Forms Of Cognitive Deficits Research Articles

Longitudinal Cognitive Decline in a Novel Rodent Model of Cerebral Amyloid Angiopathy Type-1.

Cerebral amyloid angiopathy (CAA) is a small vessel disease characterized by β-amyloid (Aβ) accumulation in and around the cerebral blood vessels and capillaries and is highly comorbid with Alzheimer’s disease (AD). Familial forms of CAA result from mutations within the Aβ domain of the amyloid β precursor protein (AβPP). Numerous transgenic mouse models have been generated around expression of human AβPP mutants and used to study cerebral amyloid pathologies. While behavioral deficits have been observed in many AβPP transgenic mouse lines, relative to rats, mice are limited in behavioral expression within specific cognitive domains. Recently, we generated a novel rat model, rTg-DI, which expresses Dutch/Iowa familial CAA Aβ in brain, develops progressive and robust accumulation of cerebral microvascular fibrillar Aβ beginning at 3 months, and mimics many pathological features of the human disease. The novel rTg-DI model provides a unique opportunity to evaluate the severity and forms of cognitive deficits that develop over the emergence and progression of CAA pathology. Here, we present an in-depth, longitudinal study aimed to complete a comprehensive assessment detailing phenotypic disease expression through extensive and sophisticated operant testing. Cohorts of rTg-DI and wild-type (WT) rats underwent operant testing from 6 to 12 months of age. Non-operant behavior was assessed prior to operant training at 4 months and after completion of training at 12 months. By 6 months, rTg-DI animals demonstrated speed–accuracy tradeoffs that later manifested across multiple operant tasks. rTg-DI animals also demonstrated delayed reaction times beginning at 7 months. Although non-operant assessments at 4 and 12 months indicated comparable mobility and balance, rTg-DI showed evidence of slowed environmental interaction. Overall, this suggests a form of sensorimotor slowing is the likely core functional impairment in rTg-DI rats and reflects similar deficits observed in human CAA.

Amelioration of cognitive impairments induced by GABA hypofunction in the male rat prefrontal cortex by direct and indirect dopamine D1 agonists SKF-81297 and d-Govadine

Deficits in prefrontal cortex (PFC) GABAergic neurotransmission are linked to cognitive impairments seen in schizophrenia and other disorders, and pharmacological reduction of PFC GABAA transmission disrupts processes including working and spatial memory. This provides an opportunity to examine whether compounds capable of neutralizing GABAergic dysfunction may ameliorate these cognitive deficits. PFC dopamine (DA) D1 receptor activation enhances GABA transmission, raising the possibly that direct or indirect agonists of DA D1 receptors would be effective in reversing working memory and other forms of cognitive deficits. To test this, male rats were pre-treated with two drugs that augment PFC D1 signalling before PFC infusion of the GABAA antagonist, bicuculline (50 ng) and assessment of spatial working and reference memory function. A moderate dose of the full D1 agonist SKF-81297 (0.1 mg/kg) completely reversed PFC GABA hypofunction-induced working memory deficits assessed in an delayed-response task, whereas lower and higher doses (0.05 and 0.3 mg/kg respectively) were associated with mild improvements or deleterious effects. Treatment with the tetrahydroprotoberberine d-govadine (0.5 or 1.0 mg/kg), a synthetic compound known to enhance DA release selectively in the PFC, also significantly improved delayed-response working memory function induced by PFC GABAA antagonism. Furthermore, administration of the optimal dose of both drugs led to a partial rescue of PFC GABA hypofunction-induced reference and short-term spatial memory impairments assessed on a radial maze task. These findings suggest that modulation of PFC DA signalling via actions on the DA D1 receptor represents a promising therapeutic strategy for working memory and other cognitive impairments observed in psychiatric disorders, including those with causes that extend beyond DA dysfunction.

Associations of oxytocin and vasopressin plasma levels with neurocognitive, social cognitive and meta cognitive function in schizophrenia

Many with schizophrenia experiences deficits in social cognition, neurocognition and metacognition. Yet the biological mechanisms which may underpin these cognitive deficits are poorly understood. Two candidate causes of these deficits are disturbances in oxytocin (OT) and vasopressin (VP). To explore this we assessed plasma OT and VP in 34 schizophrenia patients and 31 healthy controls. We also concurrently assessed social cognition using the Reading the Mind from the Eyes test, neurocognition using the Wisconsin Card Sorting Test and metacognition using the Metacognitive Assessment Scale-Abbreviated. Group comparisons revealed lower plasma OT levels in the schizophrenia group. Plasma VP levels did not differ between groups. Correlations revealed that lower levels of OT were associated with poorer levels of metacognitive functioning in the schizophrenia group but not poorer social cognition or neurocognition. In a stepwise multiple regression, plasma OT level, neurocognition and social cognition contributed uniquely to the prediction of metacognition in the schizophrenia group. Results may suggest that disturbance in OT is linked with deficits in metacognition and may interact with other forms of cognitive deficits, interfering with the person's abilities to form a complex and integrated sense of self and others.

Psychiatric aspects of pediatric epilepsy: Focus on anxiety disorder

Psychiatric co-morbidities are commonly seen with pediatric epilepsy, which can be in the form of cognitive deficits like - inattention and intellectual disability, motor disturbances like - hyperactivity, emotional disturbances like - depression and anxiety disorders and behavioral problems like - impulsivity, aggression and even psychotic behavior. Anxiety disorders like - Obsessive compulsive disorder, posttraumatic stress disorder, social phobia, separation anxiety disorder, agoraphobia and panic attacks are commonly seen with pediatric epilepsy. Presence of co-morbid anxiety disorder in pediatric epilepsy is responsible for scholastic decline, peer maladjustment and poor quality of life. Management of anxiety disorders in children with epilepsy is always a challenge. Until, there is no general consensus regarding management of anxiety disorders in pediatric epilepsy. Despite its enormous impact on an individual's life, this area has not been addressed adequately through clinical research. This review focuses on psychiatric aspects of pediatric epilepsy with specific emphasis on anxiety disorders.

Metacognition in schizophrenia spectrum disorders: Methods of assessment and associations with neurocognition and function

Background and Objectives: Research has confirmed that many with schizophrenia experience deficits in metacognitive capacity defined as impairments in the ability to think about thinking, both with regards to their own thinking and the thinking of others. These difficulties are related to, but not reducible to symptoms. One question posed here regards how these deficits are linked to other forms of cognitive deficits, including deficits in neurocognition, and how they and other forms of cognitive deficits are related to the ability to function. As neurocognition is degraded in schizophrenia, does the ability to think about one's own thinking diminish? Do deficits in metacognition affect function in a manner semi-independent of deficits in neurocognition? Methods: To explore these possibilities, this paper reviews recent studies of metacognition as assessed within personal narratives of self and illness spontaneously generated by adults with schizophrenia spectrum disorders. Results: Studies are reviewed which suggest that impairments in verbal memory and executive function may interfere with the ability to form and sustain representation of one's own internal state as well as the internal states of others. Additionally, results are de-tailed which suggest that metacognitive deficits directly affect function prospectively and may mediate the impact of neurocognitive deficits on functioning. Conclusions: Results are consistent with the possibility that a certain level of neurocognition is needed to think about thinking in a complex manner and that the ability to think about thinking is intimately related to the ability to work and relate to others among persons with schizophrenia.

Assessing cognitive-linguistic abilities in South African adults living with HIV: the Cognitive Linguistic Quick Test

HIV can cross the blood-brain barrier to enter the central nervous system. This results in cognitive deficits in the majority of patients. The assessment of these deficits and management of these patients poses challenges for healthcare workers in South Africa. This study investigates the effectiveness of the Cognitive Linguistic Quick Test (CLQT) in identifying the cognitive and linguistic abilities of adults with HIV or AIDS. Sixteen participants were recruited from an outpatient clinic in Johannesburg. The CLQT was utilised to assess the cognitive/linguistic abilities of the participants. The overall scores revealed that 87.5% of the participants presented with some form of cognitive deficit, 81% exhibited deficits in memory and executive functioning, 75% showed deficits in attention and visual perception, and 50% exhibited language deficits. Thus, this instrument may be usefully employed with patients who exhibit neurological disorders, including those caused by HIV infection. We conclude that the CLQT can be used as an alternative to more expensive, elaborate and time-consuming neuropsychometric evaluations to identify deficits in memory, attention and executive functions as experienced by adults with HIV or AIDS in South Africa.

Cognitive Impairments in Patients With Hemispatial Neglect From Acute Right Hemisphere Stroke

Little is known about cognitive differences between patients showing neglect and those without neglect in their acute stroke stage. The aim of this study was to investigate how the patients with neglect (N+) differ from those without neglect (N-) in general cognitive function assessed by the Mini-Mental State Examination (MMSE). Patients consisted of 98 consecutive patients with acute right hemisphere stroke. The patients underwent neglect test battery followed by MMSE in the same day. The frequency of cognitive deficits in N+ group was higher than that of N- group (74.1% vs. 35.0%). A regression analysis, after controlling for lesion volume, age, and education, showed that neglect was a significant predictor of low MMSE score. Among MMSE subdomains, the severity of neglect was related to poor performances on episodic memory (orientation and 3-word recall), working memory/calculation (serial 7s), and constructional praxis (interlocking pentagons). These results suggest that hemispatial neglect is associated with several forms of cognitive deficits in patients with acute right hemisphere stroke.

Brain iron deficiency and excess; cognitive impairment and neurodegenration with involvement of striatum and hippocampus

While iron deficiency is not perceived as a life threatening disorder, it is the most prevalent nutritional abnormality in the world, and a better understanding of modes and sites of action, can help devise better treatment programs for those who suffer from it. Nowhere is this more important than in infants and children that make up the bulk of iron deficiency in society. Although the effects of iron deficiency have been extensively studied in systemic organs, until very recently little attention was paid to its effects on brain function. The studies of Oski at Johns Hopkin Medical School in 1974, demonstrating the impairment of learning in young school children with iron deficiency, prompted us to study its relevance to brain biochemistry and function in an animal model of iron deficiency. Indeed, rats made iron deficient have lowered brain iron and impaired behaviours including learning. This can become irreversible especially in newborns, even after long-term iron supplementation. We have shown that in this condition it is the brain striatal dopaminergic-opiate system which becomes defective, resulting in alterations in circadian behaviours, cognitive impairment and neurochemical changes closely associated with them. More recently we have extended these studies and have established that cognitive impairment may be closely associated with neuroanatomical damage and zinc metabolism in the hippocampus due to iron deficiency, and which may result from abnormal cholinergic function. The hippocampus is the focus of many studies today, since this brain structure has high zinc concentration and is highly involved in many forms of cognitive deficits as a consequence of cholinergic deficiency and has achieved prominence because of dementia in ageing and Alzheimer's disease. Thus, it is now apparent that cognitive impairment may not be attributed to a single neurotransmitter, but rather, alterations and interactions of several systems in different brain regions. In animal models of iron deficiency it is apparent that dopaminergic interaction with the opiate system and cholinergic neurotransmission may be defective.

Role of p21-activated kinase pathway defects in the cognitive deficits of Alzheimer disease

Defects in dendritic spines are common to several forms of cognitive deficits, including mental retardation and Alzheimer disease. Because mutation of p21-activated kinase (PAK) can lead to mental retardation and because PAK-cofilin signaling is critical in dendritic spine morphogenesis and actin dynamics, we hypothesized that the PAK pathway is involved in synaptic and cognitive deficits in Alzheimer disease. Here, we show that PAK and its activity are markedly reduced in Alzheimer disease and that this is accompanied by reduced and redistributed phosphoPAK, prominent cofilin pathology and downstream loss of the spine actin-regulatory protein drebrin, which cofilin removes from actin. We found that beta-amyloid (Abeta) was directly involved in PAK signaling deficits and drebrin loss in Abeta oligomer-treated hippocampal neurons and in the Appswe transgenic mouse model bearing a double mutation leading to higher Abeta production. In addition, pharmacological PAK inhibition in adult mice was sufficient to cause similar cofilin pathology, drebrin loss and memory impairment, consistent with a potential causal role of PAK defects in cognitive deficits in Alzheimer disease.

Cognitive deficits in long-term survivors of childhood brain tumors

Improvements in survival for patients who had childhood brain tumors has led to an increasing emphasis on the quality of life for these long-term survivors. Initial survival studies relied on global descriptions of functional abilities to assess cognitive deficits and reported that from 20% to 40% of long-term survivors had obvious partial disability and less than 10% were severely disabled. Formal neuropsychological testing has revealed that from 40% to 100% of long-term survivors have some form of cognitive deficit in various intelligence quotients, visual/perceptual skills, learning abilities, and adaptive behavior. Prospective, controlled studies have found a younger age at diagnosis, radiotherapy, methotrexate chemotherapy, tumor location and time interval to testing to be important (alone or in combination) and related to a high risk of subsequent cognitive deficits. Some variables play an as yet unresolved role. However, despite the progress of the last decade, future prospective studies are needed to define the role of certain variables in the development of cognitive deficits that maximize survival while minimizing cognitive deficits.

Unrealistic expectations and problem-solving ability in maltreating and comparison mothers.

It has been suggested that maltreating parents display two forms of cognitive deficits that relate to their child's maltreatment. These are of their children's behavior and poor problem-solving ability in childrearing situations. This study documents the existence of these two deficits in a sample of maltreating versus comparison mothers. Using two measures of and a problem-solving inventory, we explored differences between two types of maltreating mothers (abuse vs. neglect). Results indicated that both groups of maltreating mothers showed significantly greater unrealistic; and poorer problemsolving skills than did the comparison mothers. No differences were found between abusing and neglectful mothers. Implications for treatment, as well as difficulties in operationaliz ing the concept of unrealistic are discussed. Behaviorally oriented researchers have suggested that child maltreatment may be the result of parental cognitive and behavioral dysfunctions. Although there is some evidence that behavioral differences exist between maltreating and nonmaltreating parents (Burgess & Conger, 1978), the existence of cognitive problems has not been well documented. One area of cognitive dysfunction that has been suggested to play an important role in child abuse is that maltreating parents have of their child's behavior (i.e., they overestimate their child's capabilities; Steele & Pollock, 1968). When the child fails to meet these inappropriate expectations, the parent becomes frustrated and aggressive against the child or neglects the child's needs. Two recent studies attempting to substantiate the existence of dysfunctional have either failed (Starr, 1980) or shown errors in both over- and underestimating children's capabilities (Twentyman & Plotkin, 1982). It must be noted, however, that both these studies chose to operationaliz e unrealistic expectations by assessing parents' knowledge of developmental milestones. This

Unrealistic expectations and problem-solving ability in maltreating and comparison mothers.

It has been suggested that maltreating parents display two forms of cognitive deficits that relate to their child's maltreatment. These are unrealistic expectations of their children's behavior and poor problem-solving ability in childrearing situations. This study documents the existence of these two deficits in a sample of maltreating versus comparison mothers. Using two measures of unrealistic expectations and a problem-solving inventory, we explored differences between two types of maltreating mothers (abuse vs. neglect). Results indicated that both groups of maltreating mothers showed significantly greater unrealistic; expectations and poorer problemsolving skills than did the comparison mothers. No differences were found between abusing and neglectful mothers. Implications for treatment, as well as difficulties in operationaliz ing the concept of "unrealistic expectations," are discussed. Behaviorally oriented researchers have suggested that child maltreatment may be the result of parental cognitive and behavioral dysfunctions. Although there is some evidence that behavioral differences exist between maltreating and nonmaltreating parents (Burgess & Conger, 1978), the existence of cognitive problems has not been well documented. One area of cognitive dysfunction that has been suggested to play an important role in child abuse is that maltreating parents have unrealistic expectations of their child's behavior (i.e., they overestimate their child's capabilities; Steele & Pollock, 1968). When the child fails to meet these inappropriate expectations, the parent becomes frustrated and aggressive against the child or neglects the child's needs. Two recent studies attempting to substantiate the existence of dysfunctional expectations have either failed (Starr, 1980) or shown errors in both over- and underestimating children's capabilities (Twentyman & Plotkin, 1982). It must be noted, however, that both these studies chose to operationaliz e "unrealistic expectations" by assessing parents' knowledge of developmental milestones. This