken together, our results suggest that dysregulation of miR-188-5p expression contributes to the pathogenesis of AD by inducing synaptic dysfunction and cognitive deficits associated with Aβ-mediated pathophysiology in the disease.

Self-Instructional Cognitive Training to Reduce Impulsive Cognitive Style in Children with Attention Deficit with Hyperactivity Disorder

ERIC Educational Resources Information Center

Rivera-Flores, Gladys Wilma

2015-01-01

Introduction: Children with attention deficit with hyperactivity disorder (ADHD) have an impulsive, rigid and field-dependent cognitive style. This study examines whether self-instructional cognitive training reduces impulsive cognitive style in children diagnosed with this disorder. Method: The subjects were 10 children between the ages of 6 and…

DADS Analogues Ameliorated the Cognitive Impairments of Alzheimer-Like Rat Model Induced by Scopolamine.

PubMed

Manral, Apra; Meena, Poonam; Saini, Vikas; Siraj, Fouzia; Shalini, Shruti; Tiwari, Manisha

2016-10-01

The development of agents that affect two or more relevant targets has drawn considerable attention in treatment of AD. Diallyl disulfide (DADS), an active principle of garlic, has been reported to prevent APP processing by amyloidogenic pathway. Recently, we have reported a new series of DADS derivatives and our findings revealed that compound 7k and 7l could provide good templates for developing new multifunctional agents for AD treatment. Thus, the present study was constructed to investigate the neuroprotective effect of DADS analogues (7k and 7l) against Aβ-induced neurotoxicity in SH-SY5Y human neuroblastoma cells and in ameliorating the cognition deficit induced by scopolamine in rat model. The results indicated that compound 7k and 7l significantly inhibited Aβ1-42-induced neuronal cell death by inhibiting ROS generation. Moreover, they prevented apoptosis, in response to ROS, by restoring normal Bax/Bcl-2 ratio. Furthermore, it was observed that scopolamine-induced memory impairment was coupled by alterations in neurotransmitters, acetylcholinesterase activity and oxidative stress markers. Histological analysis revealed severe damaging effects of scopolamine on the structure of cerebral cortex and hippocampus. Administration of compounds 7k and 7l at 5 mg/kg significantly reversed scopolamine-induced behavioural, biochemical, neurochemical and histological changes in a manner comparable to standard donepezil. Together the present findings and previous studies indicate that compounds 7k and 7l have neuroprotective and cognition-enhancing effects, which makes them a promising multi-target candidate for addressing the complex nature of AD.

A neurocomputational account of cognitive deficits in Parkinson’s disease

PubMed Central

Hélie, Sébastien; Paul, Erick J.; Ashby, F. Gregory

2014-01-01

Parkinson’s disease (PD) is caused by the accelerated death of dopamine (DA) producing neurons. Numerous studies documenting cognitive deficits of PD patients have revealed impairments in a variety of tasks related to memory, learning, visuospatial skills, and attention. While there have been several studies documenting cognitive deficits of PD patients, very few computational models have been proposed. In this article, we use the COVIS model of category learning to simulate DA depletion and show that the model suffers from cognitive symptoms similar to those of human participants affected by PD. Specifically, DA depletion in COVIS produced deficits in rule-based categorization, non-linear information-integration categorization, probabilistic classification, rule maintenance, and rule switching. These were observed by simulating results from younger controls, older controls, PD patients, and severe PD patients in five well-known tasks. Differential performance among the different age groups and clinical populations was modeled simply by changing the amount of DA available in the model. This suggests that COVIS may not only be an adequate model of the simulated tasks and phenomena but also more generally of the role of DA in these tasks and phenomena. PMID:22683450

Neurocognitive impairment in deficit and non-deficit schizophrenia: a meta-analysis.

PubMed

Bora, E; Binnur Akdede, B; Alptekin, K

2017-10-01

Most studies suggested that patients with deficit schizophrenia have more severe impairment compared with patients with non-deficit schizophrenia. However, it is not clear whether deficit and non-deficit schizophrenia are associated with differential neurocognitive profiles. The aim of this meta-analytic review was to compare cognitive performances of deficit and non-deficit patients with each other and with healthy controls. In the current meta-analysis, differences in cognitive abilities between 897 deficit and 1636 non-deficit patients with schizophrenia were examined. Cognitive performances of 899 healthy controls were also compared with 350 patients with deficit and 592 non-deficit schizophrenia. Both deficit (d = 1.04-1.53) and non-deficit (d = 0.68-1.19) schizophrenia were associated with significant deficits in all cognitive domains. Deficit patients underperformed non-deficit patients in all cognitive domains (d = 0.24-0.84) and individual tasks (d = 0.39-0.93). The relationship between deficit syndrome and impairment in olfaction, social cognition, verbal fluency, and speed-based cognitive tasks were relatively stronger. Our findings suggest that there is consistent evidence for a significant relationship between deficit syndrome and more severe cognitive impairment in schizophrenia.

Prevention, Rehabilitation, and Mitigation Strategies of Cognitive Deficits in Aging with HIV: Implications for Practice and Research

PubMed Central

Vance, David E.

2013-01-01

Highly active antiretroviral therapy has given the chance to those living with HIV to keep on living, allowing them the opportunity to age and perhaps age successfully. Yet, there are severe challenges to successful aging with HIV, one of which is cognitive deficits. Nearly half of those with HIV experience cognitive deficits that can interfere with everyday functioning, medical decision making, and quality of life. Given that cognitive deficits develop with more frequency and intensity with increasing age, concerns mount that as people age with HIV, they may experience more severe cognitive deficits. These concerns become especially germane given that by 2015, 50% of those with HIV will be 50 and older, and this older cohort of adults is expected to grow. As such, this paper focuses on the etiologies of such cognitive deficits within the context of cognitive reserve and neuroplasticity. From this, evidence-based and hypothetical prevention (i.e., cognitive prescriptions), rehabilitation (i.e., speed of processing training), and mitigation (i.e., spaced retrieval method) strategies are reviewed. Implications for nursing practice and research are posited. PMID:23431469

Osteopontin deficiency ameliorates Alport pathology by preventing tubular metabolic deficits.

PubMed

Ding, Wen; Yousefi, Keyvan; Goncalves, Stefania; Goldstein, Bradley J; Sabater, Alfonso L; Kloosterboer, Amy; Ritter, Portia; Lambert, Guerline; Mendez, Armando J; Shehadeh, Lina A

2018-03-22

Alport syndrome is a rare hereditary renal disorder with no etiologic therapy. We found that osteopontin (OPN) is highly expressed in the renal tubules of the Alport mouse and plays a causative pathological role. OPN genetic deletion ameliorated albuminuria, hypertension, tubulointerstitial proliferation, renal apoptosis, and hearing and visual deficits in the Alport mouse. In Alport renal tubules we found extensive cholesterol accumulation and increased protein expression of dynamin-3 (DNM3) and LDL receptor (LDLR) in addition to dysmorphic mitochondria with defective bioenergetics. Increased pathological cholesterol influx was confirmed by a remarkably increased uptake of injected DiI-LDL cholesterol by Alport renal tubules, and by the improved lifespan of the Alport mice when crossed with the Ldlr-/- mice with defective cholesterol influx. Moreover, OPN-deficient Alport mice demonstrated significant reduction of DNM3 and LDLR expression. In human renal epithelial cells, overexpressing DNM3 resulted in elevated LDLR protein expression and defective mitochondrial respiration. Our results suggest a potentially new pathway in Alport pathology where tubular OPN causes DNM3- and LDLR-mediated enhanced cholesterol influx and impaired mitochondrial respiration.

Disrupted reward circuits is associated with cognitive deficits and depression severity in major depressive disorder.

PubMed

Gong, Liang; Yin, Yingying; He, Cancan; Ye, Qing; Bai, Feng; Yuan, Yonggui; Zhang, Haisan; Lv, Luxian; Zhang, Hongxing; Xie, Chunming; Zhang, Zhijun

2017-01-01

Neuroimaging studies have demonstrated that major depressive disorder (MDD) patients show blunted activity responses to reward-related tasks. However, whether abnormal reward circuits affect cognition and depression in MDD patients remains unclear. Seventy-five drug-naive MDD patients and 42 cognitively normal (CN) subjects underwent a resting-state functional magnetic resonance imaging scan. The bilateral nucleus accumbens (NAc) were selected as seeds to construct reward circuits across all subjects. A multivariate linear regression analysis was employed to investigate the neural substrates of cognitive function and depression severity on the reward circuits in MDD patients. The common pathway underlying cognitive deficits and depression was identified with conjunction analysis. Compared with CN subjects, MDD patients showed decreased reward network connectivity that was primarily located in the prefrontal-striatal regions. Importantly, distinct and common neural pathways underlying cognition and depression were identified, implying the independent and synergistic effects of cognitive deficits and depression severity on reward circuits. This study demonstrated that disrupted topological organization within reward circuits was significantly associated with cognitive deficits and depression severity in MDD patients. These findings suggest that in addition to antidepressant treatment, normalized reward circuits should be a focus and a target for improving depression and cognitive deficits in MDD patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

Converging on a core cognitive deficit: the impact of various neurodevelopmental insults on cognitive control

PubMed Central

O'Reilly, Kally C.; Kao, Hsin-Yi; Lee, Heekyung; Fenton, André A.

2014-01-01

Despite substantial effort and immense need, the treatment options for major neuropsychiatric illnesses like schizophrenia are limited and largely ineffective at improving the most debilitating cognitive symptoms that are central to mental illness. These symptoms include cognitive control deficits, the inability to selectively use information that is currently relevant and ignore what is currently irrelevant. Contemporary attempts to accelerate progress are in part founded on an effort to reconceptualize neuropsychiatric illness as a disorder of neural development. This neuro-developmental framework emphasizes abnormal neural circuits on the one hand, and on the other, it suggests there are therapeutic opportunities to exploit the developmental processes of excitatory neuron pruning, inhibitory neuron proliferation, elaboration of myelination, and other circuit refinements that extend through adolescence and into early adulthood. We have crafted a preclinical research program aimed at cognition failures that may be relevant to mental illness. By working with a variety of neurodevelopmental rodent models, we strive to identify a common pathophysiology that underlies cognitive control failure as well as a common strategy for improving cognition in the face of neural circuit abnormalities. Here we review our work to characterize cognitive control deficits in rats with a neonatal ventral hippocampus lesion and rats that were exposed to Methylazoxymethanol acetate (MAM) in utero. We review our findings as they pertain to early developmental processes, including neurogenesis, as well as the power of cognitive experience to refine neural circuit function within the mature and maturing brain's cognitive circuitry. PMID:24966811

Cognitive-Linguistic Deficit and Speech Intelligibility in Chronic Progressive Multiple Sclerosis

ERIC Educational Resources Information Center

Mackenzie, Catherine; Green, Jan

2009-01-01

Background: Multiple sclerosis is a disabling neurological disease with varied symptoms, including dysarthria and cognitive and linguistic impairments. Association between dysarthria and cognitive-linguistic deficit has not been explored in clinical multiple sclerosis studies. Aims: In patients with chronic progressive multiple sclerosis, the…

Neurally dissociable cognitive components of reading deficits in subacute stroke.

PubMed

Boukrina, Olga; Barrett, A M; Alexander, Edward J; Yao, Bing; Graves, William W

2015-01-01

According to cognitive models of reading, words are processed by interacting orthographic (spelling), phonological (sound), and semantic (meaning) information. Despite extensive study of the neural basis of reading in healthy participants, little group data exist on patients with reading deficits from focal brain damage pointing to critical neural systems for reading. Here, we report on one such study. We have performed neuropsychological testing and magnetic resonance imaging on 11 patients with left-hemisphere stroke (<=5 weeks post-stroke). Patients completed tasks assessing cognitive components of reading such as semantics (matching picture or word choices to a target based on meaning), phonology (matching word choices to a target based on rhyming), and orthography (a two-alternative forced choice of the most plausible non-word). They also read aloud pseudowords and words with high or low levels of usage frequency, imageability, and spelling-sound consistency. As predicted by the cognitive model, when averaged across patients, the influence of semantics was most salient for low-frequency, low-consistency words, when phonological decoding is especially difficult. Qualitative subtraction analyses revealed lesion sites specific to phonological processing. These areas were consistent with those shown previously to activate for phonology in healthy participants, including supramarginal, posterior superior temporal, middle temporal, inferior frontal gyri, and underlying white matter. Notable divergence between this analysis and previous functional imaging is the association of lesions in the mid-fusiform gyrus and anterior temporal lobe with phonological reading deficits. This study represents progress toward identifying brain lesion-deficit relationships in the cognitive components of reading. Such correspondences are expected to help not only better understand the neural mechanisms of reading, but may also help tailor reading therapy to individual neurocognitive

Review of recent studies on interventions for cognitive deficits in patients with cancer.

PubMed

Gehring, Karin; Roukema, Jan Anne; Sitskoorn, Margriet M

2012-02-01

Research has demonstrated that patients with cancer experience cognitive deficits, often due to aggressive anticancer treatments. In this article, we critically review the interventional studies that have been conducted to investigate beneficial effects on cognitive function in cancer patients. Pharmacological agents that have been studied include psychostimulants, such as methylphenidate and modafinil, erythropoietin, and hormonal (supplement) treatments for patients who receive hormonal suppression therapy. In addition, several cognitive rehabilitation programs have been evaluated in cancer patients. Recently, the approach of physical exercise to treat cognitive deficits has received great interest, and findings from novel studies are keenly anticipated. Although, in general, the studies reviewed were well designed, future studies may wish to include larger sample sizes and pay more attention to the accurate assessment of cognitive function.

A Cross-Sectional Study of the Relationship of Physical Activity with Depression and Cognitive Deficit in Older Adults.

PubMed

Paulo T, R S; Tribess, Sheilla; Sasaki, Jeffer Eidi; Meneguci, Joilson; Martins, Cristiane A; Freitas, Ismael F; Romo-Perez, Vicente; Virtuoso, Jair S

2016-04-01

The aim of this study was to examine the association of physical activity with depression and cognition deficit, separately and combined, in Brazilian older adults. We analyzed data from 622 older adults. Physical activity was assessed using the International Physical Activity Questionnaire. Depressive symptoms were assessed using the Geriatric Depression Scale, while cognitive deficit was assessed using the Mini-Mental State Examination. Multinomial logistic regressions were used to assess associations of depression and cognitive deficit with sociodemographic, health, and behavioral variables. Prevalence of physical inactivity (< 150 min of moderate-to-vigorous physical activity/ week), depression, and cognitive deficit were 35.7%, 37.4%, and 16.7%. Physical inactivity was associated with depression (OR: 1.83, 95% CI: 1.14-2.94) and with depression and cognitive deficit combined (OR: 4.23, 95% CI: 2.01-8.91). Physically inactive participants were also more likely to present limitations in orientation and language functions. Physical inactivity was associated with depression and also with depression and cognitive deficit combined in older adults.

Reading Comprehension in Children with ADHD: Cognitive Underpinnings of the Centrality Deficit

PubMed Central

Miller, Amanda C.; Keenan, Janice M.; Betjemann, Rebecca S.; Willcutt, Erik; Pennington, Bruce F.; Olson, Richard K.

2012-01-01

We examined reading comprehension in children with ADHD by assessing their ability to build a coherent mental representation that allows them to recall central and peripheral information. We compared children with ADHD (mean age 9.78) to word reading-matched controls (mean age 9.89) on their ability to retell a passage. We found that even though children with ADHD recalled more central than peripheral information, they showed their greatest deficit, relative to controls, on central information – a centrality deficit (Miller & Keenan, 2009). We explored the cognitive underpinnings of this deficit using regressions to compare how well cognitive factors (working memory, inhibition, processing speed, and IQ) predicted the ability to recall central information, after controlling for word reading ability, and whether these cognitive factors interacted with ADHD symptoms. Working memory accounted for the most unique variance. Although previous evidence for reading comprehension difficulties in children with ADHD have been mixed, this study suggests that even when word reading ability is controlled, children with ADHD have difficulty building a coherent mental representation, and this difficulty is likely related to deficits in working memory. PMID:23054132

High fat diet-induced diabetes in mice exacerbates cognitive deficit due to chronic hypoperfusion

PubMed Central

Zuloaga, Kristen L; Johnson, Lance A; Roese, Natalie E; Marzulla, Tessa; Zhang, Wenri; Nie, Xiao; Alkayed, Farah N; Hong, Christine; Grafe, Marjorie R; Pike, Martin M; Raber, Jacob

2015-01-01

Diabetes causes endothelial dysfunction and increases the risk of vascular cognitive impairment. However, it is unknown whether diabetes causes cognitive impairment due to reductions in cerebral blood flow or through independent effects on neuronal function and cognition. We addressed this using right unilateral common carotid artery occlusion to model vascular cognitive impairment and long-term high-fat diet to model type 2 diabetes in mice. Cognition was assessed using novel object recognition task, Morris water maze, and contextual and cued fear conditioning. Cerebral blood flow was assessed using arterial spin labeling magnetic resonance imaging. Vascular cognitive impairment mice showed cognitive deficit in the novel object recognition task, decreased cerebral blood flow in the right hemisphere, and increased glial activation in white matter and hippocampus. Mice fed a high-fat diet displayed deficits in the novel object recognition task, Morris water maze and fear conditioning tasks and neuronal loss, but no impairments in cerebral blood flow. Compared to vascular cognitive impairment mice fed a low fat diet, vascular cognitive impairment mice fed a high-fat diet exhibited reduced cued fear memory, increased deficit in the Morris water maze, neuronal loss, glial activation, and global decrease in cerebral blood flow. We conclude that high-fat diet and chronic hypoperfusion impair cognitive function by different mechanisms, although they share commons features, and that high-fat diet exacerbates vascular cognitive impairment pathology. PMID:26661233

Variability in Depressive Symptoms of Cognitive Deficit and Cognitive Bias During the First 2 Years After Diagnosis in Australian Men With Prostate Cancer.

PubMed

Sharpley, Christopher F; Bitsika, Vicki; Christie, David R H

2016-01-01

The incidence and contribution to total depression of the depressive symptoms of cognitive deficit and cognitive bias in prostate cancer (PCa) patients were compared from cohorts sampled during the first 2 years after diagnosis. Survey data were collected from 394 patients with PCa, including background information, treatments, and disease status, plus total scores of depression and scores for subscales of the depressive symptoms of cognitive bias and cognitive deficit via the Zung Self-Rating Depression Scale. The sample was divided into eight 3-monthly time-since-diagnosis cohorts and according to depression severity. Mean scores for the depressive symptoms of cognitive deficit were significantly higher than those for cognitive bias for the whole sample, but the contribution of cognitive bias to total depression was stronger than that for cognitive deficit. When divided according to overall depression severity, patients with clinically significant depression showed reversed patterns of association between the two subsets of cognitive symptoms of depression and total depression compared with those patients who reported less severe depression. Differences in the incidence and contribution of these two different aspects of the cognitive symptoms of depression for patients with more severe depression argue for consideration of them when assessing and diagnosing depression in patients with PCa. Treatment requirements are also different between the two types of cognitive symptoms of depression, and several suggestions for matching treatment to illness via a personalized medicine approach are discussed. © The Author(s) 2014.

CB1 Cannabinoid Receptors Mediate Cognitive Deficits and Structural Plasticity Changes During Nicotine Withdrawal.

PubMed

Saravia, Rocio; Flores, África; Plaza-Zabala, Ainhoa; Busquets-Garcia, Arnau; Pastor, Antoni; de la Torre, Rafael; Di Marzo, Vincenzo; Marsicano, Giovanni; Ozaita, Andrés; Maldonado, Rafael; Berrendero, Fernando

2017-04-01

Tobacco withdrawal is associated with deficits in cognitive function, including attention, working memory, and episodic memory. Understanding the neurobiological mechanisms involved in these effects is crucial because cognitive deficits during nicotine withdrawal may predict relapse in humans. We investigated in mice the role of CB 1 cannabinoid receptors (CB 1 Rs) in memory impairment and spine density changes induced by nicotine withdrawal precipitated by the nicotinic antagonist mecamylamine. Drugs acting on the endocannabinoid system and genetically modified mice were used. Memory impairment during nicotine withdrawal was blocked by the CB 1 R antagonist rimonabant or the genetic deletion of CB 1 R in forebrain gamma-aminobutyric acidergic (GABAergic) neurons (GABA-CB 1 R). An increase of 2-arachidonoylglycerol (2-AG), but not anandamide, was observed during nicotine withdrawal. The selective inhibitor of 2-AG biosynthesis O7460 abolished cognitive deficits of nicotine abstinence, whereas the inhibitor of 2-AG enzymatic degradation JZL184 did not produce any effect in cognitive impairment. Moreover, memory impairment was prevented by the selective mammalian target of rapamycin inhibitor temsirolimus and the protein synthesis inhibitor anisomycin. Mature dendritic spines on CA1 pyramidal hippocampal neurons decreased 4 days after the precipitation of nicotine withdrawal, when the cognitive deficits were still present. Indeed, a correlation between memory performance and mature spine density was found. Interestingly, these structural plasticity alterations were normalized in GABA-CB 1 R conditional knockout mice and after subchronic treatment with rimonabant. These findings underline the interest of CB 1 R as a target to improve cognitive performance during early nicotine withdrawal. Cognitive deficits in early abstinence are associated with increased relapse risk. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Color discrimination deficits in Parkinson's disease are related to cognitive impairment and white-matter alterations.

PubMed

Bertrand, Josie-Anne; Bedetti, Christophe; Postuma, Ronald B; Monchi, Oury; Génier Marchand, Daphné; Jubault, Thomas; Gagnon, Jean-François

2012-12-01

Color discrimination deficit is a common nonmotor manifestation of Parkinson's disease (PD). However, the pathophysiology of this dysfunction remains poorly understood. Although retinal structure changes found in PD have been suggested to cause color discrimination deficits, the impact of cognitive impairment and cortical alterations remains to be determined. We investigated the contribution of cognitive impairment to color discrimination deficits in PD and correlated them with cortical anomalies. Sixty-six PD patients without dementia and 20 healthy controls performed the Farnsworth-Munsell 100 hue test and underwent a comprehensive neuropsychological assessment for mild cognitive impairment diagnosis. In a subgroup of 26 PD patients, we also used high-definition neuroanatomical magnetic resonance imaging for cortical thickness and diffusion tensor analysis. PD patients with mild cognitive impairment performed poorly on the Farnsworth-Munsell 100 hue test compared with PD patients without mild cognitive impairment and controls. In PD patients, performance on the Farnsworth-Munsell 100 hue test was correlated with measures of visuospatial abilities and executive functions. Neuroimaging analysis revealed higher mean and radial diffusivity values in right posterior white-matter structures that correlated with poor performance on the Farnsworth-Munsell 100 hue test. No cortical thickness correlation reached significance. This study showed that cognitive impairment makes a major contribution to the color discrimination deficits reported in PD. Thus, performance on the Farnsworth-Munsell 100 hue test may reflect cognitive impairment more than color discrimination deficits in PD. Poor performance on the Farnsworth-Munsell 100 hue test was also associated with white-matter alterations in right posterior brain regions. Copyright © 2012 Movement Disorder Society.

Cognitive rehabilitation training in patients with brain tumor-related epilepsy and cognitive deficits: a pilot study.

PubMed

Maschio, Marta; Dinapoli, Loredana; Fabi, Alessandra; Giannarelli, Diana; Cantelmi, Tonino

2015-11-01

The aim of this pilot observational study was to evaluate effect of cognitive rehabilitation training (RehabTr) on cognitive performances in patients with brain tumor-related epilepsy (BTRE) and cognitive disturbances. Medical inclusion criteria: patients (M/F) ≥ 18 years ≤ 75 with symptomatic seizures due to primary brain tumors or brain metastases in stable treatment with antiepileptic drugs; previous surgical resection or biopsy; >70 Karnofsky Performance Status; stable oncological disease. Eligible patients recruited from 100 consecutive patients with BTRE at first visit to our Center from 2011 to 2012. All recruited patients were administered battery of neuropsychological tests exploring various cognitive domains. Patients considered to have a neuropsychological deficit were those with at least one test score for a given domain indicative of impairment. Thirty patients out of 100 showed cognitive deficits, and were offered participation in RehabTr, of which 16 accepted (5 low grade glioma, 4 high grade glioma, 2 glioblastoma, 2 meningioma and 3 metastases) and 14 declined for various reasons. The RehabTr consisted of one weekly individual session of 1 h, for a total of 10 weeks, carried out by a trained psychologist. The functions trained were: memory, attention, visuo-spatial functions, language and reasoning by means of Training NeuroPsicologico (TNP(®)) software. To evaluate the effect of the RehabTr, the same battery of tests was administered directly after cognitive rehabilitation (T1), and at six-month follow-up (T2). Statistical analysis with Student T test for paired data showed that short-term verbal memory, episodic memory, fluency and long term visuo-spatial memory improved immediately after the T1 and remained stable at T2. At final follow-up all patients showed an improvement in at least one domain that had been lower than normal at baseline. Our results demonstrated a positive effect of rehabilitative training at different times, and, for

Attention and Other Cognitive Deficits in Aphasia: Presence and Relation to Language and Communication Measures

ERIC Educational Resources Information Center

Murray, Laura L.

2012-01-01

Purpose: This study was designed to further elucidate the relationship between cognition and aphasia, with a focus on attention. It was hypothesized that individuals with aphasia would display variable deficit patterns on tests of attention and other cognitive functions and that their attention deficits, particularly those of complex attention…

A cognitive psychometric model for the psychodiagnostic assessment of memory-related deficits.

PubMed

Alexander, Gregory E; Satalich, Timothy A; Shankle, W Rodman; Batchelder, William H

2016-03-01

Clinical tests used for psychodiagnostic purposes, such as the well-known Alzheimer's Disease Assessment Scale: Cognitive subscale (ADAS-Cog), include a free-recall task. The free-recall task taps into latent cognitive processes associated with learning and memory components of human cognition, any of which might be impaired with the progression of Alzheimer's disease (AD). A Hidden Markov model of free recall is developed to measure latent cognitive processes used during the free-recall task. In return, these cognitive measurements give us insight into the degree to which normal cognitive functions are differentially impaired by medical conditions, such as AD and related disorders. The model is used to analyze the free-recall data obtained from healthy elderly participants, participants diagnosed as having mild cognitive impairment, and participants diagnosed with early AD. The model is specified hierarchically to handle item differences because of the serial position curve in free recall, as well as within-group individual differences in participants' recall abilities. Bayesian hierarchical inference is used to estimate the model. The model analysis suggests that the impaired patients have the following: (1) long-term memory encoding deficits, (2) short-term memory (STM) retrieval deficits for all but very short time intervals, (3) poorer transfer into long-term memory for items successfully retrieved from STM, and (4) poorer retention of items encoded into long-term memory after longer delays. Yet, impaired patients appear to have no deficit in immediate recall of encoded words in long-term memory or for very short time intervals in STM. (c) 2016 APA, all rights reserved).

THE ORIGINS OF COGNITIVE DEFICITS IN VICTIMIZED CHILDREN: IMPLICATIONS FOR NEUROSCIENTISTS AND CLINICIANS

PubMed Central

Danese, Andrea; Moffitt, Terrie E; Arseneault, Louise; Bleiberg, Ben A; Dinardo, Perry B; Gandelman, Stephanie B; Houts, Renate; Ambler, Antony; Fisher, Helen; Poulton, Richie; Caspi, Avshalom

2016-01-01

OBJECTIVE Individuals reporting a history of childhood violence victimization have impaired brain function. However, the clinical significance, reproducibility, and causality of these findings are disputed. We directly tested these research gaps. METHOD We tested the association between prospectively-collected measures of childhood violence victimization and cognitive functions in childhood, adolescence, and adulthood among 2,232 members of the UK E-Risk Study and 1,037 members of the New Zealand Dunedin Study, who were followed-up from birth until ages 18 and 38 years, respectively. We used multiple measures of victimization and cognition, and included comparisons of cognitive scores for twins discordant for victimization. RESULTS We found that individuals exposed to childhood victimization had pervasive impairments in clinically-relevant cognitive functions including general intelligence, executive function, processing speed, memory, perceptual reasoning, and verbal comprehension in adolescence and adulthood. However, the observed cognitive deficits in victimized individuals were largely explained by cognitive deficits that predated childhood victimization and by confounding genetic and environmental risks. CONCLUSIONS Findings from two population-representative birth cohorts totaling more than 3,000 individuals and born 20 years and 20,000 kilometers apart suggest that the association between childhood violence victimization and later cognition is largely non-causal, in contrast to conventional interpretations. These findings urge adopting a more circumspect approach to causal inference in the neuroscience of stress. Clinically, cognitive deficits should be conceptualized as individual risk factors for victimization as well as potential complicating features during treatment. PMID:27794691

Memory deficits with intact cognitive control in the methylazoxymethanol acetate (MAM) exposure model of neurodevelopmental insult.

PubMed

O'Reilly, Kally C; Perica, Maria I; Fenton, André A

2016-10-01

Cognitive impairments are amongst the most debilitating deficits of schizophrenia and the best predictor of functional outcome. Schizophrenia is hypothesized to have a neurodevelopmental origin, making animal models of neurodevelopmental insult important for testing predictions that early insults will impair cognitive function. Rats exposed to methylazoxymethanol acetate (MAM) at gestational day 17 display morphological, physiological and behavioral abnormalities relevant to schizophrenia. Here we investigate the cognitive abilities of adult MAM rats. We examined brain activity in MAM rats by histochemically assessing cytochrome oxidase enzyme activity, a metabolic marker of neuronal activity. To assess cognition, we used a hippocampus-dependent two-frame active place avoidance paradigm to examine learning and spatial memory, as well as cognitive control and flexibility using the same environment and evaluating the same set of behaviors. We confirmed that adult MAM rats have altered hippocampal morphology and brain function, and that they are hyperactive in an open field. The latter likely indicates MAM rats have a sensorimotor gating deficit that is common to many animal models used for schizophrenia research. On first inspection, cognitive control seems impaired in MAM rats, indicated by more errors during the two-frame active place avoidance task. Because MAM rats are hyperactive throughout place avoidance training, we considered the possibility that the hyperlocomotion may account for the apparent cognitive deficits. These deficits were reduced on the basis of measures of cognitive performance that account for motor activity differences. However, though other aspects of memory are intact, the ability of MAM rats to express trial-to-trial memory is delayed compared to control rats. These findings suggest that spatial learning and cognitive abilities are largely intact, that the most prominent cognitive deficit is specific to acquiring memory in the MAM

Spinocerebellar ataxia: a critical review of cognitive and socio-cognitive deficits.

PubMed

Giocondo, Flora; Curcio, Giuseppe

2018-02-01

The primary aim of this contribution is to provide a critical discussion on cognitive and sociocognitive implications of spinocerebellar ataxias (SCAs) subtypes. The term SCA refers to a group of neurodegenerative disorders that have been increasingly investigated in the last years, sharing the characteristic of progressive ataxia resulting from degeneration of cerebellum and its connections. In past decades only involvement of cerebellum in behaviour and timing has been investigated, bringing to the belief about its central role in timing of movement and sensation, particularly for short intervals of time. Only very recently the cerebellum has been considered as a potentially important centre for cognitive processing and related spheres of social cognition, so that several studies with SCA patients have been carried out on these topics: as a consequence a section of this review will be dedicated to this important aspect. After a brief discussion on most commonly used methods to assess cognitive and socio-cognitive abilities in SCAs, cognitive and socio-cognitive profiles of principal SCA subtypes have been thoroughly reviewed and critically discussed. Due to the very poor literature in this field the most common SCA variants have been fully included (i.e. SCA1, SCA2, SCA3, SCA6 and SCA7). A comparative summary of the main characteristics of cognitive and social cognition deficit in SCA subtypes has been proposed together with a research agenda for future investigation in this field principally aimed at using measures of cognition and/or social cognition as potential predictors of the extent and progression of disease.

Edaravone alleviates Alzheimer's disease-type pathologies and cognitive deficits.

PubMed

Jiao, Shu-Sheng; Yao, Xiu-Qing; Liu, Yu-Hui; Wang, Qing-Hua; Zeng, Fan; Lu, Jian-Jun; Liu, Jia; Zhu, Chi; Shen, Lin-Lin; Liu, Cheng-Hui; Wang, Ye-Ran; Zeng, Gui-Hua; Parikh, Ankit; Chen, Jia; Liang, Chun-Rong; Xiang, Yang; Bu, Xian-Le; Deng, Juan; Li, Jing; Xu, Juan; Zeng, Yue-Qin; Xu, Xiang; Xu, Hai-Wei; Zhong, Jin-Hua; Zhou, Hua-Dong; Zhou, Xin-Fu; Wang, Yan-Jiang

2015-04-21

Alzheimer's disease (AD) is one of most devastating diseases affecting elderly people. Amyloid-β (Aβ) accumulation and the downstream pathological events such as oxidative stress play critical roles in pathogenesis of AD. Lessons from failures of current clinical trials suggest that targeting multiple key pathways of the AD pathogenesis is necessary to halt the disease progression. Here we show that Edaravone, a free radical scavenger that is marketed for acute ischemic stroke, has a potent capacity of inhibiting Aβ aggregation and attenuating Aβ-induced oxidation in vitro. When given before or after the onset of Aβ deposition via i.p. injection, Edaravone substantially reduces Aβ deposition, alleviates oxidative stress, attenuates the downstream pathologies including Tau hyperphosphorylation, glial activation, neuroinflammation, neuronal loss, synaptic dysfunction, and rescues the behavioral deficits of APPswe/PS1 mice. Oral administration of Edaravone also ameliorates the AD-like pathologies and memory deficits of the mice. These findings suggest that Edaravone holds a promise as a therapeutic agent for AD by targeting multiple key pathways of the disease pathogenesis.

Osteopontin deficiency ameliorates Alport pathology by preventing tubular metabolic deficits

PubMed Central

Ding, Wen; Goncalves, Stefania; Goldstein, Bradley J.; Sabater, Alfonso L.; Kloosterboer, Amy; Ritter, Portia; Lambert, Guerline; Mendez, Armando J.

2018-01-01

Alport syndrome is a rare hereditary renal disorder with no etiologic therapy. We found that osteopontin (OPN) is highly expressed in the renal tubules of the Alport mouse and plays a causative pathological role. OPN genetic deletion ameliorated albuminuria, hypertension, tubulointerstitial proliferation, renal apoptosis, and hearing and visual deficits in the Alport mouse. In Alport renal tubules we found extensive cholesterol accumulation and increased protein expression of dynamin-3 (DNM3) and LDL receptor (LDLR) in addition to dysmorphic mitochondria with defective bioenergetics. Increased pathological cholesterol influx was confirmed by a remarkably increased uptake of injected DiI-LDL cholesterol by Alport renal tubules, and by the improved lifespan of the Alport mice when crossed with the Ldlr–/– mice with defective cholesterol influx. Moreover, OPN-deficient Alport mice demonstrated significant reduction of DNM3 and LDLR expression. In human renal epithelial cells, overexpressing DNM3 resulted in elevated LDLR protein expression and defective mitochondrial respiration. Our results suggest a potentially new pathway in Alport pathology where tubular OPN causes DNM3- and LDLR-mediated enhanced cholesterol influx and impaired mitochondrial respiration. PMID:29563333

No lower cognitive functioning in older adults with attention-deficit/hyperactivity disorder.

PubMed

Semeijn, E J; Korten, N C M; Comijs, H C; Michielsen, M; Deeg, D J H; Beekman, A T F; Kooij, J J S

2015-09-01

Research illustrates cognitive deficits in children and younger adults with attention-deficit/hyperactivity disorder (ADHD). Few studies have focused on the cognitive functioning in older adults. This study investigates the association between ADHD and cognitive functioning in older adults. Data were collected in a cross-sectional side study of the Longitudinal Aging Study Amsterdam (LASA). A diagnostic interview to diagnose ADHD was administered among a subsample (N = 231, age 60-94). ADHD symptoms and diagnosis were assessed with the Diagnostic Interview for ADHD in Adults (DIVA) 2.0. Cognitive functioning was assessed with tests in the domains of executive functioning, information processing speed, memory, and attention/working memory. Regression analyses indicate that ADHD diagnosis and ADHD severity were only negatively associated with cognitive functioning in the attention/working memory domain. When adjusting for depression, these associations were no longer significant. The study shows that ADHD in older adults is associated with lower cognitive functioning in the attention/working memory domain. However, this was partly explained by depressive symptoms.

Neuronal dysfunction with aging and its amelioration

PubMed Central

ANDO, Susumu

2012-01-01

The author focused on the functional decline of synapses in the brain with aging to understand the underlying mechanisms and to ameliorate the deficits. The first attempt was to unravel the neuronal functions of gangliosides so that gangliosides could be used for enhancing synaptic activity. The second attempt was to elicit the neuronal plasticity in aged animals through enriched environmental stimulation and nutritional intervention. Environmental stimuli were revealed neurochemically and morphologically to develop synapses leading to enhanced cognitive function. Dietary restriction as a nutritional intervention restored the altered metabolism of neuronal membranes with aging, providing a possible explanation for the longevity effect of dietary restriction. These results obtained with aging and dementia models of animals would benefit aged people. PMID:22728441

Apelin-13 ameliorates cognitive impairments in 6-hydroxydopamine-induced substantia nigra lesion in rats.

PubMed

Haghparast, Elham; Esmaeili-Mahani, Saeed; Abbasnejad, Mehdi; Sheibani, Vahid

2018-04-01

Although Parkinson's disease (PD) is well known with its motor deficits, the patients often suffer from cognitive dysfunction. Apelin, as the endogenous ligand of the APJ receptor, is found in several brain regions such as substantia nigra and mesolimbic pathway. However, the role of apelin in cognition and cognitive disorders has not been fully clarified. In this study the effects of apelin-13 were investigated on cognitive disorders in rat Parkinsonism experimental model. 6-hydroxydopamine (6-OHDA) was administrated into the substantia nigra. Apelin-13 (1, 2 and 3μg/rat) was administered into the substantia nigra one week after the 6-OHDA injection. Morris water maze (MWM), object location and novel object recognition tests were performed one month after the apelin injection. 6-OHDA-treated animals showed a significant impairment in cognitive functions which was revealed by the increased in the escape latency and traveled distance in MWM test and decreased in the exploration index in novel object recognition and object location tasks. Apelin-13 (3μg/rat) significantly attenuates the mentioned cognitive impairments in 6-OHDA-treated animals. In conclusion, the data support the pro-cognitive property of apelin-13 in 6-OHDA-induced cognitive deficit and provided a new pharmacological aspect of the neuropeptide apelin. Copyright © 2018 Elsevier Ltd. All rights reserved.

Multimodal Intervention Trial for Cognitive Deficits in Neurofibromatosis Type 1: Efficacy of Computerized Cognitive Training and Stimulant Medication

DTIC Science & Technology

2017-10-01

AWARD NUMBER: W81XWH-15-1-0508 TITLE: Multimodal Intervention Trial for Cognitive Deficits in Neurofibromatosis Type 1: Efficacy of...Computerized Cognitive Training and Stimulant Medication PRINCIPAL INVESTIGATOR: Maria T. Acosta, M.D. CONTRACTING ORGANIZATION: Children’s National Health...database. 15. SUBJECT TERMS Neurofibromatosis, cognition , pediatric, computerized training programs, working memory 16. SECURITY CLASSIFICATION OF: 17

Cognitive deficits in problematic drinkers with and without mild to borderline intellectual disability.

PubMed

van Duijvenbode, Neomi; Didden, Robert; VanDerNagel, Joanne El; Korzilius, Hubert Plm; Engels, Rutger Cme

2018-03-01

We examined cognitive deficits in problematic drinkers with and without mild to borderline intellectual disability (MBID). Problematic drinkers were expected to show a significantly lower estimated performance IQ (PIQ), but not a lower estimated verbal IQ (VIQ), compared to light drinkers. Participants ( N = 474) were divided into four groups based on IQ and severity of alcohol use-related problems. IQ was estimated using (a short form of) the Wechsler Adult Intelligence Scale third edition. Severity of alcohol use-related problems was assessed using the Alcohol Use Disorder Identification Test. Overall, there were no significant differences between light and problematic drinkers on estimated VIQ. Within the group without MBID, estimated PIQ was significantly lower. Estimated PIQ was not lower in problematic drinkers with MBID compared to light drinkers with MBID. The results are indicative of cognitive deficits in problematic drinkers without MBID. Screening for cognitive deficits with additional instruments is advised.

Memory deficits for facial identity in patients with amnestic mild cognitive impairment (MCI).

PubMed

Savaskan, Egemen; Summermatter, Daniel; Schroeder, Clemens; Schächinger, Hartmut

2018-01-01

Faces are among the most relevant social stimuli revealing an encounter's identity and actual emotional state. Deficits in facial recognition may be an early sign of cognitive decline leading to social deficits. The main objective of the present study is to investigate if individuals with amnestic mild cognitive impairment show recognition deficits in facial identity. Thirty-seven individuals with amnestic mild cognitive impairment, multiple-domain (15 female; age: 75±8 yrs.) and forty-one healthy volunteers (24 female; age 71±6 yrs.) participated. All participants completed a human portrait memory test presenting unfamiliar faces with happy and angry emotional expressions. Five and thirty minutes later, old and new neutral faces were presented, and discrimination sensitivity (d') and response bias (C) were assessed as signal detection parameters of cued facial identity recognition. Memory performance was lower in amnestic mild cognitive impairment as compared to control subjects, mainly because of an altered response bias towards an increased false alarm rate (favoring false OLD ascription of NEW items). In both groups, memory performance declined between the early and later testing session, and was always better for acquired happy than angry faces. Facial identity memory is impaired in patients with amnestic mild cognitive impairment. Liberalization of the response bias may reflect a socially motivated compensatory mechanism maintaining an almost identical recognition hit rate of OLD faces in individuals with amnestic mild cognitive impairment.

Replenishment of microRNA-188-5p restores the synaptic and cognitive deficits in 5XFAD Mouse Model of Alzheimer’s Disease

PubMed Central

Lee, Kihwan; Kim, Hyunju; An, Kyongman; Kwon, Oh-Bin; Park, Sungjun; Cha, Jin Hee; Kim, Myoung-Hwan; Lee, Yoontae; Kim, Joung-Hun; Cho, Kwangwook; Kim, Hye-Sun

2016-01-01

MicroRNAs have emerged as key factors in development, neurogenesis and synaptic functions in the central nervous system. In the present study, we investigated a pathophysiological significance of microRNA-188-5p (miR-188-5p) in Alzheimer’s disease (AD). We found that oligomeric Aβ1-42 treatment diminished miR-188-5p expression in primary hippocampal neuron cultures and that miR-188-5p rescued the Aβ1-42-mediated synapse elimination and synaptic dysfunctions. Moreover, the impairments in cognitive function and synaptic transmission observed in 7-month-old five familial AD (5XFAD) transgenic mice, were ameliorated via viral-mediated expression of miR-188-5p. miR-188-5p expression was down-regulated in the brain tissues from AD patients and 5XFAD mice. The addition of miR-188-5p rescued the reduction in dendritic spine density in the primary hippocampal neurons treated with oligomeric Aβ1-42 and cultured from 5XFAD mice. The reduction in the frequency of mEPSCs was also restored by addition of miR-188-5p. The impairments in basal fEPSPs and cognition observed in 7-month-old 5XFAD mice were ameliorated via the viral-mediated expression of miR-188-5p in the hippocampus. Furthermore, we found that miR-188 expression is CREB-dependent. Taken together, our results suggest that dysregulation of miR-188-5p expression contributes to the pathogenesis of AD by inducing synaptic dysfunction and cognitive deficits associated with Aβ-mediated pathophysiology in the disease. PMID:27708404

Effects of decompressive surgery on prognosis and cognitive deficits in herpes simplex encephalitis.

PubMed

Midi, Ipek; Tuncer, Nese; Midi, Ahmet; Mollahasanoglu, Aynur; Konya, Deniz; Sav, Aydin

2007-01-01

Herpes simplex encephalitis (HSE) is a serious viral infection with a high rate of mortality. The most commonly seen complications are behavioral changes, seizures and memory deficits. We report the case of a 37-year-old man with HSE in the right temporal lobe and a severe midline shift who was treated with acyclovir. The patient underwent anterior temporal lobe resection. Although HSE can cause permanent cognitive deficits, in this case, early surgical intervention minimized any deficit, as determined by detailed neuropsychological examination. Surgical decompression is indicated as early as possible in severe cases. This case report emphasizes the effect of surgical decompression for HSE on cognitive function, which has rarely been mentioned before.

Effects of Decompressive Surgery on Prognosis and Cognitive Deficits in Herpes Simplex Encephalitis

PubMed Central

Midi, Ipek; Tuncer, Nese; Midi, Ahmet; Mollahasanoglu, Aynur; Konya, Deniz; Sav, Aydın

2007-01-01

Herpes simplex encephalitis (HSE) is a serious viral infection with a high rate of mortality. The most commonly seen complications are behavioral changes, seizures and memory deficits. We report the case of a 37-year-old man with HSE in the right temporal lobe and a severe midline shift who was treated with acyclovir. The patient underwent anterior temporal lobe resection. Although HSE can cause permanent cognitive deficits, in this case, early surgical intervention minimized any deficit, as determined by detailed neuropsychological examination. Surgical decompression is indicated as early as possible in severe cases. This case report emphasizes the effect of surgical decompression for HSE on cognitive function, which has rarely been mentioned before. PMID:18430984

Battery for ECT Related Cognitive Deficits (B4ECT-ReCoDe): development and validation.

PubMed

Viswanath, Biju; Harihara, Shashidhara N; Nahar, Abhinav; Phutane, Vivek Haridas; Taksal, Aarati; Thirthalli, Jagadisha; Gangadhar, Bangalore N

2013-06-01

The use of electroconvulsive therapy (ECT) in treatment of psychiatric disorders is associated with adverse cognitive effects. There is a need to develop a short assessment tool of cognitive functions during the course of ECT. This study aimed at developing and validating a short, sensitive battery to assess cognitive deficits associated with ECT in India. Battery for ECT Related Cognitive Deficits (B4ECT-ReCoDe), a brief cognitive battery (20-30 min) to assess verbal, visual, working and autobiographic memory, sustained attention, psychomotor speed and subjective memory impairment, was administered to 30 in-patients receiving bilateral ECT, one day after the 1st, 3rd and 6th ECT. Data was analysed using repeated measures analysis of variance and Pearson's correlation. Significant deficits were found in verbal, visual and autobiographic memory, psychomotor speed. Subjective experience of memory loss correlated positively with verbal memory impairment. B4ECT-ReCoDe, a brief, sensitive measure of cognitive impairments associated with ECT can be used in routine clinical practice. Copyright © 2013 Elsevier B.V. All rights reserved.

The Origins of Cognitive Deficits in Victimized Children: Implications for Neuroscientists and Clinicians.

PubMed

Danese, Andrea; Moffitt, Terrie E; Arseneault, Louise; Bleiberg, Ben A; Dinardo, Perry B; Gandelman, Stephanie B; Houts, Renate; Ambler, Antony; Fisher, Helen L; Poulton, Richie; Caspi, Avshalom

2017-04-01

Individuals reporting a history of childhood violence victimization have impaired brain function. However, the clinical significance, reproducibility, and causality of these findings are disputed. The authors used data from two large cohort studies to address these research questions directly. The authors tested the association between prospectively collected measures of childhood violence victimization and cognitive functions in childhood, adolescence, and adulthood among 2,232 members of the U.K. E-Risk Study and 1,037 members of the New Zealand Dunedin Study who were followed up from birth until ages 18 and 38 years, respectively. Multiple measures of victimization and cognition were used, and comparisons were made of cognitive scores for twins discordant for victimization. Individuals exposed to childhood victimization had pervasive impairments in clinically relevant cognitive functions, including general intelligence, executive function, processing speed, memory, perceptual reasoning, and verbal comprehension in adolescence and adulthood. However, the observed cognitive deficits in victimized individuals were largely explained by cognitive deficits that predated childhood victimization and by confounding genetic and environmental risks. Findings from two population-representative birth cohorts totaling more than 3,000 individuals and born 20 years and 20,000 km apart suggest that the association between childhood violence victimization and later cognition is largely noncausal, in contrast to conventional interpretations. These findings support the adoption of a more circumspect approach to causal inference in the neuroscience of stress. Clinically, cognitive deficits should be conceptualized as individual risk factors for victimization as well as potential complicating features during treatment.

Olanzapine Reverses MK-801-Induced Cognitive Deficits and Region-Specific Alterations of NMDA Receptor Subunits

PubMed Central

Liu, Xiao; Li, Jitao; Guo, Chunmei; Wang, Hongli; Sun, Yaxin; Wang, Han; Su, Yun-Ai; Li, Keqing; Si, Tianmei

2018-01-01

Cognitive dysfunction constitutes an essential component in schizophrenia for its early presence in the pathophysiology of the disease and close relatedness to life quality of patients. To develop effective treatment of cognitive deficits, it is important to understand their neurobiological causes and to identify potential therapeutic targets. In this study, adopting repeated MK-801 treatment as an animal model of schizophrenia, we investigated whether antipsychotic drugs, olanzapine and haloperidol, can reverse MK-801-induced cognitive deficits and how the reversal processes recruited proteins involved in glutamate neurotransmission in rat medial prefrontal cortex (mPFC) and hippocampus. We found that low-dose chronic MK-801 treatment impaired object-in-context recognition memory and reversal learning in the Morris water maze, leaving reference memory relatively unaffected, and that these cognitive deficits can be partially reversed by olanzapine, not haloperidol, treatment. At the molecular level, chronic MK-801 treatment resulted in the reduction of multiple N-methyl-D-aspartate (NMDA) receptor subunits in rat mPFC and olanzapine, not haloperidol, treatment restored the levels of GluN1 and phosphorylated GluN2B in this region. Taken together, MK-801-induced cognitive deficits may be associated with region-specific changes in NMDA receptor subunits and the reversal of specific NMDA receptor subunits may underlie the cognition-enhancing effects of olanzapine. PMID:29375333

Pharmacologic Treatment with GABAB Receptor Agonist of Methamphetamine-Induced Cognitive Impairment in Mice

PubMed Central

Mizoguchi, Hiroyuki; Yamada, Kiyofumi

2011-01-01

Methamphetamine (METH) is a highly addictive drug, and addiction to METH has increased to epidemic proportions worldwide. Chronic use of METH causes psychiatric symptoms, such as hallucinations and delusions, and long-term cognitive deficits, which are indistinguishable from paranoid schizophrenia. The GABA receptor system is known to play a significant role in modulating the dopaminergic neuronal system, which is related to behavioral changes induced by drug abuse. However, few studies have investigated the effects of GABA receptor agonists on cognitive deficits induced by METH. In the present review, we show that baclofen, a GABA receptor agonist, is effective in treating METH-induced impairment of object recognition memory and prepulse inhibition (PPI) of the startle reflex, a measure of sensorimotor gating in mice. Acute and repeated treatment with METH induced a significant impairment of PPI. Furthermore, repeated but not acute treatment of METH resulted in a long-lasting deficit of object recognition memory. Baclofen, a GABAB receptor agonist, dose-dependently ameliorated the METH-induced PPI deficits and object recognition memory impairment in mice. On the other hand, THIP, a GABAA receptor agonist, had no effect on METH-induced cognitive deficits. These results suggest that GABAB receptors may constitute a putative new target in treating cognitive deficits in chronic METH users. PMID:21886573

Temporary microglia-depletion after cosmic radiation modifies phagocytic activity and prevents cognitive deficits.

PubMed

Krukowski, Karen; Feng, Xi; Paladini, Maria Serena; Chou, Austin; Sacramento, Kristen; Grue, Katherine; Riparip, Lara-Kirstie; Jones, Tamako; Campbell-Beachler, Mary; Nelson, Gregory; Rosi, Susanna

2018-05-18

Microglia are the main immune component in the brain that can regulate neuronal health and synapse function. Exposure to cosmic radiation can cause long-term cognitive impairments in rodent models thereby presenting potential obstacles for astronauts engaged in deep space travel. The mechanism/s for how cosmic radiation induces cognitive deficits are currently unknown. We find that temporary microglia depletion, one week after cosmic radiation, prevents the development of long-term memory deficits. Gene array profiling reveals that acute microglia depletion alters the late neuroinflammatory response to cosmic radiation. The repopulated microglia present a modified functional phenotype with reduced expression of scavenger receptors, lysosome membrane protein and complement receptor, all shown to be involved in microglia-synapses interaction. The lower phagocytic activity observed in the repopulated microglia is paralleled by improved synaptic protein expression. Our data provide mechanistic evidence for the role of microglia in the development of cognitive deficits after cosmic radiation exposure.

Interventions for the treatment of theory of mind deficits in schizophrenia: Systematic literature review.

PubMed

Vass, Edit; Fekete, Zita; Simon, Viktória; Simon, Lajos

2018-05-22

Theory of Mind (ToM) plays a central role in regulating social interactions and its impairment is consistently reported in schizophrenia. Regarding schizophrenia, ToM is usually discussed as a sub-domain of social cognition. Since social cognitive deficits have drawn the attention of researchers, a variety of novel treatment techniques and approaches targeting social cognitive deficits have been developed. Encouraging results have repeatedly been reported on the modifiability of social cognitive impairment through these techniques. However, emotional perception seems to be over-represented in these approaches at the expense of other areas, such as ToM. This article presents a systematic review on the social cognitive interventions of the last 10 years, which focused on the remediation of ToM or used techniques primarily focusing on one or more social cognitive domains other than ToM, but with hypothetical effects on it. The aim of our systematic review was to compare these intervention techniques in order to see how effective they are in the remediation of ToM, and to find the best techniques to ameliorate ToM deficits in schizophrenia. According to our findings targeted ToM intervention produced more improvement in ToM tasks, while data regarding non-ToM interventions showed contradictory results with limited effects on ToM. Copyright © 2018. Published by Elsevier B.V.

Self-perceived cognitive deficits and occupational outcome in persons with schizophrenia.

PubMed

Verdoux, Hélène; Monello, Florence; Goumilloux, Régis; Cougnard, Audrey; Prouteau, Antoinette

2010-07-30

A two-year prospective follow-up study was used to explore whether self-perceived cognitive deficits (SPCD) predict occupational outcome in persons with schizophrenia. Cognitive complaints were assessed using the Scale to Investigate Cognition in Schizophrenia (SSTICS) in persons with schizophrenia requesting disability status. A higher level of SPCD was associated with better occupational outcome, independently from other characteristics. Persons with better social functioning may have a higher level of metacognition allowing a greater awareness of their cognitive difficulties. Measures of cognitive complaints should be complemented by objective testing to assess potential for vocational rehabilitation. Copyright 2010 Elsevier Ltd. All rights reserved.

Docosahexaenoic acid partially ameliorates deficits in social behavior and ultrasonic vocalizations caused by prenatal ethanol exposure.

PubMed

Wellmann, Kristen A; George, Finney; Brnouti, Fares; Mooney, Sandra M

2015-06-01

Prenatal ethanol exposure disrupts social behavior in humans and rodents. One system particularly important for social behavior is the somatosensory system. Prenatal ethanol exposure alters the structure and function of this area. Docosahexaenoic acid (DHA), an omega 3 polyunsaturated fatty acid, is necessary for normal brain development and brains from ethanol-exposed animals are DHA deficient. Thus, we determined whether postnatal DHA supplementation ameliorated behavioral deficits induced by prenatal ethanol exposure. Timed pregnant Long-Evans rats were assigned to one of three groups: ad libitum access to an ethanol-containing liquid diet, pair fed an isocaloric isonutritive non-alcohol liquid diet, or ad libitum access to chow and water. Pups were assigned to one of two postnatal treatment groups; gavaged intragastrically once per day between postnatal day (P)11 and P20 with DHA (10 mg/kg in artificial rat milk) or artificial rat milk. A third group was left untreated. Isolation-induced ultrasonic vocalizations (iUSVs) were recorded on P14. Social behavior and play-induced USVs were tested on P28 or P42. Somatosensory performance was tested with a gap crossing test around P33 or on P42. Anxiety was tested on elevated plus maze around P35. Animals exposed to ethanol prenatally vocalized less, play fought less, and crossed a significantly shorter gap than control-treated animals. Administration of DHA ameliorated these ethanol-induced deficits such that the ethanol-exposed animals given DHA were no longer significantly different to control-treated animals. Thus, DHA administration may have therapeutic value to reverse some of ethanol's damaging effects. Copyright © 2015 Elsevier B.V. All rights reserved.

Cognitive Patterns and Learning Disabilities in Cleft Palate Children with Verbal Deficits.

ERIC Educational Resources Information Center

Richman, Lynn C.

1980-01-01

The study examined patterns of cognitive ability in 57 cleft lip and palate children (ages 7 to 9) with verbal deficit, but without general intellectual retardation to evaluate whether the verbal disability displayed by these children was related primarily to a specific verbal expression deficit or a more general symbolic mediation problem.…

Spontaneous hypothermia ameliorated inflammation and neurologic deficit in rat cardiac arrest models following resuscitation

PubMed Central

Zhou, Minggen; Wang, Peng; Yang, Zhengfei; Wu, Haidong; Huang, Zitong

2018-01-01

Cardiac arrest (CA) is a leading cause of mortality worldwide. The majority of the associated mortalities are caused by post-CA syndrome, which includes symptoms, such as neurologic damage, myocardial dysfunction and systemic inflammation. Following CA, return of spontaneous circulation (ROSC) leads to a brain reperfusion injury, which subsequently causes adverse neurologic outcomes or mortality. Therefore, investigating the underlying mechanisms of ROSC-induced neurologic deficits and establishing potential treatments is critical to prevent and treat post-CA syndrome. In the current study, CA rat models were established by asphyxia. Following ROSC, the temperature was controlled to achieve hypothermia. The general neurologic status was assessed using the neurologic deficit scale. Changes in the concentrations of interleukin (IL)-18 and IL-1β were measured with ELISA and the dynamic change in NACHT, LRR and PYD domains-containing protein 3 inflammasome components was determined by western blot analysis and immunohistochemistry. Neuronal death and apoptosis were measured via TUNEL assays. In the CA rat models, increasing the duration of CA before cardiopulmonary resuscitation was found to aggravate the neural deficit and increase the incidence of inflammation. Following ROSC, the expression level of the inflammasome components was observed to increase in CA rat models, which was accompanied by increased secretion of IL-18 and IL-1β, indicating the promotion of inflammation. In addition, the study identified the beneficial role of spontaneous hypothermia in ameliorating the ROSC-induced inflammation and neurologic deficit in CA rat models, including the downregulation of inflammasome components and attenuating neuronal apoptosis. The present study contributes to the understanding of underlying mechanisms in CA-evoked inflammation and the subsequent neurologic damage following ROSC. A novel potential therapeutic strategy that may increase survival times and the

Forced running exercise attenuates hippocampal neurogenesis impairment and the neurocognitive deficits induced by whole-brain irradiation via the BDNF-mediated pathway

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

Ji, Jian-feng; Ji, Sheng-jun; Sun, Rui

Highlights: •Forced exercise can ameliorate WBI induced cognitive impairment in our rat model. •Mature BDNF plays an important role in the effects of forced exercise. •Exercise may be a possible treatment of the radiation-induced cognitive impairment. -- Abstract: Cranial radiotherapy induces progressive and debilitating cognitive deficits, particularly in long-term cancer survivors, which may in part be caused by the reduction of hippocampal neurogenesis. Previous studies suggested that voluntary exercise can reduce the cognitive impairment caused by radiation therapy. However, there is no study on the effect of forced wheel exercise and little is known about the molecular mechanisms mediating themore » effect of exercise. In the present study, we investigated whether the forced running exercise after irradiation had the protective effects of the radiation-induced cognitive impairment. Sixty-four Male Sprague–Dawley rats received a single dose of 20 Gy or sham whole-brain irradiation (WBI), behavioral test was evaluated using open field test and Morris water maze at 2 months after irradiation. Half of the rats accepted a 3-week forced running exercise before the behavior detection. Immunofluorescence was used to evaluate the changes in hippocampal neurogenesis and Western blotting was used to assess changes in the levels of mature brain-derived neurotrophic factor (BDNF), phosphorylated tyrosine receptor kinase B (TrkB) receptor, protein kinase B (Akt), extracellular signal-regulated kinase (ERK), calcium-calmodulin dependent kinase (CaMKII), cAMP-calcium response element binding protein (CREB) in the BDNF–pCREB signaling. We found forced running exercise significantly prevented radiation-induced cognitive deficits, ameliorated the impairment of hippocampal neurogenesis and attenuated the down-regulation of these proteins. Moreover, exercise also increased behavioral performance, hippocampal neurogenesis and elevated BDNF–pCREB signaling in non

Successful evaluation of cognitive function and the nature of cognitive deficits among people with schizophrenia in clinical rehabilitation settings.

PubMed

John, Alexander Panickacheril; Yeak, Kim; Ayres, Helen; Sevastos, Marie; Moore, Elizabeth

2016-08-01

Despite possessing considerable relevance for planning and delivery of effective rehabilitation interventions, systematic evaluation of cognitive function is often ignored in clinical practice. This paper describes a successful method for measuring cognitive function and the nature of cognitive deficits (CD) in people with schizophrenia admitted to psychiatric rehabilitation services. Data on the cognitive functioning of consecutive patients with schizophrenia / schizoaffective disorder admitted during a 5-year period to a public in-patient rehabilitation facility was collated retrospectively and analysed. The Brief Assessment of Cognition in Schizophrenia (BACS) was used to evaluate cognitive function. It was possible to administer the BACS to 122 of 135 consecutive admissions. The mean composite score on the BACS was 1.8 standard deviations below the norm, and 43% had moderate or severe CD. The BACS sub-tests of list learning and symbol coding revealed more severe deficits. The study indicates that evaluation of cognitive function using brief instruments is feasible in psychiatric rehabilitation settings. Global and domain-specific CD were prevalent among people with schizophrenia. In view of the strong association of cognitive functioning with community functioning and rehabilitation outcomes, further studies exploring the feasibility and utility of routinely evaluating cognitive function are warranted. © The Royal Australian and New Zealand College of Psychiatrists 2016.

Bacopa monnieri and Bacoside-A for ameliorating epilepsy associated behavioral deficits.

PubMed

Mathew, Jobin; Paul, Jes; Nandhu, M S; Paulose, C S

2010-07-01

Bacopa monnieri is an outstanding nervine tonic used for raising the mental performance. It helps in concentration, comprehension, recall and alertness, Brahmi is particularly beneficial as it aids in categorizing information in brain and its subsequent expression. Bacopa is also called as a natural antioxidant which may give details its neuroprotective role seen in the memory centers of the brain. Epilepsy is neuronal disorder characterized by learning, cognitive and memory impairments. The present review summarizes information concerning botany, chemistry and beneficial effect of Bacopa monnieri on epilepsy associated behavioral deficits. Copyright 2009 Elsevier B.V. All rights reserved.

Cognitive Deficits and Related Brain Lesions in Patients With Chronic Heart Failure.

PubMed

Frey, Anna; Sell, Roxane; Homola, György A; Malsch, Carolin; Kraft, Peter; Gunreben, Ignaz; Morbach, Caroline; Alkonyi, Bálint; Schmid, Eric; Colonna, Isabella; Hofer, Edith; Müllges, Wolfgang; Ertl, Georg; Heuschmann, Peter; Solymosi, László; Schmidt, Reinhold; Störk, Stefan; Stoll, Guido

2018-05-31

This study sought to determine the spectrum of brain lesions seen in heart failure (HF) patients and the extent to which lesion type contributes to cognitive impairment. Cognitive deficits have been reported in patients with HF. A total of 148 systolic and diastolic HF patients (mean age 64 ± 11 years; 16% female; mean left ventricular ejection fraction 43 ± 8%) were extensively evaluated within 2 days by cardiological, neurological, and neuropsychological testing and brain magnetic resonance imaging (MRI). A total of 288 healthy, sex- and age-matched subjects sampled from the Austrian Stroke Prevention Study served as MRI controls. Deficits in reaction times were apparent in 41% of patients and deficits in verbal memory in 46%. On brain MRI, patients showed more advanced medial temporal lobe atrophy (MTA) (Scheltens score) compared to controls (2.1 ± 0.9 vs. 1.0 ± 0.6; p < 0.001). The degree of MTA was strongly associated with the severity of cognitive impairment, whereas the extent of white matter hyperintensities was similar in patients and controls. Moreover, patients had a 2.7-fold increased risk for presence of clinically silent lacunes. HF patients exhibit cognitive deficits in the domains of attention and memory. MTA but not white matter lesion load seems to be related to cognitive impairment. Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Social-cognitive deficits in normal aging

PubMed Central

Moran, Joseph M.; Jolly, Eshin; Mitchell, Jason P.

2012-01-01

A sizeable number of studies have implicated the default network (e.g., medial prefrontal and parietal cortices) in tasks that require participants to infer the mental states of others—that is, to mentalize. Parallel research has demonstrated that default network function declines over the lifespan, suggesting that older adults may show impairments in social-cognitive tasks that require mentalizing. Older and younger human adults were scanned using functional magnetic resonance imaging (fMRI) while performing three different social-cognitive tasks. Across three mentalizing paradigms, younger and older adults viewed animated shapes in brief social vignettes, stories about a person's moral actions and false belief stories. Consistent with predictions, older adults responded less accurately to stories about others' false beliefs and made less use of actors' intentions to judge the moral permissibility of behavior. These impairments in performance during social-cognitive tasks were accompanied by age-related decreases across all three paradigms in the BOLD response of a single brain region—dorsomedial prefrontal cortex. These findings suggest specific, task-independent age-related deficits in mentalizing that are localizeable to changes in circumscribed subregions of the default network. PMID:22514317

Lithium treatment alleviates impaired cognition in a mouse model of Fragile X Syndrome

PubMed Central

King, Margaret K.; Jope, Richard S.

2013-01-01

Fragile X Syndrome (FXS) is caused by suppressed expression of fragile X mental retardation protein (FMRP), which results in intellectual disability accompanied by many variably manifested characteristics, such as hyperactivity, seizures, and autistic-like behaviors. Treatment of mice that lack FMRP, Fmr1 knockout (KO) mice, with lithium has been reported to ameliorate locomotor hyperactivity, prevent hypersensitivity to audiogenic seizures, improve passive avoidance behavior, and attenuate sociability deficits. To focus on the defining characteristic of FXS, which is cognitive impairment, we tested if lithium treatment ameliorated impairments in four cognitive tasks in Fmr1 KO mice, tested if the response to lithium differed in adolescent and adult mice, and tested if therapeutic effects persisted after discontinuation of lithium administration. Fmr1 KO mice displayed impaired cognition in the novel object detection task, temporal ordering for objects task, and coordinate and categorical spatial processing tasks. Chronic lithium treatment of adolescent (from 4–8 weeks of age) and adult (from 8–12 weeks of age) mice abolished cognitive impairments in all four cognitive tasks. Cognitive deficits returned after lithium treatment was discontinued for 4 weeks. These results demonstrate that Fmr1 KO mice exhibit severe impairments in these cognitive tasks, that lithium is equally effective in normalizing cognition in these tasks whether it is administered to young or adult mice, and that lithium administration must be continued for the cognitive improvements to be sustained. These findings provide further evidence that lithium administration may be beneficial for individuals with FXS. PMID:23941202

Pattern of social cognition deficits in individuals with borderline personality disorder.

PubMed

Anupama V; Bhola, Poornima; Thirthalli, Jagadisha; Mehta, Urvakhsh Meherwan

2018-03-01

Social cognition deficits have been implicated in the affect regulation and interpersonal difficulties seen in borderline personality disorder (BPD). The study examined patterns of social cognition abilities, using self-report and task-based measures, among individuals diagnosed with BPD. The sample included a clinical group of 20 patients diagnosed with BPD and 20 age and gender-matched control group participants from the community with no psychiatric diagnosis. The measures included the Mentalization Questionnaire, the Reading the Mind in the Eyes Test and the Social Cognition Rating Tool in Indian Setting. Results indicated that the clinical group had lower self-reported mentalizing ability. Facial emotion recognition ability was significantly lower for the clinical group, particularly for photographs of the eye region with positive and neutral valences. The clinical group had significantly higher personalizing bias, and greater difficulties in social perception. The two groups did not differ on first and second order theory of mind, recognition of faux pas and externalizing bias. The results point to the links between social cognition deficits and interpersonal difficulties among persons with BPD. Implications include the need for pre-therapy assessment of the magnitude and patterns of social cognition difficulties in BPD, the development of culturally and ecologically valid assessments and the evaluation of interventions for social cognition vulnerabilities among individuals with BPD. Copyright © 2018 Elsevier B.V. All rights reserved.

Deficits of long-term memory in ecstasy users are related to cognitive complexity of the task.

PubMed

Brown, John; McKone, Elinor; Ward, Jeff

2010-03-01

Despite animal evidence that methylenedioxymethamphetamine (ecstasy) causes lasting damage in brain regions related to long-term memory, results regarding human memory performance have been variable. This variability may reflect the cognitive complexity of the memory tasks. However, previous studies have tested only a limited range of cognitive complexity. Furthermore, comparisons across different studies are made difficult by regional variations in ecstasy composition and patterns of use. The objective of this study is to evaluate ecstasy-related deficits in human verbal memory over a wide range of cognitive complexity using subjects drawn from a single geographical population. Ecstasy users were compared to non-drug using controls on verbal tasks with low cognitive complexity (stem completion), moderate cognitive complexity (stem-cued recall and word list learning) and high cognitive complexity (California Verbal Learning Test, Verbal Paired Associates and a novel Verbal Triplet Associates test). Where significant differences were found, both groups were also compared to cannabis users. More cognitively complex memory tasks were associated with clearer ecstasy-related deficits than low complexity tasks. In the most cognitively demanding task, ecstasy-related deficits remained even after multiple learning opportunities, whereas the performance of cannabis users approached that of non-drug using controls. Ecstasy users also had weaker deliberate strategy use than both non-drug and cannabis controls. Results were consistent with the proposal that ecstasy-related memory deficits are more reliable on tasks with greater cognitive complexity. This could arise either because such tasks require a greater contribution from the frontal lobe or because they require greater interaction between multiple brain regions.

Improvement of dizocilpine-induced social recognition deficits in mice by brexpiprazole, a novel serotonin-dopamine activity modulator.

PubMed

Yoshimi, Noriko; Futamura, Takashi; Hashimoto, Kenji

2015-03-01

Cognitive impairment, including impaired social cognition, is largely responsible for the deterioration in social life suffered by patients with psychiatric disorders, such as schizophrenia and major depressive disorder (MDD). Brexpiprazole (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}quinolin-2(1H)-one), a novel serotonin-dopamine activity modulator, was developed to offer efficacious and tolerable therapy for different psychiatric disorders, including schizophrenia and adjunctive treatment of MDD. In this study, we investigated whether brexpiprazole could improve social recognition deficits (one of social cognition deficits) in mice, after administration of the N-methyl-d-aspartate (NMDA) receptor antagonist MK-801 (dizocilpine). Dosing with dizocilpine (0.1mg/kg) induced significant impairment of social recognition in mice. Brexpiprazole (0.01, 0.03, 0.1mg/kg, p.o.) significantly ameliorated dizocilpine-induced social recognition deficits, without sedation or a reduction of exploratory behavior. In addition, brexpiprazole alone had no effect on social recognition in untreated control mice. By contrast, neither risperidone (0.03mg/kg, p.o.) nor olanzapine (0.03mg/kg, p.o.) altered dizocilpine-induced social recognition deficits. Finally, the effect of brexpiprazole on dizocilpine-induced social recognition deficits was antagonized by WAY-100,635, a selective serotonin 5-HT1A antagonist. These results suggest that brexpiprazole could improve dizocilpine-induced social recognition deficits via 5-HT1A receptor activation in mice. Therefore, brexpiprazole may confer a beneficial effect on social cognition deficits in patients with psychiatric disorders. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

[Cognitive deficits in first episode psychosis patients and people at risk for psychosis: from diagnosis to treatment].

PubMed

Lecardeur, L; Meunier-Cussac, S; Dollfus, S

2013-05-01

Up to now, studies have not demonstrated significant efficacy of antipsychotics on cognitive impairments in patients with psychotic disorders. These cognitive deficits are of particular interest since they traditionally start early before the diagnosis of psychosis. They are observed during premorbid and prodromal stages, and during the first episode of psychosis. Moreover, cognitive impairments may be detected without any psychotic symptoms (such as positive symptoms) suggesting their development independently of the psychotic symptoms. Cognitive disturbances consist of impairments of episodic and working memories, intellectual functioning, executive functions (planning, inhibition, and cognitive flexibility), selective and sustained attentions and social cognition (emotion, recognition, theory of mind). The altered cognitive functions observed in schizophrenia are the same as in earlier stages but at a lower level of severity. Data suggest that cognitive deficits can be considered as vulnerability markers of psychosis since they have been described in healthy relatives of psychotic patients with high genetic risk. Cognitive deficits might also be considered as predictive of the occurrence of the disease after the first episode of psychosis. Indeed, retrospective studies suggest cognitive impairments in patients with schizophrenia during premorbid and prodromal phases but not in bipolar patients. Cognitive assessment might be of particular interest in people at risk for psychosis, in order to differentiate diagnostic outcomes. Cognitive functioning impairs until the diagnosis of first episode psychosis, even though cognitive profiles are quite heterogeneous in these patients. Once the diagnosis of schizophrenia is considered, cognitive deficits may be stable, although the literature is still controversial. Several factors such as symptoms and gender can contribute in diversifying the cognitive profiles. Moreover, age of onset might worsen the prognosis because of

Mitochondrial modulators in experimental Huntington's disease: reversal of mitochondrial dysfunctions and cognitive deficits.

PubMed

Mehrotra, Arpit; Kanwal, Abhinav; Banerjee, Sanjay Kumar; Sandhir, Rajat

2015-06-01

Huntington's disease (HD) is a chronic neurodegenerative condition involving impaired mitochondrial functions. The present study evaluates the therapeutic potential of combined administration of mitochondrial modulators: alpha-lipoic acid and acetyl-l-carnitine on mitochondrial dysfunctions in 3-NP-induced HD. Our results reveal 3-NP administration resulted in compromise of mitochondrial functions in terms of: (1) impaired activity of mitochondrial respiratory chain enzymes, altered cytochrome levels, reduced histochemical staining of complex-II and IV, reduced in-gel activity of complex-I to V, and reduced mRNA expression of respiratory chain complexes; (2) enhanced mitochondrial oxidative stress indicated by increased malondialdehyde, protein carbonyls, reactive oxygen species and nitrite levels, along with decreased Mn-superoxide dismutase and catalase activity; (3) mitochondrial structural changes measured by mitochondrial swelling, reduced mitochondrial membrane potential and ultra-structure changes; (4) increased cytosolic cytochrome c levels, caspase-3 and -9 activity along with altered expression of apoptotic proteins (AIF, Bim, Bad, and Bax); and (5) impaired cognitive functions assessed using Morris water maze and Y-maze. Combination of mitochondrial modulators (alpha-lipoic acid + acetyl-l-carnitine) on the other hand ameliorated 3-NP-induced mitochondrial dysfunctions, oxidative stress, histologic alterations, and behavioral deficits, suggesting their therapeutic efficacy in the management of HD. Copyright © 2015 Elsevier Inc. All rights reserved.

Cognitive deficits of executive functions and decision-making in obsessive-compulsive disorder.

PubMed

Dittrich, Winand H; Johansen, Thomas

2013-10-01

The nature of cognitive deficits in obsessive-compulsive disorder (OCD) is characterized by contradictory findings in terms of specific neuropsychological deficits. Selective impairments have been suggested to involve visuospatial memory, set shifting, decision-making and response inhibition. The aim of this study was to investigate cognitive deficits in decision-making and executive functioning in OCD. It was hypothesized that the OCD patients would be less accurate in their responses compared to the healthy controls in rational decision-making on a version of the Cambridge gambling task (CGT) and on the color-word interference test and on a version of the Tower of Hanoi test (tower test) of executive functioning. Thirteen participants with OCD were compared to a group of healthy controls (n = 13) matched for age, gender, education and verbal IQ. Results revealed significant differences between the OCD group and the healthy control group on quality of decision-making on the CGT and for achievement score on the tower test. On these two tasks the OCD group performed worse than the healthy control group. The symptom-dimension analysis revealed performance differences where safety checking patients were impaired on the tower test compared to contamination patients. Results are discussed in the framework of cognition and emotion processing and findings implicate that OCD models should address, specifically, the interaction between cognition and emotion. Here the emotional disruption hypothesis is forwarded to account for the dysfunctional behaviors in OCD. Further implications regarding methodological and inhibitory factors affecting cognitive information processing are highlighted. © 2013 The Scandinavian Psychological Associations.

D-Serine and a glycine transporter inhibitor improve MK-801-induced cognitive deficits in a novel object recognition test in rats.

PubMed

Karasawa, Jun-Ichi; Hashimoto, Kenji; Chaki, Shigeyuki

2008-01-10

Compounds enhancing N-methyl-d-aspartate (NMDA) glutamate receptor function have been reported to improve cognitive deficits. Since cognitive deficits are considered to be the core symptom of schizophrenia, enhancing NMDA receptor function represents a promising approach to treating schizophrenia. In the present study, we investigated whether d-serine or a glycine transporter inhibitor N-[3-(4'-fluorophenyl)-3-(4'-phenylphenoxy)propyl]sarcosine (NFPS), both of which enhance NMDA receptor function, could improve MK-801-induced cognitive deficits in rats, and compared their effects with those of the atypical antipsychotic clozapine and of the typical antipsychotic haloperidol. To assess cognitive function, we used a novel object recognition test in rats that measured spontaneous exploratory activity of a novel object when paired with a familiar object. We then evaluated the effects of the compounds on cognitive deficits induced by treatment with MK-801, the NMDA receptor antagonist. Pretreatment with clozapine (1, 5 mg/kg, i.p.) but not haloperidol (0.03, 0.1 mg/kg, i.p.) significantly improved MK-801-induced cognitive deficits. Pretreatment with D-serine at 800 mg/kg (i.p.) or NFPS (0.3, 1 mg/kg, i.p.) significantly improved MK-801-induced cognitive deficits under this test paradigm. These findings suggest that impaired preference for novel objects induced by MK-801 in the novel object recognition test could be a useful animal model for evaluating the efficacy of compounds targeting the cognitive deficits observed in schizophrenic patients. The results also suggest that enhancing NMDA receptor function is an effective way for treating the cognitive deficits associated with schizophrenia.

A Low Vision Rehabilitation Program for Patients with Mild Cognitive Deficits

PubMed Central

Whitson, Heather E.; Whitaker, Diane; Potter, Guy; McConnell, Eleanor; Tripp, Fay; Sanders, Linda L.; Muir, Kelly W.; Cohen, Harvey J.; Cousins, Scott W.

2012-01-01

Objective To design and pilot test a low vision rehabilitation program for patients with macular disease and cognitive deficits. Methods The Memory or Reasoning Enhanced Low Vision Rehabilitation (MORE-LVR) program was created by a team representing optometry, occupational therapy, ophthalmology, neuropsychology, and geriatrics. Key components of MORE-LVR are: 1) repetitive training with a therapist twice weekly over a 6-week period, 2) simplified training experience addressing no more than three individualized goals in a minimally distracting environment, 3) involvement of an informal companion (friend or family member). Eligible patients were recruited from an LVR clinic; measures were compared before and after the 6 week program. Results Twelve non-demented patients (mean age 84.5 years, 75% female) who screened positive for cognitive deficits completed the MORE-LVR intervention. Participants demonstrated improved scores on the National Eye Institute’s Visual Function Questionnaire (VFQ-25) composite score (47.2±16.3 to 54.8±13.8, p=0.01) and near activities score (21.5±14.0 to 41.0±23.1, p=0.02), timed performance measures (writing a grocery list [p=0.03], filling in a crossword puzzle answer [p=0.003]), a score indicating satisfaction with independence (p=0.05), and logical memory (p=0.02). All patients and companions reported progress toward at least one individualized goal; >70% reported progress toward all three goals. Conclusions This pilot study demonstrates feasibility of an LVR program for macular disease patients with mild cognitive deficits. Participants demonstrated improvements in vision-related function and cognitive measures and expressed high satisfaction. Future work is needed to determine if MORE-LVR is superior to usual outpatient LVR for persons with co-existing visual and cognitive impairments. PMID:23619914

Edaravone alleviates Alzheimer’s disease-type pathologies and cognitive deficits

PubMed Central

Jiao, Shu-Sheng; Yao, Xiu-Qing; Liu, Yu-Hui; Wang, Qing-Hua; Zeng, Fan; Lu, Jian-Jun; Liu, Jia; Zhu, Chi; Shen, Lin-Lin; Liu, Cheng-Hui; Wang, Ye-Ran; Zeng, Gui-Hua; Parikh, Ankit; Chen, Jia; Liang, Chun-Rong; Xiang, Yang; Bu, Xian-Le; Deng, Juan; Li, Jing; Xu, Juan; Zeng, Yue-Qin; Xu, Xiang; Xu, Hai-Wei; Zhong, Jin-Hua; Zhou, Hua-Dong; Zhou, Xin-Fu; Wang, Yan-Jiang

2015-01-01

Alzheimer’s disease (AD) is one of most devastating diseases affecting elderly people. Amyloid-β (Aβ) accumulation and the downstream pathological events such as oxidative stress play critical roles in pathogenesis of AD. Lessons from failures of current clinical trials suggest that targeting multiple key pathways of the AD pathogenesis is necessary to halt the disease progression. Here we show that Edaravone, a free radical scavenger that is marketed for acute ischemic stroke, has a potent capacity of inhibiting Aβ aggregation and attenuating Aβ-induced oxidation in vitro. When given before or after the onset of Aβ deposition via i.p. injection, Edaravone substantially reduces Aβ deposition, alleviates oxidative stress, attenuates the downstream pathologies including Tau hyperphosphorylation, glial activation, neuroinflammation, neuronal loss, synaptic dysfunction, and rescues the behavioral deficits of APPswe/PS1 mice. Oral administration of Edaravone also ameliorates the AD-like pathologies and memory deficits of the mice. These findings suggest that Edaravone holds a promise as a therapeutic agent for AD by targeting multiple key pathways of the disease pathogenesis. PMID:25847999

The Comprehension of Syntactic and Affective Prosody by Adults with Autism Spectrum Disorder without Accompanying Cognitive Deficits

ERIC Educational Resources Information Center

Martzoukou, Maria; Papadopoulou, Despina; Kosmidis, Mary-Helen

2017-01-01

The present study investigates the comprehension of syntactic and affective prosody in adults with autism spectrum disorder without accompanying cognitive deficits (ASD w/o cognitive deficits) as well as age-, education- and gender-matched unimpaired adults, while processing orally presented sentences. Two experiments were conducted: (a) an…

Cognitive deficits and predictors 3 years after diagnosis of a pilocytic astrocytoma in childhood.

PubMed

Aarsen, Femke K; Paquier, Philippe F; Arts, Willem-Frans; Van Veelen, Marie-Lise; Michiels, Erna; Lequin, Maarten; Catsman-Berrevoets, Coriene E

2009-07-20

PURPOSE To prospectively study cognitive deficits and predictors 3 years after diagnosis in a large series of pediatric patients treated for pilocytic astrocytoma (PA). PATIENTS AND METHODS Sixty-one of 67 children were grouped according to infratentorial, supratentorial midline, and supratentorial hemispheric site. Intelligence, memory, attention, language, visual-spatial, and executive functions were assessed. Included predictors were sex, age, relapse, diagnosis-assessment interval, hydrocephalus, kind of treatment, and tumor variables. Results All children with PA had problems with sustained attention and speed. In the infratentorial group, there also were deficits in verbal intelligence, visual-spatial memory, executive functioning, and naming. Verbal intelligence and verbal memory problems occurred in the brainstem tumor group. The supratentorial hemispheric tumor group had additional problems with selective attention and executive functioning, and the supratentorial midline tumor group displayed no extra impairments. More specifically, the dorsal supratentorial midline tumor group displayed problems with language and verbal memory. Predictors for lower cognitive functioning were hydrocephalus, radiotherapy, residual tumor size, and age; predictors for better functioning were chemotherapy or treatment of hydrocephalus. Almost 60% of children had problems with academic achievement, for which risk factors were relapse and younger age at diagnosis. CONCLUSION Despite normal intelligence at long-term follow-up, children treated for PA display invalidating cognitive impairments. Adequate treatment of hydrocephalus is important for a more favorable long-term cognitive outcome. Even children without initial severe deficits may develop cognitive impairments years after diagnosis, partly because of the phenomenon of growing into deficit, which has devastating implications for academic achievement and quality of life (QOL).

Mentalization deficit in bipolar patients during an acute depressive and manic episode: association with cognitive functions.

PubMed

Bodnar, Anna; Rybakowski, Janusz K

2017-12-06

A number of studies in bipolar patients have shown a deficit in mentalization (theory of mind), one of the main aspects of social cognition. The aim of current study was to assess both cognitive and affective mentalization in well-defined groups of depressed and manic bipolar patients, compared to healthy control subjects, using a battery of tests measuring mentalization processes. The second aim was to investigate a possible relationship between cognitive and affective mentalization and cognitive functions in bipolar patients during a depressive and manic episode. The study involved 25 bipolar disorder type I patients (10 male, 15 female) during a depressive episode (mean 24 ± 2 points in the 17-item Hamilton Depression Rating Scale) and 25 patients (10 male, 15 female) during a manic episode (mean 27 ± 4 points in the Young Mania Rating Scale). The control group consisted of 25 healthy subjects (10 male, 15 female) without psychiatric disorders. To measure mentalization, a revised version of the Reading the Mind in the Eyes (R-MET), the Strange Stories (SS), the Faux Pas Recognition (FPR), and the Moving Shapes Paradigm (MSP) tests were used. Assessment of cognitive functioning was made using the Digit Span, Trail Making, and Wisconsin Card Sorting Tests. In bipolar patients significant deficits in both cognitive and affective mentalization were demonstrated during both acute depressive and manic episodes. The impairment in FPR in manic patients was more severe than that in the depressive ones. On the other hand, in MSP, manic patients showed significantly increased intentionality for non-mentalization animations, compared with depressive patients and for "cause and effect" animations compared with control subjects. A significant relationship was found between the decrease in cognitive and affective mentalization and deficits of cognitive functions during both the depressive and manic episodes. The results obtained confirm the deficits of mentalization in

Subacute ibuprofen treatment rescues the synaptic and cognitive deficits in advanced-aged mice

PubMed Central

Rogers, Justin T.; Liu, Chia-Chen; Zhao, Na; Wang, Jian; Putzke, Travis; Yang, Longyu; Shinohara, Mitsuru; Fryer, John D.; Kanekiyo, Takahisa; Bu, Guojun

2017-01-01

Aging is accompanied by increased neuroinflammation, synaptic dysfunction and cognitive deficits both in rodents and humans, yet the onset and progression of these deficits throughout the life span remain unknown. These aging-related deficits affect the quality of life and present challenges to our aging society. Here, we defined age-dependent and progressive impairments of synaptic and cognitive functions and showed that reducing astrocyte-related neuroinflammation through anti-inflammatory drug treatment in aged mice reverses these events. By comparing young (3 months), middle-aged (18 months), aged (24 months) and advanced-aged wild-type mice (30 months), we found that the levels of an astrocytic marker, GFAP, progressively increased after 18 months of age, which preceded the decreases of the synaptic marker PSD-95. Hippocampal long-term potentiation (LTP) was also suppressed in an age-dependent manner, where significant deficits were observed after 24 months of age. Fear conditioning tests demonstrated that associative memory in the context and cued conditions was decreased starting at the ages of 18 and 30 months, respectively. When the mice were tested on hidden platform water maze, spatial learning memory was significantly impaired after 24 months of age. Importantly, subacute treatment with the anti-inflammatory drug ibuprofen suppressed astrocyte activation, and restored synaptic plasticity and memory function in advanced-aged mice. These results support the critical contribution of aging-related inflammatory responses to hippocampal-dependent cognitive function and synaptic plasticity, in particular during advanced aging. Our findings provide strong evidence that suppression of neuroinflammation could be a promising treatment strategy to preserve cognition during aging. PMID:28254590

16p11.2 Deletion mice display cognitive deficits in touchscreen learning and novelty recognition tasks.

PubMed

Yang, Mu; Lewis, Freeman C; Sarvi, Michael S; Foley, Gillian M; Crawley, Jacqueline N

2015-12-01

Chromosomal 16p11.2 deletion syndrome frequently presents with intellectual disabilities, speech delays, and autism. Here we investigated the Dolmetsch line of 16p11.2 heterozygous (+/-) mice on a range of cognitive tasks with different neuroanatomical substrates. Robust novel object recognition deficits were replicated in two cohorts of 16p11.2+/- mice, confirming previous findings. A similarly robust deficit in object location memory was discovered in +/-, indicating impaired spatial novelty recognition. Generalizability of novelty recognition deficits in +/- mice extended to preference for social novelty. Robust learning deficits and cognitive inflexibility were detected using Bussey-Saksida touchscreen operant chambers. During acquisition of pairwise visual discrimination, +/- mice required significantly more training trials to reach criterion than wild-type littermates (+/+), and made more errors and correction errors than +/+. In the reversal phase, all +/+ reached criterion, whereas most +/- failed to reach criterion by the 30-d cutoff. Contextual and cued fear conditioning were normal in +/-. These cognitive phenotypes may be relevant to some aspects of cognitive impairments in humans with 16p11.2 deletion, and support the use of 16p11.2+/- mice as a model system for discovering treatments for cognitive impairments in 16p11.2 deletion syndrome. © 2015 Yang et al.; Published by Cold Spring Harbor Laboratory Press.

Curcumin Improves Amyloid β-Peptide (1-42) Induced Spatial Memory Deficits through BDNF-ERK Signaling Pathway.

PubMed

Zhang, Lu; Fang, Yu; Xu, Yuming; Lian, Yajun; Xie, Nanchang; Wu, Tianwen; Zhang, Haifeng; Sun, Limin; Zhang, Ruifang; Wang, Zhenhua

2015-01-01

Curcumin, the most active component of turmeric, has various beneficial properties, such as antioxidant, anti-inflammatory, and antitumor effects. Previous studies have suggested that curcumin reduces the levels of amyloid and oxidized proteins and prevents memory deficits and thus is beneficial to patients with Alzheimer's disease (AD). However, the molecular mechanisms underlying curcumin's effect on cognitive functions are not well-understood. In the present study, we examined the working memory and spatial reference memory in rats that received a ventricular injection of amyloid-β1-42 (Aβ1-42), representing a rodent model of Alzheimer's disease (AD). The rats treated with Aβ1-42 exhibited obvious cognitive deficits in behavioral tasks. Chronic (seven consecutive days, once per day) but not acute (once a day) curcumin treatments (50, 100, and 200 mg/kg) improved the cognitive functions in a dose-dependent manner. In addition, the beneficial effect of curcumin is accompanied by increased BDNF levels and elevated levels of phosphorylated ERK in the hippocampus. Furthermore, the cognition enhancement effect of curcumin could be mimicked by the overexpression of BDNF in the hippocampus and blocked by either bilateral hippocampal injections with lentiviruses that express BDNF shRNA or a microinjection of ERK inhibitor. These findings suggest that chronic curcumin ameliorates AD-related cognitive deficits and that upregulated BDNF-ERK signaling in the hippocampus may underlie the cognitive improvement produced by curcumin.

Cognitive deficits associated with combined HIV gp120 expression and chronic methamphetamine exposure in mice

PubMed Central

Kesby, James P.; Markou, Athina; Semenova, Svetlana

2014-01-01

Methamphetamine abuse is common among individuals infected by human immunodeficiency virus (HIV). Neurocognitive outcomes tend to be worse in methamphetamine users with HIV. However, it is unclear whether discrete cognitive domains are susceptible to impairment after combined HIV infection and methamphetamine abuse. The expression of HIV/gp120 protein induces neuropathology in mice similar to HIV-induced pathology in humans. We investigated the separate and combined effects of methamphetamine exposure and gp120 expression on cognitive function in transgenic (gp120-tg) and control mice. The mice underwent an escalating methamphetamine binge regimen and were tested in novel object/location recognition, object-in-place recognition, and Barnes maze tests. gp120 expression disrupted performance in the object-in-place test (i.e., similar time spent with all objects, regardless of location), indicating deficits in associative recognition memory. gp120 expression also altered reversal learning in the Barnes maze, suggesting impairments in executive function. Methamphetamine exposure impaired spatial strategy in the Barnes maze, indicating deficits in spatial learning. Methamphetamine-exposed gp120-tg mice had the lowest spatial strategy scores in the final acquisition trials in the Barnes maze, suggesting greater deficits in spatial learning than all of the other groups. Although HIV infection involves interactions between multiple proteins and processes, in addition to gp120, our findings in gp120-tg mice suggest that humans with the dual insult of HIV infection and methamphetamine abuse may exhibit a broader spectrum of cognitive deficits than those with either factor alone. Depending on the cognitive domain, the combination of both insults may exacerbate deficits in cognitive performance compared with each individual insult. PMID:25476577

Deficits in Domains of Social Cognition in Schizophrenia: A Meta-Analysis of the Empirical Evidence

PubMed Central

Savla, Gauri N.

2013-01-01

Objective: Social cognition is strongly associated with functional outcome in schizophrenia, making it an important target for treatment. Our goal was to examine the average magnitude of differences between schizophrenia patients (SCs) and normal comparison (NCs) patients across multiple domains of social cognition recognized by the recent NIMH consensus statement: theory of mind (ToM), social perception, social knowledge, attributional bias, emotion perception, and emotion processing. Method: We conducted a meta-analysis of peer-reviewed studies of social cognition in schizophrenia, published between 1980 and November, 2011. Results: 112 studies reporting results from 3908 SCs and 3570 NCs met our inclusion criteria. SCs performed worse than NCs across all domains, with large effects for social perception (g = 1.04), ToM (g = 0.96), emotion perception (g = 0.89), and emotion processing (g = 0.88). Regression analyses showed that statistically significant heterogeneity in effects within domains was not explained by age, education, or gender. Greater deficits in social and emotion perception were associated with inpatient status, and greater deficits in emotion processing were associated with longer illness duration. Conclusions: Despite the limitations of existing studies, including lack of standardization or psychometric validation of measures, the evidence for deficits across multiple social cognitive domains in schizophrenia is clear. Future research should examine the role of neurobiological and psychosocial factors in models linking various aspects of deficit in schizophrenia, including social cognition, in order to identify targets for intervention. PMID:22949733

University Students With Poor Reading Comprehension: The Hidden Cognitive Processing Deficit.

PubMed

Georgiou, George K; Das, J P

2015-01-01

The present study aimed to examine the nature of the working memory and general cognitive ability deficits experienced by university students with a specific reading comprehension deficit. A total of 32 university students with poor reading comprehension but average word-reading skills and 60 age-matched controls with no comprehension difficulties participated in the study. The participants were assessed on three verbal working memory tasks that varied in terms of their processing demands and on the Das-Naglieri Cognitive Assessment System, which was used to operationalize intelligence. The results indicated first that the differences between poor and skilled comprehenders on working memory were amplified as the processing demands of the tasks increased. In addition, although poor comprehenders as a group had average intelligence, they experienced significant difficulties in simultaneous and successive processing. Considering that working memory and general cognitive ability are highly correlated processes, these findings suggest that the observed differences between poor and skilled comprehenders are likely a result of a deficient information processing system. © Hammill Institute on Disabilities 2013.

In search of multimodal neuroimaging biomarkers of cognitive deficits in schizophrenia.

PubMed

Sui, Jing; Pearlson, Godfrey D; Du, Yuhui; Yu, Qingbao; Jones, Thomas R; Chen, Jiayu; Jiang, Tianzi; Bustillo, Juan; Calhoun, Vince D

2015-12-01

The cognitive deficits of schizophrenia are largely resistant to current treatments and thus are a lifelong illness burden. The Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) provides a reliable and valid assessment of cognition across major cognitive domains; however, the multimodal brain alterations specifically associated with MCCB in schizophrenia have not been examined. The interrelationships between MCCB and the abnormalities seen in three types of neuroimaging-derived maps-fractional amplitude of low-frequency fluctuations (fALFF) from resting-state functional magnetic resonance imaging (MRI), gray matter (GM) density from structural MRI, and fractional anisotropy from diffusion MRI-were investigated by using multiset canonical correlation analysis in data from 47 schizophrenia patients treated with antipsychotic medications and 50 age-matched healthy control subjects. One multimodal component (canonical variant 8) was identified as both group differentiating and significantly correlated with the MCCB composite. It demonstrated 1) increased cognitive performance associated with higher fALFF (intensity of regional spontaneous brain activity) and higher GM volumes in thalamus, striatum, hippocampus, and the mid-occipital region, with co-occurring fractional anisotropy changes in superior longitudinal fascicules, anterior thalamic radiation, and forceps major; 2) higher fALFF but lower GM volume in dorsolateral prefrontal cortex related to worse cognition in schizophrenia; and 3) distinct domains of MCCB might exhibit dissociable multimodal signatures, e.g., increased fALFF in inferior parietal lobule particularly correlated with decreased social cognition. Medication dose did not relate to these findings in schizophrenia. Our results suggest linked functional and structural deficits in distributed cortico-striato-thalamic circuits may be closely related to MCCB-measured cognitive

Potential ameliorative effects of grape seed-derived polyphenols against cadmium induced prostatic deficits.

PubMed

Lei, Yongfang; Chen, Qian; Chen, Jinglou; Liu, Dong

2017-07-01

Grape (Vitis vinifera) is consumed as fruit and wine for people. In this study, rat model of prostatic deficits was induced by orally receiving 60mg/L cadmium chlorine (CdCl 2 ) through drinking water for 20 weeks. Grape seed-derived polyphenols extract (GSP) was orally given for 20 weeks. Finally, the prostatic levels of E-cadherin, fibronectin, and α-smooth muscle actin were measured by immunohistochemical and qPCR analysis. The oxidative stress was measured by detecting the levels of malondialdehyde, nitric oxide, reduced glutathione/oxidized glutathione and enzymatic antioxidant status. Additionally, the prostatic expressions of transforming growth factor-β1 (TGF-β1), type I TGF-β receptor (TGF-βRI), Smad3, phosphorylation-Smad3 (p-Smad3), Smad7, nuclear related factor-2 (Nrf-2), heme oxygenase-1 (HO-1) and γ-glutamate cysteine ligase catalytic subunit (γ-GCLC) were measured by western blot. The levels of microRNA (miR)-133a/b were measured by qPCR. It was observed that GSP ameliorated the prostatic oxidative stress and fibrosis induced by CdCl 2 . GSP also inhibited the over-generation of TGF-β1 and p-Smad3, as well as enhanced the levels of Smad7, Nrf-2, HO-1, γ-GCLC and miR-133a/b. These results showed that GSP could attenuate Cd-induced prostatic deficits. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Hypoglycemia induced by insulin as a triggering factor of cognitive deficit in diabetic children.

PubMed

Rodrigues Vilela, Vanessa; de Castro Ruiz Marques, Any; Schamber, Christiano Rodrigues; Bazotte, Roberto Barbosa

2014-01-01

This paper provides an overview of insulin-induced hypoglycemia as a triggering factor of cognitive deficit in children with type 1 diabetes mellitus. For this purpose, databases from 1961 to 2013 were used with the objective of detecting the primary publications that address the impact of hypoglycemia on cognitive performance of diabetic children. The results obtained from experimental animals were excluded. The majority of studies demonstrated that the cognitive deficit in diabetic children involves multiple factors including duration, intensity, severity, and frequency of hypoglycemia episodes. Additionally, age at the onset of type 1 diabetes also influences the cognitive performance, considering that early inception of the disease is a predisposing factor for severe hypoglycemia. Furthermore, the results suggest that there is a strong correlation between brain damage caused by hypoglycemia and cognitive deterioration. Therefore, a more cautious follow-up and education are needed to impede and treat hypoglycemia in children with diabetes mellitus.

Hypoglycemia Induced by Insulin as a Triggering Factor of Cognitive Deficit in Diabetic Children

PubMed Central

Rodrigues Vilela, Vanessa; de Castro Ruiz Marques, Any; Schamber, Christiano Rodrigues

2014-01-01

This paper provides an overview of insulin-induced hypoglycemia as a triggering factor of cognitive deficit in children with type 1 diabetes mellitus. For this purpose, databases from 1961 to 2013 were used with the objective of detecting the primary publications that address the impact of hypoglycemia on cognitive performance of diabetic children. The results obtained from experimental animals were excluded. The majority of studies demonstrated that the cognitive deficit in diabetic children involves multiple factors including duration, intensity, severity, and frequency of hypoglycemia episodes. Additionally, age at the onset of type 1 diabetes also influences the cognitive performance, considering that early inception of the disease is a predisposing factor for severe hypoglycemia. Furthermore, the results suggest that there is a strong correlation between brain damage caused by hypoglycemia and cognitive deterioration. Therefore, a more cautious follow-up and education are needed to impede and treat hypoglycemia in children with diabetes mellitus. PMID:24790575

Rutin protects against cognitive deficits and brain damage in rats with chronic cerebral hypoperfusion.

PubMed

Qu, Jie; Zhou, Qiong; Du, Ying; Zhang, Wei; Bai, Miao; Zhang, Zhuo; Xi, Ye; Li, Zhuyi; Miao, Jianting

2014-08-01

Chronic cerebral hypoperfusion is a critical causative factor for the development of cognitive decline and dementia in the elderly, which involves many pathophysiological processes. Consequently, inhibition of several pathophysiological pathways is an attractive therapeutic strategy for this disorder. Rutin, a biologically active flavonoid, protects the brain against several insults through its antioxidant and anti-inflammatory properties, but its effect on cognitive deficits and brain damage caused by chronic cerebral hypoperfusion remains unknown. Here, we investigated the neuroprotective effect of rutin on cognitive impairments and the potential mechanisms underlying its action in rats with chronic cerebral hypoperfusion. We used Sprague-Dawley rats with permanent bilateral common carotid artery occlusion (BCCAO), a well-established model of chronic cerebral hypoperfusion. After rutin treatment for 12 weeks, the neuroprotective effect of rutin in rats was evaluated by behavioural tests, biochemical and histopathological analyses. BCCAO rats showed marked cognitive deficits, which were improved by rutin treatment. Moreover, BCCAO rats exhibited central cholinergic dysfunction, oxidative damage, inflammatory responses and neuronal damage in the cerebral cortex and hippocampus, compared with sham-operated rats. All these effects were significantly alleviated by treatment with rutin. Our results provide new insights into the pharmacological actions of rutin and suggest that rutin has multi-targeted therapeutical potential on cognitive deficits associated with conditions with chronic cerebral hypoperfusion such as vascular dementia and Alzheimer's disease. © 2014 The British Pharmacological Society.

Cognitive deficits associated with combined HIV gp120 expression and chronic methamphetamine exposure in mice.

PubMed

Kesby, James P; Markou, Athina; Semenova, Svetlana

2015-01-01

Methamphetamine abuse is common among individuals infected by human immunodeficiency virus (HIV). Neurocognitive outcomes tend to be worse in methamphetamine users with HIV. However, it is unclear whether discrete cognitive domains are susceptible to impairment after combined HIV infection and methamphetamine abuse. The expression of HIV/gp120 protein induces neuropathology in mice similar to HIV-induced pathology in humans. We investigated the separate and combined effects of methamphetamine exposure and gp120 expression on cognitive function in transgenic (gp120-tg) and control mice. The mice underwent an escalating methamphetamine binge regimen and were tested in novel object/location recognition, object-in-place recognition, and Barnes maze tests. gp120 expression disrupted performance in the object-in-place test (i.e. similar time spent with all objects, regardless of location), indicating deficits in associative recognition memory. gp120 expression also altered reversal learning in the Barnes maze, suggesting impairments in executive function. Methamphetamine exposure impaired spatial strategy in the Barnes maze, indicating deficits in spatial learning. Methamphetamine-exposed gp120-tg mice had the lowest spatial strategy scores in the final acquisition trials in the Barnes maze, suggesting greater deficits in spatial learning than all of the other groups. Although HIV infection involves interactions between multiple proteins and processes, in addition to gp120, our findings in gp120-tg mice suggest that humans with the dual insult of HIV infection and methamphetamine abuse may exhibit a broader spectrum of cognitive deficits than those with either factor alone. Depending on the cognitive domain, the combination of both insults may exacerbate deficits in cognitive performance compared with each individual insult. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

Stable cognitive deficits in schizophrenia patients with comorbid obsessive-compulsive symptoms: a 12-month longitudinal study.

PubMed

Schirmbeck, Frederike; Rausch, Franziska; Englisch, Susanne; Eifler, Sarah; Esslinger, Christine; Meyer-Lindenberg, Andreas; Zink, Mathias

2013-11-01

Amongst schizophrenia patients, a large subgroup of up to 25% also suffers from comorbid obsessive-compulsive symptoms (OCSs). The association between comorbid OCSs in these patients and neuropsychological impairment remains unclear and somewhat contradictory. Longitudinal approaches investigating the stability of OCS-associated cognitive deficits are missing. Thirty-seven patients with schizophrenia and comorbid OCSs and 43 schizophrenia patients without OCS were assessed with a comprehensive cognitive test battery and compared at baseline and, again, 12 months later. Schizophrenia patients with comorbid OCSs showed significant pronounced deficits, with increasing effect sizes over the 12-month assessment period in specific cognitive areas such as visuospatial perception and visual memory (WAIS-R block design, Rey-Osterrieth Complex Figure Test), executive functioning (perseveration in the Wisconsin Card Sorting test), and cognitive flexibility (Trail Making test B). These cognitive domains are correlated with OCS severity and are known to be candidate cognitive domains in obsessive-compulsive disorder (OCD). OCSs in schizophrenia is associated with specific and longitudinally stable cognitive deficits, strongly arguing for at least partially overlapping neurobiological mechanisms with OCD. Prospective studies involving patients with at-risk mental states for psychosis are necessary to decipher the interaction of cognitive impairment and the clinical manifestations of schizophrenia and OCSs. This might facilitate the definition of patients at high risk for OCSs, an early detection of subclinical levels, therapeutic interventions, and clinical monitoring.

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

Cognitive Deficits in Adults with ADHD Go beyond Comorbidity Effects

ERIC Educational Resources Information Center

Silva, Katiane L.; Guimaraes-da-Silva, Paula O.; Grevet, Eugenio H.; Victor, Marcelo M.; Salgado, Carlos A. I.; Vitola, Eduardo S.; Mota, Nina R.; Fischer, Aline G.; Contini, Veronica; Picon, Felipe A.; Karam, Rafael G.; Belmonte-de-Abreu, Paulo; Rohde, Luis A.; Bau, Claiton H. D.

2013-01-01

Objective: This study addresses if deficits in cognitive, attention, and inhibitory control performance in adults with ADHD are better explained by the disorder itself or by comorbid conditions. Method Adult patients with ADHD ("n" = 352) and controls ("n" = 94) were evaluated in the ADHD program of a tertiary hospital. The…

Executive Functions, Memory, and Social Cognitive Deficits and Recovery in Chronic Alcoholism: A Critical Review to Inform Future Research.

PubMed

Le Berre, Anne-Pascale; Fama, Rosemary; Sullivan, Edith V

2017-08-01

Alcoholism is a complex and dynamic disease, punctuated by periods of abstinence and relapse, and influenced by a multitude of vulnerability factors. Chronic excessive alcohol consumption is associated with cognitive deficits, ranging from mild to severe, in executive functions, memory, and metacognitive abilities, with associated impairment in emotional processes and social cognition. These deficits can compromise efforts in initiating and sustaining abstinence by hampering efficacy of clinical treatment and can obstruct efforts in enabling good decision making success in interpersonal/social interactions, and awareness of cognitive and behavioral dysfunctions. Despite evidence for differences in recovery levels of selective cognitive processes, certain deficits can persist even with prolonged sobriety. Herein is presented a review of alcohol-related cognitive impairments affecting component processes of executive functioning, memory, and the recently investigated cognitive domains of metamemory, social cognition, and emotional processing; also considered are trajectories of cognitive recovery with abstinence. Finally, in the spirit of critical review, limitations of current knowledge are noted and avenues for new research efforts are proposed that focus on (i) the interaction among emotion-cognition processes and identification of vulnerability factors contributing to the development of emotional and social processing deficits and (ii) the time line of cognitive recovery by tracking alcoholism's dynamic course of sobriety and relapse. Knowledge about the heterochronicity of cognitive recovery in alcoholism has the potential of indicating at which points during recovery intervention may be most beneficial. Copyright © 2017 by the Research Society on Alcoholism.

Combined uridine and choline administration improves cognitive deficits in spontaneously hypertensive rats.

PubMed

De Bruin, N M W J; Kiliaan, A J; De Wilde, M C; Broersen, L M

2003-07-01

Rationale. Hypertension is considered a risk factor for the development of cognitive disorders, because of its negative effects on cerebral vasculature and blood flow. Genetically induced hypertension in rats has been associated with a range of cognitive impairments. Therefore, spontaneously hypertensive rats (SHR) can potentially be used as a model for cognitive deficits in human subjects. Consecutively, it can be determined whether certain food components can improve cognition in these rats. Objective. The present study aimed to determine whether SHR display specific deficits in attention, learning, and memory function. Additionally, effects of chronic uridine and choline administration were studied. Methods. 5-7 months old SHR were compared with normotensive Wistar-Kyoto (WKY) and Sprague-Dawley (SD) rats. (a) The operant delayed non-matching-to-position (DNMTP) test was used to study short-term memory function. (b) The five-choice serial reaction time (5-CSRT) task was used to assess selective visual attention processes. (c) Finally, the Morris water maze (MWM) acquisition was used as a measure for spatial learning and mnemonic capabilities. Results. (1) SHR exhibited significantly impaired performance in the 5-CSRT test in comparison with the two other rat strains. Both the SHR and WKY showed deficits in spatial learning when compared with the SD rats. (2) Uridine and choline supplementation normalized performance of SHR in the 5-CSRT test. (3) In addition, uridine and choline treatment improved MWM acquisition in both WKY and SHR rats. Conclusion. The present results show that the SHR have a deficiency in visual selective attention and spatial learning. Therefore, the SHR may provide an interesting model in the screening of substances with therapeutic potential for treatment of cognitive disorders. A combination of uridine and choline administration improved selective attention and spatial learning in SHR.

Novel Dopamine Therapeutics for Cognitive Deficits in Schizophrenia.

PubMed

Arnsten, Amy F T; Girgis, Ragy R; Gray, David L; Mailman, Richard B

2017-01-01

Schizophrenia is characterized by profound cognitive deficits that are not alleviated by currently available medications. Many of these cognitive deficits involve dysfunction of the newly evolved, dorsolateral prefrontal cortex (dlPFC). The brains of patients with schizophrenia show evidence of dlPFC pyramidal cell dendritic atrophy, likely reductions in cortical dopamine, and possible changes in dopamine D 1 receptors (D 1 R). It has been appreciated for decades that optimal levels of dopamine are essential for dlPFC working memory function, with many beneficial actions arising from D 1 R stimulation. D 1 R are concentrated on dendritic spines in the primate dlPFC, where their stimulation produces an inverted-U dose response on dlPFC neuronal firing and cognitive performance during working memory tasks. Research in both academia and the pharmaceutical industry has led to the development of selective D 1 agonists, e.g., the first full D 1 agonist, dihydrexidine, which at low doses improved working memory in monkeys. Dihydrexidine has begun to be tested in patients with schizophrenia or schizotypal disorder. Initial results are encouraging, but studies are limited by the pharmacokinetics of the drug. These data, however, have spurred efforts toward the discovery and development of improved or novel new compounds, including D 1 agonists with better pharmacokinetics, functionally selective D 1 ligands, and D 1 R positive allosteric modulators. One or several of these approaches should allow optimization of the beneficial effects of D 1 R stimulation in the dlPFC that can be translated into clinical practice. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Number Processing and Heterogeneity of Developmental Dyscalculia: Subtypes with Different Cognitive Profiles and Deficits

ERIC Educational Resources Information Center

Skagerlund, Kenny; Träff, Ulf

2016-01-01

This study investigated if developmental dyscalculia (DD) in children with different profiles of mathematical deficits has the same or different cognitive origins. The defective approximate number system hypothesis and the access deficit hypothesis were tested using two different groups of children with DD (11-13 years old): a group with…

Deficit of entropy modulation of the EEG in schizophrenia associated to cognitive performance and symptoms. A replication study.

PubMed

Molina, Vicente; Bachiller, Alejandro; Gomez-Pilar, Javier; Lubeiro, Alba; Hornero, Roberto; Cea-Cañas, Benjamín; Valcárcel, César; Haidar, Mahmoun-Karim; Poza, Jesús

2018-05-01

Spectral entropy (SE) is a measurement from information theory field that provides an estimation of EEG regularity and may be useful as a summary of its spectral properties. Previous studies using small samples reported a deficit of EEG entropy modulation in schizophrenia during cognitive activity. The present study is aimed at replicating this finding in a larger sample, to explore its cognitive and clinical correlates and to discard antipsychotic treatment as the main source of that deficit. We included 64 schizophrenia patients (21 first episodes, FE) and 65 healthy controls. We computed SE during performance of an odd-ball paradigm, at the windows prior (-300 to 0ms) and following (150 to 450ms) stimulus presentation. Modulation of SE was defined as the difference between post- and pre-stimulus windows. In comparison to controls, patients showed a deficit of SE modulation over frontal and central regions, also shown by FE patients. Baseline SE did not differ between patients and controls. Modulation deficit was directly associated with cognitive deficits and negative symptoms, and inversely with positive symptoms. SE modulation was not related to antipsychotic doses. Patients also showed a smaller change of median frequency (i.e., smaller slowing of oscillatory activity) of the EEG from pre- to post-stimulus windows. These results support that a deficit of fast modulation contributes to cognitive deficits and symptoms in schizophrenia patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Deficits in visual working-memory capacity and general cognition in African Americans with psychosis.

PubMed

Mathias, Samuel R; Knowles, Emma E M; Barrett, Jennifer; Beetham, Tamara; Leach, Olivia; Buccheri, Sebastiano; Aberizk, Katrina; Blangero, John; Poldrack, Russell A; Glahn, David C

2018-03-01

On average, patients with psychosis perform worse than controls on visual change-detection tasks, implying that psychosis is associated with reduced capacity of visual working memory (WM). In the present study, 79 patients diagnosed with various psychotic disorders and 166 controls, all African Americans, completed a change-detection task and several other neurocognitive measures. The aims of the study were to (1) determine whether we could observe a between-group difference in performance on the change-detection task in this sample; (2) establish whether such a difference could be specifically attributed to reduced WM capacity (k); and (3) estimate k in the context of the general cognitive deficit in psychosis. Consistent with previous studies, patients performed worse than controls on the change-detection task, on average. Bayesian hierarchical cognitive modeling of the data suggested that this between-group difference was driven by reduced k in patients, rather than differences in other psychologically meaningful model parameters (guessing behavior and lapse rate). Using the same modeling framework, we estimated the effect of psychosis on k while controlling for general intellectual ability (g, obtained from the other neurocognitive measures). The results suggested that reduced k in patients was stronger than predicted by the between-group difference in g. Moreover, a mediation analysis suggested that the relationship between psychosis and g (i.e., the general cognitive deficit) was mediated by k. The results were consistent with the idea that reduced k is a specific deficit in psychosis, which contributes to the general cognitive deficit. Copyright © 2017 Elsevier B.V. All rights reserved.

Modafinil Reverses Phencyclidine-Induced Deficits in Cognitive Flexibility, Cerebral Metabolism, and Functional Brain Connectivity

PubMed Central

Dawson, Neil; Thompson, Rhiannon J.; McVie, Allan; Thomson, David M.; Morris, Brian J.; Pratt, Judith A.

2012-01-01

Objective: In the present study, we employ mathematical modeling (partial least squares regression, PLSR) to elucidate the functional connectivity signatures of discrete brain regions in order to identify the functional networks subserving PCP-induced disruption of distinct cognitive functions and their restoration by the procognitive drug modafinil. Methods: We examine the functional connectivity signatures of discrete brain regions that show overt alterations in metabolism, as measured by semiquantitative 2-deoxyglucose autoradiography, in an animal model (subchronic phencyclidine [PCP] treatment), which shows cognitive inflexibility with relevance to the cognitive deficits seen in schizophrenia. Results: We identify the specific components of functional connectivity that contribute to the rescue of this cognitive inflexibility and to the restoration of overt cerebral metabolism by modafinil. We demonstrate that modafinil reversed both the PCP-induced deficit in the ability to switch attentional set and the PCP-induced hypometabolism in the prefrontal (anterior prelimbic) and retrosplenial cortices. Furthermore, modafinil selectively enhanced metabolism in the medial prelimbic cortex. The functional connectivity signatures of these regions identified a unifying functional subsystem underlying the influence of modafinil on cerebral metabolism and cognitive flexibility that included the nucleus accumbens core and locus coeruleus. In addition, these functional connectivity signatures identified coupling events specific to each brain region, which relate to known anatomical connectivity. Conclusions: These data support clinical evidence that modafinil may alleviate cognitive deficits in schizophrenia and also demonstrate the benefit of applying PLSR modeling to characterize functional brain networks in translational models relevant to central nervous system dysfunction. PMID:20810469

Potential Ameliorative Effects of Qing Ye Dan Against Cadmium Induced Prostatic Deficits via Regulating Nrf-2/HO-1 and TGF-β1/Smad Pathways.

PubMed

Du, Lifen; Lei, Yongfang; Chen, Jinglou; Song, Hongping; Wu, Xinying

2017-01-01

Cadmium (Cd) is an environmental pollutant with reproductive toxicity. Swertia mileensis is used in Chinese medicine for the treatment of prostatic deficits and named as Qing Ye Dan (QYD). This study was undertaken to investigate the potential protective effects of QYD against Cd-induced prostatic deficits. Rat model of prostatic deficits was induced by 0.2 mg/kg/d CdCl2 subcutaneous injection for 15 days. The prostatic oxidative stress was evaluated by detecting the levels of malondialdehyde, nitric oxide, reduced/ oxidized glutathione, total sulfhydryl groups and enzymatic antioxidant status. The prostatic inflammation was estimated by testing the levels of pro-inflammatory cytokines. The levels of epithelial-mesenchymal transition (EMT) markers E-cadherin, fibronectin, vimentin and α-smooth muscle actin were measured by qPCR analysis. Additionally, the prostatic expressions of transforming growth factor-β1 (TGF-β1), type I TGF-β receptor (TGF-βRI), Smad2, phosphorylation-Smad2 (p-Smad2), Smad3, p-Smad3, Smad7, nuclear related factor-2 (Nrf-2), heme oxygenase-1 (HO-1), B-cell CLL/lymphoma (Bcl)-2 and Bcl-2-associated X protein (Bax) were measured by western blot assay. It was found that QYD ameliorated the Cd-induced prostatic oxidative stress and inflammation, attenuated prostatic EMT, inhibited the TGF-β1/Smad pathway, increased Bcl-2/Bax ratio and enhanced the activity of Nrf-2/HO-1 pathway. These results showed that QYD could ameliorate Cd-induced prostatic deficits via modulating Nrf-2/HO-1 and TGF-β1/Smad pathways. © 2017 The Author(s). Published by S. Karger AG, Basel.

The association between cognitive deficits and prefrontal hemodynamic responses during performance of working memory task in patients with schizophrenia.

PubMed

Pu, Shenghong; Nakagome, Kazuyuki; Itakura, Masashi; Iwata, Masaaki; Nagata, Izumi; Kaneko, Koichi

2016-04-01

Schizophrenia-associated cognitive deficits are resistant to treatment and thus pose a lifelong burden. The Brief Assessment of Cognition in Schizophrenia (BACS) provides reliable and valid assessments across cognitive domains. However, because the prefrontal functional abnormalities specifically associated with the level of cognitive deficits in schizophrenia have not been examined, we explored this relationship. Patients with schizophrenia (N=87) and matched healthy controls (N=50) participated in the study. Using near-infrared spectroscopy (NIRS), we measured the hemodynamic responses in the prefrontal and superior temporal cortical surface areas during a working memory task. Correlation analyses revealed a relationship between the hemodynamics and the BACS composite and domain scores. Hemodynamic responses of the left dorsolateral prefrontal cortex (DLPFC) and left frontopolar cortex (FPC) in the higher-level-of-cognitive-function schizophrenia group were weaker than the responses of the controls but similar to those of the lower-level-of-cognitive-function schizophrenia group. However, hemodynamic responses in the right DLPFC, bilateral ventrolateral PFC (VLPFC), and right temporal regions decreased with increasing cognitive deficits. In addition, the hemodynamic response correlated positively with the level of cognitive function (BACS composite scores) in the right DLPFC, bilateral VLPFC, right FPC, and bilateral temporal regions in schizophrenia. The correlation was driven by all BACS domains. Our results suggest that the linked functional deficits in the right DLPFC, bilateral VLPFC, right FPC, and bilateral temporal regions may be related to BACS-measured cognitive impairments in schizophrenia and show that linking the neurocognitive deficits and brain abnormalities can increase our understanding of schizophrenia pathophysiology. Copyright © 2015 Elsevier B.V. All rights reserved.

Using upper limb kinematics to assess cognitive deficits in people living with both HIV and stroke.

PubMed

Bui, Kevin D; Rai, Roshan; Johnson, Michelle J

2017-07-01

In this study, we aim to explore ways to objectively assess cognitive deficits in the stroke and HIV/stroke populations, where cognitive and motor impairments can be hard to separate. Using an upper limb rehabilitation robot called the Haptic TheraDrive, we collect performance error scores and motor learning data on the impaired and unimpaired limb during a trajectory tracking task. We compare these data to clinical cognitive scores. The preliminary results suggest a possible relationship between unimpaired upper limb performance error and visuospatial/executive function cognitive domains, but more work needs to be done to further investigate this. The potential of using robot-assisted technologies to measure unimpaired limb kinematics as a tool to assess cognitive deficits would be useful to inform more effective rehabilitation strategies for HIV, stroke, and HIV/stroke populations.

Effect of Neuroscience-Based Cognitive Skill Training on Growth of Cognitive Deficits Associated with Learning Disabilities in Children Grades 2-4

ERIC Educational Resources Information Center

Avtzon, Sarah Abitbol

2012-01-01

Working memory, executive functions, and cognitive processes associated with specific academic areas, are empirically identified as being the core underlying cognitive deficits in students with specific learning disabilities. Using Hebb's theory of neuroplasticity and the principle of automaticity as theoretical bases, this experimental study…

Cognitive impairments accompanying rodent mild traumatic brain injury involve p53-dependent neuronal cell death and are ameliorated by the tetrahydrobenzothiazole PFT-α.

PubMed

Rachmany, Lital; Tweedie, David; Rubovitch, Vardit; Yu, Qian-Sheng; Li, Yazhou; Wang, Jia-Yi; Pick, Chaim G; Greig, Nigel H

2013-01-01

With parallels to concussive mild traumatic brain injury (mTBI) occurring in humans, anesthetized mice subjected to a single 30 g weight drop mTBI event to the right parietal cortex exhibited significant diffuse neuronal degeneration that was accompanied by delayed impairments in recognition and spatial memory. To elucidate the involvement of reversible p53-dependent apoptosis in this neuronal loss and associated cognitive deficits, mice were subjected to experimental mTBI followed by the systemic administration of the tetrahydrobenzothiazole p53 inactivator, PFT-α, or vehicle. Neuronal loss was quantified immunohistochemically at 72 hr. post-injury by the use of fluoro-Jade B and NeuN within the dentate gyrus on both sides of the brain, and recognition and spatial memory were assessed by novel object recognition and Y-maze paradigms at 7 and 30 days post injury. Systemic administration of a single dose of PFT-α 1 hr. post-injury significantly ameliorated both neuronal cell death and cognitive impairments, which were no different from sham control animals. Cellular studies on human SH-SY5Y cells and rat primary neurons challenged with glutamate excitotoxicity and H2O2 induced oxidative stress, confirmed the ability of PFT-α and a close analog to protect against these TBI associated mechanisms mediating neuronal loss. These studies suggest that p53-dependent apoptotic mechanisms underpin the neuronal and cognitive losses accompanying mTBI, and that these are potentially reversible by p53 inactivation.

Visual cognition in amnesic H.M.: selective deficits on the What's-Wrong-Here and Hidden-Figure tasks.

PubMed

MacKay, Donald G; James, Lori E

2009-10-01

Two experiments compared the visual cognition performance of amnesic H.M. and memory-normal controls matched for age, background, intelligence, and education. In Experiment 1 H.M. exhibited deficits relative to the controls in detecting "erroneous objects" in complex visual scenes--for example, a bird flying inside a fishbowl. In Experiment 2 H.M. exhibited deficits relative to the controls in standard Hidden-Figure tasks when detecting unfamiliar targets but not when detecting familiar targets--for example, circles, squares, and right-angle triangles. H.M.'s visual cognition deficits were not due to his well-known problems in explicit learning and recall, inability to comprehend or remember the instructions, general slowness, motoric difficulties, low motivation, low IQ relative to the controls, or working-memory limitations. Parallels between H.M.'s selective deficits in visual cognition, language, and memory are discussed. These parallels contradict the standard "systems theory" account of H.M.'s condition but comport with the hypothesis that H.M. has difficulty representing unfamiliar but not familiar information in visual cognition, language, and memory. Implications of our results are discussed for binding theory and the ongoing debate over what counts as "memory" versus "not-memory."

Association of Social Frailty With Both Cognitive and Physical Deficits Among Older People.

PubMed

Tsutsumimoto, Kota; Doi, Takehiko; Makizako, Hyuma; Hotta, Ryo; Nakakubo, Sho; Makino, Keitaro; Suzuki, Takao; Shimada, Hiroyuki

2017-07-01

Our objective was to investigate the association between social frailty and cognitive and physical function among older adults. This was a cross-sectional study. We examined community-dwelling adults in Japan. Participants comprised 4425 older Japanese people from the National Center for Geriatrics and Gerontology-Study of Geriatric Syndromes. Social frailty was defined by using responses to 5 questions (going out less frequently, rarely visiting friends, feeling unhelpful to friends or family, living alone, and not talking with someone every day). Participants showing none of these components were considered nonfrail; those showing 1 component were considered prefrail; and those showing 2 or more components were considered frail. To screen for cognitive deficits, we assessed memory, attention, executive function, and processing speed. Having 2 or more tests with age-adjusted scores of at least 1.5 standard deviations below the reference threshold was sufficient to be characterized as cognitively deficient. To screen for physical function deficits, we assessed walking speed (<1.0 m/s cut-off) and grip strength (<26 kg for men; <18 kg for women cut-off). Scoring below the cut-off point on 1 or more tests was sufficient to be characterized as physically deficient. The prevalence of social frailty was the following: nonfrailty, 64.1% (N = 2835); social prefrailty, 24.8% (N = 1097); social frailty, 11.1% (N = 493; P for trend < .001). All cognitive function tests (word list memory, Trail Making Test parts A and B, and the symbol digit-substitution task) significantly varied between social frailty groups; physical function (gait speed and grip strength) also varied between social frailty groups (all Ps for trend <.001). Referred to social nonfrailty, social frailty was independently associated with each cognitive deficit (odds ratio = 1.61, 95% confidence interval 1.13-2.30) and deficits in physical function (odds ratio = 1.99, 95% confidence interval 1

Correlation between insight dimensions and cognitive functions in patients with deficit and nondeficit schizophrenia.

PubMed

Pegoraro, Luiz F L; Dantas, Clarissa R; Banzato, Claudio E M; Fuentes, Daniel

2013-06-01

Previous studies have shown correlations between poor insight and neurocognitive impairment in schizophrenia. Deficit schizophrenia has been associated with worse cognitive functioning and poorer insight. This study aimed at investigating the relationship between insight dimensions (measured by Schedule for the Assessment of Insight-Expanded Version and its factors) and specific neurocognitive functions (assessed through a battery of neuropsychological tests) considering separately patients with deficit (n=29) and nondeficit schizophrenia (n=44), categorized according to the Schedule for the Deficit Syndrome. We found that working memory correlated positively and significantly with awareness of mental illness in both groups. In nondeficit group, awareness of mental illness correlated additionally with verbal fluency and attention. If confirmed by further studies, these results may have important consequences, such as the need of tailoring differently cognitive rehabilitation for each group. Copyright © 2013 Elsevier B.V. All rights reserved.

Comparative Study of Different Polar Groups of EPA-Enriched Phospholipids on Ameliorating Memory Loss and Cognitive Deficiency in Aged SAMP8 Mice.

PubMed

Zhou, Miao-Miao; Che, Hong-Xia; Huang, Jia-Qi; Zhang, Tian-Tian; Xu, Jie; Xue, Chang-Hu; Wang, Yu-Ming

2018-04-01

Recent studies have shown that omega-3 PUFAs enriched phospholipids (n-3 PUFA-PLs) have beneficial effects on memory and cognition. However, most reports only attribute the benefit to docosahexaenoic acid (DHA) and pay little attention to eicosapentaenoic acid (EPA). We investigate the effect of EPA-enriched phospholipids on cognitive deficiency in senescence-accelerated prone 8 (SAMP8) mouse. Ten-month-old SAMP8 mice are fed with 2% (w/w) EPA-enriched phosphatidylcholine/phosphatidyl ethanolamine (EPA-PC/PE; EPA:DHA = 46.8:3.01) or 2% EPA-enriched phosphatidylserine (EPA-PS; biosynthesized from EPA-PC/PE) for 8 weeks; we then test the behavioral performances in the Barnes maze test and Morris maze test; the changes of oxidative stress, apoptosis, neurotrophic factors, tau phosphorylation, and Aβ pathology are also measured. The results of behavior tests indicate that both EPA-PC/PE and EPA-PS significantly improve memory and cognitive deficiency. It is found that remarkable amelioration of oxidative stress and apoptosis occurs in both EPA-PC/PE and EPA-PS groups. EPA-PS shows more ameliorative effects than EPA-PC/PE on neurotrophic activity by decreasing hyper-phosphorylation of tau and depressing the generation and accumulation of β-amyloid peptide (Aβ). These data suggest that EPA-PS exhibits better effects than EPA-PC/PE on ameliorating memory and cognitive function, which might be attributed to the phospholipid polar groups. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

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

PubMed Central

Li, Min; Zhang, Ping; Wei, Hai-jun; Li, Man-Hong; Li, Xiang; Gu, Hong-Feng

2017-01-01

Abstract Background: 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. Methods: 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. Results: 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. Conclusion: 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. PMID:27988490

Social cognition deficits and the 'ultra high risk' for psychosis population: a review of literature.

PubMed

Thompson, Andrew D; Bartholomeusz, Cali; Yung, Alison R

2011-08-01

A number of risk factors for developing a psychotic disorder have been investigated in the 'ultra high risk' (UHR) population, including neurocognitive abilities, social functioning and, more recently, social cognition. We aimed to review the literature on social cognition in the UHR population. Literature was restricted to English articles and identified using Pubmed, Medline, PsychINFO and CINAHLplus, as well as the reference lists of published studies and reviews. Search terms included social cognition, theory of mind, emotion recognition, attributional style, social knowledge, social perception, 'at risk mental state', psychosis prodrome 'clinical high risk' and 'ultra high risk'. Inclusion criteria were an outcome measure of a social cognition task and an UHR population defined by a structured validated instrument. Seven original research articles met the inclusion criteria, one of which was a conference abstract. One of the two studies that assessed theory of mind, two of the four studies that assessed emotion recognition and both the two studies that assessed social perception/knowledge found significant deficits in UHR patients. The single study that assessed attributional bias also reported differences in UHR patients compared with healthy controls. There is limited published literature on social cognitive performance in the UHR population. Despite this, deficits in certain social cognitive abilities do appear to be present, but further research with more reliable cross-cultural measures is needed. The characterization of social cognitive deficits in the UHR populations may aid in the identification of potential markers for development of a subsequent psychotic disorder, as well as targets for early intervention. © 2011 Blackwell Publishing Asia Pty Ltd.

Ameliorating mitochondrial dysfunction restores carbon ion-induced cognitive deficits via co-activation of NRF2 and PINK1 signaling pathway.

PubMed

Liu, Yang; Yan, Jiawei; Sun, Cao; Li, Guo; Li, Sirui; Zhang, Luwei; Di, Cuixia; Gan, Lu; Wang, Yupei; Zhou, Rong; Si, Jing; Zhang, Hong

2018-07-01

Carbon ion therapy is a promising modality in radiotherapy to treat tumors, however, a potential risk of induction of late normal tissue damage should still be investigated and protected. The aim of the present study was to explore the long-term cognitive deficits provoked by a high-linear energy transfer (high-LET) carbon ions in mice by targeting to hippocampus which plays a crucial role in memory and learning. Our data showed that, one month after 4 Gy carbon ion exposure, carbon ion irradiation conspicuously resulted in the impaired cognitive performance, neurodegeneration and neuronal cell death, as well as the reduced mitochondrial integrity, the disrupted activities of tricarboxylic acid cycle flux and electron transport chain, and the depressed antioxidant defense system, consequently leading to a decline of ATP production and persistent oxidative damage in the hippocampus region. Mechanistically, we demonstrated the disruptions of mitochondrial homeostasis and redox balance typically characterized by the disordered mitochondrial dynamics, mitophagy and glutathione redox couple, which is closely associated with the inhibitions of PINK1 and NRF2 signaling pathway as the key regulators of molecular responses in the context of neurotoxicity and neurodegenerative disorders. Most importantly, we found that administration with melatonin as a mitochondria-targeted antioxidant promoted the PINK1 accumulation on the mitochondrial membrane, and augmented the NRF2 accumulation and translocation. Moreover, melatonin pronouncedly enhanced the molecular interplay between NRF2 and PINK1. Furthermore, in the mouse hippocampal neuronal cells, overexpression of NRF2/PINK1 strikingly protected the hippocampal neurons from carbon ion-elicited toxic insults. Thus, these data suggest that alleviation of the sustained mitochondrial dysfunction and oxidative stress through co-modulation of NRF2 and PINK1 may be in charge of restoration of the cognitive impairments in a mouse

Methyl Salicylate Lactoside Protects Neurons Ameliorating Cognitive Disorder Through Inhibiting Amyloid Beta-Induced Neuroinflammatory Response in Alzheimer’s Disease

PubMed Central

Li, Jinze; Ma, Xiaowei; Wang, Yu; Chen, Chengjuan; Hu, Min; Wang, Linlin; Fu, Junmin; Shi, Gaona; Zhang, Dongming; Zhang, Tiantai

2018-01-01

Neuroinflammatory reactions mediated by microglia and astrocytes have been shown to play a key role in early progression of Alzheimer’s disease (AD). Increased evidences have demonstrated that neurons exacerbate local inflammatory reactions by producing inflammatory mediators and act as an important participant in the pathogenesis of AD. Methyl salicylate lactoside (MSL) is an isolated natural product that is part of a class of novel non-steroidal anti-inflammatory drugs (NSAID). In our previous studies, we demonstrated that MSL exhibited therapeutic effects on arthritis-induced mice and suppressed the activation of glial cells. In the current study, we investigated the effects of MSL on cognitive function and neuronal protection induced by amyloid-beta peptides (Aβ) and explored potential underlying mechanisms involved. Amyloid precursor protein (APP) and presenilin 1 (PS1) double transgenic mice were used to evaluate the effects of MSL through behavioral testing and neuronal degenerative changes. In addition, copper-injured APP Swedish mutation overexpressing SH-SY5Y cells were used to determine the transduction of cyclooxygenase (COX) and mitogen-activated protein kinase (MAPK) pathways. Our results indicated that at an early stage, MSL treatment ameliorated cognitive impairment and neurodegeneration in APP/PS1 mice. Moreover, in an in vitro AD model, MSL treatment protected injured cells by increasing cell viability, improving mitochondrial dysfunction, and decreasing oxidative damage. In addition, MSL inhibited the phosphorylated level of c-Jun N-terminal kinase (JNK) and p38 MAPK, and suppressed the expression of COX-1/2. As a novel NSAIDs and used for the treatment in early stage of AD, MSL clearly demonstrated cognitive preservation by protecting neurons via a pleiotropic anti-inflammatory effect in the context of AD-associated deficits. Therefore, early treatment of anti-inflammatory therapy may be an effective strategy for treating AD. PMID:29636677

Resveratrol prevents cognitive deficits induced by chronic unpredictable mild stress: Sirt1/miR-134 signalling pathway regulates CREB/BDNF expression in hippocampus in vivo and in vitro.

PubMed

Shen, Jun; Xu, Linling; Qu, Chujie; Sun, Huimin; Zhang, Junjian

2018-04-30

Chronic unpredictable mild stress (CUMS) leads to neuropsychiatric disorders, such as depression, anxiety and cognitive impairment. Resveratrol is a natural polyphenol existed in polygonum cuspidatum and has been demonstrated to be a potent activator of Sirtuin 1 (Sirt1). Previous studies reported that resveratrol treatment ameliorated CUMS-induced depressive-like behavior and cognitive deficits through upregulating cAMP response element-binding protein (CREB) and brain derived neurotrophic factor (BDNF) expression. However, the upstream signalling pathway mediating CREB/BDNF expression and then exerting a protective role on cognitive function remains unclear. The present study aims to investigate the possible mechanism of resveratrol on CUMS-induced cognitive deficits. Male Sprague Dawley rats were adminstrated resveratrol (40 and 80 mg/kg) every day for 4 consecutive weeks before exposure to CUMS procedure. Morris Water Maze test was used to appraise spatial learing and memory of rats. Sirt1/miR-134 signalling pathway and CREB/BDNF expression in hippocampus of rats were measured. We also explored Sirt1/miR-134 signalling pathway and CREB/BDNF expression in primary cultured hippocampus neurons with resveratrol (25, 50 and 100 μmol/L) treatment. We found that resveratrol treatment prevented spatial learing and memory impairment induced by CUMS. Meanwhile the potential mechanism of resveratrol was associated with increased levels of Sirt1, CREB phosphorylation (p-CREB), CREB, BDNF and decreased levels of miR-134 in vivo and in vitro. In conclusion, our study showed that the neuroprotective effect of resveratrol on CUMS-induced cognitive impairment may rely on activating Sirt1/miR-134 pathway and then upregulating its downstream CREB/BDNF expression in hippocampus. Copyright © 2018 Elsevier B.V. All rights reserved.

Resting fMRI measures are associated with cognitive deficits in schizophrenia assessed by the MATRICS consensus cognitive battery

NASA Astrophysics Data System (ADS)

He, Hao; Bustillo, Juan; Du, Yuhui; Yu, Qingbao; Jones, Thomas R.; Jiang, Tianzi; Calhoun, Vince D.; Sui, Jing

2015-03-01

The cognitive deficits of schizophrenia are largely resistant to current treatment, and are thus a life-long burden to patients. The MATRICS consensus cognitive battery (MCCB) provides a reliable and valid assessment of cognition across a comprehensive set of cognitive domains for schizophrenia. In resting-state fMRI, functional connectivity associated with MCCB has not yet been examined. In this paper, the interrelationships between MCCB and the abnormalities seen in two types of functional measures from resting-state fMRI—fractional amplitude of low frequency fluctuations (fALFF) and functional network connectivity (FNC) maps were investigated in data from 47 schizophrenia patients and 50 age-matched healthy controls. First, the fALFF maps were generated and decomposed by independent component analysis (ICA), and then the component showing the highest correlation with MCCB composite scores was selected. Second, the whole brain was separated into functional networks by group ICA, and the FNC maps were calculated. The FNC strengths with most significant correlations with MCCB were displayed and spatially overlapped with the fALFF component of interest. It demonstrated increased cognitive performance associated with higher fALFF values (intensity of regional spontaneous brain activity) in prefrontal regions, inferior parietal lobe (IPL) but lower ALFF values in thalamus, striatum, and superior temporal gyrus (STG). Interestingly, the FNC showing significant correlations with MCCB were in well agreement with the activated regions with highest z-values in fALFF component. Our results support the view that functional deficits in distributed cortico-striato-thalamic circuits and inferior parietal lobe may account for several aspects of cognitive impairment in schizophrenia.

Ascorbic acid ameliorates behavioural deficits and neuropathological alterations in rat model of Alzheimer's disease.

PubMed

Olajide, Olayemi Joseph; Yawson, Emmanuel Olusola; Gbadamosi, Ismail Temitayo; Arogundade, Tolulope Timothy; Lambe, Ezra; Obasi, Kosisochukwu; Lawal, Ismail Tayo; Ibrahim, Abdulmumin; Ogunrinola, Kehinde Yomi

2017-03-01

Exploring the links between neural pathobiology and behavioural deficits in Alzheimer's disease (AD), and investigating substances with known therapeutic advantages over subcellular mechanisms underlying these dysfunctions could advance the development of potent therapeutic molecules for AD treatment. Here we investigated the efficacy of ascorbic acid (AA) in reversing aluminium chloride (AlCl 3 )-induced behavioural deficits and neurotoxic cascades within prefrontal cortex (PFC) and hippocampus of rats. A group of rats administered oral AlCl 3 (100mg/kg) daily for 15days showed degenerative changes characterised by significant weight loss, reduced exploratory/working memory, frontal-dependent motor deficits, cognitive decline, memory dysfunction and anxiety during behavioural assessments compared to control. Subsequent analysis showed that oxidative impairment-indicated by depleted superoxide dismutase and lipid peroxidation (related to glutathione-S-transferase activity), cholinergic deficits seen by increased neural acetylcholinesterase (AChE) expression and elevated lactate dehydrogenase underlie behavioural alterations. Furthermore, evidences of proteolysis were seen by reduced Nissl profiles in neuronal axons and dendrites which correspond to apoptotic changes observed in H&E staining of PFC and hippocampal sections. Interestingly, AA (100mg/kg daily for 15days) significantly attenuated behavioural deficits in rats through inhibition of molecular and cellular stressor proteins activated by AlCl 3. Our results showed that the primary mechanisms underlying AA therapeutic advantages relates closely with its abilities to scavenge free radicals, prevent membrane lipid peroxidation, modulate neuronal bioenergetics, act as AChE inhibitor and through its anti-proteolytic properties. These findings suggest that supplementing endogenous AA capacity through its pharmacological intake may inhibit progression of AD-related neurodegenerative processes and behavioural

Shedding light on the association between repetitive negative thinking and deficits in cognitive control - A meta-analysis.

PubMed

Zetsche, Ulrike; Bürkner, Paul-Christian; Schulze, Lars

2018-06-11

Individuals who experience recurrent negative thoughts are at elevated risk for mood and anxiety disorders. It is thus essential to understand why some individuals get stuck in recurrent negative thinking (RNT), whereas others are able to disengage eventually. Theoretical models propose that individuals high in recurrent negative thinking suffer from deficits in controlling the contents of working memory. Empirical findings, however, are inconclusive. In this meta-analysis, we synthesize findings from 94 studies to examine the proposed association between RNT and deficits in cognitive control. We included numerous effect sizes not reported in the primary publications. Moderator analyses tested the influence of variables, such as stimuli valence, cognitive control function (e.g., shifting, discarding), or type of RNT (i.e., rumination or worry). Results demonstrated an association between repetitive negative thinking and deficits in only one specific cognitive control function, namely difficulty discarding no longer relevant material from working memory (r = -0.20). This association remained significant after controlling for level of psychopathology. There was no substantial association between RNT and deficits in any other cognitive control function. All other moderators were not significant. We discuss limitations (e.g., primary sample sizes, reliability of paradigms) and highlight implications for future research and clinical interventions. Copyright © 2018 Elsevier Ltd. All rights reserved.

How culture shapes social cognition deficits in mental disorders: A review.

PubMed

Koelkebeck, Katja; Uwatoko, Teruhisa; Tanaka, Jiro; Kret, Mariska Esther

2017-04-01

Social cognitive skills are indispensable for successful communication with others. Substantial research has determined deficits in these abilities in patients with mental disorders. In neurobiological development and continuing into adulthood, cross-cultural differences in social cognition have been demonstrated. Moreover, symptomatic patterns in mental disorders may vary according to the cultural background of an individual. Cross-cultural studies can thus help in understanding underlying (biological) mechanisms and factors that influence behavior in health and disease. In addition, studies that apply novel paradigms assessing the impact of culture on cognition may benefit and advance neuroscience research. In this review, the authors give an overview of cross-cultural research in the field of social cognition in health and in mental disorders and provide an outlook on future research directions, taking a neuroscience perspective.

How to Cheat and Not Feel Guilty: Cognitive Dissonance and Its Amelioration in the Domain of Academic Dishonesty

ERIC Educational Resources Information Center

Stephens, Jason M.

2017-01-01

The belief that cheating is wrong doesn't prevent its enactment. For example, many students cheat despite believing that is wrong or unjustifiable. The question taken up in this article concerns how the resulting cognitive dissonance is ameliorated; that is, how do students cheat and not feel guilty? This article will describe two "good"…

Treadmill Exercise Ameliorates Spatial Learning and Memory Deficits Through Improving the Clearance of Peripheral and Central Amyloid-Beta Levels.

PubMed

Khodadadi, Davar; Gharakhanlou, Reza; Naghdi, Naser; Salimi, Mona; Azimi, Mohammad; Shahed, Atabak; Heysieattalab, Soomaayeh

2018-06-11

Aggregated amyloid beta (Aβ) peptides are believed to play a decisive role in the pathology of Alzheimer's disease (AD). Previous evidence suggested that exercise contributes to the improvement of cognitive decline and slows down pathogenesis of AD; however, the exact mechanisms for this have not been fully understood. Here, we evaluated the effect of a 4-week moderate treadmill exercise on spatial memory via central and peripheral Aβ clearance mechanisms following developed AD-like neuropathology induced by intra-hippocampal Aβ 1-42 injection in male Wistar rats. We found Aβ 1-42 -treated animals showed spatial learning and memory impairment which was accompanied by increased levels of amyloid plaque load and soluble Aβ 1-42 (sAβ 1-42 ), decreased mRNA and protein expression of neprilysin (NEP), insulin degrading enzyme (IDE) and low-density lipoprotein receptor-related protein-1 (LRP-1) in the hippocampus. Aβ 1-42 -treated animals also exhibited a higher level of sAβ 1-42 and a lower level of soluble LRP-1 (sLRP-1) in plasma, as well as a decreased level of LRP-1 mRNA and protein content in the liver. However, exercise training improved the spatial learning and memory deficits, reduced both plaque load and sAβ 1-42 levels, and up-regulated expression of NEP, IDE, and LRP-1 in the hippocampus of Aβ 1-42 -treated animals. Aβ 1-42 -treated animals subjected to treadmill exercise also revealed decreased levels of sAβ 1-42 and increased levels of sLRP-1 in plasma, as well as increased levels of LRP-1 mRNA and protein in the liver. In conclusion, our findings suggest that exercise-induced improvement in both of central and peripheral Aβ clearance are likely involved in ameliorating spatial learning and memory deficits in an animal model of AD. Future studies need to determine their relative contribution.

Exercise ameliorates neurocognitive impairments in a translational model of pediatric radiotherapy.

PubMed

Sahnoune, Iman; Inoue, Taeko; Kesler, Shelli R; Rodgers, Shaefali P; Sabek, Omaima M; Pedersen, Steen E; Zawaski, Janice A; Nelson, Katharine H; Ris, M Douglas; Leasure, J Leigh; Gaber, M Waleed

2018-04-09

While cranial radiation therapy (CRT) is an effective treatment, healthy areas surrounding irradiation sites are negatively affected. Frontal lobe functions involving attention, processing speed, and inhibition control are impaired. These deficits appear months to years after CRT and impair quality of life. Exercise has been shown to rejuvenate the brain and aid in recovery post-injury through its effects on neurogenesis and cognition. We developed a juvenile rodent CRT model that reproduces neurocognitive deficits. Next, we utilized the model to test whether exercise ameliorates these deficits. Fischer rats (31 days old) were irradiated with a fractionated dose of 4 Gy × 5 days, trained and tested at 6, 9, and 12 months post-CRT using 5-choice serial reaction time task. After testing, fixed rat brains were imaged using diffusion tensor imaging and immunohistochemistry. CRT caused early and lasting impairments in task acquisition, accuracy, and latency to correct response, as well as causing stunting of growth and changes in brain volume and diffusion. Exercising after irradiation improved acquisition, behavioral control, and processing speed, mitigated the stunting of brain size, and increased brain fiber numbers compared with sedentary CRT values. Further, exercise partially restored global connectome organization, including assortativity and characteristic path length, and while it did not improve the specific regional connections that were lowered by CRT, it appeared to remodel these connections by increasing connectivity between alternate regional pairs. Our data strongly suggest that exercise may be useful in combination with interventions aimed at improving cognitive outcome following pediatric CRT.

Cognitive remediation therapy (CRT) benefits more to patients with schizophrenia with low initial memory performances.

PubMed

Pillet, Benoit; Morvan, Yannick; Todd, Aurelia; Franck, Nicolas; Duboc, Chloé; Grosz, Aimé; Launay, Corinne; Demily, Caroline; Gaillard, Raphaël; Krebs, Marie-Odile; Amado, Isabelle

2015-01-01

Cognitive deficits in schizophrenia mainly affect memory, attention and executive functions. Cognitive remediation is a technique derived from neuropsychology, which aims to improve or compensate for these deficits. Working memory, verbal learning, and executive functions are crucial factors for functional outcome. Our purpose was to assess the impact of the cognitive remediation therapy (CRT) program on cognitive difficulties in patients with schizophrenia, especially on working memory, verbal memory, and cognitive flexibility. We collected data from clinical and neuropsychological assessments in 24 patients suffering from schizophrenia (Diagnostic and Statistical Manual of mental Disorders-Fourth Edition, DSM-IV) who followed a 3-month (CRT) program. Verbal and visuo-spatial working memory, verbal memory, and cognitive flexibility were assessed before and after CRT. The Wilcoxon test showed significant improvements on the backward digit span, on the visual working memory span, on verbal memory and on flexibility. Cognitive improvement was substantial when baseline performance was low, independently from clinical benefit. CRT is effective on crucial cognitive domains and provides a huge benefit for patients having low baseline performance. Such cognitive amelioration appears highly promising for improving the outcome in cognitively impaired patients.

Insulin signaling misregulation underlies circadian and cognitive deficits in a Drosophila fragile X model.

PubMed

Monyak, R E; Emerson, D; Schoenfeld, B P; Zheng, X; Chambers, D B; Rosenfelt, C; Langer, S; Hinchey, P; Choi, C H; McDonald, T V; Bolduc, F V; Sehgal, A; McBride, S M J; Jongens, T A

2017-08-01

Fragile X syndrome (FXS) is an undertreated neurodevelopmental disorder characterized by low intelligence quotent and a wide range of other symptoms including disordered sleep and autism. Although FXS is the most prevalent inherited cause of intellectual disability, its mechanistic underpinnings are not well understood. Using Drosophila as a model of FXS, we showed that select expression of dfmr1 in the insulin-producing cells (IPCs) of the brain was sufficient to restore normal circadian behavior and to rescue the memory deficits in the fragile X mutant fly. Examination of the insulin signaling (IS) pathway revealed elevated levels of Drosophila insulin-like peptide 2 (Dilp2) in the IPCs and elevated IS in the dfmr1 mutant brain. Consistent with a causal role for elevated IS in dfmr1 mutant phenotypes, the expression of dfmr1 specifically in the IPCs reduced IS, and genetic reduction of the insulin pathway also led to amelioration of circadian and memory defects. Furthermore, we showed that treatment with the FDA-approved drug metformin also rescued memory. Finally, we showed that reduction of IS is required at different time points to rescue circadian behavior and memory. Our results indicate that insulin misregulation underlies the circadian and cognitive phenotypes displayed by the Drosophila fragile X model, and thus reveal a metabolic pathway that can be targeted by new and already approved drugs to treat fragile X patients.

Is a picture worth a thousand (forgotten) words?: neuroimaging evidence for the cognitive deficits in 'chemo-fog'/'chemo-brain'.

PubMed

Raffa, R B

2010-02-01

The diminution in cognitive function reported to occur in patients treated with adjuvant cancer chemotherapy (a phenomenon known as 'chemo-fog, 'chemo-brain' or similar designation) is supported with varying degrees of evidence by prospective and retrospective clinical studies. However, the cognitive deficits are often subtle and the methodologies used to measure them not consistent. Additionally, patients might be able to compensate for the deficits, thereby leading to underestimates of the problem by this type of assessment. For these reasons, direct neuroimaging techniques might provide additional insight. The relatively few such studies, and fewer electrophysiological studies, offer an alternative way to evaluate changes that might be related to cognitive deficits in patients treated with cancer chemotherapeutic regimens.

Dopaminergic basis for deficits in working memory but not attentional set-shifting in Parkinson's disease.

PubMed

Lewis, Simon J G; Slabosz, Aleksandra; Robbins, Trevor W; Barker, Roger A; Owen, Adrian M

2005-01-01

Although Parkinson's disease is a common neurodegenerative disorder characterised by its motoric symptoms, there is an increasing recognition of accompanying impairments in cognition that have a profound impact on the quality of life of these patients. These deficits predominantly affect executive function and impairments of working memory have been frequently reported. However, the underlying neurochemical and pathological basis for these deficits are not well understood. In this study, 20 patients were tested 'on' and 'off' levodopa (L-dopa) medication on a task that allowed different aspects of working memory function such as maintenance, retrieval and manipulation to be tested within the same general paradigm as well as on an unrelated test of attentional set-shifting, which is known to be sensitive to deficits in early Parkinson's disease. Compared to healthy volunteers, PD patients were impaired at manipulation more than maintenance or retrieval of information within working memory. The patients were also impaired at the attentional set-shifting task. However, whereas L-dopa ameliorated the working memory deficit in manipulation (improving both accuracy and cognitive response time), it had no effect on the attentional set-shifting impairment. These results confirm that working memory deficits in PD are both psychologically specific and related to dopamine depletion. It is anticipated that greater understanding of these mechanisms will lead to future therapeutic improvements.

Abnormal frontal theta oscillations underlie the cognitive flexibility deficits in children with high-functioning autism spectrum disorders.

PubMed

Yeung, Michael K; Han, Yvonne M Y; Sze, Sophia L; Chan, Agnes S

2016-03-01

Deficits in cognitive flexibility have been suggested to underlie the repetitive and stereotyped behavior in individuals with autism spectrum disorders (ASD). Because cognitive flexibility is primarily mediated by the frontal lobe, where structural and functional abnormalities have been extensively found in these individuals, it is conceivable that their deficits in cognitive flexibility are related to abnormal activations of the frontal lobe. The present study investigates cognitive flexibility and its underlying neurophysiological activities as indicated by theta oscillations in children with ASD. Twenty-five children with high-functioning ASD and 25 IQ- and age-matched typically developing (TD) children were subjected to neuropsychological assessments on cognitive flexibility and electroencephalography recordings. The children with ASD performed significantly worse than the TD children across the tasks of cognitive flexibility, including the modified Wisconsin Card Sorting Test (WCST). These children also demonstrated a reduced increase of the theta power localized in multiple brain regions, including various sectors of the frontal lobe at the late stage (i.e., 600 ms-900 ms poststimulus interval) but not the early stage (i.e., 250 ms-550 ms poststimulus interval) of the performance of the modified WCST. The suppressed late frontal theta activities were further shown to be significantly correlated with a poorer performance on the cognitive flexibility measures. Our findings suggest that abnormal activations of multiple cortical regions, especially the frontal lobe, form the neural basis of the cognitive flexibility deficits in children with ASD. In addition, we found an EEG marker of cognitive flexibility which could be used to monitor treatment outcomes objectively. (c) 2016 APA, all rights reserved).

Decreasing self-reported cognitive biases and increasing clinical insight through meta-cognitive training in patients with chronic schizophrenia.

PubMed

Gawęda, Łukasz; Krężołek, Martyna; Olbryś, Joanna; Turska, Agnieszka; Kokoszka, Andrzej

2015-09-01

The aim of this study was to assess the impact of meta-cognitive training (MCT) on cognitive biases, symptoms, clinical insight, and general functioning among low-level functioning persons diagnosed with chronic schizophrenia who were attending a daily Community Social Support Group Program; we compared the treatment-as-usual (TAU) condition with the MCT + TAU condition. Forty-four patients diagnosed with chronic schizophrenia were allocated to either the MCT + treatment-as-usual condition or the treatment-as-usual (TAU) condition. Delusion and hallucination severity, cognitive biases, clinical insight, and global functioning were assessed pre- and post-treatment (clinical trial NCT02187692). No significant changes were found in symptom severity as measured with the PSYRATS. Conversely, a medium to large effect size was observed for delusional ideation changes when assessed by the self-report measure (Paranoia Checklist). MCT was found to ameliorate cognitive biases as measured by the self-report scale at large effect size, however, no changes in jumping to conclusions (the Fish Task) and theory of mind deficits ("Reading the Mind in the Eyes" Test) were found in the behavioral tasks. MCT increased insight at large effect size. No changes in global functioning were found between the two conditions. Low intensity intervention. No follow-up assessment was provided. Only PSYRATS was assessed blind to patient allocation. MCT has a beneficial effect on low-functioning chronic schizophrenic patients in ameliorating cognitive biases and increasing clinical insight. Copyright © 2015 Elsevier Ltd. All rights reserved.

Motivational deficits and cognitive test performance in schizophrenia.

PubMed

Fervaha, Gagan; Zakzanis, Konstantine K; Foussias, George; Graff-Guerrero, Ariel; Agid, Ofer; Remington, Gary

2014-09-01

Motivational and cognitive deficits are core features of schizophrenia, both closely linked with functional outcomes. Although poor effort and decreased motivation are known to affect performance on cognitive tests, the extent of this relationship is unclear in patients with schizophrenia. To evaluate the association between intrinsic motivation and cognitive test performance in patients with schizophrenia. Cross-sectional and 6-month prospective follow-up study performed at 57 sites in the United States, including academic and community medical treatment centers, participating in the Clinical Antipsychotic Trials of Intervention Effectiveness study. The primary sample included 431 stable patients with a DSM-IV diagnosis of schizophrenia currently receiving a stable medication regimen. Cognitive performance and intrinsic motivation were evaluated using a comprehensive neuropsychological test battery and a derived measure from the Heinrichs-Carpenter Quality of Life Scale, respectively. Symptom severity and functional status were also assessed. The primary outcome variable was global neurocognition. Individual domains of cognition were also evaluated for their association with motivation. Level of intrinsic motivation was significantly and positively correlated with global cognitive test performance, a relationship that held for each domain of cognition evaluated (correlation range, 0.20-0.34; P < .001). This association was found to be reliable after statistically accounting for positive, negative, depressive, and overall symptom severity (P < .05) and after accounting for community functioning (P < .001). The relationship between motivation and cognitive performance also remained significant after controlling for antipsychotic dose (P < .05). Prospective increase in motivation during the 6-month follow-up was also found to be significantly related to improvement in global cognitive performance (P < .05). The present findings provide strong

Tauopathy contributes to synaptic and cognitive deficits in a murine model for Alzheimer's disease.

PubMed

Stancu, Ilie-Cosmin; Ris, Laurence; Vasconcelos, Bruno; Marinangeli, Claudia; Goeminne, Léonie; Laporte, Vincent; Haylani, Laetitia E; Couturier, Julien; Schakman, Olivier; Gailly, Philippe; Pierrot, Nathalie; Kienlen-Campard, Pascal; Octave, Jean-Noël; Dewachter, Ilse

2014-06-01

Tau alterations are now considered an executor of neuronal demise and cognitive dysfunction in Alzheimer's disease (AD). Mouse models combining amyloidosis and tauopathy and their parental counterparts are important tools to further investigate the interplay of abnormal amyloid-β (Aβ) and Tau species in pathogenesis, synaptic and neuronal dysfunction, and cognitive decline. Here, we crossed APP/PS1 mice with 5 early-onset familial AD mutations (5xFAD) and TauP301S (PS19) transgenic mice, denoted F(+)/T(+) mice, and phenotypically compared them to their respective parental strains, denoted F(+)/T(-) and F(-)/T(+) respectively, as controls. We found dramatically aggravated tauopathy (~10-fold) in F(+)/T(+) mice compared to the parental F(-)/T(+) mice. In contrast, amyloidosis was unaltered compared to the parental F(+)/T(-) mice. Tauopathy was invariably and very robustly aggravated in hippocampal and cortical brain regions. Most important, F(+)/T(+) displayed aggravated cognitive deficits in a hippocampus-dependent spatial navigation task, compared to the parental F(+)/T(-) strain, while parental F(-)/T(+) mice did not display cognitive impairment. Basal synaptic transmission was impaired in F(+)/T(+) mice compared to nontransgenic mice and the parental strains (≥40%). Finally, F(+)/T(+) mice displayed a significant hippocampal atrophy (~20%) compared to nontransgenic mice, in contrast to the parental strains. Our data indicate for the first time that pathological Aβ species (or APP/PS1) induced changes in Tau contribute to cognitive deficits correlating with synaptic deficits and hippocampal atrophy in an AD model. Our data lend support to the amyloid cascade hypothesis with a role of pathological Aβ species as initiator and pathological Tau species as executor. © FASEB.

Pharmacological and genetic reversal of age-dependent cognitive deficits attributable to decreased presenilin function.

PubMed

McBride, Sean M J; Choi, Catherine H; Schoenfeld, Brian P; Bell, Aaron J; Liebelt, David A; Ferreiro, David; Choi, Richard J; Hinchey, Paul; Kollaros, Maria; Terlizzi, Allison M; Ferrick, Neal J; Koenigsberg, Eric; Rudominer, Rebecca L; Sumida, Ai; Chiorean, Stephanie; Siwicki, Kathleen K; Nguyen, Hanh T; Fortini, Mark E; McDonald, Thomas V; Jongens, Thomas A

2010-07-14

Alzheimer's disease (AD) is the leading cause of cognitive loss and neurodegeneration in the developed world. Although its genetic and environmental causes are not generally known, familial forms of the disease (FAD) are attributable to mutations in a single copy of the Presenilin (PS) and amyloid precursor protein genes. The dominant inheritance pattern of FAD indicates that it may be attributable to gain or change of function mutations. Studies of FAD-linked forms of presenilin (psn) in model organisms, however, indicate that they are loss of function, leading to the possibility that a reduction in PS activity might contribute to FAD and that proper psn levels are important for maintaining normal cognition throughout life. To explore this issue further, we have tested the effect of reducing psn activity during aging in Drosophila melanogaster males. We have found that flies in which the dosage of psn function is reduced by 50% display age-onset impairments in learning and memory. Treatment with metabotropic glutamate receptor (mGluR) antagonists or lithium during the aging process prevented the onset of these deficits, and treatment of aged flies reversed the age-dependent deficits. Genetic reduction of Drosophila metabotropic glutamate receptor (DmGluRA), the inositol trisphosphate receptor (InsP(3)R), or inositol polyphosphate 1-phosphatase also prevented these age-onset cognitive deficits. These findings suggest that reduced psn activity may contribute to the age-onset cognitive loss observed with FAD. They also indicate that enhanced mGluR signaling and calcium release regulated by InsP(3)R as underlying causes of the age-dependent cognitive phenotypes observed when psn activity is reduced.

Impact of statins on cognitive deficits in adult male rodents after traumatic brain injury: a systematic review.

PubMed

Peng, Weijun; Yang, Jingjing; Yang, Bo; Wang, Lexing; Xiong, Xin-gui; Liang, Qinghua

2014-01-01

The efficacy of statin treatment on cognitive decline is controversial, and the effect of statins on cognitive deficits in individuals with traumatic brain injury (TBI) has yet to be investigated. Therefore, we systematically reviewed the effect of statins on cognitive deficits in adult male rodents after TBI. After identifying eligible studies by searching four electronic databases on February 28, 2014, we assessed study quality, evaluated the efficacy of statin treatment, and performed stratified metaregression and metaregression to assess the influence of study design on statin efficacy. Eleven studies fulfilled our inclusion criteria from a total of 183 publications. The overall methodological quality of these studies was poor. Meta-analysis showed that statins exert statistically significant positive effects on cognitive performance after TBI. Stratified analysis showed that atorvastatin has the greatest effect on acquisition memory, simvastatin has the greatest effect on retention memory, and statin effects on acquisition memory are higher in closed head injury models. Metaregression analysis further showed that that animal species, study quality, and anesthetic agent impact statin effects on retention memory. We conclude that statins might reduce cognitive deficits after TBI. However, additional well-designed and well-reported animal studies are needed to inform further clinical study.

Cognitive deficits and educational loss in children with schistosome infection—A systematic review and meta-analysis

PubMed Central

Bustinduy, Amaya L.; Nkwata, Allan K.; Martinez, Leonardo; Pabalan, Noel; Boivin, Michael J.; King, Charles H.

2018-01-01

Background By means of meta-analysis of information from all relevant epidemiologic studies, we examined the hypothesis that Schistosoma infection in school-aged children (SAC) is associated with educational loss and cognitive deficits. Methodology/Principal findings This review was prospectively registered in the PROSPERO database (CRD42016040052). Medline, Biosis, and Web of Science were searched for studies published before August 2016 that evaluated associations between Schistosoma infection and cognitive or educational outcomes. Cognitive function was defined in four domains—learning, memory, reaction time, and innate intelligence. Educational outcome measures were defined as attendance and scholastic achievement. Risk of bias (ROB) was evaluated using the Newcastle-Ottawa quality assessment scale. Standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated to compare cognitive and educational measures for Schistosoma infected /not dewormed vs. uninfected/dewormed children. Sensitivity analyses by study design, ROB, and sequential exclusion of individual studies were implemented. Thirty studies from 14 countries, including 38,992 SAC between 5–19 years old, were identified. Compared to uninfected children and children dewormed with praziquantel, the presence of Schistosoma infection and/or non-dewormed status was associated with deficits in school attendance (SMD = -0.36, 95%CI: -0.60, -0.12), scholastic achievement (SMD = -0.58, 95%CI: -0.96, -0.20), learning (SMD = -0.39, 95%CI: -0.70, -0.09) and memory (SMD = -0.28, 95%CI: -0.52, -0.04) tests. By contrast, Schistosoma-infected/non-dewormed and uninfected/dewormed children were similar with respect to performance in tests of reaction time (SMD = -0.06, 95%CI: -0.42, 0.30) and intelligence (SMD = -0.25, 95%CI: -0.57, 0.06). Schistosoma infection-associated deficits in educational measures were robust among observational studies, but not among interventional studies. The

Cognitive deficits and educational loss in children with schistosome infection-A systematic review and meta-analysis.

PubMed

Ezeamama, Amara E; Bustinduy, Amaya L; Nkwata, Allan K; Martinez, Leonardo; Pabalan, Noel; Boivin, Michael J; King, Charles H

2018-01-01

By means of meta-analysis of information from all relevant epidemiologic studies, we examined the hypothesis that Schistosoma infection in school-aged children (SAC) is associated with educational loss and cognitive deficits. This review was prospectively registered in the PROSPERO database (CRD42016040052). Medline, Biosis, and Web of Science were searched for studies published before August 2016 that evaluated associations between Schistosoma infection and cognitive or educational outcomes. Cognitive function was defined in four domains-learning, memory, reaction time, and innate intelligence. Educational outcome measures were defined as attendance and scholastic achievement. Risk of bias (ROB) was evaluated using the Newcastle-Ottawa quality assessment scale. Standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated to compare cognitive and educational measures for Schistosoma infected /not dewormed vs. uninfected/dewormed children. Sensitivity analyses by study design, ROB, and sequential exclusion of individual studies were implemented. Thirty studies from 14 countries, including 38,992 SAC between 5-19 years old, were identified. Compared to uninfected children and children dewormed with praziquantel, the presence of Schistosoma infection and/or non-dewormed status was associated with deficits in school attendance (SMD = -0.36, 95%CI: -0.60, -0.12), scholastic achievement (SMD = -0.58, 95%CI: -0.96, -0.20), learning (SMD = -0.39, 95%CI: -0.70, -0.09) and memory (SMD = -0.28, 95%CI: -0.52, -0.04) tests. By contrast, Schistosoma-infected/non-dewormed and uninfected/dewormed children were similar with respect to performance in tests of reaction time (SMD = -0.06, 95%CI: -0.42, 0.30) and intelligence (SMD = -0.25, 95%CI: -0.57, 0.06). Schistosoma infection-associated deficits in educational measures were robust among observational studies, but not among interventional studies. The significance of infection-associated deficits in

Cognitive deficit in methamphetamine users relative to childhood academic performance: link to cortical thickness.

PubMed

Dean, Andy C; Morales, Angelica M; Hellemann, Gerhard; London, Edythe D

2018-04-20

Individuals with cognitive problems may be predisposed to develop substance use disorders; therefore, differences in cognitive function between methamphetamine users and control participants may be attributable to premorbid factors rather than methamphetamine use. The goal of this study was to clarify the extent to which this is the case. Childhood academic transcripts were obtained for 37 methamphetamine-dependent adults and 41 control participants of similar educational level and premorbid IQ. Each participant completed a comprehensive cognitive battery and received a structural magnetic resonance imaging scan. Data from control participants and linear regression were used to develop a normative model to describe the relationship between childhood academic performance and scores on the cognitive battery. Using this model, cognitive performance of methamphetamine users was predicted from their premorbid academic scores. Results indicated that methamphetamine users' childhood grade point average was significantly lower than that of the control group (p < 0.05). Further, methamphetamine users' overall cognitive performance was lower than was predicted from their grade point average prior to methamphetamine use (p = 0.001), with specific deficits in attention/concentration and memory (ps < 0.01). Memory deficits were associated with lower whole-brain cortical thickness (p < 0.05). Thus, in addition to having an apparent premorbid weakness in cognition, methamphetamine users exhibit subsequent cognitive function that is significantly lower than premorbid estimates would predict. The results support the view that chronic methamphetamine use causes a decline in cognition and/or a failure to develop normative cognitive abilities, although aside from methamphetamine use per se, other drug use and unidentified factors likely contribute to the observed effects.

Biochanin-A ameliorates behavioural and neurochemical derangements in cognitive-deficit mice for the betterment of Alzheimer's disease.

PubMed

Biradar, S M; Joshi, H; Chheda, T K

2014-04-01

Biochanin-A (BCA), a potent phytoconstituent, has been previously used as an antitumour, a dopaminergic neuron protective agent, an antioxidant, an anticholinergic and on other pharmacological activities including neuroprotection. The present study was aimed to evaluate the behavioural and neurochemical evidence of BCA in cognitive-deficit mice in scopolamine challenged and natural aged-induced amnesia models in young and aged mice, respectively. BCA has exhibited decrease in the transfer latency and increase in step through latency significantly (p < 0.001) in scopolamine-treated and natural aged mice of exteroceptive behavioural models such as elevated plus maze and passive shock avoidance paradigm, respectively. A decrease in acetylcholinesterase activity of whole brain was seen in scopolamine and aged mice with standard piracetam (Pira; p < 0.001) and BCA in dose-dependent manner. The antioxidant property of BCA was proven by increase in GSH (p < 0.01) and decrease in thiobarbituric acid reactive substances level significantly in a scopolamine-challenged and aged mice. The scopolamine-treated mice exhibited significant (p < 0.01) increase in the content of noradrenalin and dopamine, which is a sign of dementia, and these excess increased neurotransmitters were reversed by BCA 40 mg kg(-1) (p < 0.05), BCA 20 mg kg(-1) (p > 0.05), BCA 10 mg kg(-1) (p < 0.05) and standard Pira (p < 0.05) when compared with scopolamine group. Furthermore, in histopathology of hippocampus, the Pira and BCA-treated mice were protected from the formation of pyknotic neurons, increases in the viable cells count and decreases in the number of degenerative cells compared with the scopolamine group. Hence, BCA could be potential enough for the betterment of Alzheimer's disease.

The allusive cognitive deficit in paranoia: the case for mental time travel or cognitive self-projection.

PubMed

Corcoran, R

2010-08-01

Delusional beliefs are characteristic of psychosis and, of the delusions, the paranoid delusion is the single most common type associated with psychosis. The many years of research focused on neurocognition in schizophrenia, using standardized neurocognitive tests, have failed to find conclusive cognitive deficits in relation to positive symptoms. However, UK-based psychological research has identified sociocognitive anomalies in relation to paranoid thinking in the form of theory of mind (ToM), causal reasoning and threat-related processing anomalies. Drawing from recent neuroscientific research on the default mode network, this paper asserts that the common theme running through the psychological tests that are sensitive to the cognitive impairment of paranoia is the need to cognitively project the self through time, referred to as mental time travel. Such an understanding of the cognitive roots of paranoid ideation provides a synthesis between psychological and biological accounts of psychosis while also retaining the powerful argument that understanding abnormal thinking must start with models of normal cognition. This is the core theme running through the cognitive psychological literature of psychiatric disorders that enables research from this area to inform psychological therapy.

Motivational deficits after brain injury: effects of bromocriptine in 11 patients.

PubMed Central

Powell, J H; al-Adawi, S; Morgan, J; Greenwood, R J

1996-01-01

OBJECTIVE: To test the hypothesis that treatment with bromocriptine would ameliorate deficits in clinical motivation, responsiveness to reward, and frontal cognitive function after brain injury. METHOD: An open trial in six men and five women who had had either traumatic brain injury or subarachnoid haemorrhage between two months and five years previously. After repeated baseline assessments, bromocriptine was given in gradually increasing doses. Assessments were repeated at increasing doses, during maintenance, and after withdrawal. Novel structured instruments for quantifying motivation were developed; measures of anxiety and depression, and cognitive tests sensitive to motivation or frontal lobe involvement were also given. RESULTS: Bromocriptine treatment was followed by improved scores on all measures other than mood. Improvement was maintained after bromocriptine withdrawal in eight of the patients. CONCLUSION: Poor motivation in patients with brain injury may result from dysfunction in the mesolimbic/mesocortical dopaminergic circuitry, giving rise to associated deficiencies in reward responsiveness and frontal cognitive function. PMID:8774407

Multifamily group psychoeducation and cognitive remediation for first-episode psychosis: a randomized controlled trial.

PubMed

Breitborde, Nicholas Jk; Moreno, Francisco A; Mai-Dixon, Natalie; Peterson, Rachele; Durst, Linda; Bernstein, Beth; Byreddy, Seenaiah; McFarlane, William R

2011-01-12

Multifamily group psychoeducation (MFG) has been shown to reduce relapse rates among individuals with first-episode psychosis. However, given the cognitive demands associated with participating in this intervention (e.g., learning and applying a structured problem-solving activity), the cognitive deficits that accompany psychotic disorders may limit the ability of certain individuals to benefit from this intervention. Thus, the goal of this study is to examine whether individuals with first-episode psychosis who participate simultaneously in MFG and cognitive remediation--an intervention shown to improve cognitive functioning among individuals with psychotic disorders--will be less likely to experience a relapse than individuals who participate in MFG alone. Forty individuals with first-episode psychosis and their caregiving relative will be recruited to participate in this study. Individuals with first-episode psychosis will be randomized to one of two conditions: (i) MFG with concurrent participation in cognitive remediation or (ii) MFG alone. The primary outcome for this study is relapse of psychotic symptoms. We will also examine secondary outcomes among both individuals with first-episode psychosis (i.e., social and vocational functioning, health-related quality of life, service utilization, independent living status, and cognitive functioning) and their caregiving relatives (i.e., caregiver burden, anxiety, and depression) Cognitive remediation offers the possibility of ameliorating a specific deficit (i.e., deficits in cognitive functioning) that often accompanies psychotic symptoms and may restrict the magnitude of the clinical benefits derived from MFG. ClinicalTrials (NCT): NCT01196286.

The effects of sigma (σ1) receptor-selective ligands on muscarinic receptor antagonist-induced cognitive deficits in mice

PubMed Central

Malik, Maninder; Rangel-Barajas, Claudia; Sumien, Nathalie; Su, Chang; Singh, Meharvan; Chen, Zhenglan; Huang, Ren-Qi; Meunier, Johann; Maurice, Tangui; Mach, Robert H; Luedtke, Robert R

2015-01-01

Background and Purpose Cognitive deficits in patients with Alzheimer's disease, Parkinson's disease, traumatic brain injury and stroke often involve alterations in cholinergic signalling. Currently available therapeutic drugs provide only symptomatic relief. Therefore, novel therapeutic strategies are needed to retard and/or arrest the progressive loss of memory. Experimental Approach Scopolamine-induced memory impairment provides a rapid and reversible phenotypic screening paradigm for cognition enhancement drug discovery. Male C57BL/6J mice given scopolamine (1 mg·kg−1) were used to evaluate the ability of LS-1–137, a novel sigma (σ1) receptor-selective agonist, to improve the cognitive deficits associated with muscarinic antagonist administration. Key Results LS-1–137 is a high-affinity (Ki = 3.2 nM) σ1 receptor agonist that is 80-fold selective for σ1, compared with σ2 receptors. LS-1–137 binds with low affinity at D2-like (D2, D3 and D4) dopamine and muscarinic receptors. LS-1–137 was found to partially reverse the learning deficits associated with scopolamine administration using a water maze test and an active avoidance task. LS-1–137 treatment was also found to trigger the release of brain-derived neurotrophic factor from rat astrocytes. Conclusions and Implications The σ1 receptor-selective compound LS-1–137 may represent a novel candidate cognitive enhancer for the treatment of muscarinic receptor-dependent cognitive deficits. PMID:25573298

Protective effects of Bacopa monnieri on ischemia-induced cognitive deficits in mice: the possible contribution of bacopaside I and underlying mechanism.

PubMed

Le, Xoan Thi; Nguyet Pham, Hang Thi; Van Nguyen, Tai; Minh Nguyen, Khoi; Tanaka, Ken; Fujiwara, Hironori; Matsumoto, Kinzo

2015-04-22

Bacopa monnieri (L.) Wettst. (BM) is a medicinal plant which has been not only used as a traditional medicine to improve intelligence and memory but also taken as vegetables in Vietnam for a long time. We previously demonstrated that Bacopa monnieri (BM) alcohol extract attenuated olfactory bulbectomy-induced cognitive deficits and the deterioration of septo-hippocampal cholinergic neurons, suggesting the beneficial effects of BM for dementia patients. The present study was conducted to further clarify the anti-dementia effects of BM, using transient 2 vessels occlusion (T2VO)-induced cognitive deficits in mice, an animal model of vascular dementia, and also to investigate the constituent(s) contributing to the actions of BM, using oxygen- and glucose-deprivation (OGD)-induced hippocampal cell damage as an in vitro model of ischemia. In the in vivo experiments, T2VO mice were treated daily with a standardized BM extract (50mg/kg, p.o.) 1 week before and continuously 3 days after surgery. In the in vitro experiments, organotypic hippocampal slice cultures (OHSCs) were incubated with triterpenoid saponins from BM (bacosides) or MK-801 1h before and during a 45-min period of OGD. Neuronal cell damage in OHSCs was analyzed by measurement of propidium iodide uptake 24h after OGD. The BM treatment significantly ameliorated T2VO-induced impairments in non-spatial short term memory performance in the object recognition test. Among the bacosides tested in the in vitro experiments using OHSCs, bacopaside I (25 μM) exhibited potent neuroprotective effects against OGD-induced neuronal cell damage. Double staining with TUNEL and PI revealed that OGD caused necrosis and apoptosis and that bacopaside I attenuated the effects of OGD. The neuroprotective effects of bacopaside I were blocked by the PKC inhibitor Ro-31-8220 and PI3K inhibitor LY294002, but not by the ERK inhibitor U0126. OGD reduced the level of phospho-Akt (p-Akt), an anti-apoptotic factor, in OHSCs. This decrease

Emotional bias of cognitive control in adults with childhood attention-deficit/hyperactivity disorder

PubMed Central

Schulz, Kurt P.; Bédard, Anne-Claude V.; Fan, Jin; Clerkin, Suzanne M.; Dima, Danai; Newcorn, Jeffrey H.; Halperin, Jeffrey M.

2014-01-01

Affect recognition deficits found in individuals with attention-deficit/hyperactivity disorder (ADHD) across the lifespan may bias the development of cognitive control processes implicated in the pathophysiology of the disorder. This study aimed to determine the mechanism through which facial expressions influence cognitive control in young adults diagnosed with ADHD in childhood. Fourteen probands with childhood ADHD and 14 comparison subjects with no history of ADHD were scanned with functional magnetic resonance imaging while performing a face emotion go/no-go task. Event-related analyses contrasted activation and functional connectivity for cognitive control collapsed over face valence and tested for variations in activation for response execution and inhibition as a function of face valence. Probands with childhood ADHD made fewer correct responses and inhibitions overall than comparison subjects, but demonstrated comparable effects of face emotion on response execution and inhibition. The two groups showed similar frontotemporal activation for cognitive control collapsed across face valence, but differed in the functional connectivity of the right dorsolateral prefrontal cortex, with fewer interactions with the subgenual cingulate cortex, inferior frontal gyrus, and putamen in probands than in comparison subjects. Further, valence-dependent activation for response execution was seen in the amygdala, ventral striatum, subgenual cingulate cortex, and orbitofrontal cortex in comparison subjects but not in probands. The findings point to functional anomalies in limbic networks for both the valence-dependent biasing of cognitive control and the valence-independent cognitive control of face emotion processing in probands with childhood ADHD. This limbic dysfunction could impact cognitive control in emotional contexts and may contribute to the social and emotional problems associated with ADHD. PMID:24918067

Emotional bias of cognitive control in adults with childhood attention-deficit/hyperactivity disorder.

PubMed

Schulz, Kurt P; Bédard, Anne-Claude V; Fan, Jin; Clerkin, Suzanne M; Dima, Danai; Newcorn, Jeffrey H; Halperin, Jeffrey M

2014-01-01

Affect recognition deficits found in individuals with attention-deficit/hyperactivity disorder (ADHD) across the lifespan may bias the development of cognitive control processes implicated in the pathophysiology of the disorder. This study aimed to determine the mechanism through which facial expressions influence cognitive control in young adults diagnosed with ADHD in childhood. Fourteen probands with childhood ADHD and 14 comparison subjects with no history of ADHD were scanned with functional magnetic resonance imaging while performing a face emotion go/no-go task. Event-related analyses contrasted activation and functional connectivity for cognitive control collapsed over face valence and tested for variations in activation for response execution and inhibition as a function of face valence. Probands with childhood ADHD made fewer correct responses and inhibitions overall than comparison subjects, but demonstrated comparable effects of face emotion on response execution and inhibition. The two groups showed similar frontotemporal activation for cognitive control collapsed across face valence, but differed in the functional connectivity of the right dorsolateral prefrontal cortex, with fewer interactions with the subgenual cingulate cortex, inferior frontal gyrus, and putamen in probands than in comparison subjects. Further, valence-dependent activation for response execution was seen in the amygdala, ventral striatum, subgenual cingulate cortex, and orbitofrontal cortex in comparison subjects but not in probands. The findings point to functional anomalies in limbic networks for both the valence-dependent biasing of cognitive control and the valence-independent cognitive control of face emotion processing in probands with childhood ADHD. This limbic dysfunction could impact cognitive control in emotional contexts and may contribute to the social and emotional problems associated with ADHD.

Electroacupuncture ameliorates cognitive impairment and regulates the expression of apoptosis-related genes Bcl-2 and Bax in rats with cerebral ischaemia-reperfusion injury.

PubMed

Liu, Fang; Jiang, Yi-Jing; Zhao, Hong-Jia; Yao, Li-Qun; Chen, Li-Dian

2015-12-01

Post-stroke cognitive impairment seriously affects the quality of life and functional rehabilitation of patients with stroke. To examine the effects of electroacupuncture (EA) at GV20 and GV24 on cognitive impairment and apoptosis including expression of apoptosis-related genes Bcl-2 and Bax in a rat model of cerebral ischaemia-reperfusion (IR) induced by middle cerebral artery occlusion (MCAO). Thirty-five Sprague-Dawley rats were allocated to a sham operation control group (SC group, n=10) or underwent surgery and MCAO (n=25). Postoperatively the latter group was randomly subdivided into EA or untreated (IR) groups. Cognitive impairment was assessed using the Morris water maze (MWM). Apoptosis was examined by detection of Bcl-2 and Bax expression in the cerebral cortex. The EA group had significantly decreased neurological deficit scores compared to the IR group (p<0.05). In the MWM test, significant differences in escape latency and route were observed between the EA and IR groups (p<0.05). Rats in the EA group performed better in the probe trial than those in the IR group (p<0.05). EA treatment markedly reduced the number of TUNEL-positive cells compared to the IR group (20.13±4.30% vs 38.40±3.38%; p<0.001). Reverse transcription-polymerase chain reaction (RT-PCR) results showed the Bcl-2/Bax ratio was significantly increased in the EA group compared to the IR group (1.61±0.19 vs 0.50±0.05, p<0.01). These findings suggest that EA ameliorates cognitive impairment of rats with IR injury by modulating Bcl-2 and Bax expression. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Teacher Beliefs and Responses toward Student Misbehavior: Influence of Cognitive Skill Deficits

ERIC Educational Resources Information Center

Hart, Susan Crandall; DiPerna, James Clyde

2017-01-01

This study aimed to examine whether having knowledge of student cognitive skill deficits changes teacher beliefs and responses in regard to classroom misbehavior. Teachers (N = 272) were randomly assigned to an experimental or control condition. Although teachers in both conditions read the same vignette describing a student's misbehavior, the…

Cognitive and behavior deficits in sickle cell mice are associated with profound neuropathologic changes in hippocampus and cerebellum

PubMed Central

Wang, Li; Almeida, Luis E.F.; de Souza Batista, Celia M.; Khaibullina, Alfia; Xu, Nuo; Albani, Sarah; Guth, Kira A.; Seo, Ji Sung; Quezado, Martha; Quezado, Zenaide M.N.

2015-01-01

Strokes are perhaps the most serious complications of sickle cell disease (SCD) and by the fifth decade occur in approximately 25% of patients. While most patients do not develop strokes, mounting evidence indicates that even without brain abnormalities on imaging studies, SCD patients can present profound neurocognitive dysfunction. We sought to evaluate the neurocognitive behavior profile of humanized SCD mice (Townes, BERK) and to identify hematologic and neuropathologic abnormalities associated with the behavioral alterations observed in these mice. Heterozygous and homozygous Townes mice displayed severe cognitive deficits shown by significant delays in spatial learning compared to controls. Homozygous Townes also had increased depression- and anxiety-like behaviors as well as reduced performance on voluntary wheel running compared to controls. Behavior deficits observed in Townes were also seen in BERKs. Interestingly, most deficits in homozygotes were observed in older mice and were associated with worsening anemia. Further, neuropathologic abnormalities including the presence of large bands of dark/pyknotic (shrunken) neurons in CA1 and CA3 fields of hippocampus and evidence of neuronal dropout in cerebellum were present in homozygotes but not control Townes. These observations suggest that cognitive and behavioral deficits in SCD mice mirror those described in SCD patients and that aging, anemia, and profound neuropathologic changes in hippocampus and cerebellum are possible biologic correlates of those deficits. These findings support using SCD mice for studies of cognitive deficits in SCD and point to vulnerable brain areas with susceptibility to neuronal injury in SCD and to mechanisms that potentially underlie those deficits. PMID:26462816

Passive immunization reduces behavioral and neuropathological deficits in an alpha-synuclein transgenic model of Lewy body disease.

PubMed

Masliah, Eliezer; Rockenstein, Edward; Mante, Michael; Crews, Leslie; Spencer, Brian; Adame, Anthony; Patrick, Christina; Trejo, Margarita; Ubhi, Kiren; Rohn, Troy T; Mueller-Steiner, Sarah; Seubert, Peter; Barbour, Robin; McConlogue, Lisa; Buttini, Manuel; Games, Dora; Schenk, Dale

2011-04-29

Dementia with Lewy bodies (DLB) and Parkinson's Disease (PD) are common causes of motor and cognitive deficits and are associated with the abnormal accumulation of alpha-synuclein (α-syn). This study investigated whether passive immunization with a novel monoclonal α-syn antibody (9E4) against the C-terminus (CT) of α-syn was able to cross into the CNS and ameliorate the deficits associated with α-syn accumulation. In this study we demonstrate that 9E4 was effective at reducing behavioral deficits in the water maze, moreover, immunization with 9E4 reduced the accumulation of calpain-cleaved α-syn in axons and synapses and the associated neurodegenerative deficits. In vivo studies demonstrated that 9E4 traffics into the CNS, binds to cells that display α-syn accumulation and promotes α-syn clearance via the lysosomal pathway. These results suggest that passive immunization with monoclonal antibodies against the CT of α-syn may be of therapeutic relevance in patients with PD and DLB.

Methylphenidate, cognition, and epilepsy

PubMed Central

Alipio-Jocson, Valerie; Inoyama, Katherine; Bartlett, Victoria; Sandhu, Saira; Oso, Jemima; Barry, John J.; Loring, David W.; Meador, Kimford

2017-01-01

Objective: To evaluate the potential efficacy of immediate-release methylphenidate (MPH) for treating cognitive deficits in epilepsy. Methods: This was a double-blind, randomized, single-dose, 3-period crossover study in patients with epilepsy and chronic cognitive complaints comparing the effects of placebo and MPH 10 and 20 mg given 1 week apart. Cognitive outcome was evaluated on the basis of an omnibus z score calculated from performance on the Conners Continuous Performance Test 3 (ability to discriminate between target and nontarget stimuli [d'] and hit reaction time standard deviation), Symbol-Digit Modalities Test, and Medical College of Georgia Paragraph Memory Test. Adverse events and seizure frequency were monitored. An open-label follow-up is reported elsewhere. Results: Thirty-five adult patients with epilepsy participated, of whom 31 finished. Demographics included the following: mean age = 35.3 years (range 20–62 years), 13 men and 18 women, and baseline seizure frequency of 2.8 per month. Epilepsy types were focal (n = 24), generalized (n = 6), or unclassified (n = 1). Mean epilepsy duration was 12.5 years. A statistically significant performance benefit was present at both 10-mg (p = 0.030) and 20-mg (p = 0.034) MPH doses. No seizures were associated with either MPH dose. Adverse effects leading to withdrawal included cognitive “fogginess” (n = 1 on 20 mg), anxiety/agitation (n = 1 on 10 mg), and tachycardia (n = 1). One participant was lost to follow-up after one 20-mg dose without side effect. Conclusions: This single-dose study suggests that MPH may be effective in ameliorating some cognitive deficits in patients with epilepsy. Additional studies are required. ClinicalTrials.gov identifier: NCT02178995. Classification of evidence: This study provides Class II evidence that single doses of MPH improve cognitive performance on some measures of attention and processing speed in patients with epilepsy and cognitive complaints. PMID:28031390

Cognitive processes in spatial mapping: Evidence from a developmental spatial deficit.

PubMed

Hatfield, Miles; Reilhac, Caroline; Cowley, Hannah; Chang, Elizabeth; McCloskey, Michael

2017-07-01

We report a case study of an adolescent girl (N.K.Y.) with a developmental deficit affecting spatial processing. In a simple spatial mapping task, N.K.Y. shows a striking dissociation: She succeeds in one variant of the experiment in which the stimuli are objects, but struggles in a structurally identical task with people as stimuli. We present evidence that this dissociation stems from a tendency to automatically adopt the spatial perspective of other people, but not objects-a phenomenon also observed in neurotypical individuals. When adopting another person's perspective, N.K.Y. imagines herself in the other's position, representing the other's left and right as if it were her own. N.K.Y.'s deficit in relating left-right information to her own body then disrupts her performance. Our results shed light on the nature of N.K.Y.'s deficit as well as the cognitive operations involved in spatial perspective taking.

Paradoxical effect of dopamine medication on cognition in Parkinson's disease: relationship to side of motor onset.

PubMed

Hanna-Pladdy, Brenda; Pahwa, Rajesh; Lyons, Kelly E

2015-04-01

Parkinson's disease (PD) is characterized by asymmetric motor symptom onset attributed to greater degeneration of dopamine neurons contralateral to the affected side. However, whether motor asymmetries predict cognitive profiles in PD, and to what extent dopamine influences cognition remains controversial. This study evaluated cognitive variability in PD by measuring differential response to dopamine replacement therapy (DRT) based on hemispheric asymmetries. The influence of DRT on cognition was evaluated in mild PD patients (n = 36) with left or right motor onset symptoms. All subjects were evaluated on neuropsychological measures on and off DRT and compared to controls (n = 42). PD patients were impaired in executive, memory and motor domains irrespective of side of motor onset, although patients with left hemisphere deficit displayed greater cognitive impairment. Patients with right hemisphere deficit responded to DRT with significant improvement in sensorimotor deficits, and with corresponding improvement in attention and verbal memory functions. Conversely, patients with greater left hemisphere dopamine deficiency did not improve in attentional functions and declined in verbal memory recall following DRT. These findings support the presence of extensive mild cognitive deficits in early PD not fully explained by dopamine depletion alone. The paradoxical effects of levodopa on verbal memory were predicted by extent of fine motor impairment and sensorimotor response to levodopa, which reflects extent of dopamine depletion. The findings are discussed with respect to factors influencing variable cognitive profiles in early PD, including hemispheric asymmetries and differential response to levodopa based on dopamine levels predicting amelioration or overdosing.

[Negative symptoms, emotion and cognition in schizophrenia].

PubMed

Fakra, E; Belzeaux, R; Azorin, J-M; Adida, M

2015-12-01

For a long time, treatment of schizophrenia has been essentially focussed on positive symptoms managing. Yet, even if these symptoms are the most noticeable, negative symptoms are more enduring, resistant to pharmacological treatment and associated with a worse prognosis. In the two last decades, attention has shift towards cognitive deficit, as this deficit is most robustly associated to functional outcome. But it appears that the modest improvement in cognition, obtained in schizophrenia through pharmacological treatment or, more purposely, by cognitive enhancement therapy, has only lead to limited amelioration of functional outcome. Authors have claimed that pure cognitive processes, such as those evaluated and trained in lots of these programs, may be too distant from real-life conditions, as the latter are largely based on social interactions. Consequently, the field of social cognition, at the interface of cognition and emotion, has emerged. In a first part of this article we examined the links, in schizophrenia, between negative symptoms, cognition and emotions from a therapeutic standpoint. Nonetheless, investigation of emotion in schizophrenia may also hold relevant premises for understanding the physiopathology of this disorder. In a second part, we propose to illustrate this research by relying on the heuristic value of an elementary marker of social cognition, facial affect recognition. Facial affect recognition has been repeatedly reported to be impaired in schizophrenia and some authors have argued that this deficit could constitute an endophenotype of the illness. We here examined how facial affect processing has been used to explore broader emotion dysfunction in schizophrenia, through behavioural and imaging studies. In particular, fMRI paradigms using facial affect have shown particular patterns of amygdala engagement in schizophrenia, suggesting an intact potential to elicit the limbic system which may however not be advantageous. Finally, we

Neuroprotective and cognitive enhancing effects of a multi-targeted food intervention in an animal model of neurodegeneration and depression.

PubMed

Borre, Yuliya E; Panagaki, Theodora; Koelink, Pim J; Morgan, Mary E; Hendriksen, Hendrikus; Garssen, Johan; Kraneveld, Aletta D; Olivier, Berend; Oosting, Ronald S

2014-04-01

Rising neurodegenerative and depressive disease prevalence combined with the lack of effective pharmaceutical treatments and dangerous side effects, has created an urgent need for the development of effective therapies. Considering that these disorders are multifactorial in origin, treatments designed to interfere at different mechanistic levels may be more effective than the traditional single-targeted pharmacological concepts. To that end, an experimental diet composed of zinc, melatonin, curcumin, piperine, eicosapentaenoic acid (EPA, 20:5, n-3), docosahexaenoic acid (DHA, 22:6, n-3), uridine, and choline was formulated. This diet was tested on the olfactory bulbectomized rat (OBX), an established animal model of depression and cognitive decline. The ingredients of the diet have been individually shown to attenuate glutamate excitoxicity, exert potent anti-oxidant/anti-inflammatory properties, and improve synaptogenesis; processes that all have been implicated in neurodegenerative diseases and in the cognitive deficits following OBX in rodents. Dietary treatment started 2 weeks before OBX surgery, continuing for 6 weeks in total. The diet attenuated OBX-induced cognitive and behavioral deficits, except long-term spatial memory. Ameliorating effects of the diet extended to the control animals. Furthermore, the experimental diet reduced hippocampal atrophy and decreased the peripheral immune activation in the OBX rats. The ameliorating effects of the diet on the OBX-induced changes were comparable to those of the NMDA receptor antagonist, memantine, a drug used for the management of Alzheimer's disease. This proof-of-concept study suggests that a diet, which simultaneously targets multiple disease etiologies, can prevent/impede the development of a neurodegenerative and depressive disorders and the concomitant cognitive deficits. Copyright © 2014. Published by Elsevier Ltd.

Modeling cognitive deficits following neurodegenerative diseases and traumatic brain injuries with deep convolutional neural networks.

PubMed

Lusch, Bethany; Weholt, Jake; Maia, Pedro D; Kutz, J Nathan

2018-06-01

The accurate diagnosis and assessment of neurodegenerative disease and traumatic brain injuries (TBI) remain open challenges. Both cause cognitive and functional deficits due to focal axonal swellings (FAS), but it is difficult to deliver a prognosis due to our limited ability to assess damaged neurons at a cellular level in vivo. We simulate the effects of neurodegenerative disease and TBI using convolutional neural networks (CNNs) as our model of cognition. We utilize biophysically relevant statistical data on FAS to damage the connections in CNNs in a functionally relevant way. We incorporate energy constraints on the brain by pruning the CNNs to be less over-engineered. Qualitatively, we demonstrate that damage leads to human-like mistakes. Our experiments also provide quantitative assessments of how accuracy is affected by various types and levels of damage. The deficit resulting from a fixed amount of damage greatly depends on which connections are randomly injured, providing intuition for why it is difficult to predict impairments. There is a large degree of subjectivity when it comes to interpreting cognitive deficits from complex systems such as the human brain. However, we provide important insight and a quantitative framework for disorders in which FAS are implicated. Copyright © 2018 Elsevier Inc. All rights reserved.

Cognitive Effects of Stimulant, Guanfacine, and Combined Treatment in Child and Adolescent Attention-Deficit/Hyperactivity Disorder

PubMed Central

Bilder, Robert M.; Loo, Sandra; McGough, James J.; Whelan, Fiona; Hellemann, Gerhard; Sugar, Catherine; Del’Homme, Melissa; Sturm, Alexandra; Cowen, Jennifer; Hanada, Grant; McCracken, James T.

2016-01-01

Objective Psychostimulants are partially effective in reducing cognitive dysfunction associated with attention-deficit/hyperactivity disorder (ADHD). Cognitive effects of guanfacine, an alternative treatment, are poorly understood. Given its distinct action on α2A receptors, guanfacine may have different or complementary effects relative to stimulants. This study tested stimulant and guanfacine monotherapies relative to combined treatment on cognitive functions important in ADHD. Method Children with ADHD (n = 182; age 7–14 years) completed an eight-week double blind randomized controlled trial with three arms: d-methylphenidate (DMPH), guanfacine (GUAN), or combination treatment with DMPH and GUAN (COMB). A non-clinical comparison group (n = 93) had baseline testing, and a subset was re-tested 8 weeks later (n = 38). Analyses examined treatment effects in four cognitive domains (working memory, response inhibition, reaction time, and reaction time variability) constructed from 20 variables. Results The ADHD group showed impaired working memory relative to the non-clinical comparison group (effect size = −0.53 SD units). The treatments differed in effects on working memory but not other cognitive domains. Combination treatment improved working memory more than GUAN, but was not significantly better than DMPH alone. Treatment did not fully normalize the initial deficit in ADHD relative to the comparison group. Conclusion Combined treatment with DMPH and GUAN yielded greater improvements in working memory than placebo or GUAN alone, but the combined treatment was not superior to DMPH alone, and did not extend to other cognitive domains. Although GUAN may be a useful add-on treatment to psychostimulants, additional strategies appear necessary to achieve normalization of cognitive function in ADHD. Clinical trial registration information Single Versus Combination Medication Treatment for Children With Attention Deficit Hyperactivity Disorder; http

The Coumarin Derivative Osthole Stimulates Adult Neural Stem Cells, Promotes Neurogenesis in the Hippocampus, and Ameliorates Cognitive Impairment in APP/PS1 Transgenic Mice.

PubMed

Kong, Liang; Hu, Yu; Yao, Yingjia; Jiao, Yanan; Li, Shaoheng; Yang, Jingxian

2015-01-01

It is believed that neuronal death caused by abnormal deposition of amyloid-beta peptide is the major cause of the cognitive decline in Alzheimer's disease. Adult neurogenesis plays a key role in the rescue of impaired neurons and amelioration of cognitive impairment. In the present study, we demonstrated that osthole, a natural coumarin derivative, was capable of promoting neuronal stem cell (NSC) survival and inducing NSC proliferation in vitro. In osthole-treated APP/PS1 transgenic mice, a significant improvement in learning and memory function was seen, which was associated with a significant increase in the number of new neurons (Ki67(+)/NF-M(+)) and a decrease in apoptotic cells in the hippocampal region of the brain. These observations suggested that osthole promoted NSC proliferation, supported neurogenesis, and thus efficiently rescued impaired neurons in the hippocampus and ameliorated cognitive impairment. We also found that osthole treatment activated the Notch pathway and upregulated the expression of self-renewal genes Notch 1 and Hes 1 mRNA in NSCs. However, when Notch activity was blocked by the γ-secretase inhibitor DAPT, the augmentation of Notch 1 and Hes 1 protein was ameliorated, and the proliferation-inducing effect of osthole was abolished, suggesting that the effects of osthole are at least in part mediated by activation of the Notch pathway.

Effects of Mangifera indica fruit extract on cognitive deficits in mice.

PubMed

Kumar, Sokindra; Maheshwari, Kamal Kishore; Singh, Vijender

2009-07-01

Mangos are a source of bioactive compounds with potential health-promoting activity. The present work was undertaken to evaluate the ethanolic extract of Mangifera indica L. fruit on cognitive performances. The models used to study the effect on cognitive performances are step down passive avoidance task and elevated plus maze task in mice. Chronic treatment (7 days) of extract and vitamin C significantly (p < 0.05) reversed the aging and scopolamine induced memory deficits in both paradigms. Preliminary phytochemical screening revealed the presence of free sugars, saponins, tannins, and flavonoids. The results suggestthe extract contained pharmacologically active principles that are memory-enhancing in nature.

Cognitive Neuroscience of Attention Deficit Hyperactivity Disorder (ADHD) and Its Clinical Translation

PubMed Central

Rubia, Katya

2018-01-01

This review focuses on the cognitive neuroscience of Attention Deficit Hyperactivity Disorder (ADHD) based on functional magnetic resonance imaging (fMRI) studies and on recent clinically relevant applications such as fMRI-based diagnostic classification or neuromodulation therapies targeting fMRI deficits with neurofeedback (NF) or brain stimulation. Meta-analyses of fMRI studies of executive functions (EFs) show that ADHD patients have cognitive-domain dissociated complex multisystem impairments in several right and left hemispheric dorsal, ventral and medial fronto-cingulo-striato-thalamic and fronto-parieto-cerebellar networks that mediate cognitive control, attention, timing and working memory (WM). There is furthermore emerging evidence for abnormalities in orbital and ventromedial prefrontal and limbic areas that mediate motivation and emotion control. In addition, poor deactivation of the default mode network (DMN) suggests an abnormal interrelationship between hypo-engaged task-positive and poorly “switched off” hyper-engaged task-negative networks, both of which are related to impaired cognition. Translational cognitive neuroscience in ADHD is still in its infancy. Pattern recognition analyses have attempted to provide diagnostic classification of ADHD using fMRI data with respectable classification accuracies of over 80%. Necessary replication studies, however, are still outstanding. Brain stimulation has been tested in heterogeneously designed, small numbered proof of concept studies targeting key frontal functional impairments in ADHD. Transcranial direct current stimulation (tDCS) appears to be promising to improve ADHD symptoms and cognitive functions based on some studies, but larger clinical trials of repeated stimulation with and without cognitive training are needed to test clinical efficacy and potential costs on non-targeted functions. Only three studies have piloted NF of fMRI-based frontal dysfunctions in ADHD using fMRI or near

Cognitive Neuroscience of Attention Deficit Hyperactivity Disorder (ADHD) and Its Clinical Translation.

PubMed

Rubia, Katya

2018-01-01

This review focuses on the cognitive neuroscience of Attention Deficit Hyperactivity Disorder (ADHD) based on functional magnetic resonance imaging (fMRI) studies and on recent clinically relevant applications such as fMRI-based diagnostic classification or neuromodulation therapies targeting fMRI deficits with neurofeedback (NF) or brain stimulation. Meta-analyses of fMRI studies of executive functions (EFs) show that ADHD patients have cognitive-domain dissociated complex multisystem impairments in several right and left hemispheric dorsal, ventral and medial fronto-cingulo-striato-thalamic and fronto-parieto-cerebellar networks that mediate cognitive control, attention, timing and working memory (WM). There is furthermore emerging evidence for abnormalities in orbital and ventromedial prefrontal and limbic areas that mediate motivation and emotion control. In addition, poor deactivation of the default mode network (DMN) suggests an abnormal interrelationship between hypo-engaged task-positive and poorly "switched off" hyper-engaged task-negative networks, both of which are related to impaired cognition. Translational cognitive neuroscience in ADHD is still in its infancy. Pattern recognition analyses have attempted to provide diagnostic classification of ADHD using fMRI data with respectable classification accuracies of over 80%. Necessary replication studies, however, are still outstanding. Brain stimulation has been tested in heterogeneously designed, small numbered proof of concept studies targeting key frontal functional impairments in ADHD. Transcranial direct current stimulation (tDCS) appears to be promising to improve ADHD symptoms and cognitive functions based on some studies, but larger clinical trials of repeated stimulation with and without cognitive training are needed to test clinical efficacy and potential costs on non-targeted functions. Only three studies have piloted NF of fMRI-based frontal dysfunctions in ADHD using fMRI or near

Novel technology for treating individuals with aphasia and concomitant cognitive deficits.

PubMed

Cherney, Leora R; Halper, Anita S

2008-01-01

This article describes three individuals with aphasia and concomitant cognitive deficits who used state-of-theart computer software for training conversational scripts. Participants were assessed before and after 9 weeks of a computer script training program. For each participant, three individualized scripts were developed, recorded on the software, and practiced sequentially at home. Weekly meetings with the speech-language pathologist occurred to monitor practice and assess progress. Baseline and posttreatment scripts were audiotaped, transcribed, and compared to the target scripts for content, grammatical productivity, and rate of production of script-related words. Interviews were conducted at the conclusion of treatment. There was great variability in improvements across scripts, with two participants improving on two of their three scripts in measures of content, grammatical productivity, and rate of production of scriptrelated words. One participant gained more than 5 points on the Aphasia Quotient of the Western Aphasia Battery. Five positive themes were consistently identified from exit interviews: increased verbal communication, improvements in other modalities and situations, communication changes noticed by others, increased confidence, and satisfaction with the software. Computer-based script training potentially may be an effective intervention for persons with chronic aphasia and concomitant cognitive deficits.

Evaluating the Specificity of Cognitive Control Deficits in Schizophrenia Using Antisaccades, Functional Magnetic Resonance Imaging, and Healthy Individuals With Poor Cognitive Control.

PubMed

Rodrigue, Amanda L; Schaeffer, David J; Pierce, Jordan E; Clementz, Brett A; McDowell, Jennifer E

2018-01-01

Cognitive control impairments in schizophrenia (SZ) can be evaluated using antisaccade tasks and functional magnetic resonance imaging (fMRI). Studies, however, often compare people with SZ to high performing healthy people, making it unclear if antisaccade-related disruptions are specific to the disease or due to generalized deficits in cognitive control. We included two healthy comparison groups in addition to people with SZ: healthy people with high cognitive control (HCC), who represent a more typical comparison group, and healthy people with low cognitive control (LCC), who perform similarly on antisaccade measures as people with SZ. Using two healthy comparison groups may help determine which antisaccade-related deficits are specific to SZ (distinguish SZ from LCC and HCC groups) and which are due to poor cognitive control (distinguish the LCC and SZ groups from the HCC group). People with SZ and healthy people with HCC or LCC performed an antisaccade task during fMRI acquisition. LCC and SZ groups showed under-activation of saccade circuitry. SZ-specific disruptions were observed in the left superior temporal gyrus and insula during error trials (suppression of activation in the SZ group compared to the LCC and HCC group). Differences related to antisaccade errors may distinguish people with SZ from healthy people with LCC.

Neuroprotective potential of sesamol and its loaded solid lipid nanoparticles in ICV-STZ-induced cognitive deficits: behavioral and biochemical evidence.

PubMed

Sachdeva, Anand Kamal; Misra, Shubham; Pal Kaur, Indu; Chopra, Kanwaljit

2015-01-15

Neuroinflammation is a prominent feature of Alzheimer disease (AD) and other chronic neurodegenerative disorders. Intracerebroventricular (ICV) streptozotocin (STZ) induced-cognitive impairment has been widely used as an experimental paradigm of Alzheimer׳s disease. Sesamol is a potent inhibitor of cytokine production as well as an antioxidant. The present study was designed to evaluate the effectiveness of sesamol in ICV-STZ-induced cognitive deficits in rats by incorporating it into solid lipid nanoparticles (SLNs). ICV-STZ administration produced significant cognitive deficits as assessed by both Morris water maze and elevated plus maze task which is accompanied by significantly enhanced nitrodative stress, altered acetylcholinesterase in rat brain along with significantly increased serum TNF-α levels. Chronic treatment with sesamol and sesamol loaded SLNs dose dependently restored cognitive deficits in ICV-STZ rats along with mitigation of nitrodative stress and cytokine release. Effectiveness of SLNs to deliver sesamol to the brain was shown by a significantly better alleviation of the oxidative stress parameters. Our findings demonstrate that loading of sesamol in SLNs is an effective strategy to mitigate ICV-STZ-induced neuronal dysfunction and memory deficits. Copyright © 2014 Elsevier B.V. All rights reserved.

The Outcome of a Social Cognitive Training for Mainstream Adolescents with Social Communication Deficits in a Chinese Community

ERIC Educational Resources Information Center

Lee, Kathy Y. S.; Crooke, Pamela J.; Lui, Aster L. Y.; Kan, Peggy P. K.; Mark, Yuen-mai; van Hasselt, Charles Andrew; Tong, Michael C. F.

2016-01-01

The use of cognitive-based strategies for improving social communication behaviours for individuals who have solid language and cognition is an important question. This study investigated the outcome of teaching Social Thinking®, a framework based in social-cognition, to Chinese adolescents with social communication deficits. Thirty-nine students…

Understanding Cognitive Deficits in Parkinson's Disease: Lessons from Preclinical Animal Models

ERIC Educational Resources Information Center

Solari, Nicola; Bonito-Oliva, Alessandra; Fisone, Gilberto; Brambilla, Riccardo

2013-01-01

Parkinson's disease (PD) has been, until recently, mainly defined by the presence of characteristic motor symptoms, such as rigidity, tremor, bradykinesia/akinesia, and postural instability. Accordingly, pharmacological and surgical treatments have so far addressed these motor disturbances, leaving nonmotor, cognitive deficits an unmet…

Dietary supplementation with fruit polyphenolics ameliorates age-related deficits in behavior and neuronal markers of inflammation and oxidative stress.

PubMed

Shukitt-Hale, Barbara; Galli, Rachel L; Meterko, Vanessa; Carey, Amanda; Bielinski, Donna F; McGhie, Tony; Joseph, James A

2005-03-01

Dietary supplementation with fruit or vegetable extracts can ameliorate age-related declines in measures of learning, memory, motor performance, and neuronal signal transduction in a rat model. To date, blueberries have proved most effective at improving measures of motor performance, spatial learning and memory, and neuronal functioning in old rats. In an effort to further characterize the bioactive properties of fruits rich in color and correspondingly high in anthocyanins and other polyphenolics, 19-month-old male Fischer rats were fed a well-balanced control diet, or the diet supplemented with 2% extract from either blueberry, cranberry, blackcurrant, or Boysenberry fruit for eight weeks before testing began. The blackcurrant and cranberry diets enhanced neuronal signal transduction as measured by striatal dopamine release, while the blueberry and cranberry diets were effective in ameliorating deficits in motor performance and hippocampal HSP70 neuroprotection; these changes in HSP70 were positively correlated with performance on the inclined screen. It appears that the polyphenols in blueberries and cranberries have the ability to improve muscle tone, strength and balance in aging rats, whereas polyphenols in blueberries, cranberries and blackcurrants have the ability to enhance neuronal functioning and restore the brain's ability to generate a neuroprotective response to stress.

Emotion recognition and cognitive empathy deficits in adolescent offenders revealed by context-sensitive tasks

PubMed Central

Gonzalez-Gadea, Maria Luz; Herrera, Eduar; Parra, Mario; Gomez Mendez, Pedro; Baez, Sandra; Manes, Facundo; Ibanez, Agustin

2014-01-01

Emotion recognition and empathy abilities require the integration of contextual information in real-life scenarios. Previous reports have explored these domains in adolescent offenders (AOs) but have not used tasks that replicate everyday situations. In this study we included ecological measures with different levels of contextual dependence to evaluate emotion recognition and empathy in AOs relative to non-offenders, controlling for the effect of demographic variables. We also explored the influence of fluid intelligence (FI) and executive functions (EFs) in the prediction of relevant deficits in these domains. Our results showed that AOs exhibit deficits in context-sensitive measures of emotion recognition and cognitive empathy. Difficulties in these tasks were neither explained by demographic variables nor predicted by FI or EFs. However, performance on measures that included simpler stimuli or could be solved by explicit knowledge was either only partially affected by demographic variables or preserved in AOs. These findings indicate that AOs show contextual social-cognition impairments which are relatively independent of basic cognitive functioning and demographic variables. PMID:25374529

Lack of association between mutation size and cognitive/behavior deficits in fragile X males: A brief report

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

Fisch, G.S.; Carpenter, N.; Simensen, R.

1996-08-09

Previously, researchers reported molecular-neurobehavioral or molecular-cognitive associations in individuals with fra(X) (fragile X) mutation. However, not all investigators have noted molecular-behavioral relationships. Consequently, we examined prospectively 30 fra(X) males age 3-15 years from four testing sites to determine whether there was a relationship between mutation size and degree of either cognitive or adaptive behavior deficit. To measure cognitive abilities, all individuals were administered the Stanford-Binet (4th edition) IQ test. To evaluate adaptive behavior (DQ) skills, all individuals were assessed using the Vineland Adaptive Behavior Scale. To determine fra(X) status, genomic DNA from all individuals was extracted and digested with EcoRImore » and EagI restriction enzymes. Southern blots were prepared and hybridized with the pE5.1 probe. The Pearson correlation coefficient between full mutation size and composite IQ score revealed a non-significant, near-zero association (r = 0.06; P > .76). The Pearson coefficient between mutation size and DQ also showed a non-significant, near-zero association (r = 0.06; P >.73). We conclude that while fra(X) mutation produces cognitive and behavior deficits in males who inherit the defective gene, there is no relationship between mutation size and degree of deficit. 14 refs., 2 figs.« less

Understanding the effects of stimulant medications on cognition in individuals with attention-deficit hyperactivity disorder: a decade of progress.

PubMed

Swanson, James; Baler, Ruben D; Volkow, Nora D

2011-01-01

The use of stimulant drugs for the treatment of children with attention-deficit hyperactivity disorder (ADHD) is one of the most widespread pharmacological interventions in child psychiatry and behavioral pediatrics. This treatment is well grounded on controlled studies showing efficacy of low oral doses of methylphenidate and amphetamine in reducing the behavioral symptoms of the disorder as reported by parents and teachers, both for the cognitive (inattention and impulsivity) and non-cognitive (hyperactivity) domains. Our main aim is to review the objectively measured cognitive effects that accompany the subjectively assessed clinical responses to stimulant medications. Recently, methods from the cognitive neurosciences have been used to provide information about brain processes that underlie the cognitive deficits of ADHD and the cognitive effects of stimulant medications. We will review some key findings from the recent literature, and then offer interpretations of the progress that has been made over the past decade in understanding the cognitive effects of stimulant medication on individuals with ADHD.

Late-Life Depressive Symptoms and Lifetime History of Major Depression: Cognitive Deficits are Largely Due to Incipient Dementia rather than Depression.

PubMed

Heser, Kathrin; Bleckwenn, Markus; Wiese, Birgitt; Mamone, Silke; Riedel-Heller, Steffi G; Stein, Janine; Lühmann, Dagmar; Posselt, Tina; Fuchs, Angela; Pentzek, Michael; Weyerer, Siegfried; Werle, Jochen; Weeg, Dagmar; Bickel, Horst; Brettschneider, Christian; König, Hans-Helmut; Maier, Wolfgang; Scherer, Martin; Wagner, Michael

2016-08-01

Late-life depression is frequently accompanied by cognitive impairments. Whether these impairments indicate a prodromal state of dementia, or are a symptomatic expression of depression per se is not well-studied. In a cohort of very old initially non-demented primary care patients (n = 2,709, mean age = 81.1 y), cognitive performance was compared between groups of participants with or without elevated depressive symptoms and with or without subsequent dementia using ANCOVA (adjusted for age, sex, and education). Logistic regression analyses were computed to predict subsequent dementia over up to six years of follow-up. The same analytical approach was performed for lifetime major depression. Participants with elevated depressive symptoms without subsequent dementia showed only small to medium cognitive deficits. In contrast, participants with depressive symptoms with subsequent dementia showed medium to very large cognitive deficits. In adjusted logistic regression models, learning and memory deficits predicted the risk for subsequent dementia in participants with depressive symptoms. Participants with a lifetime history of major depression without subsequent dementia showed no cognitive deficits. However, in adjusted logistic regression models, learning and orientation deficits predicted the risk for subsequent dementia also in participants with lifetime major depression. Marked cognitive impairments in old age depression should not be dismissed as "depressive pseudodementia", but require clinical attention as a possible sign of incipient dementia. Non-depressed elderly with a lifetime history of major depression, who remained free of dementia during follow-up, had largely normal cognitive performance.

Cognitive remediation of attention deficits following acquired brain injury: A systematic review and meta-analysis.

PubMed

Virk, Sohaib; Williams, Tracey; Brunsdon, Ruth; Suh, Flora; Morrow, Angie

2015-01-01

Attention deficits are common after acquired brain injury (ABI) and adversely impact academic, vocational and social outcomes. The role of cognitive interventions in post-ABI attention rehabilitation remains unclear. To evaluate effectiveness of cognitive interventions in treating attention deficits following ABI and to explore differences in treatment effect between ABI etiologies. MEDLINE, EMBASE, PsycINFO and CENTRAL databases were searched for randomized controlled trials (RCTs). Studies were selected by three reviewers. Study quality was assessed using Cochrane Collaboration tool for RCTs. Effect sizes (Hedge's g) for each attentional domain were meta-analyzed with subgroup analysis by ABI etiology. Twelve RCTs with 584 participants were included, representing individuals with stroke, traumatic brain injury (TBI) and CNS-impacting malignancy. Cognitive rehabilitation improved divided attention in stroke survivors (g 0.67; 95% confidence interval, 0.35-0.98; p <  0.0001) but not other ABI populations. Sustained, selective and alternating attention, and inhibition were not significantly improved in any ABI population. Follow-up data showed no evidence of long-term benefit. Cognitive rehabilitation resulted in short-term improvements in divided attention following stroke, but not after TBI or CNS-impacting malignancy. Cognitive interventions did not significantly improve other attentional domains in participants with stroke, TBI or CNS-impacting malignancy.

Dopamine dysregulation in the prefrontal cortex relates to cognitive deficits in the sub-chronic PCP-model for schizophrenia: A preliminary investigation.

PubMed

McLean, Samantha L; Harte, Michael K; Neill, Joanna C; Young, Andrew Mj

2017-06-01

Dopamine dysregulation in the prefrontal cortex (PFC) plays an important role in cognitive dysfunction in schizophrenia. Sub-chronic phencyclidine (scPCP) treatment produces cognitive impairments in rodents and is a thoroughly validated animal model for cognitive deficits in schizophrenia. The aim of our study was to investigate the role of PFC dopamine in scPCP-induced deficits in a cognitive task of relevance to the disorder, novel object recognition (NOR). Twelve adult female Lister Hooded rats received scPCP (2 mg/kg) or vehicle via the intraperitoneal route twice daily for 7 days, followed by 7 days washout. In vivo microdialysis was carried out prior to, during and following the NOR task. Vehicle rats successfully discriminated between novel and familiar objects and this was accompanied by a significant increase in dopamine in the PFC during the retention trial ( p < 0.01). scPCP produced a significant deficit in NOR ( p < 0.05 vs. control) and no PFC dopamine increase was observed. These data demonstrate an increase in dopamine during the retention trial in vehicle rats that was not observed in scPCP-treated rats accompanied by cognitive disruption in the scPCP group. This novel finding suggests a mechanism by which cognitive deficits are produced in this animal model and support its use for investigating disorders in which PFC dopamine is central to the pathophysiology.

Multifamily Group Psychoeducation and Cognitive Remediation for First-Episode Psychosis: A Randomized Controlled Trial

PubMed Central

2011-01-01

Background Multifamily group psychoeducation (MFG) has been shown to reduce relapse rates among individuals with first-episode psychosis. However, given the cognitive demands associated with participating in this intervention (e.g., learning and applying a structured problem-solving activity), the cognitive deficits that accompany psychotic disorders may limit the ability of certain individuals to benefit from this intervention. Thus, the goal of this study is to examine whether individuals with first-episode psychosis who participate simultaneously in MFG and cognitive remediation--an intervention shown to improve cognitive functioning among individuals with psychotic disorders--will be less likely to experience a relapse than individuals who participate in MFG alone. Methods/Design Forty individuals with first-episode psychosis and their caregiving relative will be recruited to participate in this study. Individuals with first-episode psychosis will be randomized to one of two conditions: (i) MFG with concurrent participation in cognitive remediation or (ii) MFG alone. The primary outcome for this study is relapse of psychotic symptoms. We will also examine secondary outcomes among both individuals with first-episode psychosis (i.e., social and vocational functioning, health-related quality of life, service utilization, independent living status, and cognitive functioning) and their caregiving relatives (i.e., caregiver burden, anxiety, and depression) Discussion Cognitive remediation offers the possibility of ameliorating a specific deficit (i.e., deficits in cognitive functioning) that often accompanies psychotic symptoms and may restrict the magnitude of the clinical benefits derived from MFG. Trial Registration ClinicalTrials (NCT): NCT01196286 PMID:21226941

The alteration of autophagy and apoptosis in the hippocampus of rats with natural aging-dependent cognitive deficits.

PubMed

Yu, Yang; Feng, Linjing; Li, Junnan; Lan, Xiaoxin; A, Lixiang; Lv, Xiaoyan; Zhang, Ming; Chen, Li

2017-09-15

The present study was aim to explore aging-dependent changes in hippocampal autophagy and apoptosis in a natural aging rat model from adult to old stages and to discover a suitable age for treating neurodegenerative diseases. Wistar rats at 5, 18 and 24months of age were used to mimic the adulthood, initial old, and old phases, respectively. The learning and cognitive ability of the rats was detected by the Morris water maze test. Morphological changes in the hippocampus were observed. Expressions of apoptosis and autophagy-related proteins were examined by Western blot. The adult group (5months) exhibited high levels of autophagy related p-ULK p-ULK-1/ULK-1 ratio, Beclin-1, LC3II and cell survival, maintaining normal learning and cognitive function and integrated hippocampal morphology. The initial old group (18 months) presented a reduced number of neurons and cognitive deficits, and exhibited high levels of apoptosis related Bax/Bcl-2 ratio, Caspase-3 activation and autophagy related p-ULK p-ULK-1/ULK-1 ratio, Beclin-1, LC3II compared to the adult group. The old group (24 months) exhibited a high level of apoptosis related Bax/Bcl-2 ratio, Caspase-3 activation and a low level of autophagy related p-ULK p-ULK-1/ULK-1 ratio, Beclin-1, LC3II compared to its younger group, as well as significant neuronal death and cognitive deficits. The degree of autophagy was generally consistent with its negative regulator, the PI3K/Akt/mTOR axis, in all groups. Our data suggest that cognitive deficits are first observed in the initial old stage. The levels of autophagy and apoptosis tend to be opposite in the adult and old phases. High levels of autophagy and apoptosis coexist in the initial old stage. Our study indicates that up-regulation of autophagy in the initial old phase to anti-cognitive deficits must be further evaluated. Copyright © 2017 Elsevier B.V. All rights reserved.

Rivastigmine reverses cognitive deficit and acetylcholinesterase activity induced by ketamine in an animal model of schizophrenia.

PubMed

Zugno, Alexandra I; Julião, Ricardo Filipe; Budni, Josiane; Volpato, Ana Maria; Fraga, Daiane B; Pacheco, Felipe D; Deroza, Pedro F; Luca, Renata D; de Oliveira, Mariana B; Heylmann, Alexandra S; Quevedo, João

2013-09-01

Schizophrenia is one of the most disabling mental disorders that affects up to 1 % of the population worldwide. Although the causes of this disorder remain unknown, it has been extensively characterized by a broad range of emotional, ideational and cognitive impairments. Studies indicate that schizophrenia affects neurotransmitters such as dopamine, glutamate and acetylcholine. Recent studies suggest that rivastigmine (an acetylcholinesterase inhibitor) is important to improve the cognitive symptoms of schizophrenia. Therefore, the present study evaluated the protective effect of rivastigmine against the ketamine-induced behavioral (hyperlocomotion and cognitive deficit) and biochemical (increase of acetylcholinesterase activity) changes which characterize an animal model of schizophrenia in rats. Our results indicated that rivastigmine was effective to improve the cognitive deficit in different task (immediate memory, long term memory and short term memory) induced by ketamine in rats. Moreover, we observed that rivastigmina reversed the increase of acetylcholinesterase activity induced by ketamine in the cerebral cortex, hippocampus and striatum. However, rivastigmine was not able to prevent the ketamine-induced hyperlocomotion. In conslusion, ours results indicate that cholinergic system might be an important therapeutic target in the physiopathology of schizophrenia, mainly in the cognition, but additional studies should be carried.

Stress and Cognition: A Cognitive Psychological Perspective

NASA Technical Reports Server (NTRS)

Bourne, Lyle E., Jr.; Yaroush, Rita A.

2003-01-01

Complex operations can be performed successfully in Space by human beings, but more slowly than doing the same tasks on Earth, Fowler, et al. (2000) and Manzey (2000) propose two hypotheses to account for this performance degradation-(1) the direct effects of microgravity on the central nervous system and the motor system of the body and (2) the non-specific effects of multiple stressors. Evidence available to date is consistent with both hypotheses and further experiments are required to settle this question. The issue has practical implications because the countermeasures needed to ameliorate or prevent performance deficits will differ according to which hypothesis is correct. Understanding and ameliorating performance deficits will surely help ensure safer operations aboard the International Space Station and during a mission to Mars.

Mice heterozygous for an inactivated allele of the schizophrenia associated Brd1 gene display selective cognitive deficits with translational relevance to schizophrenia.

PubMed

Qvist, Per; Rajkumar, Anto P; Redrobe, John P; Nyegaard, Mette; Christensen, Jane H; Mors, Ole; Wegener, Gregers; Didriksen, Michael; Børglum, Anders D

2017-05-01

Schizophrenia is a debilitating brain disorder characterized by disturbances of emotion, perception and cognition. Cognitive impairments predict functional outcome in schizophrenia and are detectable even in the prodromal stage of the disorder. However, our understanding of the underlying neurobiology is limited and procognitive treatments remain elusive. We recently demonstrated that mice heterozygous for an inactivated allele of the schizophrenia-associated Brd1 gene (Brd1 +/ - mice) display behaviors reminiscent of schizophrenia, including impaired social cognition and long-term memory. Here, we further characterize performance of these mice by following the preclinical guidelines recommended by the 'Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS)' and 'Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS)' initiatives to maximize translational value. Brd1 +/- mice exhibit relational encoding deficits, compromised working and long term memory, as well as impaired executive cognitive functioning with cognitive behaviors relying on medial prefrontal cortex being particularly affected. Akin to patients with schizophrenia, the cognitive deficits displayed by Brd1 +/ - mice are not global, but selective. Our results underline the value of Brd1 +/ - mice as a promising tool for studying the neurobiology of cognitive deficits in schizophrenia. Copyright © 2017 Elsevier Inc. All rights reserved.

Minocycline Transiently Reduces Microglia/Macrophage Activation but Exacerbates Cognitive Deficits Following Repetitive Traumatic Brain Injury in the Neonatal Rat

PubMed Central

Hanlon, Lauren A.; Huh, Jimmy W.

2016-01-01

Elevated microglial/macrophage-associated biomarkers in the cerebrospinal fluid of infant victims of abusive head trauma (AHT) suggest that these cells play a role in the pathophysiology of the injury. In a model of AHT in 11-day-old rats, 3 impacts (24 hours apart) resulted in spatial learning and memory deficits and increased brain microglial/macrophage reactivity, traumatic axonal injury, neuronal degeneration, and cortical and white-matter atrophy. The antibiotic minocycline has been effective in decreasing injury-induced microglial/macrophage activation while simultaneously attenuating cellular and functional deficits in models of neonatal hypoxic ischemia, but the potential for this compound to rescue deficits after impact-based trauma to the immature brain remains unexplored. Acute minocycline administration in this model of AHT decreased microglial/macrophage reactivity in the corpus callosum of brain-injured animals at 3 days postinjury, but this effect was lost by 7 days postinjury. Additionally, minocycline treatment had no effect on traumatic axonal injury, neurodegeneration, tissue atrophy, or spatial learning deficits. Interestingly, minocycline-treated animals demonstrated exacerbated injury-induced spatial memory deficits. These results contrast with previous findings in other models of brain injury and suggest that minocycline is ineffective in reducing microglial/macrophage activation and ameliorating injury-induced deficits following repetitive neonatal traumatic brain injury. PMID:26825312

Cognitive Training and Work Therapy for the Treatment of Verbal Learning and Memory Deficits in Veterans With Alcohol Use Disorders.

PubMed

Bell, Morris D; Vissicchio, Nicholas A; Weinstein, Andrea J

2016-01-01

This study focused on the efficacy of cognitive training for verbal learning and memory deficits in a population of older veterans with alcohol use disorders. Veterans with alcohol use disorders, who were in outpatient treatment at VA facilities and in early-phase recovery (N = 31), were randomized to receive a three-month trial of daily cognitive training plus work therapy (n = 15) or work therapy alone (n = 16), along with treatment as usual. Participants completed assessments at baseline and at three- and six-month follow-ups; the Hopkins Verbal Learning Task (HVLT) was the primary outcome measure. Participants were primarily male (97%) and in their mid-50s (M = 55.16, SD = 5.16) and had been sober for 1.64 (SD = 2.81) months. Study retention was excellent (91% at three-month follow-up) and adherence to treatment in both conditions was very good. On average, participants in the cognitive training condition had more than 41 hours of cognitive training, and both conditions had more than 230 hours of productive activity. HVLT results at three-month follow-up revealed significant condition effects favoring cognitive training for verbal learning (HVLT Trial-3 T-score, p < .005, Cohen's d = 1.3) and verbal memory (HVLT Total T-score, p < .01, Cohen's d = 1.1). Condition effects were sustained at six-month follow-up. At baseline, 55.9% of participants showed a significant deficit in verbal memory and 58.8% showed a deficit in verbal learning compared with a premorbid estimate of verbal IQ. At three-month follow-up there was a significant reduction in the number of participants in the cognitive training condition with clinically significant verbal memory deficits (p < .01, number needed to treat = 3.0) compared with the work therapy alone condition and a trend toward significance for verbal learning deficits, which was not sustained at six-month follow-up. This National Institute on Drug Abuse-funded pilot study demonstrates that cognitive training within the context

Face-Name Associative Recognition Deficits in Subjective Cognitive Decline and Mild Cognitive Impairment.

PubMed

Polcher, Alexandra; Frommann, Ingo; Koppara, Alexander; Wolfsgruber, Steffen; Jessen, Frank; Wagner, Michael

2017-01-01

There is a need for more sensitive neuropsychological tests to detect subtle cognitive deficits emerging in the preclinical stage of Alzheimer's disease (AD). Associative memory is a cognitive function supported by the hippocampus and affected early in the process of AD. We developed a short computerized face-name associative recognition test (FNART) and tested whether it would detect memory impairment in memory clinic patients with mild cognitive impairment (MCI) and subjective cognitive decline (SCD). We recruited 61 elderly patients with either SCD (n = 32) or MCI (n = 29) and 28 healthy controls (HC) and compared performance on FNART, self-reported cognitive deterioration in different domains (ECog-39), and, in a reduced sample (n = 46), performance on the visual Paired Associates Learning of the CANTAB battery. A significant effect of group on FNART test performance in the total sample was found (p < 0.001). Planned contrasts indicated a significantly lower associative memory performance in the SCD (p = 0.001, d = 0.82) and MCI group (p < 0.001, d = 1.54), as compared to HCs, respectively. The CANTAB-PAL discriminated only between HC and MCI, possibly because of reduced statistical power. Adjusted for depression, performance on FNART was significantly related to ECog-39 Memory in SCD patients (p = 0.024) but not in MCI patients. Associative memory is substantially impaired in memory clinic patients with SCD and correlates specifically with memory complaints at this putative preclinical stage of AD. Further studies will need to examine the predictive validity of the FNART in SCD patients with regard to longitudinal (i.e., conversion to MCI/AD) and biomarker outcomes.

Parsing cognitive and emotional empathy deficits for negative and positive stimuli in frontotemporal dementia.

PubMed

Oliver, Lindsay D; Mitchell, Derek G V; Dziobek, Isabel; MacKinley, Julia; Coleman, Kristy; Rankin, Katherine P; Finger, Elizabeth C

2015-01-01

Behavioural variant frontotemporal dementia (bvFTD) is a debilitating neurodegenerative disorder characterized by frontal and temporal lobe atrophy primarily affecting social cognition and emotion, including loss of empathy. Many consider empathy to be a multidimensional construct, including cognitive empathy (the ability to adopt and understand another's perspective) and emotional empathy (the capacity to share another's emotional experience). Cognitive and emotional empathy deficits have been associated with bvFTD; however, little is known regarding the performance of patients with bvFTD on behavioural measures of emotional empathy, and whether empathic responses differ for negative versus positive stimuli. 24 patients with bvFTD and 24 healthy controls completed the Multifaceted Empathy Test (MET; Dziobek et al., 2008), a performance-based task that taps both cognitive and emotional facets of empathy, and allows for the discrimination of responses to negative versus positive realistic images. MET scores were also compared with caregiver ratings of patient behaviour on the Interpersonal Reactivity Index, which assesses patients' everyday demonstrations of perspective taking and empathic concern. Patients with bvFTD were less accurate than controls at inferring mental states for negative and positive stimuli. They also demonstrated lower levels of shared emotional experience, more positive emotional reactions, and diminished arousal to negative social stimuli relative to controls. Patients showed reduced emotional reactions to negative non-social stimuli as well. Lastly, the MET and IRI measures of emotional empathy were found to be significantly correlated within the bvFTD group. The results suggest that patients with bvFTD show a global deficit in cognitive empathy, and deficient emotional empathy for negative, but not positive, experiences. Further, a generalized emotional processing impairment for negative stimuli was observed, which could contribute to the

Can rhythmic auditory cuing remediate language-related deficits in Parkinson's disease?

PubMed

Kotz, Sonja A; Gunter, Thomas C

2015-03-01

Neurodegenerative changes of the basal ganglia in idiopathic Parkinson's disease (IPD) lead to motor deficits as well as general cognitive decline. Given these impairments, the question arises as to whether motor and nonmotor deficits can be ameliorated similarly. We reason that a domain-general sensorimotor circuit involved in temporal processing may support the remediation of such deficits. Following findings that auditory cuing benefits gait kinematics, we explored whether reported language-processing deficits in IPD can also be remediated via auditory cuing. During continuous EEG measurement, an individual diagnosed with IPD heard two types of temporally predictable but metrically different auditory beat-based cues: a march, which metrically aligned with the speech accent structure, a waltz that did not metrically align, or no cue before listening to naturally spoken sentences that were either grammatically well formed or were semantically or syntactically incorrect. Results confirmed that only the cuing with a march led to improved computation of syntactic and semantic information. We infer that a marching rhythm may lead to a stronger engagement of the cerebello-thalamo-cortical circuit that compensates dysfunctional striato-cortical timing. Reinforcing temporal realignment, in turn, may lead to the timely processing of linguistic information embedded in the temporally variable speech signal. © 2014 New York Academy of Sciences.

Cognitive Effects of Stimulant, Guanfacine, and Combined Treatment in Child and Adolescent Attention-Deficit/Hyperactivity Disorder.

PubMed

Bilder, Robert M; Loo, Sandra K; McGough, James J; Whelan, Fiona; Hellemann, Gerhard; Sugar, Catherine; Del'Homme, Melissa; Sturm, Alexandra; Cowen, Jennifer; Hanada, Grant; McCracken, James T

2016-08-01

Psychostimulants are partially effective in reducing cognitive dysfunction associated with attention-deficit/hyperactivity disorder (ADHD). Cognitive effects of guanfacine, an alternative treatment, are poorly understood. Given its distinct action on α2A receptors, guanfacine may have different or complementary effects relative to stimulants. This study tested stimulant and guanfacine monotherapies relative to combined treatment on cognitive functions important in ADHD. Children with ADHD (n = 182; aged 7-14 years) completed an 8-week, double blind, randomized, controlled trial with 3 arms: d-methylphenidate (DMPH), guanfacine (GUAN), or combination treatment with DMPH and GUAN (COMB). A nonclinical comparison group (n = 93) had baseline testing, and a subset was retested 8 weeks later (n = 38). Analyses examined treatment effects in 4 cognitive domains (working memory, response inhibition, reaction time, and reaction time variability) constructed from 20 variables. The ADHD group showed impaired working memory relative to the nonclinical comparison group (effect size = -0.53 SD unit). The treatments differed in effects on working memory but not other cognitive domains. Combination treatment improved working memory more than GUAN but was not significantly better than DMPH alone. Treatment did not fully normalize the initial deficit in ADHD relative to the comparison group. Combined treatment with DMPH and GUAN yielded greater improvements in working memory than placebo or GUAN alone, but the combined treatment was not superior to DMPH alone and did not extend to other cognitive domains. Although GUAN may be a useful add-on treatment to psychostimulants, additional strategies appear to be necessary to achieve normalization of cognitive function in ADHD. Single Versus Combination Medication Treatment for Children With Attention Deficit Hyperactivity Disorder; http://clinicaltrials.gov/; NCT00429273. Copyright © 2016 American Academy of Child and Adolescent

Disrupted white matter structure underlies cognitive deficit in hypertensive patients.

PubMed

Li, Xin; Ma, Chao; Sun, Xuan; Zhang, Junying; Chen, Yaojing; Chen, Kewei; Zhang, Zhanjun

2016-09-01

Hypertension is considered a risk factor of cognitive impairments and could result in white matter changes. Current studies on hypertension-related white matter (WM) changes focus only on regional changes, and the information about global changes in WM structure network is limited. We assessed the cognitive function in 39 hypertensive patients and 37 healthy controls with a battery of neuropsychological tests. The WM structural networks were constructed by utilizing diffusion tensor tractography and calculated topological properties of the networks using a graph theoretical method. The direct and indirect correlations among cognitive impairments, brain WM network disruptions and hypertension were analyzed with structural equation modelling (SEM). Hypertensive patients showed deficits in executive function, memory and attention compared with controls. An aberrant connectivity of WM networks was found in the hypertensive patients (P Eglob = 0.005, P Lp = 0.005), especially in the frontal and parietal regions. Importantly, SEM analysis showed that the decline of executive function resulted from aberrant WM networks in hypertensive patients (p = 0.3788, CFI = 0.99). These results suggest that the cognitive decline in hypertensive patients was due to frontal and parietal WM disconnections. Our findings highlight the importance of brain protection in hypertension patients. • Hypertension has a negative effect on the performance of the cognitive domains • Reduced efficiencies of white matter networks were shown in hypertension • Disrupted white matter networks are responsible for poor cognitive function in hypertension.

Polygenic risk score, genome-wide association, and gene set analyses of cognitive domain deficits in schizophrenia.

PubMed

Nakahara, Soichiro; Medland, Sarah; Turner, Jessica A; Calhoun, Vince D; Lim, Kelvin O; Mueller, Bryon A; Bustillo, Juan R; O'Leary, Daniel S; Vaidya, Jatin G; McEwen, Sarah; Voyvodic, James; Belger, Aysenil; Mathalon, Daniel H; Ford, Judith M; Guffanti, Guia; Macciardi, Fabio; Potkin, Steven G; van Erp, Theo G M

2018-06-12

This study assessed genetic contributions to six cognitive domains, identified by the MATRICS Cognitive Consensus Battery as relevant for schizophrenia, cognition-enhancing, clinical trials. Psychiatric Genomics Consortium Schizophrenia polygenic risk scores showed significant negative correlations with each cognitive domain. Genome-wide association analyses identified loci associated with attention/vigilance (rs830786 within HNF4G), verbal memory (rs67017972 near NDUFS4), and reasoning/problem solving (rs76872642 within HDAC9). Gene set analysis identified unique and shared genes across cognitive domains. These findings suggest involvement of common and unique mechanisms across cognitive domains and may contribute to the discovery of new therapeutic targets to treat cognitive deficits in schizophrenia. Copyright © 2018 Elsevier B.V. All rights reserved.

Tongluo Xingnao Effervescent Tablet preserves mitochondrial energy metabolism and attenuates cognition deficits in APPswe/PS1De9 mice.

PubMed

Dai, Yuan; Ma, Tao; Ren, Xiangyi; Wei, Jiangping; Fu, Wenjun; Ma, Yuntong; Xu, Shijun; Zhang, Zhanjun

2016-09-06

Tongluo Xingnao Effervescent Tablet (TXET), a traditional Chinese herbal formula composed of Ligusticum chuanxiong hor, Scutellaria baicalensis Georgi and Angelica sinensis, has been widely used to treat Alzheimer's disease (AD) and related dementias for decades in China. In the present study, we investigated the effects of TXET on mitochondrial function, energy metabolism and cognitive amelioration in the APPswe/PS1De9 transgenetic mouse model of AD. The energy charge and phosphocreatine, activity of the mitochondrial electron transport chain complexes, mitochondrial membrane potential, activity of Na(+)-K(+) ATPase and the expression levels of Bcl-2 and Bax in the brains were measured, respectively. TXET exhibits significant protection on mitochondrial function and energy supply in addition to ameliorating cognitive decline in APPswe/PS1De9 mice. TXET rescues mitochondrial function by increasing the mitochondrial membrane potential, energy charge levels, activity of respiratory chain complexes and Na(+)-K(+) ATPase activity. These findings suggest that TXET may attenuate cognition impairment through the restoration of mitochondrial function and energy metabolism in the brains in APPswe/PS1De9 mice. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Cognitive Deficits in Problematic Drinkers with and without Mild to Borderline Intellectual Disability

ERIC Educational Resources Information Center

van Duijvenbode, Neomi; Didden, Robert; VanDerNagel, Joanne E. L.; Korzilius, Hubert P. L. M.; Engels, Rutger C. M. E.

2018-01-01

We examined cognitive deficits in problematic drinkers with and without mild to borderline intellectual disability (MBID). Problematic drinkers were expected to show a significantly lower estimated performance IQ (PIQ), but not a lower estimated verbal IQ (VIQ), compared to light drinkers. Participants (N = 474) were divided into four groups based…

Novel Technology for Treating Individuals with Aphasia and Concomitant Cognitive Deficits

PubMed Central

Cherney, Leora R.; Halper, Anita S.

2009-01-01

Purpose This article describes three individuals with aphasia and concomitant cognitive deficits who used state-of-the-art computer software for training conversational scripts. Method Participants were assessed before and after 9 weeks of a computer script training program. For each participant, three individualized scripts were developed, recorded on the software, and practiced sequentially at home. Weekly meetings with the speech-language pathologist occurred to monitor practice and assess progress. Baseline and posttreatment scripts were audiotaped, transcribed, and compared to the target scripts for content, grammatical productivity, and rate of production of script-related words. Interviews were conducted at the conclusion of treatment. Results There was great variability in improvements across scripts, with two participants improving on two of their three scripts in measures of content, grammatical productivity, and rate of production of script-related words. One participant gained more than 5 points on the Aphasia Quotient of the Western Aphasia Battery. Five positive themes were consistently identified from exit interviews: increased verbal communication, improvements in other modalities and situations, communication changes noticed by others, increased confidence, and satisfaction with the software. Conclusion Computer-based script training potentially may be an effective intervention for persons with chronic aphasia and concomitant cognitive deficits. PMID:19158062

[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.

Air pollution, cognitive deficits and brain abnormalities: a pilot study with children and dogs.

PubMed

Calderón-Garcidueñas, Lilian; Mora-Tiscareño, Antonieta; Ontiveros, Esperanza; Gómez-Garza, Gilberto; Barragán-Mejía, Gerardo; Broadway, James; Chapman, Susan; Valencia-Salazar, Gildardo; Jewells, Valerie; Maronpot, Robert R; Henríquez-Roldán, Carlos; Pérez-Guillé, Beatriz; Torres-Jardón, Ricardo; Herrit, Lou; Brooks, Diane; Osnaya-Brizuela, Norma; Monroy, Maria E; González-Maciel, Angelica; Reynoso-Robles, Rafael; Villarreal-Calderon, Rafael; Solt, Anna C; Engle, Randall W

2008-11-01

Exposure to air pollution is associated with neuroinflammation in healthy children and dogs in Mexico City. Comparative studies were carried out in healthy children and young dogs similarly exposed to ambient pollution in Mexico City. Children from Mexico City (n: 55) and a low polluted city (n:18) underwent psychometric testing and brain magnetic resonance imaging MRI. Seven healthy young dogs with similar exposure to Mexico City air pollution had brain MRI, measurement of mRNA abundance of two inflammatory genes cyclooxygenase-2, and interleukin 1 beta in target brain areas, and histopathological evaluation of brain tissue. Children with no known risk factors for neurological or cognitive disorders residing in a polluted urban environment exhibited significant deficits in a combination of fluid and crystallized cognition tasks. Fifty-six percent of Mexico City children tested showed prefrontal white matter hyperintense lesions and similar lesions were observed in dogs (57%). Exposed dogs had frontal lesions with vascular subcortical pathology associated with neuroinflammation, enlarged Virchow-Robin spaces, gliosis, and ultrafine particulate matter deposition. Based on the MRI findings, the prefrontal cortex was a target anatomical region in Mexico City children and its damage could have contributed to their cognitive dysfunction. The present work presents a groundbreaking, interdisciplinary methodology for addressing relationships between environmental pollution, structural brain alterations by MRI, and cognitive deficits/delays in healthy children.

Comparison of the recovery patterns of language and cognitive functions in patients with post-traumatic language processing deficits and in patients with aphasia following a stroke.

PubMed

Vukovic, Mile; Vuksanovic, Jasmina; Vukovic, Irena

2008-01-01

In this study we investigated the recovery patterns of language and cognitive functions in patients with post-traumatic language processing deficits and in patients with aphasia following a stroke. The correlation of specific language functions and cognitive functions was analyzed in the acute phase and 6 months later. Significant recovery of the tested functions was observed in both groups. However, in patients with post-traumatic language processing deficits the degree of recovery of most language functions and some cognitive functions was higher. A significantly greater correlation was revealed within language and cognitive functions, as well as between language functions and other aspects of cognition in patients with post-traumatic language processing deficits than in patients with aphasia following a stroke. Our results show that patients with post-traumatic language processing deficits have a different recovery pattern and a different pattern of correlation between language and cognitive functions compared to patients with aphasia following a stroke. (1) Better understanding of the differences in recovery of language and cognitive functions in patients who have suffered strokes and those who have experienced traumatic brain injury. (2) Better understanding of the relationship between language and cognitive functions in patients with post-traumatic language processing deficits and in patients with aphasia following a stroke. (3) Better understanding of the factors influencing recovery.

Cognitive deficits in obese persons with and without binge eating disorder. Investigation using a mental flexibility task.

PubMed

Mobbs, Olivia; Iglesias, Katia; Golay, Alain; Van der Linden, Martial

2011-08-01

Studies suggest that cognitive deficits and attentional biases play a role in the development and maintenance of obesity and eating disorders. In this study, we simultaneously examine attentional biases, as well as inhibitory control and mental flexibility, which are keys to controlling unwanted behaviors and thoughts in obese patients with and without binge eating disorder. 16 obese patients with binge eating disorder and 16 patients without binge eating disorder were compared with 16 normal-weight controls on a "food/body-mental flexibility task", which allows the investigation of inhibitory control, mental flexibility and attention for stimuli related to the body and food. All obese patients made significantly more errors (i.e., pressing a key when a distracter displayed) and more omissions (i.e., not pressing a key when a target displayed) than controls in both food and body sections of the task. Obese participants with binge eating disorder made significantly more errors and omissions than those without binge eating disorder. No difference between groups was found concerning mental flexibility and cognitive biases for food- and body-related targets. These results suggest that obese patients have a general inhibition problem and difficulty focusing attention, which do not depend on the types of stimuli processed. The results also suggest that these cognitive deficits are more severe in obese patients with binge eating disorder, which indicates that there is a continuum of increasing inhibition and cognitive problems with increasingly disordered eating. These cognitive deficits may contribute to problematic eating behaviors. Copyright © 2011 Elsevier Ltd. All rights reserved.

Social Cognition Deficits: The Key to Discriminate Behavioral Variant Frontotemporal Dementia from Alzheimer's Disease Regardless of Amnesia?

PubMed

Bertoux, Maxime; de Souza, Leonardo Cruz; O'Callaghan, Claire; Greve, Andrea; Sarazin, Marie; Dubois, Bruno; Hornberger, Michael

2016-01-01

Relative sparing of episodic memory is a diagnostic criterion of behavioral variant frontotemporal dementia (bvFTD). However, increasing evidence suggests that bvFTD patients can show episodic memory deficits at a similar level as Alzheimer's disease (AD). Social cognition tasks have been proposed to distinguish bvFTD, but no study to date has explored the utility of such tasks for the diagnosis of amnestic bvFTD. Here, we contrasted social cognition performance of amnestic and non-amnestic bvFTD from AD, with a subgroup having confirmed in vivo pathology markers. Ninety-six participants (38 bvFTD and 28 AD patients as well as 30 controls) performed the short Social-cognition and Emotional Assessment (mini-SEA). BvFTD patients were divided into amnestic versus non-amnestic presentation using the validated Free and Cued Selective Reminding Test (FCSRT) assessing episodic memory. As expected, the accuracy of the FCSRT to distinguish the overall bvFTD group from AD was low (69.7% ) with ∼50% of bvFTD patients being amnestic. By contrast, the diagnostic accuracy of the mini-SEA was high (87.9% ). When bvFTD patients were split on the level of amnesia, mini-SEA diagnostic accuracy remained high (85.1% ) for amnestic bvFTD versus AD and increased to very high (93.9% ) for non-amnestic bvFTD versus AD. Social cognition deficits can distinguish bvFTD and AD regardless of amnesia to a high degree and provide a simple way to distinguish both diseases at presentation. These findings have clear implications for the diagnostic criteria of bvFTD. They suggest that the emphasis should be on social cognition deficits with episodic memory deficits not being a helpful diagnostic criterion in bvFTD.

Concussive Brain Trauma in the Mouse Results in Acute Cognitive Deficits and Sustained Impairment of Axonal Function

PubMed Central

Creed, Jennifer A.; DiLeonardi, Ann Mae; Fox, Douglas P.; Tessler, Alan R.

2011-01-01

Abstract Concussive brain injury (CBI) accounts for approximately 75% of all brain-injured people in the United States each year and is particularly prevalent in contact sports. Concussion is the mildest form of diffuse traumatic brain injury (TBI) and results in transient cognitive dysfunction, the neuropathologic basis for which is traumatic axonal injury (TAI). To evaluate the structural and functional changes associated with concussion-induced cognitive deficits, adult mice were subjected to an impact on the intact skull over the midline suture that resulted in a brief apneic period and loss of the righting reflex. Closed head injury also resulted in an increase in the wet weight:dry weight ratio in the cortex suggestive of edema in the first 24 h, and the appearance of Fluoro-Jade-B-labeled degenerating neurons in the cortex and dentate gyrus of the hippocampus within the first 3 days post-injury. Compared to sham-injured mice, brain-injured mice exhibited significant deficits in spatial acquisition and working memory as measured using the Morris water maze over the first 3 days (p<0.001), but not after the fourth day post-injury. At 1 and 3 days post-injury, intra-axonal accumulation of amyloid precursor protein in the corpus callosum and cingulum was accompanied by neurofilament dephosphorylation, impaired transport of Fluoro-Gold and synaptophysin, and deficits in axonal conductance. Importantly, deficits in retrograde transport and in action potential of myelinated axons continued to be observed until 14 days post-injury, at which time axonal degeneration was apparent. These data suggest that despite recovery from acute cognitive deficits, concussive brain trauma leads to axonal degeneration and a sustained perturbation of axonal function. PMID:21299360

Passive Immunization Reduces Behavioral and Neuropathological Deficits in an Alpha-Synuclein Transgenic Model of Lewy Body Disease

PubMed Central

Masliah, Eliezer; Rockenstein, Edward; Mante, Michael; Crews, Leslie; Spencer, Brian; Adame, Anthony; Patrick, Christina; Trejo, Margarita; Ubhi, Kiren; Rohn, Troy T.; Mueller-Steiner, Sarah; Seubert, Peter; Barbour, Robin; McConlogue, Lisa; Buttini, Manuel; Games, Dora; Schenk, Dale

2011-01-01

Dementia with Lewy bodies (DLB) and Parkinson's Disease (PD) are common causes of motor and cognitive deficits and are associated with the abnormal accumulation of alpha-synuclein (α-syn). This study investigated whether passive immunization with a novel monoclonal α-syn antibody (9E4) against the C-terminus (CT) of α-syn was able to cross into the CNS and ameliorate the deficits associated with α-syn accumulation. In this study we demonstrate that 9E4 was effective at reducing behavioral deficits in the water maze, moreover, immunization with 9E4 reduced the accumulation of calpain-cleaved α-syn in axons and synapses and the associated neurodegenerative deficits. In vivo studies demonstrated that 9E4 traffics into the CNS, binds to cells that display α-syn accumulation and promotes α-syn clearance via the lysosomal pathway. These results suggest that passive immunization with monoclonal antibodies against the CT of α-syn may be of therapeutic relevance in patients with PD and DLB. PMID:21559417

Tetrahydrohyperforin prevents cognitive deficit, Aβ deposition, tau phosphorylation and synaptotoxicity in the APPswe/PSEN1ΔE9 model of Alzheimer's disease: a possible effect on APP processing

PubMed Central

Inestrosa, N C; Tapia-Rojas, C; Griffith, T N; Carvajal, F J; Benito, M J; Rivera-Dictter, A; Alvarez, A R; Serrano, F G; Hancke, J L; Burgos, P V; Parodi, J; Varela-Nallar, L

2011-01-01

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a progressive deterioration of cognitive abilities, amyloid-β peptide (Aβ) accumulation and synaptic alterations. Previous studies indicated that hyperforin, a component of the St John's Wort, prevents Aβ neurotoxicity and some behavioral impairments in a rat model of AD. In this study we examined the ability of tetrahydrohyperforin (IDN5607), a stable hyperforin derivative, to prevent the cognitive deficit and synaptic impairment in an in vivo model of AD. In double transgenic APPswe/PSEN1ΔE9 mice, IDN5706 improves memory and prevents the impairment of synaptic plasticity in a dose-dependent manner, inducing a recovery of long-term potentiation. In agreement with these findings, IDN5706 prevented the decrease in synaptic proteins in hippocampus and cortex. In addition, decreased levels of tau hyperphosphorylation, astrogliosis, and total fibrillar and oligomeric forms of Aβ were determined in double transgenic mice treated with IDN5706. In cultured cells, IDN5706 decreased the proteolytic processing of the amyloid precursor protein that leads to Aβ peptide generation. These findings indicate that IDN5706 ameliorates AD neuropathology and could be considered of therapeutic relevance in AD treatment. PMID:22832522

Mori Folium and Mori Fructus Mixture Attenuates High-Fat Diet-Induced Cognitive Deficits in Mice

PubMed Central

Jeong, Hyun Uk; Park, Gunhyuk; Kim, Hocheol; Lim, Yunsook; Oh, Myung Sook

2015-01-01

Obesity has become a global health problem, contributing to various diseases including diabetes, hypertension, cancer, and dementia. Increasing evidence suggests that obesity can also cause neuronal damage, long-term memory loss, and cognitive impairment. The leaves and the fruits of Morus alba L., containing active phytochemicals, have been shown to possess antiobesity and hypolipidemic properties. Thus, in the present study, we assessed their effects on cognitive functioning in mice fed a high-fat diet by performing immunohistochemistry, using antibodies against c-Fos, synaptophysin, and postsynaptic density protein 95 and a behavioral test. C57BL/6 mice fed a high-fat diet for 21 weeks exhibited increased body weight, but mice coadministered an optimized Mori Folium and Mori Fructus extract mixture (2 : 1; MFE) for the final 12 weeks exhibited significant body weight loss. Additionally, obese mice exhibited not only reduced neural activity, but also decreased presynaptic and postsynaptic activities, while MFE-treated mice exhibited recovery of these activities. Finally, cognitive deficits induced by the high-fat diet were recovered by cotreatment with MFE in the novel object recognition test. Our findings suggest that the antiobesity effects of MFE resulted in recovery of the cognitive deficits induced by the high-fat diet by regulation of neural and synaptic activities. PMID:25945108

Mori folium and mori fructus mixture attenuates high-fat diet-induced cognitive deficits in mice.

PubMed

Kim, Hyo Geun; Jeong, Hyun Uk; Park, Gunhyuk; Kim, Hocheol; Lim, Yunsook; Oh, Myung Sook

2015-01-01

Obesity has become a global health problem, contributing to various diseases including diabetes, hypertension, cancer, and dementia. Increasing evidence suggests that obesity can also cause neuronal damage, long-term memory loss, and cognitive impairment. The leaves and the fruits of Morus alba L., containing active phytochemicals, have been shown to possess antiobesity and hypolipidemic properties. Thus, in the present study, we assessed their effects on cognitive functioning in mice fed a high-fat diet by performing immunohistochemistry, using antibodies against c-Fos, synaptophysin, and postsynaptic density protein 95 and a behavioral test. C57BL/6 mice fed a high-fat diet for 21 weeks exhibited increased body weight, but mice coadministered an optimized Mori Folium and Mori Fructus extract mixture (2 : 1; MFE) for the final 12 weeks exhibited significant body weight loss. Additionally, obese mice exhibited not only reduced neural activity, but also decreased presynaptic and postsynaptic activities, while MFE-treated mice exhibited recovery of these activities. Finally, cognitive deficits induced by the high-fat diet were recovered by cotreatment with MFE in the novel object recognition test. Our findings suggest that the antiobesity effects of MFE resulted in recovery of the cognitive deficits induced by the high-fat diet by regulation of neural and synaptic activities.

Stimulation of 5-HT2C Receptors Improves Cognitive Deficits Induced by Human Tryptophan Hydroxylase 2 Loss of Function Mutation

PubMed Central

Del'Guidice, Thomas; Lemay, Francis; Lemasson, Morgane; Levasseur-Moreau, Jean; Manta, Stella; Etievant, Adeline; Escoffier, Guy; Doré, François Y; Roman, François S; Beaulieu, Jean-Martin

2014-01-01

Polymorphisms in the gene encoding the serotonin synthesis enzyme Tph2 have been identified in mental illnesses, including bipolar disorder, major depression, autism, schizophrenia, and ADHD. Deficits in cognitive flexibility and perseverative behaviors are shared common symptoms in these disorders. However, little is known about the impact of Tph2 gene variants on cognition. Mice expressing a human TPH2 variant (Tph2-KI) were used to investigate cognitive consequences of TPH2 loss of function and pharmacological treatments. We applied a recently developed behavioral assay, the automated H-maze, to study cognitive functions in Tph2-KI mice. This assay involves the consecutive discovery of three different rules: a delayed alternation task, a non-alternation task, and a delayed reversal task. Possible contribution of locomotion, reward, and sensory perception were also investigated. The expression of loss-of-function mutant Tph2 in mice was associated with impairments in reversal learning and cognitive flexibility, accompanied by perseverative behaviors similar to those observed in human clinical studies. Pharmacological restoration of 5-HT synthesis with 5-hydroxytryptophan or treatment with the 5-HT2C receptor agonist CP809.101 reduced cognitive deficits in Tph2-KI mice and abolished perseveration. In contrast, treatment with the psychostimulant methylphenidate exacerbated cognitive deficits in mutant mice. Results from this study suggest a contribution of TPH2 in the regulation of cognition. Furthermore, identification of a role for a 5-HT2 receptor agonist as a cognition-enhancing agent in mutant mice suggests a potential avenue to explore for the personalized treatment of cognitive symptoms in humans with reduced 5-HT synthesis and TPH2 polymorphisms. PMID:24196946

Planning music-based amelioration and training in infancy and childhood based on neural evidence.

PubMed

Huotilainen, Minna; Tervaniemi, Mari

2018-05-04

Music-based amelioration and training of the developing auditory system has a long tradition, and recent neuroscientific evidence supports using music in this manner. Here, we present the available evidence showing that various music-related activities result in positive changes in brain structure and function, becoming helpful for auditory cognitive processes in everyday life situations for individuals with typical neural development and especially for individuals with hearing, learning, attention, or other deficits that may compromise auditory processing. We also compare different types of music-based training and show how their effects have been investigated with neural methods. Finally, we take a critical position on the multitude of error sources found in amelioration and training studies and on publication bias in the field. We discuss some future improvements of these issues in the field of music-based training and their potential results at the neural and behavioral levels in infants and children for the advancement of the field and for a more complete understanding of the possibilities and significance of the training. © 2018 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals, Inc. on behalf of New York Academy of Sciences.

White matter lesions and the cholinergic deficit in aging and mild cognitive impairment.

PubMed

Richter, Nils; Michel, Anne; Onur, Oezguer A; Kracht, Lutz; Dietlein, Markus; Tittgemeyer, Marc; Neumaier, Bernd; Fink, Gereon R; Kukolja, Juraj

2017-05-01

In Alzheimer's disease (AD), white matter lesions (WMLs) are associated with an increased risk of progression from mild cognitive impairment (MCI) to dementia, while memory deficits have, at least in part, been linked to a cholinergic deficit. We investigated the relationship between WML load assessed with the Scheltens scale, cerebral acetylcholinesterase (AChE) activity measured with [ 11 C]N-methyl-4-piperidyl acetate PET, and neuropsychological performance in 17 patients with MCI due to AD and 18 cognitively normal older participants. Only periventricular, not nonperiventricular, WML load negatively correlated with AChE activity in both groups. Memory performance depended on periventricular and total WML load across groups. Crucially, AChE activity predicted memory function better than WML load, gray matter atrophy, or age. The effects of WML load on memory were fully mediated by AChE activity. Data suggest that the contribution of WML to the dysfunction of the cholinergic system in MCI due to AD depends on WML distribution. Pharmacologic studies are warranted to explore whether this influences the response to cholinergic treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

Cognitive deficit and poverty in the first 5 years of childhood in Bangladesh.

PubMed

Hamadani, Jena D; Tofail, Fahmida; Huda, Syed N; Alam, Dewan S; Ridout, Deborah A; Attanasio, Orazio; Grantham-McGregor, Sally M

2014-10-01

We aimed to determine the timing and size of the cognitive deficit associated with poverty in the first 5 years of life and to examine the role of parental characteristics, pre- and postnatal growth, and stimulation in the home in Bangladeshi children. We hypothesized that the effect of poverty on cognition begins in infancy and is mainly mediated by these factors. We enrolled 2853 singletons, a subsample from a pregnancy supplementation trial in a poor rural area. We assessed mental development at 7, 18, and 64 months; anthropometry at birth, 12, 24, and 64 months; home stimulation at 18 and 64 months; and family's socioeconomic background. In multiple regression analyses, we examined the effect of poverty at birth on IQ at 64 months and the extent that other factors mediated the effect. A mean cognitive deficit of 0.2 (95% confidence interval -0.4 to -0.02) z scores between the first and fifth wealth quintiles was apparent at 7 months and increased to 1.2 (95% confidence interval -1.3 to -1.0) z scores of IQ by 64 months. Parental education, pre- and postnatal growth in length, and home stimulation mediated 86% of the effects of poverty on IQ and had independent effects. Growth in the first 2 years had larger effects than later growth. Home stimulation had effects throughout the period. Effects of poverty on children's cognition are mostly mediated through parental education, birth size, growth in the first 24 months, and home stimulation in the first 5 years. Copyright © 2014 by the American Academy of Pediatrics.

Neurocognitive impairment in the deficit subtype of schizophrenia.

PubMed

Fervaha, Gagan; Agid, Ofer; Foussias, George; Siddiqui, Ishraq; Takeuchi, Hiroyoshi; Remington, Gary

2016-08-01

Schizophrenia is a heterogeneous disorder characterized by numerous diverse signs and symptoms. Individuals with prominent, persistent, and idiopathic negative symptoms are thought to encompass a distinct subtype of schizophrenia. Previous work, including studies involving neuropsychological evaluations, has supported this position. The present study sought to further examine whether deficit patients are cognitively distinct from non-deficit patients with schizophrenia. A comprehensive neurocognitive battery including tests of verbal memory, vigilance, processing speed, reasoning, and working memory was administered to 657 patients with schizophrenia. Of these, 144 (22 %) patients were classified as deficit patients using a proxy identification method based on severity, persistence over time, and possible secondary sources (e.g., depression) of negative symptoms. Deficit patients with schizophrenia performed worse on all tests of cognition relative to non-deficit patients. These patients were characterized by a generalized cognitive impairment on the order of about 0.4 standard deviations below that of non-deficit patients. However, when comparing deficit patients to non-deficit patients who also present with negative symptoms, albeit not enduring or primary, no group differences in cognitive performance were found. Furthermore, a discriminant function analysis classifying patients into deficit/non-deficit groups based on cognitive scores demonstrated only 62.3 % accuracy, meaning over one-third of individuals were misclassified. The deficit subtype of schizophrenia is not markedly distinct from non-deficit schizophrenia in terms of neurocognitive performance. While deficit patients tend to have poorer performance on cognitive tests, the magnitude of this effect is relatively modest, translating to over 70 % overlap in scores between groups.

Tandospirone, a 5-HT1A partial agonist, ameliorates aberrant lactate production in the prefrontal cortex of rats exposed to blockade of N-methy-D-aspartate receptors; Toward the therapeutics of cognitive impairment of schizophrenia.

PubMed

Uehara, Takashi; Matsuoka, Tadasu; Sumiyoshi, Tomiki

2014-01-01

Augmentation therapy with serotonin-1A (5-HT1A) receptor partial agonists has been suggested to improve cognitive impairment in patients with schizophrenia. Decreased activity of prefrontal cortex may provide a basis for cognitive deficits of the disease. Lactate plays a significant role in the supply of energy to the brain, and glutamatergic neurotransmission contributes to lactate production. The purposes of this study were to examine the effect of repeated administration (once a daily for 4 days) of tandospirone (0.05 or 5 mg/kg) on brain energy metabolism, as represented by extracellular lactate concentration (eLAC) in the medial prefrontal cortex (mPFC) of a rat model of schizophrenia. Four-day treatment with MK-801, an NMDA-R antagonist, prolonged eLAC elevation induced by foot-shock stress (FS). Co-administration with the high-dose tandospirone suppressed prolonged FS-induced eLAC elevation in rats receiving MK-801, whereas tandospirone by itself did not affected eLAC increment. These results suggest that stimulation of 5-HT1A receptors ameliorates abnormalities of energy metabolism in the mPFC due to blockade of NMDA receptors. These findings provide a possible mechanism, based on brain energy metabolism, by which 5-HT1A agonism improve cognitive impairment of schizophrenia and related disorders.

Different MK-801 administration schedules induce mild to severe learning impairments in an operant conditioning task: role of buspirone and risperidone in ameliorating these cognitive deficits.

PubMed

Rapanelli, Maximiliano; Frick, Luciana Romina; Bernardez-Vidal, Micaela; Zanutto, Bonifacio Silvano

2013-11-15

Blockade of N-methyl-d-aspartate receptor (NMDA) by the noncompetitive NMDA receptor (NMDAR) antagonist MK-801 produces behavioral abnormalities and alterations in prefrontal cortex (PFC) functioning. Due to the critical role of the PFC in operant conditioning task learning, we evaluated the effects of acute, repeated postnatal injections of MK-801 (0.1mg/kg) on learning performance. We injected Long-Evans rats i.p. with MK-801 (0.1mg/kg) using three different administration schedules: injection 40 min before beginning the task (during) (n=12); injection twice daily for six consecutive days prior to beginning the experimental procedures (prior) (n=12); or twice daily subcutaneous injections from postnatal day 7 to 11 (postnatal) (n=12). Next, we orally administered risperidone (serotonin receptor 2A and dopamine receptor 2 antagonist, 1mg/kg) or buspirone (serotonin receptor 1A partial agonist, 10mg/kg) to animals treated with the MK-801 schedule described above. The postnatal and prior administration schedules produced severe learning deficits, whereas injection of MK-801 just before training sessions had only mild effects on acquisition of an operant conditioning. Risperidone was able to reverse the detrimental effect of MK-801 in the animals that were treated with MK-801 during and prior training sessions. In contrast, buspirone was only effective at mitigating the cognitive deficits induced by MK-801 when administered during the training procedures. The data demonstrates that NMDA antagonism disrupts basic mechanisms of learning in a simple PFC-mediated operant conditioning task, and that buspirone and risperidone failed to attenuate the learning deficits when NMDA neurotransmission was blocked in the early stages of the postnatal period. Copyright © 2013 Elsevier B.V. All rights reserved.

Nicotinic alpha 7 receptor agonists EVP-6124 and BMS-933043, attenuate scopolamine-induced deficits in visuo-spatial paired associates learning.

PubMed

Weed, Michael R; Polino, Joseph; Signor, Laura; Bookbinder, Mark; Keavy, Deborah; Benitex, Yulia; Morgan, Daniel G; King, Dalton; Macor, John E; Zaczek, Robert; Olson, Richard; Bristow, Linda J

2017-01-01

Agonists at the nicotinic acetylcholine alpha 7 receptor (nAChR α7) subtype have the potential to treat cognitive deficits in patients with Alzheimer's disease (AD) or schizophrenia. Visuo-spatial paired associates learning (vsPAL) is a task that has been shown to reliably predict conversion from mild cognitive impairment to AD in humans and can also be performed by nonhuman primates. Reversal of scopolamine-induced impairment of vsPAL performance may represent a translational approach for the development of nAChR α7 agonists. The present study investigated the effect of treatment with the acetylcholinesterase inhibitor, donepezil, or three nAChR α7 agonists, BMS-933043, EVP-6124 and RG3487, on vsPAL performance in scopolamine-treated cynomolgus monkeys. Scopolamine administration impaired vsPAL performance accuracy in a dose- and difficulty- dependent manner. The impairment of eventual accuracy, a measure of visuo-spatial learning during the task, was significantly ameliorated by treatment with donepezil (0.3 mg/kg, i.m.), EVP-6124 (0.01 mg/kg, i.m.) or BMS-933043 (0.03, 0.1 and 0.3 mg/kg, i.m.). Both nAChR α7 agonists showed inverted-U shaped dose-effect relationships with EVP-6124 effective at a single dose only whereas BMS-933043 was effective across at least a 10 fold dose/exposure range. RG3487 was not efficacious in this paradigm at the dose range examined (0.03-1 mg/kg, i.m.). These results are the first demonstration that the nAChR α7 agonists, EVP-6124 and BMS-933043, can ameliorate scopolamine-induced cognitive deficits in nonhuman primates performing the vsPAL task.

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.

Integrative Transcriptome Profiling of Cognitive Aging and Its Preservation through Ser/Thr Protein Phosphatase Regulation.

PubMed

Park, C Sehwan; Valomon, Amandine; Welzl, Hans

2015-01-01

Environmental enrichment has been reported to delay or restore age-related cognitive deficits, however, a mechanism to account for the cause and progression of normal cognitive decline and its preservation by environmental enrichment is lacking. Using genome-wide SAGE-Seq, we provide a global assessment of differentially expressed genes altered with age and environmental enrichment in the hippocampus. Qualitative and quantitative proteomics in naïve young and aged mice was used to further identify phosphorylated proteins differentially expressed with age. We found that increased expression of endogenous protein phosphatase-1 inhibitors in aged mice may be characteristic of long-term environmental enrichment and improved cognitive status. As such, hippocampus-dependent performances in spatial, recognition, and associative memories, which are sensitive to aging, were preserved by environmental enrichment and accompanied by decreased protein phosphatase activity. Age-associated phosphorylated proteins were also found to correspond to the functional categories of age-associated genes identified through transcriptome analysis. Together, this study provides a comprehensive map of the transcriptome and proteome in the aging brain, and elucidates endogenous protein phosphatase-1 inhibition as a potential means through which environmental enrichment may ameliorate age-related cognitive deficits.

Cognitive Deficits Underlying Error Behavior on a Naturalistic Task after Severe Traumatic Brain Injury

PubMed Central

Hendry, Kathryn; Ownsworth, Tamara; Beadle, Elizabeth; Chevignard, Mathilde P.; Fleming, Jennifer; Griffin, Janelle; Shum, David H. K.

2016-01-01

People with severe traumatic brain injury (TBI) often make errors on everyday tasks that compromise their safety and independence. Such errors potentially arise from the breakdown or failure of multiple cognitive processes. This study aimed to investigate cognitive deficits underlying error behavior on a home-based version of the Cooking Task (HBCT) following TBI. Participants included 45 adults (9 females, 36 males) with severe TBI aged 18–64 years (M = 37.91, SD = 13.43). Participants were administered the HBCT in their home kitchens, with audiovisual recordings taken to enable scoring of total errors and error subtypes (Omissions, Additions, Estimations, Substitutions, Commentary/Questions, Dangerous Behavior, Goal Achievement). Participants also completed a battery of neuropsychological tests, including the Trail Making Test, Hopkins Verbal Learning Test-Revised, Digit Span, Zoo Map test, Modified Stroop Test, and Hayling Sentence Completion Test. After controlling for cooking experience, greater Omissions and Estimation errors, lack of goal achievement, and longer completion time were significantly associated with poorer attention, memory, and executive functioning. These findings indicate that errors on naturalistic tasks arise from deficits in multiple cognitive domains. Assessment of error behavior in a real life setting provides insight into individuals' functional abilities which can guide rehabilitation planning and lifestyle support. PMID:27790099

Relationships among cognitive deficits and component skills of reading in younger and older students with developmental dyslexia.

PubMed

Park, Heeyoung; Lombardino, Linda J

2013-09-01

Processing speed deficits along with phonological awareness deficits have been identified as risk factors for dyslexia. This study was designed to examine the behavioral profiles of two groups, a younger (6-8 years) and an older (10-15 years) group of dyslexic children for the purposes of (1) evaluating the degree to which phonological awareness and processing speed deficits occur in the two developmental cohorts; (2) determining the strength of relationships between the groups' respective mean scores on cognitive tasks of phonological awareness and processing speed and their scores on component skills of reading; and (3) evaluating the degree to which phonological awareness and processing speed serve as concurrent predictors of component reading skills for each group. The mean scaled scores for both groups were similar on all but one processing speed task. The older group was significantly more depressed on a visual matching test of attention, scanning, and speed. Correlations between reading skills and the cognitive constructs were very similar for both age-groups. Neither of the two phonological awareness tasks correlated with either of the two processing speed tasks or with any of the three measures of reading. One of the two processing speed measures served as a concurrent predictor of word- and text-level reading in the younger, however, only the rapid naming measure functioned as a concurrent predictor of word reading in the older group. Conversely, phonological processing measures did not serve as concurrent predictors for word-level or text-level reading in either of the groups. Descriptive analyses of individual subjects' deficits in the domains of phonological awareness and processing speed revealed that (1) both linguistic and nonlinguistic processing speed deficits in the younger dyslexic children occurred at higher rates than deficits in phonological awareness and (2) cognitive deficits within and across these two domains were greater in the older

Effects of APOE ε4, age, and HIV on glial metabolites and cognitive deficits.

PubMed

Chang, Linda; Jiang, Caroline; Cunningham, Eric; Buchthal, Steven; Douet, Vanessa; Andres, Marilou; Ernst, Thomas

2014-06-17

We aimed to evaluate the combined effects of HIV and APOE ε4 allele(s) on glial metabolite levels, and on known cognitive deficits associated with either condition, across the ages. One hundred seventy-seven participants, primarily of white and mixed race (97 seronegative subjects: aged 44.7 ± 1.3 years, 85 [87.6%] men, 28 [28.9%] APOE ε4+; 80 HIV+ subjects: aged 47.3 ± 1.1 years, 73 [91.3%] men, 23 [28.8%] APOE ε4+), were assessed cross-sectionally for metabolite concentrations using proton magnetic resonance spectroscopy in 4 brain regions and for neuropsychological performance. Frontal white matter myo-inositol was elevated in subjects with HIV across the age span but showed age-dependent increase in seronegative subjects, especially in APOE ε4+ carriers. In contrast, only seronegative APOE ε4+ subjects showed elevated myo-inositol in parietal cortex. All APOE ε4+ subjects had lower total creatine in basal ganglia. While all HIV subjects showed greater cognitive deficits, HIV+ APOE ε4+ subjects had the poorest executive function, fluency memory, and attention/working memory. Higher myo-inositol levels were associated with poorer fine motor function across all subjects, slower speed of information processing in APOE ε4+ subjects, and worse fluency in HIV+ APOE ε4+ subjects. In frontal white matter of subjects with HIV, the persistent elevation and lack of normal age-dependent increase in myo-inositol suggest that persistent glial activation attenuated the typical antagonistic pleiotropic effects of APOE ε4 on neuroinflammation. APOE ε4 negatively affects energy metabolism in brain regions rich in dopaminergic synapses. The combined effects of HIV infection and APOE ε4 may lead to greater cognitive deficits, especially in those with greater neuroinflammation. APOE ε4 allele(s) may be a useful genetic marker to identify white and mixed-race HIV subjects at risk for cognitive decline. © 2014 American Academy of Neurology.

Overstimulation of newborn mice leads to behavioral differences and deficits in cognitive performance

PubMed Central

Christakis, D. A.; Ramirez, J. S. B.; Ramirez, J. M.

2012-01-01

Observational studies in humans have found associations between overstimulation in infancy via excessive television viewing and subsequent deficits in cognition and attention. We developed and tested a mouse model of overstimulation whereby p10 mice were subjected to audio (70 db) and visual stimulation (flashing lights) for six hours per day for a total of 42 days. 10 days later cognition and behavior were tested using the following tests: Light Dark Latency, Elevated Plus Maze, Novel Object Recognition, and Barnes Maze. In all tests, overstimulated mice performed significantly worse compared to controls suggesting increased activity and risk taking, diminished short term memory, and decreased cognitive function. These findings suggest that excessive non-normative stimulation during critical periods of brain development can have demonstrable untoward effects on subsequent neurocognitive function. PMID:22855702

Emotional Intelligence deficits in schizophrenia: The impact of non-social cognition.

PubMed

Frajo-Apor, Beatrice; Pardeller, Silvia; Kemmler, Georg; Welte, Anna-Sophia; Hofer, Alex

2016-04-01

Previous studies using the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) revealed significant performance deficits across all areas of Emotional Intelligence (EI) in schizophrenia patients compared to healthy controls. However, none of these studies has investigated a potential influence of non-social cognition on these findings. 56 schizophrenia outpatients and 84 control subjects were investigated using the MSCEIT and the Brief Assessment of Cognition in Schizophrenia (BACS). Analyses of covariance were performed with adjustment for the BACS composite score and education. To investigate this issue in more detail, a mediation analysis was conducted. Patients showed significantly lower EI and non-social cognition levels compared to healthy controls. After adjustment for BACS composite score and education, only the group difference in the "managing emotions" branch and thus in the "strategic" EI part of the MSCEIT remained statistically significant, whereas for all other MSCEIT branches (perceiving, using, understanding emotions) statistical significance was lost. The mediation analysis revealed that the difference between schizophrenia patients and controls regarding the MSCEIT total score was almost fully attributable to the mediating effect of non-social cognition. Our findings suggest that in schizophrenia patients EI is largely influenced by non-social cognitive functioning. Only the "managing emotions" branch was found to be independent of non-social cognition. Consequently, non-social cognitive performance was mainly responsible for the observed differences in EI between schizophrenia patients and controls. This has to be taken into account when interpreting MSCEIT data in this population. Copyright © 2016 Elsevier B.V. All rights reserved.

Pioglitazone Improves Cognitive Function via Increasing Insulin Sensitivity and Strengthening Antioxidant Defense System in Fructose-Drinking Insulin Resistance Rats

PubMed Central

Yin, Qing-Qing; Pei, Jin-Jing; Xu, Song; Luo, Ding-Zhen; Dong, Si-Qing; Sun, Meng-Han; You, Li; Sun, Zhi-Jian; Liu, Xue-Ping

2013-01-01

Insulin resistance (IR) links Alzheimer’s disease (AD) with oxidative damage, cholinergic deficit, and cognitive impairment. Peroxisome proliferator-activated receptor γ (PPARγ) agonist pioglitazone previously used to treat type 2 diabetes mellitus (T2DM) has also been demonstrated to be effective in anti-inflammatory reaction and anti-oxidative stress in the animal models of AD and other neuroinflammatory diseases. Here, we investigated the effect of pioglitazone on learning and memory impairment and the molecular events that may cause it in fructose-drinking insulin resistance rats. We found that long-term fructose-drinking causes insulin resistance, oxidative stress, down-regulated activity of cholinergic system, and cognitive deficit, which could be ameliorated by pioglitazone administration. The results from the present study provide experimental evidence for using pioglitazone in the treatment of brain damage caused by insulin resistance. PMID:23527159

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.

Deficits in temporal order memory induced by interferon-alpha (IFN-α) treatment are rescued by aerobic exercise.

PubMed

Barlow, Sally; Fahey, Briana; Smith, Kimberley J; Passecker, Johannes; Della-Chiesa, Andrea; Hok, Vincent; Day, Jennifer S; Callaghan, Charlotte K; O'Mara, Shane M

2018-05-18

Patients receiving cytokine immunotherapy with IFN-α frequently present with neuropsychiatric consequences and cognitive impairments, including a profound depressive-like symptomatology. While the neurobiological substrates of the dysfunction that leads to adverse events in IFN-α-treated patients remains ill-defined, dysfunctions of the hippocampus and prefrontal cortex (PFC) are strong possibilities. To date, hippocampal deficits have been well-characterised; there does however remain a lack of insight into the nature of prefrontal participation. Here, we used a PFC-supported temporal order memory paradigm to examine if IFN-α treatment induced deficits in performance; additionally, we used an object recognition task to assess the integrity of the perirhinal cortex (PRH). Finally, the utility of exercise as an ameliorative strategy to recover temporal order deficits in rats was also explored. We found that IFN-α-treatment impaired temporal order memory discriminations, whereas recognition memory remained intact, reflecting a possible dissociation between recognition and temporal order memory processing. Further characterisation of temporal order memory impairments using a longitudinal design revealed that deficits persisted for 10 weeks following cessation of IFN-α-treatment. Finally, a 6 week forced exercise regime reversed IFN-α-induced deficits in temporal order memory. These data provide further insight into the circuitry involved in cognitive impairments arising from IFN-α-treatment. Here we suggest that PFC (or the hippocampo-prefrontal pathway) may be compromised whilst the function of the PRH is preserved. Deficits may persist after cessation of IFN-α-treatment which suggests that extended patient monitoring is required. Aerobic exercise may be restorative and could prove beneficial for patients treated with IFN-α. Copyright © 2018 Elsevier Inc. All rights reserved.

Cognitive deficits in amyotrophic lateral sclerosis evaluated by event-related potentials.

PubMed

Ogawa, Tomohiro; Tanaka, Hideaki; Hirata, Koichi

2009-04-01

To determine the cognitive profiles in non-demented, relatively less handicapped patients with early-stage sporadic amyotrophic lateral sclerosis (ALS) by using neuropsychological tests, event-related potentials (ERPs) and clinical scale. We recruited 19 patients with sporadic ALS (eight with limb-onset, 11 with bulbar-onset) and 19 controls. In addition to the mini-mental state examination and the Wechsler adult intelligence scale-revised, we assessed the frontal lobe function with Wisconsin card sorting test, Stroop test and trail making test. We used auditory 'oddball' counting paradigm for the ERPs under 20-channel electroencephalogram (EEG) recording. Global field power (GFP) was computed, and its peak amplitudes and latencies of N1/N2/P3 were determined. The results of ERP and neuropsychological tests were correlated with respiratory function and clinical scale. No global cognitive impairment except for subtle frontal dysfunction was detected, although N1/N2/P3 GFP latencies were significantly prolonged in ALS patients than in the controls. Vital capacity correlated with P3 GFP amplitude, and the relative bulbar functional rating scale correlated with P3 GFP latency. Our findings indicated the presence of sub-clinical cognitive deficits in non-demented, sporadic ALS patients. In addition, clinical sub-types and respiratory function dependently influenced cognitive function in patients with sporadic ALS. ERP confirmed cognitive impairment in patients with sporadic ALS.

Exosomes derived from hypoxia-preconditioned mesenchymal stromal cells ameliorate cognitive decline by rescuing synaptic dysfunction and regulating inflammatory responses in APP/PS1 mice.

PubMed

Cui, Guo-Hong; Wu, Jing; Mou, Fang-Fang; Xie, Wei-Hua; Wang, Fu-Bo; Wang, Qiang-Li; Fang, Jie; Xu, Yan-Wu; Dong, You-Rong; Liu, Jian-Ren; Guo, Hai-Dong

2018-02-01

Administration of exosomes derived from mesenchymal stromal cells (MSCs) could improve some neurologic conditions by transferring functional biomolecules to recipient cells. Furthermore, exosomes from hypoxic progenitor cells exerted better therapeutic effects in organ injury through specific cargoes. However, there are no related reports about whether exosomes derived from MSCs or hypoxia-preconditioned MSCs (PC-MSCs) could prevent memory deficits in Alzheimer disease (AD). In this study, the exosomes derived from MSCs or PC-MSCs were systemically administered to transgenic APP/PS1 mice. The expression of miR-21 in MSCs was significantly increased after hypoxic treatment. Injection of exosomes from normoxic MSCs could rescue cognition and memory impairment according to results of the Morris water maze test, reduced plaque deposition, and Aβ levels in the brain; could decrease the activation of astrocytes and microglia; could down-regulate proinflammatory cytokines (TNF-α and IL-1β); and could up-regulate anti-inflammatory cytokines (IL-4 and -10) in AD mice, as well as reduce the activation of signal transducer and activator of transcription 3 (STAT3) and NF-κB. Compared to the group administered exosomes from normoxic MSCs, in the group administered exosomes from PC-MSCs, learning and memory capabilities were significantly improved; the plaque deposition and Aβ levels were lower, and expression of growth-associated protein 43, synapsin 1, and IL-10 was increased; and the levels of glial fibrillary acidic protein, ionized calcium-binding adaptor molecule 1, TNF-α, IL-1β, and activation of STAT3 and NF-κB were sharply decreased. More importantly, exosomes from PC-MSCs effectively increased the level of miR-21 in the brain of AD mice. Additionally, replenishment of miR-21 restored the cognitive deficits in APP/PS1 mice and prevented pathologic features. Taken together, these findings suggest that exosomes from PC-MSCs could improve the learning and memory

A continuum of executive function deficits in early subcortical vascular cognitive impairment: A systematic review and meta-analysis.

PubMed

Sudo, Felipe Kenji; Amado, Patricia; Alves, Gilberto Sousa; Laks, Jerson; Engelhardt, Eliasz

2017-01-01

Subcortical Vascular Cognitive Impairment (SVCI) is a clinical continuum of vascular-related cognitive impairment, including Vascular Mild Cognitive Impairment (VaMCI) and Vascular Dementia. Deficits in Executive Function (EF) are hallmarks of the disorder, but the best methods to assess this function have yet to be determined. The insidious and almost predictable course of SVCI and the multidimensional concept of EF suggest that a temporal dissociation of impairments in EF domains exists early in the disorder. This study aims to review and analyze data from the literature about performance of VaMCI patients on the most used EF tests through a meta-analytic approach. Medline, Web of Knowledge and PsycINFO were searched, using the terms: "vascular mild cognitive impairment" OR "vascular cognitive impairment no dementia" OR "vascular mild neurocognitive disorder" AND "dysexecutive" OR "executive function". Meta-analyses were conducted for each of the selected tests, using random-effect models. Systematic review showed major discrepancies among the results of the studies included. Meta-analyses evidenced poorer performance on the Trail-Making Test part B and the Stroop color test by VaMCI patients compared to controls. A continuum of EF impairments has been proposed in SVCI. Early deficits appear to occur in cognitive flexibility and inhibitory control.

Fronto-temporal connectivity predicts cognitive empathy deficits and experiential negative symptoms in schizophrenia.

PubMed

Abram, Samantha V; Wisner, Krista M; Fox, Jaclyn M; Barch, Deanna M; Wang, Lei; Csernansky, John G; MacDonald, Angus W; Smith, Matthew J

2017-03-01

Impaired cognitive empathy is a core social cognitive deficit in schizophrenia associated with negative symptoms and social functioning. Cognitive empathy and negative symptoms have also been linked to medial prefrontal and temporal brain networks. While shared behavioral and neural underpinnings are suspected for cognitive empathy and negative symptoms, research is needed to test these hypotheses. In two studies, we evaluated whether resting-state functional connectivity between data-driven networks, or components (referred to as, inter-component connectivity), predicted cognitive empathy and experiential and expressive negative symptoms in schizophrenia subjects. Study 1: We examined associations between cognitive empathy and medial prefrontal and temporal inter-component connectivity at rest using a group-matched schizophrenia and control sample. We then assessed whether inter-component connectivity metrics associated with cognitive empathy were also related to negative symptoms. Study 2: We sought to replicate the connectivity-symptom associations observed in Study 1 using an independent schizophrenia sample. Study 1 results revealed that while the groups did not differ in average inter-component connectivity, a medial-fronto-temporal metric and an orbito-fronto-temporal metric were related to cognitive empathy. Moreover, the medial-fronto-temporal metric was associated with experiential negative symptoms in both schizophrenia samples. These findings support recent models that link social cognition and negative symptoms in schizophrenia. Hum Brain Mapp 38:1111-1124, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Blocking leukotriene synthesis attenuates the pathophysiology of traumatic brain injury and associated cognitive deficits

PubMed Central

Corser-Jensen, Chelsea E.; Goodell, Dayton J.; Freund, Ronald K.; Serbedzija, Predrag; Murphy, Robert C.; Farias, Santiago E.; Dell'Acqua, Mark L.; Frey, Lauren C.; Serkova, Natalie; Heidenreich, Kim A.

2014-01-01

Neuroinflammation is a component of secondary injury following traumatic brain injury (TBI) that can persist beyond the acute phase. Leukotrienes are potent, pro-inflammatory lipid mediators generated from membrane phospholipids. In the absence of injury, leukotrienes are undetectable in brain, but after trauma they are rapidly synthesized by a transcellular event involving infiltrating neutrophils and endogenous brain cells. Here, we investigate the efficacy of MK-886, an inhibitor of 5-lipoxygenase activating protein (FLAP), in blocking leukotriene synthesis, secondary brain damage, synaptic dysfunction, and cognitive impairments after TBI. Male Sprague Dawley rats (9-11 weeks) received either MK-886 or vehicle after they were subjected to unilateral moderate fluid percussion injury (FPI) to assess the potential clinical use of FLAP inhibitors for TBI. MK-886 was also administered before FPI to determine the preventative potential of FLAP inhibitors. MK-886 given before or after injury significantly blocked the production of leukotrienes, measured by reverse-phase liquid chromatography coupled to tandem mass spectrometry (RP LC-MS/MS), and brain edema, measured by T2-weighted magnetic resonance imaging (MRI). MK-886 significantly attenuated blood-brain barrier disruption in the CA1 hippocampal region and deficits in long-term potentiation (LTP) at CA1 hippocampal synapses. The prevention of FPI-induced synaptic dysfunction by MK-886 was accompanied by fewer deficits in post-injury spatial learning and memory performance in the radial arms water maze (RAWM). These results indicate that leukotrienes contribute significantly to secondary brain injury and subsequent cognitive deficits. FLAP inhibitors represent a novel anti-inflammatory approach for treating human TBI that is feasible for both intervention and prevention of brain injury and neurologic deficits. PMID:24681156

Longitudinal deficits to attention, executive, and working memory in subtypes of mild cognitive impairment.

PubMed

Saunders, Nichole L J; Summers, Mathew J

2011-03-01

Mild cognitive impairment (MCI) has emerged as a classification for a prodromal phase of cognitive decline that may precede the emergence of Alzheimer's disease (AD). Recent research suggests that attention, executive, and working memory deficits may appear much earlier in the progression of AD than traditionally conceptualized, and may be more consistently associated with the later development of AD than memory processing deficits. The present study longitudinally tracked attention, executive and working memory functions in subtypes of MCI. In a longitudinal study, 52 amnestic MCI (a-MCI), 29 nonamnestic MCI (na-MCI), and 25 age- and education-matched controls undertook neuropsychological assessment of visual and verbal memory, attentional processing, executive functioning, working memory capacity, and semantic language at 10 month intervals. Analysis by repeated measures ANOVA indicate that the a-MCI and na-MCI groups displayed a decline in simple sustained attention (ηp² = .054) with a significant decline on a task of divided attention (ηp² = .053) being evident in the a-MCI group. Stable deficits were found on other measures of attention, working memory and executive function in the a-MCI and na-MCI groups. The a-MCI group displayed stable impairments to visual and verbal memory. The results indicate that a-MCI and na-MCI display a stable pattern of deficits to attention, working memory, and executive function. The decline in simple sustained attention in a-MCI and n-MCI groups and to divided attention in a-MCI may be early indicators of possible transition to dementia from MCI. However, further research is required to determine this. (c) 2011 APA, all rights reserved

[PASS neurocognitive dysfunction in attention deficit].

PubMed

Pérez-Alvarez, F; Timoneda-Gallart, C

Attention deficit disorder shows both cognitive and behavioral patterns. To determine a particular PASS (planning, attention, successive and simultaneous) pattern in order to early diagnosis and remediation according to PASS theory. 80 patients were selected from the neuropediatric attendance, aged 6 to 12 years old, 55 boys and 25 girls. Inclusion criteria were inattention (80 cases) and inattention with hyperactive symptoms (40 cases) according to the Diagnostic and Statistical Manual (DSM-IV). Exclusion criteria were the criteria of phonologic awareness previously reported, considered useful to diagnose dyslexia. A control group of 300 individuals, aged 5 to 12 years old, was used, criteria above mentioned being controlled. DN:CAS (Das-Naglieri Cognitive Assessment System) battery, translated to native language, was given to assess PASS cognitive processes. Results were analyzed with cluster analysis and t-Student test. Statistical factor analysis of the control group had previously identified the four PASS processes: planning, attention, successive and simultaneous. The dendrogram of the cluster analysis discriminated three categories of attention deficit disorder: 1. The most frequent, with planning deficit; 2. Without planning deficit but with deficit in other processes, and 3. Just only a few cases, without cognitive processing deficit. Cognitive deficiency in terms of means of scores was statistically significant when compared to control group (p = 0.001). According to PASS pattern, planning deficiency is a relevant factor. Neurological planning is not exactly the same than neurological executive function. The behavioral pattern is mainly linked to planning deficiency, but also to other PASS processing deficits and even to no processing deficit.

Reversal of Trimethyltin-Induced Learning and Memory Deficits by 3,5-Dicaffeoylquinic Acid.

PubMed

Kang, Jin Yong; Park, Seon Kyeong; Guo, Tian Jiao; Ha, Jeong Su; Lee, Du Sang; Kim, Jong Min; Lee, Uk; Kim, Dae Ok; Heo, Ho Jin

2016-01-01

The antiamnesic effect of 3,5-dicaffeoylquinic acid (3,5-diCQA) as the main phenolic compound in Artemisia argyi H. extract on cognitive dysfunction induced by trimethyltin (TMT) (7.1  μ g/kg of body weight; intraperitoneal injection) was investigated in order to assess its ameliorating function in mice. In several behavioral tests, namely, the Y-maze, passive avoidance, and Morris water maze (MWM) test, 3,5-diCQA significantly ameliorated learning and memory deficits. After the behavioral tests, brain tissues from the mice were analyzed to characterize the basis of the neuroprotective effect. Acetylcholine (ACh) levels increased, whereas the activity of acetylcholinesterase (AChE) decreased upon administration of 3,5-diCQA. In addition, 3,5-diCQA effectively protected against an increase in malondialdehyde (MDA) content, an increase in the oxidized glutathione (GSH) ratio, and a decline of total superoxide dismutase (SOD) level. 3,5-diCQA may prevent neuronal apoptosis through the protection of mitochondrial activities and the repression of apoptotic signaling molecules such as p-Akt, BAX, and p-tau (Ser 404).

Reversal of Trimethyltin-Induced Learning and Memory Deficits by 3,5-Dicaffeoylquinic Acid

PubMed Central

Kang, Jin Yong; Park, Seon Kyeong; Guo, Tian Jiao; Ha, Jeong Su; Lee, Du Sang; Kim, Jong Min; Lee, Uk; Kim, Dae Ok

2016-01-01

The antiamnesic effect of 3,5-dicaffeoylquinic acid (3,5-diCQA) as the main phenolic compound in Artemisia argyi H. extract on cognitive dysfunction induced by trimethyltin (TMT) (7.1 μg/kg of body weight; intraperitoneal injection) was investigated in order to assess its ameliorating function in mice. In several behavioral tests, namely, the Y-maze, passive avoidance, and Morris water maze (MWM) test, 3,5-diCQA significantly ameliorated learning and memory deficits. After the behavioral tests, brain tissues from the mice were analyzed to characterize the basis of the neuroprotective effect. Acetylcholine (ACh) levels increased, whereas the activity of acetylcholinesterase (AChE) decreased upon administration of 3,5-diCQA. In addition, 3,5-diCQA effectively protected against an increase in malondialdehyde (MDA) content, an increase in the oxidized glutathione (GSH) ratio, and a decline of total superoxide dismutase (SOD) level. 3,5-diCQA may prevent neuronal apoptosis through the protection of mitochondrial activities and the repression of apoptotic signaling molecules such as p-Akt, BAX, and p-tau (Ser 404). PMID:28105250

Effects of β-hydroxy-β-methyl butyrate on working memory and cognitive flexibility in an animal model of aging.

PubMed

Hankosky, Emily R; Sherrill, Luke K; Ruvola, Lauren A; Haake, Rachel M; Kim, Taehyeon; Hammerslag, Lindsey R; Kougias, Daniel G; Juraska, Janice M; Gulley, Joshua M

2017-09-01

Normal aging results in cognitive decline and nutritional interventions have been suggested as potential approaches for mitigating these deficits. Here, we used rats to investigate the effects of short- and long-term dietary supplementation with the leucine metabolite β-hydroxy-β-methyl butyrate (HMB) on working memory and cognitive flexibility. Beginning ∼12 months of age, male and female Long-Evans rats were given twice daily access to sipper tubes containing calcium HMB (450 mg/kg) or vehicle (285 mg/kg calcium lactate) in a sucrose solution (20% w/v). Supplementation continued for 1 or 7 months (middle- and old-age (OA) groups, respectively) before testing began. Working memory was assessed by requiring rats to respond on a previously sampled lever following various delays. Cognitive flexibility was assessed by training rats to earn food according to a visual strategy and then, once acquired, shifting to an egocentric response strategy. Treatment with HMB improved working memory performance in middle-age (MA) males and OA rats of both sexes. In the cognitive flexibility task, there was a significant age-dependent deficit in acquisition of the visual strategy that was not apparent in OA males treated with HMB. Furthermore, HMB ameliorated an apparent deficit in visual strategy acquisition in MA females. Together, these findings suggest that daily nutritional supplementation with HMB facilitates learning and improves working memory performance. As such, HMB supplementation may mitigate age-related cognitive deficits and may therefore be an effective tool to combat this undesirable feature of the aging process.

Diabetes and Cognitive Deficits in Chronic Schizophrenia: A Case-Control Study

PubMed Central

Han, Mei; Huang, Xu-Feng; Chen, Da Chun; Xiu, Meihong; Kosten, Thomas R.; Zhang, Xiang Yang

2013-01-01

Cognitive impairment occurs in both schizophrenia and diabetes. There is currently limited understanding whether schizophrenia with diabetes has more serious cognitive deficits than schizophrenia without diabetes or diabetes only. This study assessed cognitive performance in 190 healthy controls, 106 diabetes only, 127 schizophrenia without diabetes and 55 schizophrenia with diabetes. This study was conducted from January 2008 to December 2010. Compared to healthy controls, all patient groups had significantly decreased total and five index RBANS scores (all p<0.01–p<0.001), except for the visuospatial/constructional index. Schizophrenia with diabetes performed worse than schizophrenia without diabetes in immediate memory (p<0.01) and total RBANS scores (<0.05), and showed a trend for decreased attention (p = 0.052) and visuospatial/constructional capacity (p = 0.063). Schizophrenia with diabetes performed worse than diabetes only in immediate memory (p<0.001) and attention (p<0.05), and showed a trend for decreased total RBANS scores (p = 0.069). Regression analysis showed that the RBANS had modest correlations with schizophrenia’ PANSS scores, their duration of current antipsychotic treatment, and diagnosis of diabetes. Schizophrenia with co-morbid diabetes showed more cognitive impairment than schizophrenia without diabetes and diabetes only, especially in immediate memory and attention. PMID:23840437

Treadmill exercise ameliorates symptoms of attention deficit/hyperactivity disorder through reducing Purkinje cell loss and astrocytic reaction in spontaneous hypertensive rats

PubMed Central

Yun, Hyo-Soon; Park, Mi-Sook; Ji, Eun-Sang; Kim, Tae-Woon; Ko, Il-Gyu; Kim, Hyun-Bae; Kim, Hong

2014-01-01

Attention deficit/hyperactivity disorder (ADHD) is a neurobehavioral disorder of cognition. We investigated the effects of treadmill exercise on Purkinje cell and astrocytic reaction in the cerebellum of the ADHD rat. Adult male spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKYR) weighing 210± 10 g were used. The animals were randomly divided into four groups (n= 15): control group, ADHD group, ADHD and methylphenidate (MPH)-treated group, ADHD and treadmill exercise group. The rats in the MPH-treated group as a positive control received 1 mg/kg MPH orally once a day for 28 consecutive days. The rats in the treadmill exercise group were made to run on a treadmill for 30 min once a day for 28 days. Motor coordination and balance were determined by vertical pole test. Immunohistochemistry for the expression of calbindinD-28 and glial fibrillary acidic protein (GFAP) in the cerebellar vermis and Western blot for GFAP, Bax, and Bcl-2 were conducted. In the present results, ADHD significantly decreased balance and the number of calbindin-positive cells, while GFAP expression and Bax/Bcl-2 ratio in the cerebellum were significantly increased in the ADHD group compared to the control group (P< 0.05, respectively). In contrast, treadmill exercise and MPH alleviated the ADHD-induced the decrease of balance and the number of calbindine-positive cells, and the increase of GFAP expression and Bax/Bcl-2 ratio in the cerebellum (P< 0.05, respectively). Therefore, the present results suggested that treadmill exercise might exert ameliorating effect on ADHD through reduction of Purkinje cell loss and astrocytic reaction in the cerebellum. PMID:24678501

Blue-yellow colour vision impairment and cognitive deficits in occasional and dependent stimulant users.

PubMed

Hulka, Lea M; Wagner, Michael; Preller, Katrin H; Jenni, Daniela; Quednow, Boris B

2013-04-01

Specific blue-yellow colour vision impairment has been reported in dependent cocaine users and it was postulated that drug-induced changes in retinal dopamine neurotransmission are responsible. However, it is unclear whether these changes are confined to chronic cocaine users, whether they are specific for dopaminergic stimulants such as cocaine and amphetamine and whether they are related to cognitive functions such as working memory, encoding and consolidation. In 47 occasional and 29 dependent cocaine users, 23 MDMA (commonly known as 'ecstasy') users and 47 stimulant-naive controls, colour vision discrimination was measured with the Lanthony Desaturated Panel D-15 Test and memory performance with the Auditory Verbal Learning Test. Both occasional and dependent cocaine users showed higher colour confusion indices than controls. Users of the serotonergic stimulant MDMA (26%), occasional (30%) and dependent cocaine users (34%) exhibited more frequent blue-yellow colour vision disorders compared to controls (9%). Inferior performance of MDMA users was caused by a subgroup with high amphetamine co-use (55%), while MDMA use alone was not associated with decreased blue-yellow discrimination (0%). Cognitive performance was worse in cocaine users with colour vision disorder compared to users and controls with intact colour vision and both colour vision impairment and cognitive deficits were related to cocaine use. Occasional cocaine and amphetamine use might induce blue-yellow colour vision impairment, whereas the serotonergic stimulant MDMA does not impair colour vision. The association between colour vision impairment and cognitive deficits in cocaine users may reflect that retinal and cerebral dopamine alterations are linked to a certain degree.

Microstructural white matter alterations and hippocampal volumes are associated with cognitive deficits in craniopharyngioma.

PubMed

Fjalldal, S; Follin, C; Svärd, D; Rylander, L; Gabery, S; Petersén, Å; van Westen, D; Sundgren, P C; Björkman-Burtscher, I M; Lätt, J; Ekman, B; Johanson, A; Erfurth, E M

2018-06-01

Patients with craniopharyngioma (CP) and hypothalamic lesions (HL) have cognitive deficits. Which neural pathways are affected is unknown. To determine whether there is a relationship between microstructural white matter (WM) alterations detected with diffusion tensor imaging (DTI) and cognition in adults with childhood-onset CP. A cross-sectional study with a median follow-up time of 22 (6-49) years after operation. The South Medical Region of Sweden (2.5 million inhabitants). Included were 41 patients (24 women, ≥17 years) surgically treated for childhood-onset CP between 1958-2010 and 32 controls with similar age and gender distributions. HL was found in 23 patients. Subjects performed cognitive tests and magnetic resonance imaging, and images were analyzed using DTI of uncinate fasciculus, fornix, cingulum, hippocampus and hypothalamus as well as hippocampal volumetry. Right uncinate fasciculus was significantly altered ( P  ≤ 0.01). Microstructural WM alterations in left ventral cingulum were significantly associated with worse performance in visual episodic memory, explaining approximately 50% of the variation. Alterations in dorsal cingulum were associated with worse performance in immediate, delayed recall and recognition, explaining 26-38% of the variation, and with visuospatial ability and executive function, explaining 19-29%. Patients who had smaller hippocampal volume had worse general knowledge ( P  = 0.028), and microstructural WM alterations in hippocampus were associated with a decline in general knowledge and episodic visual memory. A structure to function relationship is suggested between microstructural WM alterations in cingulum and in hippocampus with cognitive deficits in CP. © 2018 The authors.

A new computerized cognitive and social cognition training specifically designed for patients with schizophrenia/schizoaffective disorder in early stages of illness: A pilot study.

PubMed

Fernandez-Gonzalo, Sol; Turon, Marc; Jodar, Merce; Pousa, Esther; Hernandez Rambla, Carla; García, Rebeca; Palao, Diego

2015-08-30

People with schizophrenia/schizoaffective disorders at early stages of the illness present cognitive and social cognition deficits that have a great impact in functional outcomes. Cognitive Remediation Therapy (CRT) has demonstrated consistent effect in cognitive performance, symptoms and psychosocial functioning. However, any CRT intervention or social cognition training have been specifically designed for patients in the early stages of psychosis. The aim of this pilot study is to assess the efficacy of a new computerized cognitive and social cognition program for patients with schizophrenia/schizoaffective disorder with recent diagnosis. A comprehensive assessment of clinical, social and non-social cognitive and functional measures was carried out in 53 randomized participants before and after the 4-months treatment. Significant results were observed in Spatial Span Forwards, Immediate Logical Memory and Pictures of Facial Affect (POFA) total score. None of these results were explained by medication, premorbid social functioning or psychopathological symptoms. No impact of the intervention was observed in other cognitive and social cognition outcome neither in clinical and functional outcomes. This new computerized intervention may result effective ameliorating visual attention, logical memory and emotional processing in patients in the early stages of schizophrenia/schizoaffective disorder. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Novel spiroimidazopyridine derivative SAK3 improves methimazole-induced cognitive deficits in mice.

PubMed

Noreen, Husain; Yabuki, Yasushi; Fukunaga, Kohji

2017-09-01

Methimazole (MMI) is a first-line therapy used to manage hyperthyroidism and Graves' disease. Despite its therapeutic benefit, chronic MMI administration can lead to hypothyroidism and perturb brain homeostasis in patients, resulting in neuropsychiatric disorders such as depression and cognitive dysfunction. We recently developed the spiroimidazopyridine derivative SAK3 as cognitive enhancer; however, mechanisms underlying its activity remained unclear. Here, we show that SAK3 potentially improves cognitive impairment seen following MMI-induced hypothyroidism. Twenty-four hours after MMI (75 mg/kg, i.p.) treatment, we administered SAK3 (0.1, 0.5 and 1 mg/kg, p.o.) to mice daily for 7 days. MMI treatment alone disrupted olfactory bulb (OB) glomerular structure, as assessed by staining with the olfactory marker protein (OMP), reduced the number of choline acetyl transferase (ChAT)-immunoreactive neurons in medial septum (MS), and significantly impaired cognition. SAK3 (0.5 and 1 mg/kg, p.o.) administration significantly restored the number of cholinergic MS neurons in MMI-treated mice, and SAK3 treatment at a higher dose significantly improved cognitive deficits seen in MMI-treated control mice. Overall, our study suggests that SAK3 treatment could antagonize such impairment in patients with hypothyroidism. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dietary Intake of Sulforaphane-Rich Broccoli Sprout Extracts during Juvenile and Adolescence Can Prevent Phencyclidine-Induced Cognitive Deficits at Adulthood.

PubMed

Shirai, Yumi; Fujita, Yuko; Hashimoto, Ryota; Ohi, Kazutaka; Yamamori, Hidenaga; Yasuda, Yuka; Ishima, Tamaki; Suganuma, Hiroyuki; Ushida, Yusuke; Takeda, Masatoshi; Hashimoto, Kenji

2015-01-01

Oxidative stress and inflammation play a role in cognitive impairment, which is a core symptom of schizophrenia. Furthermore, a hallmark of the pathophysiology of this disease is the dysfunction of cortical inhibitory γ-aminobutyric acid (GABA) neurons expressing parvalbumin (PV), which is also involved in cognitive impairment. Sulforaphane (SFN), an isothiocyanate derived from broccoli, is a potent activator of the transcription factor Nrf2, which plays a central role in the inducible expressions of many cytoprotective genes in response to oxidative stress. Keap1 is a cytoplasmic protein that is essential for the regulation of Nrf2 activity. Here, we found that pretreatment with SFN attenuated cognitive deficits, the increase in 8-oxo-dG-positive cells, and the decrease in PV-positive cells in the medial prefrontal cortex and hippocampus after repeated administration of phencyclidine (PCP). Furthermore, PCP-induced cognitive deficits were improved by the subsequent subchronic administration of SFN. Interestingly, the dietary intake of glucoraphanin (a glucosinolate precursor of SFN) during the juvenile and adolescence prevented the onset of PCP-induced cognitive deficits as well as the increase in 8-oxo-dG-positive cells and the decrease in PV-positive cells in the brain at adulthood. Moreover, the NRF2 gene and the KEAP1 gene had an epistatic effect on cognitive impairment (e.g., working memory and processing speed) in patients with schizophrenia. These findings suggest that SFN may have prophylactic and therapeutic effects on cognitive impairment in schizophrenia. Therefore, the dietary intake of SFN-rich broccoli sprouts during the juvenile and adolescence may prevent the onset of psychosis at adulthood.

Dietary Intake of Sulforaphane-Rich Broccoli Sprout Extracts during Juvenile and Adolescence Can Prevent Phencyclidine-Induced Cognitive Deficits at Adulthood

PubMed Central

Shirai, Yumi; Fujita, Yuko; Hashimoto, Ryota; Ohi, Kazutaka; Yamamori, Hidenaga; Yasuda, Yuka; Ishima, Tamaki; Suganuma, Hiroyuki; Ushida, Yusuke; Takeda, Masatoshi; Hashimoto, Kenji

2015-01-01

Oxidative stress and inflammation play a role in cognitive impairment, which is a core symptom of schizophrenia. Furthermore, a hallmark of the pathophysiology of this disease is the dysfunction of cortical inhibitory γ-aminobutyric acid (GABA) neurons expressing parvalbumin (PV), which is also involved in cognitive impairment. Sulforaphane (SFN), an isothiocyanate derived from broccoli, is a potent activator of the transcription factor Nrf2, which plays a central role in the inducible expressions of many cytoprotective genes in response to oxidative stress. Keap1 is a cytoplasmic protein that is essential for the regulation of Nrf2 activity. Here, we found that pretreatment with SFN attenuated cognitive deficits, the increase in 8-oxo-dG-positive cells, and the decrease in PV-positive cells in the medial prefrontal cortex and hippocampus after repeated administration of phencyclidine (PCP). Furthermore, PCP-induced cognitive deficits were improved by the subsequent subchronic administration of SFN. Interestingly, the dietary intake of glucoraphanin (a glucosinolate precursor of SFN) during the juvenile and adolescence prevented the onset of PCP-induced cognitive deficits as well as the increase in 8-oxo-dG-positive cells and the decrease in PV-positive cells in the brain at adulthood. Moreover, the NRF2 gene and the KEAP1 gene had an epistatic effect on cognitive impairment (e.g., working memory and processing speed) in patients with schizophrenia. These findings suggest that SFN may have prophylactic and therapeutic effects on cognitive impairment in schizophrenia. Therefore, the dietary intake of SFN-rich broccoli sprouts during the juvenile and adolescence may prevent the onset of psychosis at adulthood. PMID:26107664

On-road driving impairments and associated cognitive deficits after stroke.

PubMed

Devos, Hannes; Tant, Mark; Akinwuntan, Abiodun E

2014-01-01

Little is known about the critical on-road driving skills that get affected after a stroke. The purpose of this study was to investigate the key on-road driving impairments and their associated cognitive deficits after a stroke. A second aim was to investigate if lateralization of stroke impacts results of the cognitive and on-road driving tests. In this cross-sectional study, 99 participants with a first-ever stroke who were actively driving prior to stroke underwent a cognitive battery and a standardized road test that evaluated 13 specific on-road driving skills. These on-road driving skills were mapped onto an existing, theoretical framework that categorized the on-road items into hierarchic clusters of operational, tactical, visuo-integrative, and mixed driving skills. The total score on the road test and the on-road decision, made by a certified fitness-to-drive expert, decided the main outcome. The critical on-road driving skills predicting the on-road decision were identified using logistic regression analysis. Linear regression analysis was employed to determine the cognitive impairments leading to poor total on-road scores. Analyses were repeated for right- and left-sided strokes. In all, 37 persons scored poorly on the road test. These participants performed worse in all hierarchic clusters of on-road driving. Performances on the operational cluster and the visuo-integrative cluster best predicted on-road decisions (R(2) = 0.60). 'Lane changing' and 'understanding, insight, and quality of traffic participation' were the critical skill deficits leading to poor performance on the road test (R(2) = 0.65). Divided attention was the main determinant of on-road scores in the total group (R(2) = 0.06). Participants with right-sided stroke performed worse on visual field, visual neglect, visual scanning, visuo-constructive skills, and divided attention compared with those with left-sided stroke. Divided attention was the main determinant of total on-road scores

The nature of social cognitive deficits in children and adults with Klinefelter syndrome (47,XXY).

PubMed

van Rijn, S; de Sonneville, L; Swaab, H

2018-02-06

About 1 in 650 boys are born with an extra X chromosome (47,XXY or Klinefelter syndrome). 47,XXY is associated with vulnerabilities in socio-emotional development. This study was designed to assess types of cognitive deficits in individuals with 47,XXY that may contribute to social-emotional dysfunction, and to evaluate the nature of such deficits at various levels: ranging from basic visuospatial processing deficits, impairments in face recognition (FR), to emotion expression impairments. A total of 70 boys and men with 47,XXY, aged 8 to 60 years old, participated in the study. The subtests feature identification, FR and identification of facial emotions of the Amsterdam Neuropsychological Tasks were used. Level of intellectual functioning was assessed with the child and adult versions of the Wechsler Intelligence Scales. Reaction time data showed that in the 47,XXY group, 17% had difficulties in visuospatial processing (no social load), 26% had difficulties with FR (medium social load) and an even higher number of 33% had difficulties with facial expressions of emotions (high-social load). Information processing impairments increased as a function of "social load" of the stimuli, independent of intellectual functioning. Taken together, our data suggest that on average individuals with XXY may have more difficulties in information processing when "social load" increases, suggesting a specific difficulty in the higher-order labeling and interpretation of social cues, which cannot be explained by more basic visuospatial perceptual skills. Considering the increased risk for social cognitive impairments, routine assessment of social cognitive functioning as part of neuropsychological screening is warranted. © 2018 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Increased stress reactivity is associated with cognitive deficits and decreased hippocampal brain-derived neurotrophic factor in a mouse model of affective disorders.

PubMed

Knapman, A; Heinzmann, J-M; Hellweg, R; Holsboer, F; Landgraf, R; Touma, C

2010-07-01

Cognitive deficits are a common feature of major depression (MD), with largely unknown biological underpinnings. In addition to the affective and cognitive symptoms of MD, a dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is commonly observed in these patients. Increased plasma glucocorticoid levels are known to render the hippocampus susceptible to neuronal damage. This structure is important for learning and memory, creating a potential link between HPA axis dysregulation and cognitive deficits in depression. In order to further elucidate how altered stress responsiveness may contribute to the etiology of MD, three mouse lines with high (HR), intermediate (IR), or low (LR) stress reactivity were generated by selective breeding. The aim of the present study was to investigate whether increased stress reactivity is associated with deficits in hippocampus-dependent memory tests. To this end, we subjected mice from the HR, IR, and LR breeding lines to tests of recognition memory, spatial memory, and depression-like behavior. In addition, measurements of brain-derived neurotrophic factor (BDNF) in the hippocampus and plasma of these animals were conducted. Our results demonstrate that HR mice exhibit hippocampus-dependent memory deficits along with decreased hippocampal, but not plasma, BDNF levels. Thus, the stress reactivity mouse lines are a promising animal model of the cognitive deficits in MD with the unique feature of a genetic predisposition for an altered HPA axis reactivity, which provides the opportunity to explore the progression of the symptoms of MD, predisposing genetic factors as well as new treatment strategies. Copyright 2009 Elsevier Ltd. All rights reserved.

Effects of Ketamine on Context-Processing Performance in Monkeys: A New Animal Model of Cognitive Deficits in Schizophrenia

PubMed Central

Blackman, Rachael K; MacDonald, Angus W; Chafee, Matthew V

2013-01-01

Cognitive deficits are at the crux of why many schizophrenia patients have poor functional outcomes. One of the cognitive symptoms experienced by schizophrenia patients is a deficit in context processing, the ability to use contextual information stored in working memory to adaptively respond to subsequent stimuli. As such, context processing can be thought of as the intersection between working memory and executive control. Although deficits in context processing have been extensively characterized by neuropsychological testing in schizophrenia patients, they have never been effectively translated to an animal model of the disease. To bridge that gap, we trained monkeys to perform the same dot pattern expectancy (DPX) task, which has been used to measure context-processing deficits in human patients with schizophrenia. In the DPX task, the first stimulus in each trial provides the contextual information that subjects must remember in order to appropriately respond to the second stimulus in the trial. We found that administration of ketamine, an N-methyl-D-aspartate receptor antagonist, in monkeys caused a dose-dependent failure in context processing, replicating in monkeys the same specific pattern of errors committed by patients with schizophrenia when performing the same task. Therefore, our results provide the first evidence that context-processing dysfunction can be modeled in animals. Replicating a schizophrenia-like behavioral performance pattern in monkeys performing the same task used in humans provides a strong bridge to better understand the biological basis for this psychiatric disease and its cognitive manifestations using animal models. PMID:23660706

An Integrative, Cognitive-Behavioral, Systemic Approach to Working with Students Diagnosed with Attention Deficit Hyperactive Disorder

ERIC Educational Resources Information Center

Shillingford, Margaret Ann; Lambie, Glenn W.; Walter, Sara Meghan

2007-01-01

Attention deficit hyperactive disorder (ADHD) is a prevalent diagnostic disorder for many students, which correlates with negative academic, social, and personal consequences. This article presents an integrative, cognitive-behavioral, systemic approach that offers behaviorally based interventions for professional school counselors to support…

Berry fruit can improve age-associated neuronal and cognitive deficits: from the laboratory to the clinic

USDA-ARS?s Scientific Manuscript database

Research has demonstrated, in both human and animals, that cognitive functioning decreases with age, to include deficits in processing speed, executive function, memory, and spatial learning. The cause of these functional declines is not entirely understood; however, neuronal losses and the associat...

Nicotinic alpha 7 receptor agonists EVP-6124 and BMS-933043, attenuate scopolamine-induced deficits in visuo-spatial paired associates learning

PubMed Central

Polino, Joseph; Signor, Laura; Bookbinder, Mark; Keavy, Deborah; Benitex, Yulia; Morgan, Daniel G.; King, Dalton; Macor, John E.; Zaczek, Robert; Olson, Richard; Bristow, Linda J.

2017-01-01

Agonists at the nicotinic acetylcholine alpha 7 receptor (nAChR α7) subtype have the potential to treat cognitive deficits in patients with Alzheimer’s disease (AD) or schizophrenia. Visuo-spatial paired associates learning (vsPAL) is a task that has been shown to reliably predict conversion from mild cognitive impairment to AD in humans and can also be performed by nonhuman primates. Reversal of scopolamine-induced impairment of vsPAL performance may represent a translational approach for the development of nAChR α7 agonists. The present study investigated the effect of treatment with the acetylcholinesterase inhibitor, donepezil, or three nAChR α7 agonists, BMS-933043, EVP-6124 and RG3487, on vsPAL performance in scopolamine-treated cynomolgus monkeys. Scopolamine administration impaired vsPAL performance accuracy in a dose- and difficulty- dependent manner. The impairment of eventual accuracy, a measure of visuo-spatial learning during the task, was significantly ameliorated by treatment with donepezil (0.3 mg/kg, i.m.), EVP-6124 (0.01 mg/kg, i.m.) or BMS-933043 (0.03, 0.1 and 0.3 mg/kg, i.m.). Both nAChR α7 agonists showed inverted-U shaped dose-effect relationships with EVP-6124 effective at a single dose only whereas BMS-933043 was effective across at least a 10 fold dose/exposure range. RG3487 was not efficacious in this paradigm at the dose range examined (0.03–1 mg/kg, i.m.). These results are the first demonstration that the nAChR α7 agonists, EVP-6124 and BMS-933043, can ameliorate scopolamine-induced cognitive deficits in nonhuman primates performing the vsPAL task. PMID:29261656

Differential profiles in auditory social cognition deficits between adults with autism and schizophrenia spectrum disorders: A preliminary analysis.

PubMed

Tobe, Russell H; Corcoran, Cheryl M; Breland, Melissa; MacKay-Brandt, Anna; Klim, Casimir; Colcombe, Stanley J; Leventhal, Bennett L; Javitt, Daniel C

2016-08-01

Impairment in social cognition, including emotion recognition, has been extensively studied in both Autism Spectrum Disorders (ASD) and Schizophrenia (SZ). However, the relative patterns of deficit between disorders have been studied to a lesser degree. Here, we applied a social cognition battery incorporating both auditory (AER) and visual (VER) emotion recognition measures to a group of 19 high-functioning individuals with ASD relative to 92 individuals with SZ, and 73 healthy control adult participants. We examined group differences and correlates of basic auditory processing and processing speed. Individuals with SZ were impaired in both AER and VER while ASD individuals were impaired in VER only. In contrast to SZ participants, those with ASD showed intact basic auditory function. Our finding of a dissociation between AER and VER deficits in ASD relative to Sz support modality-specific theories of emotion recognition dysfunction. Future studies should focus on visual system-specific contributions to social cognitive impairment in ASD. Copyright © 2016 Elsevier Ltd. All rights reserved.

Mapping the neuroanatomic substrates of cognition in familial attention deficit hyperactivity disorder.

PubMed

Muster, Rachel; Choudhury, Saadia; Sharp, Wendy; Kasparek, Steven; Sudre, Gustavo; Shaw, Philip

2018-05-24

While the neuroanatomic substrates of symptoms of attention deficit hyperactivity disorder (ADHD) have been investigated, less is known about the neuroanatomic correlates of cognitive abilities pertinent to the disorder, particularly in adults. Here we define the neuroanatomic correlates of key cognitive abilities and determine if there are associations with histories of psychostimulant medication. We acquired neuroanatomic magnetic resonance imaging data from 264 members of 60 families (mean age 29.5; s.d. 18.4, 116 with ADHD). Using linear mixed model regression, we tested for associations between cognitive abilities (working memory, information processing, intelligence, and attention), symptoms and both cortical and subcortical volumes. Symptom severity was associated with spatial working memory (t = -3.77, p = 0.0002), processing speed (t = -2.95, p = 0.004) and a measure of impulsive responding (t = 2.19, p = 0.03); these associations did not vary with age (all p > 0.1). Neuroanatomic associations of cognition varied by task but centered on prefrontal, lateral parietal and temporal cortical regions, the thalamus and putamen. The neuroanatomic correlates of ADHD symptoms overlapped significantly with those of working memory (Dice's overlap coefficient: spatial, p = 0.003; verbal, p = 0.001) and information processing (p = 0.02). Psychostimulant medication history was associated with neither cognitive skills nor with a brain-cognition relationships. Diagnostic differences in the cognitive profile of ADHD does not vary significantly with age; nor were cognitive differences associated with psychostimulant medication history. The neuroanatomic substrates of working memory and information overlapped with those for symptoms within these extended families, consistent with a pathophysiological role for these cognitive skills in familial ADHD.

A continuum of executive function deficits in early subcortical vascular cognitive impairment: A systematic review and meta-analysis

PubMed Central

Sudo, Felipe Kenji; Amado, Patricia; Alves, Gilberto Sousa; Laks, Jerson; Engelhardt, Eliasz

2017-01-01

ABSTRACT. Background. Subcortical Vascular Cognitive Impairment (SVCI) is a clinical continuum of vascular-related cognitive impairment, including Vascular Mild Cognitive Impairment (VaMCI) and Vascular Dementia. Deficits in Executive Function (EF) are hallmarks of the disorder, but the best methods to assess this function have yet to be determined. The insidious and almost predictable course of SVCI and the multidimensional concept of EF suggest that a temporal dissociation of impairments in EF domains exists early in the disorder. Objective: This study aims to review and analyze data from the literature about performance of VaMCI patients on the most used EF tests through a meta-analytic approach. Methods: Medline, Web of Knowledge and PsycINFO were searched, using the terms: “vascular mild cognitive impairment” OR “vascular cognitive impairment no dementia” OR “vascular mild neurocognitive disorder” AND “dysexecutive” OR “executive function”. Meta-analyses were conducted for each of the selected tests, using random-effect models. Results: Systematic review showed major discrepancies among the results of the studies included. Meta-analyses evidenced poorer performance on the Trail-Making Test part B and the Stroop color test by VaMCI patients compared to controls. Conclusion: A continuum of EF impairments has been proposed in SVCI. Early deficits appear to occur in cognitive flexibility and inhibitory control. PMID:29354217

Phenylbutyrate ameliorates cognitive deficit and reduces tau pathology in an Alzheimer's disease mouse model.

PubMed

Ricobaraza, Ana; Cuadrado-Tejedor, Mar; Pérez-Mediavilla, Alberto; Frechilla, Diana; Del Río, Joaquin; García-Osta, Ana

2009-06-01

Chromatin modification through histone acetylation is a molecular pathway involved in the regulation of transcription underlying memory storage. Sodium 4-phenylbutyrate (4-PBA) is a well-known histone deacetylase inhibitor, which increases gene transcription of a number of genes, and also exerts neuroprotective effects. In this study, we report that administration of 4-PBA reversed spatial learning and memory deficits in an established mouse model of Alzheimer's disease (AD) without altering beta-amyloid burden. We also observed that the phosphorylated form of tau was decreased in the AD mouse brain after 4-PBA treatment, an effect probably due to an increase in the inactive form of the glycogen synthase kinase 3beta (GSK3beta). Interestingly, we found a dramatic decrease in brain histone acetylation in the transgenic mice that may reflect an indirect transcriptional repression underlying memory impairment. The administration of 4-PBA restored brain histone acetylation levels and, as a most likely consequence, activated the transcription of synaptic plasticity markers such as the GluR1 subunit of the AMPA receptor, PSD95, and microtubule-associated protein-2. The results suggest that 4-PBA, a drug already approved for clinical use, may provide a novel approach for the treatment of AD.

Cognitive and behavioral deficits in premature graduates of intensive care.

PubMed

Perlman, Jeffrey M

2002-12-01

A substantial number of VLBW graduates of intensive care develop cognitive and behavioral problems, even in the absence of neuroimaging abnormalities. Although this article has highlighted the potential, important, contributing role of medical and stressful, neonatal, environmental conditions to the development of these deficits, it is not all-encompassing, and there are additional prenatal (ie, in utero stress, drug exposure) and neonatal (ie, infectious) contributing factors. The long-term, outcome data presented in this article are pertinent to the more mature, VLBW infant, and it remains unclear and critically important to delineate the long-term, neurobehavioral outcome of those extremely low birth-weight survivors born at the cutting limit of viability.

Involvement of Neuroinflammation during Brain Development in Social Cognitive Deficits in Autism Spectrum Disorder and Schizophrenia.

PubMed

Nakagawa, Yutaka; Chiba, Kenji

2016-09-01

Development of social cognition, a unique and high-order function, depends on brain maturation from childhood to adulthood in humans. Autism spectrum disorder (ASD) and schizophrenia have similar social cognitive deficits, although age of onset in each disorder is different. Pathogenesis of these disorders is complex and contains several features, including genetic risk factors, environmental risk factors, and sites of abnormalities in the brain. Although several hypotheses have been postulated, they seem to be insufficient to explain how brain alterations associated with symptoms in these disorders develop at distinct developmental stages. Development of ASD appears to be related to cerebellar dysfunction and subsequent thalamic hyperactivation in early childhood. By contrast, schizophrenia seems to be triggered by thalamic hyperactivation in late adolescence, whereas hippocampal aberration has been possibly initiated in childhood. One of the possible culprits is metal homeostasis disturbances that can induce dysfunction of blood-cerebrospinal fluid barrier. Thalamic hyperactivation is thought to be induced by microglia-mediated neuroinflammation and abnormalities of intracerebral environment. Consequently, it is likely that the thalamic hyperactivation triggers dysregulation of the dorsolateral prefrontal cortex for lower brain regions related to social cognition. In this review, we summarize the brain aberration in ASD and schizophrenia and provide a possible mechanism underlying social cognitive deficits in these disorders based on their distinct ages of onset. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

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

Canonical correlation analysis of synchronous neural interactions and cognitive deficits in Alzheimer's dementia

NASA Astrophysics Data System (ADS)

Karageorgiou, Elissaios; Lewis, Scott M.; Riley McCarten, J.; Leuthold, Arthur C.; Hemmy, Laura S.; McPherson, Susan E.; Rottunda, Susan J.; Rubins, David M.; Georgopoulos, Apostolos P.

2012-10-01

In previous work (Georgopoulos et al 2007 J. Neural Eng. 4 349-55) we reported on the use of magnetoencephalographic (MEG) synchronous neural interactions (SNI) as a functional biomarker in Alzheimer's dementia (AD) diagnosis. Here we report on the application of canonical correlation analysis to investigate the relations between SNI and cognitive neuropsychological (NP) domains in AD patients. First, we performed individual correlations between each SNI and each NP, which provided an initial link between SNI and specific cognitive tests. Next, we performed factor analysis on each set, followed by a canonical correlation analysis between the derived SNI and NP factors. This last analysis optimally associated the entire MEG signal with cognitive function. The results revealed that SNI as a whole were mostly associated with memory and language, and, slightly less, executive function, processing speed and visuospatial abilities, thus differentiating functions subserved by the frontoparietal and the temporal cortices. These findings provide a direct interpretation of the information carried by the SNI and set the basis for identifying specific neural disease phenotypes according to cognitive deficits.

The Cognitive Abilities and Skills of Children Who Suffer from Attention Deficit and Hyperactivity Disorder (ADHD) in Kuwait State

ERIC Educational Resources Information Center

Mohammed, Ali Mohammed Haidar

2016-01-01

The present study aims to identify the level of cognitive skills and abilities of children who suffer from the Attention Deficit and Hyperactivity Disorder (ADHD) and the differences in the level of cognitive skills and abilities according to the age group and the level of academic achievement. To achieve the objective of the study, a…

Enriched endogenous n-3 polyunsaturated fatty acids alleviate cognitive and behavioral deficits in a mice model of Alzheimer's disease.

PubMed

Wu, Kefeng; Gao, Xiang; Shi, Baoyan; Chen, Shiyu; Zhou, Xin; Li, Zhidong; Gan, Yuhong; Cui, Liao; Kang, Jing Xuan; Li, Wende; Huang, Ren

2016-10-01

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that accompanied by memory deficits and neuropsychiatric dysfunction. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have seemly therapeutic potential in AD, but the benefit of n-3 PUFAs is still in debates. Here, we employed a transgenic mice carry fat-1 gene to encode n-3 desaturase from Caenorhabditis elegans, which increase endogenous n-3 PUFAs by converting n-6 PUFAs to n-3 PUFAs crossed with amyloid precursor protein (APP) Tg mice to evaluate the protective effects of endogenous n-3 PUFAs on cognitive and behavioral deficits of APP Tg mice. We fed APP, APP/fat-1 and fat-1 mice with n-6 PUFAs rich diet. Brain tissues were collected at 3, 9 and 12 months for fatty acid and gene expression analysis, histology and protein assays. Morris Water Maze Test, open field test and elevated plus maze test were performed to measure the behavior capability. From the results, the expression of fat-1 transgene increased cortical n-3: n-6 PUFAs ratio and n-3 PUFAs concentrations, and sensorimotor dysfunction and cognitive deficits in AD were significantly less severe in APP/fat-1 mice with endogenous n-3 PUFAs than in APP mice controls. The protection against disturbance of spontaneous motor activity and cognitive deficits in AD was strongly correlated with increased n-3: n-6 PUFAs ratio and endogenous n-3 PUFAs, reduced APP generation, inhibited amyloid β peptide aggregation, suppressed nuclear factor-kappa B and astroglia activation, and reduced death of neurons in the cortex of APP/fat-1 mice compared with APP mice controls. In conclusion, our study demonstrates that an available medication with the maintenance of enriched n-3 PUFAs in the brain could slow down cognitive decline and prevent neuropsychological disorder in AD. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

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.

Piracetam inhibits ethanol (EtOH)-induced memory deficit by mediating multiple pathways.

PubMed

Yang, Yifan; Feng, Jian; Xu, Fangyuan; Wang, Jianglin

2017-12-01

Excessive ethanol (EtOH) intake, especially to prenatal exposure, can significantly affect cognitive function and cause permanent learning and memory injures in children. As a result, how to protect children from EtOH neurotoxicity has gained increasing attention in recent years. Piracetam (Pir) is a nootropic drug derived from c-aminobutyric acid and can manage cognition impairments in multiple neurological disorders. Studies have shown that Pir can exert therapeutic effects on EtOH-induced memory impairments, but the underlying mechanism is still unknown. In this study, we found that Pir inhibited ethanol-induced memory deficit by mediating multiple pathways. Treatment with EtOH could cause cognitive deficit in juvenile rats, and triggered the alteration of synaptic plasticity. Administration with Pir significantly increased long-term potentiation and protected hippocampus neurons from EtOH neurotoxicity. Pir intervention ameliorated EtOH-induced cell apoptosis and inhibited the activation of Caspase-3 in vitro, suggesting that Pir protected neurons by anti-apoptotic effects. Pir could decrease the expression of LC3-II and Beclin-1 induced by EtOH, and increase the phosphorylation of mTOR and reduce the phosphorylation of Akt, which suggested that the protective effect of Pir was involved in regulation of autophagic process and mTOR/Akt pathways. In conclusion, we speculate that Pir reduces EtOH-induced neuronal damage by regulation of apoptotic action and autophagic action, and our research offers preclinical evidence for the application of Pir in ethanol toxicity. Copyright © 2017 Elsevier B.V. All rights reserved.

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

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.

Loss of M5 muscarinic acetylcholine receptors leads to cerebrovascular and neuronal abnormalities and cognitive deficits in mice.

PubMed

Araya, Runa; Noguchi, Takanori; Yuhki, Munehiro; Kitamura, Naohito; Higuchi, Makoto; Saido, Takaomi C; Seki, Kenjiro; Itohara, Shigeyoshi; Kawano, Masako; Tanemura, Kentaro; Takashima, Akihiko; Yamada, Kazuyuki; Kondoh, Yasushi; Kanno, Iwao; Wess, Jürgen; Yamada, Masahisa

2006-11-01

The M5 muscarinic acetylcholine receptor (M5R) has been shown to play a crucial role in mediating acetylcholine-dependent dilation of cerebral blood vessels. We show that male M5R-/- mice displayed constitutive constriction of cerebral arteries using magnetic resonance angiography in vivo. Male M5R-/- mice exhibited a significantly reduced cerebral blood flow (CBF) in the cerebral cortex, hippocampus, basal ganglia, and thalamus. Cortical and hippocampal pyramidal neurons from M5R-/- mice showed neuronal atrophy. Hippocampus-dependent spatial and nonspatial memory was also impaired in M5R-/- mice. In M5R-/- mice, CA3 pyramidal cells displayed a significantly attenuated frequency of the spontaneous postsynaptic current and long-term potentiation was significantly impaired at the mossy fiber-CA3 synapse. Our findings suggest that impaired M5R signaling may play a role in the pathophysiology of cerebrovascular deficits. The M5 receptor may represent an attractive novel therapeutic target to ameliorate memory deficits caused by impaired cerebrovascular function.

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

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

Rapamycin rescues vascular, metabolic and learning deficits in apolipoprotein E4 transgenic mice with pre-symptomatic Alzheimer's disease.

PubMed

Lin, Ai-Ling; Jahrling, Jordan B; Zhang, Wei; DeRosa, Nicholas; Bakshi, Vikas; Romero, Peter; Galvan, Veronica; Richardson, Arlan

2017-01-01

Apolipoprotein E ɛ4 allele is a common susceptibility gene for late-onset Alzheimer's disease. Brain vascular and metabolic deficits can occur in cognitively normal apolipoprotein E ɛ4 carriers decades before the onset of Alzheimer's disease. The goal of this study was to determine whether early intervention using rapamycin could restore neurovascular and neurometabolic functions, and thus impede pathological progression of Alzheimer's disease-like symptoms in pre-symptomatic Apolipoprotein E ɛ4 transgenic mice. Using in vivo, multimodal neuroimaging, we found that apolipoprotein E ɛ4 mice treated with rapamycin had restored cerebral blood flow, blood-brain barrier integrity and glucose metabolism, compared to age- and gender-matched wild-type controls. The preserved vasculature and metabolism were associated with amelioration of incipient learning deficits. We also found that rapamycin restored the levels of the proinflammatory cyclophilin A in vasculature, which may contribute to the preservation of cerebrovascular function in the apolipoprotein E ɛ4 transgenics. Our results show that rapamycin improves functional outcomes in this mouse model and may have potential as an effective intervention to block progression of vascular, metabolic and early cognitive deficits in human Apolipoprotein E ɛ4 carriers. As rapamycin is FDA-approved and neuroimaging is readily used in humans, the results of the present study may provide the basis for future Alzheimer's disease intervention studies in human subjects. © The Author(s) 2015.

The selective positive allosteric M1 muscarinic receptor modulator PQCA attenuates learning and memory deficits in the Tg2576 Alzheimer's disease mouse model.

PubMed

Puri, Vanita; Wang, Xiaohai; Vardigan, Joshua D; Kuduk, Scott D; Uslaner, Jason M

2015-01-01

We have recently shown that the M1 muscarinic receptor positive allosteric modulator, PQCA, improves cognitive performance in rodents and non-human primates administered the muscarinic receptor antagonist scopolamine. The purpose of the present experiments was to characterize the effects of PQCA in a model more relevant to the disease pathology of Alzheimer's disease. Tg2576 transgenic mice that have elevated Aβ were tested in the novel object recognition task to characterize recognition memory as a function of age and treatment with the PQCA. The effects of PQCA were compared to the acetylcholinesterase inhibitor donepezil, the standard of care for Alzheimer's disease. In addition, the effect of co-administering PQCA and donepezil was evaluated. Aged Tg2576 mice demonstrated a deficit in recognition memory that was significantly attenuated by PQCA. The positive control donepezil also reversed the deficit. Furthermore, doses of PQCA and donepezil that were inactive on their own were found to improve recognition memory when given together. These studies suggest that M1 muscarinic receptor positive allosteric modulation can ameliorate memory deficits in disease relevant models of Alzheimer's disease. These data, combined with our previous findings demonstrating PQCA improves scopolamine-induced cognitive deficits in both rodents and non-human primates, suggest that M1 positive allosteric modulators have therapeutic potential for the treatment of Alzheimer's disease. Copyright © 2015 Elsevier B.V. All rights reserved.

Phosphodiesterase 2A Inhibitor TAK-915 Ameliorates Cognitive Impairments and Social Withdrawal in N-Methyl-d-Aspartate Receptor Antagonist-Induced Rat Models of Schizophrenia.

PubMed

Nakashima, Masato; Imada, Haruka; Shiraishi, Eri; Ito, Yuki; Suzuki, Noriko; Miyamoto, Maki; Taniguchi, Takahiko; Iwashita, Hiroki

2018-04-01

The pathophysiology of schizophrenia has been associated with glutamatergic dysfunction. Modulation of the glutamatergic signaling pathway, including N -methyl-d-aspartate (NMDA) receptors, can provide a new therapeutic target for schizophrenia. Phosphodiesterase 2A (PDE2A) is highly expressed in the forebrain, and is a dual substrate enzyme that hydrolyzes both cAMP and cGMP, which play pivotal roles as intracellular second messengers downstream of NMDA receptors. Here we characterize the in vivo pharmacological profile of a selective and brain-penetrant PDE2A inhibitor, ( N -{(1 S )-1-[3-fluoro-4-(trifluoromethoxy)phenyl]-2-methoxyethyl}-7-methoxy-2-oxo-2,3-dihydropyrido[2,3- b ]pyrazine-4(1 H )-carboxamide) (TAK-915) as a novel treatment of schizophrenia. Oral administration of TAK-915 at 3 and 10 mg/kg significantly increased cGMP levels in the frontal cortex, hippocampus, and striatum of rats. TAK-915 at 10 mg/kg significantly upregulated the phosphorylation of α -amino-3-hydroxy-5-methylisoxazole-4-proprionic acid receptor subunit GluR1 in the rat hippocampus. TAK-915 at 3 and 10 mg/kg significantly attenuated episodic memory deficits induced by the NMDA receptor antagonist (+)-MK-801 hydrogen maleate (MK-801) in the rat passive avoidance test. TAK-915 at 10 mg/kg significantly attenuated working memory deficits induced by MK-801 in the rat radial arm maze test. Additionally, TAK-915 at 10 mg/kg prevented subchronic phencyclidine-induced social withdrawal in social interaction in rats. In contrast, TAK-915 did not produce antipsychotic-like activity; TAK-915 had little effect on MK-801- or methamphetamine-induced hyperlocomotion in rats. These results suggest that TAK-915 has a potential to ameliorate cognitive impairments and social withdrawal in schizophrenia. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

Manganese exposure and cognitive deficits: a growing concern for manganese neurotoxicity.

PubMed

Roels, H A; Bowler, R M; Kim, Y; Claus Henn, B; Mergler, D; Hoet, P; Gocheva, V V; Bellinger, D C; Wright, R O; Harris, M G; Chang, Y; Bouchard, M F; Riojas-Rodriguez, H; Menezes-Filho, J A; Téllez-Rojo, Martha Maria

2012-08-01

This symposium comprised five oral presentations dealing with recent findings on Mn-related cognitive and motor changes from epidemiological studies across the life span. The first contribution highlighted the usefulness of functional neuroimaging of the central nervous system (CNS) to evaluate cognitive as well as motor deficits in Mn-exposed welders. The second dealt with results of two prospective studies in Mn-exposed workers or welders showing that after decrease of Mn exposure the outcome of reversibility in adverse CNS effects may differ for motor and cognitive function and, in addition the issue of plasma Mn as a reliable biomarker for Mn exposure in welders has been addressed. The third presentation showed a brief overview of the results of an ongoing study assessing the relationship between environmental airborne Mn exposure and neurological or neuropsychological effects in adult Ohio residents living near a Mn point source. The fourth paper focused on the association between blood Mn and neurodevelopment in early childhood which seems to be sensitive to both low and high Mn concentrations. The fifth contribution gave an overview of six studies indicating a negative impact of excess environmental Mn exposure from air and drinking water on children's cognitive performance, with special attention to hair Mn as a potential biomarker of exposure. These studies highlight a series of questions about Mn neurotoxicity with respect to cognitive processes, forms and routes of exposure, adequate biomarkers of exposure, gender differences, susceptibility and exposure limits with regard to age. Copyright © 2012 Elsevier Inc. All rights reserved.

Mitigation of postnatal ethanol-induced neuroinflammation ameliorates trace fear memory deficits in juvenile rats.

PubMed

Goodfellow, Molly J; Shin, Youn Ju; Lindquist, Derick H

2018-02-15

Impairments in behavior and cognition are common in individuals diagnosed with fetal alcohol spectrum disorders (FASD). In this study, FASD model rats were intragastrically intubated with ethanol (5g/kg/day; 5E), sham-intubated (SI), or maintained as naïve controls (NC) over postnatal days (PD) 4-9. Ethanol exposure during this human third trimester-equivalent period induces persistent impairments in hippocampus-dependent learning and memory. The ability of ibuprofen (IBU), a non-steroidal anti-inflammatory drug, to diminish ethanol-induced neuroinflammation and rescue deficits in hippocampus-dependent trace fear conditioning (TFC) was investigated in 5E rats. Phosphate buffered saline vehicle (VEH) or IBU was injected 2h following ethanol exposure over PD4-9, followed by quantification of inflammation-related genes in the dorsal hippocampus of PD10 rats. The 5E-VEH rats exhibited significant increases in Il1b and Tnf, but not Itgam or Gfap, relative to NC, SI-VEH, and 5E-IBU rats. In separate groups of PD31-33 rats, conditioned fear (freezing) was significantly reduced in 5E-VEH rats during TFC testing, but not acquisition, compared to SI-VEH and, critically, 5E-IBU rats. Results suggest neuroimmune activation in response to ethanol within the neonate hippocampus contributes to later-life cognitive dysfunction. Copyright © 2017 Elsevier B.V. All rights reserved.

Vagus nerve stimulation ameliorated deficits in one-way active avoidance learning and stimulated hippocampal neurogenesis in bulbectomized rats.

PubMed

Gebhardt, Nils; Bär, Karl-Jürgen; Boettger, Michael K; Grecksch, Gisela; Keilhoff, Gerburg; Reichart, Rupert; Becker, Axel

2013-01-01

Vagus nerve stimulation (VNS) has been introduced as a therapeutic option for treatment-resistant depression. The neural and chemical mechanisms responsible for the effects of VNS are largely unclear. Bilateral removal of the olfactory bulbs (OBX) is a validated animal model in depression research. We studied the effects of vagus nerve stimulation (VNS) on disturbed one-way active avoidance learning and neurogenesis in the hippocampal dentate gyrus of rats. After a stimulation period of 3 weeks, OBX rats acquired the learning task as controls. In addition, the OBX-related decrease of neuronal differentiated BrdU positive cells in the dentate gyrus was prevented by VNS. This suggests that chronic VNS and changes in hippocampal neurogenesis induced by VNS may also account for the amelioration of behavioral deficits in OBX rats. To the best of our knowledge, this is the first report on the restorative effects of VNS on behavioral function in an animal model of depression that can be compared with the effects of antidepressants. Copyright © 2013 Elsevier Inc. All rights reserved.

Effects of mindfulness-based cognitive therapy on neurophysiological correlates of performance monitoring in adult attention-deficit/hyperactivity disorder.

PubMed

Schoenberg, Poppy L A; Hepark, Sevket; Kan, Cornelis C; Barendregt, Henk P; Buitelaar, Jan K; Speckens, Anne E M

2014-07-01

To examine whether mindfulness-based cognitive therapy (MBCT) would enhance attenuated amplitudes of event-related potentials (ERPs) indexing performance monitoring biomarkers of attention-deficit/hyperactivity disorder (ADHD). Fifty adult ADHD patients took part in a randomised controlled study investigating ERP and clinical measures pre-to-post MBCT. Twenty-six patients were randomly allocated to MBCT, 24 to a wait-list control. Main outcome measures included error processing (ERN, Pe), conflict monitoring (NoGo-N2), and inhibitory control (NoGo-P3) ERPs concomitant to a continuous performance task (CPT-X). Inattention and hyperactivity-impulsivity ADHD symptoms, psychological distress and social functioning, and mindfulness skills were also assessed. MBCT was associated with increased Pe and NoGo-P3 amplitudes, coinciding with reduced 'hyperactivity/impulsivity' and 'inattention' symptomatology. Specific to the MBCT; enhanced Pe amplitudes correlated with a decrease in hyperactivity/impulsivity symptoms and increased 'act-with-awareness' mindfulness skill, whereas, enhanced P3 correlated with amelioration in inattention symptoms. MBCT enhanced ERP amplitudes associated with motivational saliency and error awareness, leading to improved inhibitory regulation. MBCT suggests having comparable modulation on performance monitoring ERP amplitudes as pharmacological treatments. Further study and development of MBCT as a treatment for ADHD is warranted, in addition to its potential scope for clinical applicability to broader defined externalising disorders and clinical problems associated with impairments of the prefrontal cortex. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Social Cognitive Training for Schizophrenia: A Meta-Analytic Investigation of Controlled Research

PubMed Central

Kurtz, Matthew M.; Richardson, Christi L.

2012-01-01

A wealth of evidence has revealed that deficits in social cognitive skills (including facial affect recognition (FAR), social cue perception, Theory of Mind (ToM), and attributional style) are evident in schizophrenia and are linked to a variety of domains of functional outcome. In light of these associations, a growing number of studies have attempted to ameliorate these deficits as a means of improving outcome in the disorder through the use of structured behavioral training. This study used quantitative methods of meta-analysis to assess the efficacy of behavioral training programs designed to improve social cognitive function. A total of 19 studies consisting of 692 clients were aggregated from relevant databases. Outcome measures were organized according to whether they were social cognitive tests proximal to the intervention or whether they represented measures of treatment generalization (symptoms, observer-rated community, and institutional function). With respect to social cognitive measures, weighted effect-size analysis revealed that there were moderate-large effects of social cognitive training procedures on FAR (identification, d = 0.71 and discrimination, d = 1.01) and small-moderate effects of training on ToM (d = 0.46), while effects on social cue perception and attributional style were not significant. For measures of generalization, weighted effect-size analysis revealed that there were moderate-large effect on total symptoms (d = 0.68) and observer-rated community and institutional function (d = 0.78). Effects of social cognitive training programs on positive and negative symptoms of schizophrenia were nonsignificant. Moderating variables and implications for future research and treatment development are discussed. PMID:21525166

A Case Study of the Cognitive and Behavioral Deficits of Temporal Lobe Damage in Herpes Simplex Encephalitis.

ERIC Educational Resources Information Center

Greer, Margaret K.; And Others

1989-01-01

This case study illustrates the highly significant language difficulties, marked memory deficits, and propensity for physical aggression following temporal lobe damage brought about by herpes encephalitis, and presents the usefulness of a new diagnostic measure in delineating such a variable cognitive pattern. (Author)

Cognitive impairment in COPD: should cognitive evaluation be part of respiratory assessment?

PubMed Central

Gloeckl, Rainer; Vogiatzis, Ioannis; Kenn, Klaus

2017-01-01

Cognitive impairment is highly prevalent in patients with COPD and demonstrates multiple detrimental effects on many aspects of patient state and therapeutic outcomes. It is attributed to several overlapping pathophysiological factors, with the most common being the low level of oxygen saturation due to respiratory insufficiency. Despite the impact of cognitive impairment on clinical outcomes, the screening for coexisting cognitive deficits which may interfere with the successful progress of respiratory treatment is yet neglected. There is a special consideration that cognitive deficits should be taken into account when developing respiratory therapy plans. Cognitively impaired patients are likely to require more support and have need of an individualised respiratory care plan which can also be beneficial for their cognitive deficits. Pulmonary rehabilitation as a multidisciplinary approach could be prioritised for COPD patients with cognitive impairment. Educational aims To illustrate the common signs of cognitive impairment and define potential associations between lung and cognitive dysfunction. To illustrate the potential influence of cognitive deficits on the optimal progress of respiratory therapy. To illustrate the importance of cognitive evaluation as part of a comprehensive clinical assessment for patients suspected of suffering cognitive impairment. PMID:29184593

Satureja bachtiarica ameliorate beta-amyloid induced memory impairment, oxidative stress and cholinergic deficit in animal model of Alzheimer's disease.

PubMed

Soodi, Maliheh; Saeidnia, Soodabeh; Sharifzadeh, Mohammad; Hajimehdipoor, Homa; Dashti, Abolfazl; Sepand, Mohammad Reza; Moradi, Shahla

2016-04-01

Extracellular deposition of Beta-amyloid peptide (Aβ) is the main finding in the pathophysiology of Alzheimer's disease (AD), which damages cholinergic neurons through oxidative stress and reduces the cholinergic neurotransmission. Satureja bachtiarica is a medicinal plant from the Lamiaceae family which was widely used in Iranian traditional medicine. The aim of the present study was to investigate possible protective effects of S. bachtiarica methanolic extract on Aβ induced spatial memory impairment in Morris Water Maze (MWM), oxidative stress and cholinergic neuron degeneration. Pre- aggregated Aβ was injected into the hippocampus of each rat bilaterally (10 μg/rat) and MWM task was performed 14 days later to evaluate learning and memory function. Methanolic extract of S.bachtiarica (10, 50 and 100 mg/Kg) was injected intraperitoneally for 19 consecutive days, after Aβ injection. After the probe test the brain tissue were collected and lipid peroxidation, Acetylcholinesterase (AChE) activity and Cholin Acetyl Transferees (ChAT) immunorectivity were measured in the hippocampus. Intrahipocampal injection of Aβ impaired learning and memory in MWM in training days and probe trail. Methanolic extract of S. bachtiarica (50 and 100 mg/Kg) could attenuate Aβ-induced memory deficit. ChAT immunostaining revealed that cholinergic neurons were loss in Aβ- injected group and S. bachtiarica (100 mg/Kg) could ameliorate Aβ- induced ChAT reduction in the hippocampus. Also S. bachtiarica could ameliorate Aβ-induced lipid peroxidation and AChE activity increase in the hippocampus. In conclusion our study represent that S.bachtiarica methanolic extract can improve Aβ-induced memory impairment and cholinergic loss then we recommended this extract as a candidate for further investigation in treatment of AD.

Blonanserin ameliorates phencyclidine-induced visual-recognition memory deficits: the complex mechanism of blonanserin action involving D₃-5-HT₂A and D₁-NMDA receptors in the mPFC.

PubMed

Hida, Hirotake; Mouri, Akihiro; Mori, Kentaro; Matsumoto, Yurie; Seki, Takeshi; Taniguchi, Masayuki; Yamada, Kiyofumi; Iwamoto, Kunihiro; Ozaki, Norio; Nabeshima, Toshitaka; Noda, Yukihiro

2015-02-01

Blonanserin differs from currently used serotonin 5-HT₂A/dopamine-D₂ receptor antagonists in that it exhibits higher affinity for dopamine-D₂/₃ receptors than for serotonin 5-HT₂A receptors. We investigated the involvement of dopamine-D₃ receptors in the effects of blonanserin on cognitive impairment in an animal model of schizophrenia. We also sought to elucidate the molecular mechanism underlying this involvement. Blonanserin, as well as olanzapine, significantly ameliorated phencyclidine (PCP)-induced impairment of visual-recognition memory, as demonstrated by the novel-object recognition test (NORT) and increased extracellular dopamine levels in the medial prefrontal cortex (mPFC). With blonanserin, both of these effects were antagonized by DOI (a serotonin 5-HT₂A receptor agonist) and 7-OH-DPAT (a dopamine-D₃ receptor agonist), whereas the effects of olanzapine were antagonized by DOI but not by 7-OH-DPAT. The ameliorating effect was also antagonized by SCH23390 (a dopamine-D₁ receptor antagonist) and H-89 (a protein kinase A (PKA) inhibitor). Blonanserin significantly remediated the decrease in phosphorylation levels of PKA at Thr(197) and of NR1 (an essential subunit of N-methyl-D-aspartate (NMDA) receptors) at Ser(897) by PKA in the mPFC after a NORT training session in the PCP-administered mice. There were no differences in the levels of NR1 phosphorylated at Ser(896) by PKC in any group. These results suggest that the ameliorating effect of blonanserin on PCP-induced cognitive impairment is associated with indirect functional stimulation of the dopamine-D₁-PKA-NMDA receptor pathway following augmentation of dopaminergic neurotransmission due to inhibition of both dopamine-D₃ and serotonin 5-HT₂A receptors in the mPFC.

Awake craniotomy in a developmentally delayed blind man with cognitive deficits.

PubMed

Burbridge, Mark; Raazi, Mateen

2013-04-01

To describe the complex perioperative considerations and anesthetic management of a cognitively delayed blind adult male who underwent awake craniotomy to remove a left anterior temporal lobe epileptic focus. A 28-yr-old left-handed blind cognitively delayed man was scheduled for awake craniotomy to resect a left anterior temporal lobe epileptic focus due to intractable epilepsy despite multiple medications. His medical history was also significant for retinopathy of prematurity that rendered him legally blind in both eyes and an intracerebral hemorrhage shortly after birth that resulted in a chronic brain injury and developmental delay. His cognitive capacity was comparable with that of an eight year old. Since patient cooperation was the primary concern during the awake electrocorticography phase of surgery, careful assessment of the patient's ability to tolerate the procedure was undertaken. There was extensive planning between surgeons and anesthesiologists, and a patient-specific pharmacological strategy was devised to facilitate surgery. The operation proceeded without complication, the patient has remained seizure-free since the procedure, and his quality of life has improved dramatically. This case shows that careful patient assessment, effective interdisciplinary communication, and a carefully tailored anesthetic strategy can facilitate an awake craniotomy in a potentially uncooperative adult patient with diminished mental capacity and sensory deficits.

Performances on a cognitive theory of mind task: specific decline or general cognitive deficits? Evidence from normal aging.

PubMed

Fliss, Rafika; Lemerre, Marion; Mollard, Audrey

2016-06-01

Compromised theory of mind (ToM) can be explained either by a failure to implement specific representational capacities (mental state representations) or by more general executive selection demands. In older adult populations, evidence supporting affected executive functioning and cognitive ToM in normal aging are reported. However, links between these two functions remain unclear. In the present paper, we address these shortcomings by using a specific task of ToM and classical executive tasks. We studied, using an original cognitive ToM task, the effect of age on ToM performances, in link with the progressive executive decline. 96 elderly participants were recruited. They were asked to perform a cognitive ToM task, and 5 executive tests (Stroop test and Hayling Sentence Completion Test to appreciate inhibitory process, Trail Making Test and Verbal Fluency for shifting assessment and backward span dedicated to estimate working memory capacity). The results show changes in cognitive ToM performance according to executive demands. Correlational studies indicate a significant relationship between ToM performance and the selected executive measures. Regression analyzes demonstrates that level of vocabulary and age as the best predictors of ToM performance. The results are consistent with the hypothesis that ToM deficits are related to age-related domain-general decline rather than as to a breakdown in specialized representational system. The implications of these findings for the nature of social cognition tests in normal aging are also discussed.

Failures of cognitive control or attention? The case of stop-signal deficits in schizophrenia.

PubMed

Matzke, Dora; Hughes, Matthew; Badcock, Johanna C; Michie, Patricia; Heathcote, Andrew

2017-05-01

We used Bayesian cognitive modelling to identify the underlying causes of apparent inhibitory deficits in the stop-signal paradigm. The analysis was applied to stop-signal data reported by Badcock et al. (Psychological Medicine 32: 87-297, 2002) and Hughes et al. (Biological Psychology 89: 220-231, 2012), where schizophrenia patients and control participants made rapid choice responses, but on some trials were signalled to stop their ongoing response. Previous research has assumed an inhibitory deficit in schizophrenia, because estimates of the mean time taken to react to the stop signal are longer in patients than controls. We showed that these longer estimates are partly due to failing to react to the stop signal ("trigger failures") and partly due to a slower initiation of inhibition, implicating a failure of attention rather than a deficit in the inhibitory process itself. Correlations between the probability of trigger failures and event-related potentials reported by Hughes et al. are interpreted as supporting the attentional account of inhibitory deficits. Our results, and those of Matzke et al. (2016), who report that controls also display a substantial although lower trigger-failure rate, indicate that attentional factors need to be taken into account when interpreting results from the stop-signal paradigm.

The Neural Substrates of Cognitive Control Deficits in Autism Spectrum Disorders

PubMed Central

Solomon, Marjorie; Ozonoff, Sally; Ursu, Stefan; Ravizza, Susan; Cummings, Neil; Ly, Stanford; Carter, Cameron

2009-01-01

Executive functions deficits are among the most frequently reported symptoms of autism spectrum disorders (ASDs), however, there have been few functional magnetic resonance imaging (fMRI) studies that investigate the neural substrates of executive functions deficits in ASDs, and only one in adolescents. The current study examined cognitive control –the ability to maintain task context online to support adaptive functioning in the face of response competition—in 22 adolescents aged 12–18 with autism spectrum disorders and 23 age, gender, and IQ matched typically developing subjects. During the cue phase of the task, where subjects must maintain information online to overcome a prepotent response tendency, typically developing subjects recruited significantly more anterior frontal (BA 10), parietal (BA 7, 40), and occipital regions (BA 18) for high control trials (25% of trials) versus low control trials (75% of trials). Both groups showed similar activation for low control cues, however the ASD group exhibited significantly less activation for high control cues. Functional connectivity analysis using time series correlation, factor analysis, and beta series correlation methods provided convergent evidence that the ASD group exhibited lower levels of functional connectivity and less network integration between frontal, parietal, and occipital regions. In the typically developing group, fronto-parietal connectivity was related to lower error rates on high control trials. In the autism group, reduced fronto-parietal connectivity was related to attention deficit hyperactivity disorder symptoms. PMID:19410583

Dangguijakyak-san ameliorates memory deficits in ovariectomized mice by upregulating hippocampal estrogen synthesis.

PubMed

Hwang, Deok-Sang; Kim, Namkwon; Choi, Jin Gyu; Kim, Hyo Geun; Kim, Hocheol; Oh, Myung Sook

2017-11-25

Dangguijakyak-san (DJS) is an herbal formulation that has been clinically applicable for treating postmenopausal symptoms and neurological disorders. It is reported that hippocampal estrogen attenuates memory impairment via neuroprotection and synaptogenesis. However, the effect of DJS on hippocampal estrogen synthesis remains unknown. In this study, we explored the effect of DJS and its neuroprotective mechanism against memory impairment in ovariectomized (OVX) mice, with respect to hippocampal estrogen stimulation. Cell cultures were prepared from the hippocampi of 18-day-old embryos from timed pregnant Sprague-Dawley rats. The hippocampi were dissected, collected, dissociated, and plated in 60-mm dishes. The cells were treated with DJS for 48 h and the supernatant was collected to determine estrogen levels. Female ICR mice (8-weeks-old) were housed for 1 week and ovariectomy was performed to remove the influence of ovary-synthesized estrogens. Following a 2-week post-surgical recovery period, the mice were administrated with DJS (50 and 100 mg/kg/day, p.o.) or 17β-estradiol (200 μg/kg/day, i.p.) once daily for 21 days. Hippocampal and serum estrogen levels were determined using enzyme-linked immunosorbent assay kit. Memory behavioral tests, western blot, and immunohistochemical analyses were performed to evaluate the neuroprotective effects of DJS in this model. DJS treatment promoted estrogen synthesis in primary hippocampal cells and the hippocampus of OVX mice, resulting in the amelioration of OVX-induced memory impairment. Hippocampal estrogen stimulated by DJS treatment contributed to the activation of cAMP response element-binding protein and synaptic protein in OVX mice. DJS may attenuate memory deficits in postmenopausal women via hippocampal estrogen synthesis.

Assessing cognitive dysfunction in Parkinson's disease: An online tool to detect visuo‐perceptual deficits

PubMed Central

Schwarzkopf, Dietrich S.; Bahrami, Bahador; Fleming, Stephen M.; Jackson, Ben M.; Goch, Tristam J. C.; Saygin, Ayse P.; Miller, Luke E.; Pappa, Katerina; Pavisic, Ivanna; Schade, Rachel N.; Noyce, Alastair J.; Crutch, Sebastian J.; O'Keeffe, Aidan G.; Schrag, Anette E.; Morris, Huw R.

2018-01-01

ABSTRACT Background: People with Parkinson's disease (PD) who develop visuo‐perceptual deficits are at higher risk of dementia, but we lack tests that detect subtle visuo‐perceptual deficits and can be performed by untrained personnel. Hallucinations are associated with cognitive impairment and typically involve perception of complex objects. Changes in object perception may therefore be a sensitive marker of visuo‐perceptual deficits in PD. Objective: We developed an online platform to test visuo‐perceptual function. We hypothesised that (1) visuo‐perceptual deficits in PD could be detected using online tests, (2) object perception would be preferentially affected, and (3) these deficits would be caused by changes in perception rather than response bias. Methods: We assessed 91 people with PD and 275 controls. Performance was compared using classical frequentist statistics. We then fitted a hierarchical Bayesian signal detection theory model to a subset of tasks. Results: People with PD were worse than controls at object recognition, showing no deficits in other visuo‐perceptual tests. Specifically, they were worse at identifying skewed images (P < .0001); at detecting hidden objects (P = .0039); at identifying objects in peripheral vision (P < .0001); and at detecting biological motion (P = .0065). In contrast, people with PD were not worse at mental rotation or subjective size perception. Using signal detection modelling, we found this effect was driven by change in perceptual sensitivity rather than response bias. Conclusions: Online tests can detect visuo‐perceptual deficits in people with PD, with object recognition particularly affected. Ultimately, visuo‐perceptual tests may be developed to identify at‐risk patients for clinical trials to slow PD dementia. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society. PMID:29473691

Number Processing and Heterogeneity of Developmental Dyscalculia: Subtypes With Different Cognitive Profiles and Deficits.

PubMed

Skagerlund, Kenny; Träff, Ulf

2016-01-01

This study investigated if developmental dyscalculia (DD) in children with different profiles of mathematical deficits has the same or different cognitive origins. The defective approximate number system hypothesis and the access deficit hypothesis were tested using two different groups of children with DD (11-13 years old): a group with arithmetic fact dyscalculia (AFD) and a group with general dyscalculia (GD). Several different aspects of number magnitude processing were assessed in these two groups and compared with age-matched typically achieving children. The GD group displayed weaknesses with both symbolic and nonsymbolic number processing, whereas the AFD group displayed problems only with symbolic number processing. These findings provide evidence that the origins of DD in children with different profiles of mathematical problems diverge. Children with GD have impairment in the innate approximate number system, whereas children with AFD suffer from an access deficit. These findings have implications for researchers' selection procedures when studying dyscalculia, and also for practitioners in the educational setting. © Hammill Institute on Disabilities 2014.

Activation of the canonical nuclear factor-κB pathway is involved in isoflurane-induced hippocampal interleukin-1β elevation and the resultant cognitive deficits in aged rats

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

Li, Zheng-Qian; Rong, Xiao-Ying; Liu, Ya-Jie

Highlights: •Isoflurane induces hippocampal IL-1β elevation and cognitive deficits in aged rats. •Isoflurane transiently activates the canonical NF-κB pathway in aged rat hippocampus. •NF-κB inhibitor mitigates isoflurane-induced IL-1β elevation and cognitive deficits. •We report a linkage between NF-κB signaling, IL-1β expression, and cognitive changes. -- Abstract: Although much recent evidence has demonstrated that neuroinflammation contributes to volatile anesthetic-induced cognitive deficits, there are few existing mechanistic explanations for this inflammatory process. This study was conducted to investigate the effects of the volatile anesthetic isoflurane on canonical nuclear factor (NF)-κB signaling, and to explore its association with hippocampal interleukin (IL)-1β levels andmore » anesthetic-related cognitive changes in aged rats. After a 4-h exposure to 1.5% isoflurane in 20-month-old rats, increases in IκB kinase and IκB phosphorylation, as well as a reduction in the NF-κB inhibitory protein (IκBα), were observed in the hippocampi of isoflurane-exposed rats compared with control rats. These events were accompanied by an increase in NF-κB p65 nuclear translocation at 6 h after isoflurane exposure and hippocampal IL-1β elevation from 1 to 6 h after isoflurane exposure. Nevertheless, no significant neuroglia activation was observed. Pharmacological inhibition of NF-κB activation by pyrrolidine dithiocarbamate markedly suppressed the IL-1β increase and NF-κB signaling, and also mitigated the severity of cognitive deficits in the Morris water maze task. Overall, our results demonstrate that isoflurane-induced cognitive deficits may stem from upregulation of hippocampal IL-1β, partially via activation of the canonical NF-κB pathway, in aged rats.« less

Intra-regional and inter-regional abnormalities and cognitive control deficits in young adult smokers.

PubMed

Feng, Dan; Yuan, Kai; Li, Yangding; Cai, Chenxi; Yin, Junsen; Bi, Yanzhi; Cheng, Jiadong; Guan, Yanyan; Shi, Sha; Yu, Dahua; Jin, Chenwang; Lu, Xiaoqi; Qin, Wei; Tian, Jie

2016-06-01

Tobacco use during later adolescence and young adulthood may cause serious neurophysiological changes; rationally, it is extremely important to study the relationship between brain dysfunction and behavioral performances in young adult smokers. Previous resting state studies investigated the neural mechanisms in smokers. Unfortunately, few studies focused on spontaneous activity differences between young adult smokers and nonsmokers from both intra-regional and inter-regional levels, less is known about the association between resting state abnormalities and behavioral deficits. Therefore, we used fractional amplitude of low frequency fluctuation (fALFF) and resting state functional connectivity (RSFC) to investigate the resting state spontaneous activity differences between young adult smokers and nonsmokers. A correlation analysis was carried out to assess the relationship between neuroimaging findings and clinical information (pack-years, cigarette dependence, age of onset and craving score) as well as cognitive control deficits measured by the Stroop task. Consistent with previous addiction findings, our results revealed the resting state abnormalities within frontostriatal circuits, i.e., enhanced spontaneous activity of the caudate and reduced functional strength between the caudate and anterior cingulate cortex (ACC) in young adult smokers. Moreover, the fALFF values of the caudate were correlated with craving and RSFC strength between the caudate and ACC was associated with the cognitive control impairments in young adult smokers. Our findings could lead to a better understanding of intrinsic functional architecture of baseline brain activity in young smokers by providing regional and brain circuit spontaneous neuronal activity properties as well as their association with cognitive control impairments.

Do complaints of everyday cognitive failures in high schizotypy relate to emotional working memory deficits in the lab?

PubMed

Carrigan, Nicole; Barkus, Emma; Ong, Adriel; Wei, Maryann

2017-10-01

Individuals high on schizotypy complain of increased cognitive failures in everyday life. However, the neuropsychological performance of this group does not consistently indicate underlying ability deficits. It is possible that current neuropsychological tests lack ecological validity. Given the increased affective reactivity of high schizotypes, they may be more sensitive to emotional content interfering with cognitive ability. This study sought to explore whether an affective n-back working memory task would elicit impaired performance in schizotypy, echoing complaints concerning real world cognition. 127 healthy participants completed self-report measures of schizotypy and cognitive failures and an affective n-back working memory task. This task was varied across three levels of load (1- to 3-back) and four types of stimulus emotion (neutral, fearful, happy, sad). Differences between high (n=39) and low (n=48) schizotypy groups on performance outcomes of hits and false alarms were examined, with emotion and load as within-groups variables. As expected, high schizotypes reported heightened vulnerability to cognitive failures. They also demonstrated a relative working memory impairment for emotional versus neutral stimuli, whereas low schizotypes did not. High schizotypes performed most poorly in response to fearful stimuli. For false alarms, there was an interaction between schizotypy, load, and emotion, such that high schizotypy was associated with deficits in response to fearful stimuli only at higher levels of task difficulty. Inclusion of self-reported cognitive failures did not account for this. These findings suggest that the "gap" between subjective and objective cognition in schizotypy may reflect the heightened emotional demands associated with cognitive functioning in the real world, although other factors also seem to play a role. There is a need to improve the ecological validity of objective assessments, whilst also recognizing that self