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Posterior cingulate gyrus metabolic changes in chronic schizophrenia with generalized cognitive deficits.

N-Methyl-d-aspartate (NMDA) receptor antagonists are known to induce schizophrenia-like psychotic symptoms and cognitive deficits in humans, and have been shown to cause neuronal damage in the posterior cingulate gyrus (PCG) of rodents. Patients with chronic schizophrenia exhibit generalized cognitive deficits, but it remains unclear whether or not the PCG is related to their cognitive dysfunction. To determine what biochemical changes may occur in the PCG of patients with chronic schizophrenia, and to ascertain whether or not such abnormalities may be related to the incidence of cognitive deficits, we obtained cognitive scores and proton magnetic resonance spectra (MRS) from the PCG and the left and right medial temporal lobes (MTL) of 19 patients with schizophrenia and 18 age- and sex-matched normal healthy controls. Compared to the normal controls, the patients with chronic schizophrenia showed significantly worse cognitive performance on verbal and visual memory tests, verbal fluency tests, and the Trail Making Test. The ratio of N-acetylaspartate to creatine and phosphocreatine (NAA/Cr) in the PCG of the patients was significantly lower than that of the controls. Moreover, the NAA/Cr in the PCG of the healthy controls exhibited age-related decline, whereas in the patients with schizophrenia, the corresponding values were consistently low, regardless of age. These findings are thus in accord with current speculation about neuronal dysfunction in the PCG based on the NMDA hypofunction hypothesis regarding the pathophysiology of chronic schizophrenia.

Adult↗

T-588, a novel neuroprotective agent, delays progression of neuromuscular dysfunction in wobbler mouse motoneuron disease.

R(-)-1-(benzo[b]thiophen-5-yl)-2-[2-(N,N-diethylamino) ethoxy]ethanol hydrochloride (T-588) enhances acetylcholine release from the frontal cortex and hippocampus in rats, and can ameliorate cognitive dysfunction in various amnesia models of rodents. T-588 protects rat cerebellar granule cells from glutamate neurotoxicity in culture. This agent also inhibits facilitation in the crayfish neuromuscular junction and mammalian cerebellum. Clinical trials of T-588 are underway in patients with Alzheimer's disease. We attempted to determine whether T-588 treatment ameliorates neuromuscular dysfunction in the wobbler mouse, an animal model of motoneuron disease (MND). After the initial diagnosis of MND at the age of 3-4 weeks, wobbler mice were orally administered T-588 (3, 10, 30 mg/kg) or vehicle daily for 4 weeks in a blinded fashion. We compared symptomatic, pathological and biochemical changes among the groups. In comparison with vehicle, T-588 administration potentiated grip strength, attenuated forelimb contracture and increased the weight of the biceps muscles. T-588-treated mice had retarded denervation muscle atrophy and elevated activities of choline acetyltransferase (ChAT) or lactate dehydrogenase in the biceps muscles. T-588 treatment also enhanced ChAT activities and promoted formation of cyclic adenosine monophosphate in the cervical cord. Pharmacokinetic study also showed that T-588 was transported efficiently into the cerebrum and spinal cord following oral administration. Thus, T-588 treatment delayed the progression of wobbler murine MND. Our findings suggest that this agent has therapeutic potential in human motor neuropathy or MND.

Administration, Oral↗

Cognitive and neurobehavioral dysfunction after cardiac bypass procedures.

From a cognitive standpoint, CABG as currently practiced appears to be safe for the great majority of patients, but transient changes involving memory, executive functions, and motor speed may still occur in a subset of patients during the first few days to weeks after CABG. The etiology most likely is multifactorial and includes a synergistic effect of microemboli, hypo-perfusion, and other variables associated with major surgery. Older age and degree of pre-existing cerebrovascular disease have been identified as important risk factors. The short-term cognitive changes appear to be reversible by 3 months after surgery for most patients. Late cognitive decline after CABG,occurring between 1 and 5 years after the surgery, has been well documented,but controlled studies demonstrating that this decline is specifically attributable to the use of cardiopulmonary bypass itself rather than to progression of underlying cerebrovascular disease or other age-related changes are pending.

Atrial Fibrillation↗

[Cognitive and affective dysfunction in MS].

Prevalence studies have shown cognitive and affective disorders to be common in multiple sclerosis (MS). Although much is known about the manifestations of such disorders, our knowledge of the cerebral systems involved remains poor. Functional techniques will enable cerebral blood flow to be measured, and sophisticated SPECT (single photon emission computed tomography) techniques can provide a clearer picture of the dynamics of cognitive and affective processes in MS. Increased knowledge of these disorders would enable the management and rehabilitation of MS patients to be improved.

Affective Symptoms↗

Phantom boarder symptom in dementia.

OBJECTIVE: Phantom boarder symptom (PBS), which has been labelled a misidentification and is commonly observed in cases of Alzheimer's disease, is the perceptual dysfunction where it is imagined that there are people in the home. It may also be encountered in cases of vascular dementia and other variants of this cognitive dysfunction. This study was undertaken to investigate PBS frequency and characteristics for a sample of dementia inpatients, and to determine the strength of the association with other psychotic symptoms. METHODS: The sample population consisted of 240 dementia patients admitted to our geropsychiatric ward. Patients with and without PBS were compared in terms of general characteristics and psychotic symptoms. RESULTS: Of the 240 dementia patients, PBS was identified in 56 (23.3%). There were no significant gender differences between the PBS and non-PBS groups. Means for age and onset-age were higher for the PBS group, and the prevalence of hallucinations and other misidentifications was greater compared to the non-PBS analog. Occurrence of PBS was not significantly associated with delusions or physical aggression. CONCLUSIONS: PBS is a common symptom in dementia of various etiologies. Our association findings suggest that it may be more productive to classify PBS as a type of misidentification, instead of as a delusion.

Age of Onset↗

The cerebellum and cognition. Intellectual function in spinocerebellar ataxia type 6 (SCA6).

The aim of this study was to assess cognitive function in patients with spinocerebellar ataxia type 6 (SCA6), an autosomal-dominantly inherited disease leading to a progressive cerebellar syndrome. In contrast to other SCA types, the pathological changes are mostly restricted to the cerebellum. Cognitive function was studied in 12 patients with genetically confirmed SCA6 (mean duration of disease: 9.2 +/- 11.6 years) and 12 age- and IQ-matched controls using a test battery comprising tests for IQ, attention, verbal and visuospatial memory, as well as executive function. While none of the SCA6 subjects had features of general intellectual impairment, only mild deficits in single subtests especially in fronto-executive tasks were observed, but without reaching statistical significance. Thus the current findings do not demonstrate severe cognitive dysfunction in SCA6.

Adult↗

Cognitive and emotion recognition deficits in obsessive-compulsive disorder.

Previous investigations have demonstrated impaired recognition of facial affect and cognitive dysfunction in several psychiatric disorders. The specificity of these deficits is still debated. The aim of this study was to investigate the deficits in emotion recognition and cognition in obsessive-compulsive disorder (OCD). Forty patients with OCD (DSM-IV, 16 women, 34.7+/-10.4 years) and 40 healthy volunteers (16 women, 34.7+/-8.7 years) were compared. All participants underwent a computerized neuropsychological test battery (Gur, R.C., Erwin, R.J., Gur, R.E., Zwil, A.S., Heimberg, C., Kraemer, H.C., 1992. Facial emotion discrimination II. Behavioral findings in depression. Psychiatry Research 42, 241-251; Gur, R.C., Ragland, J.D., Moberg, P.J., Turner, T.H., Bilker, W.B., Kohler, C., Siegel, S.J., Gur, R.E., 2001. Computerized neurocognitive scanning: I. Methodology and validation in healthy people. Neuropsychopharmacology 25, 766-776). A German version of the Penn Facial Emotion Acuity Test, the Facial Emotion Intensity Differentiation, including happy, sad and neutral faces, and the Facial Memory Test were administered. Executive functions were assessed by a computerized version of the Wisconsin Card Sorting Test and attention was evaluated using the Continuous Performance Test. OCD patients performed more poorly than healthy controls in facial memory tests (especially delayed), as well as in attention and executive functions. The only significant difference between the groups in emotion processing was poorer recognition of sad female faces in patients, who misperceived neutral faces as sad. The results point to memory and executive deficits in addition to a "negative" bias in emotion recognition in OCD patients.

Adult↗

Comparison of cognitive style in bulimia nervosa and depression.

This study investigated the global and specific cognitive style associated with bulimia nervosa. Three groups of women (women with bulimia nervosa, women with major depression, and controls) completed measures of eating disorder severity, depression, dysfunctional cognitions and irrational beliefs. The control group was found to report significantly lower levels of cognitive distortions and irrational beliefs overall than both women with bulimia nervosa and women with depression. However, no difference was found between the latter two groups. Furthermore, the pattern of individual cognitions and beliefs was exactly the same. When depression was statistically controlled, cognitive style no longer differentiated between the control group and two clinical groups. These results have implications for improving the effectiveness of cognitive behaviour therapy for bulimia nervosa.

Adolescent↗

Landmark discrimination learning in the dog: effects of age, an antioxidant fortified food, and cognitive strategy.

The landmark discrimination learning test can be used to assess the ability to utilize allocentric spatial information to locate targets. The present experiments examined the role of various factors on performance of a landmark discrimination learning task in beagle dogs. Experiments 1 and 2 looked at the effects of age and food composition. Experiments 3 and 4 were aimed at characterizing the cognitive strategies used in performance on this task and in long-term retention. Cognitively equivalent groups of old and young dogs were placed into either a test group maintained on food enriched with a broad-spectrum of antioxidants and mitochondrial cofactors, or a control group maintained on a complete and balanced food formulated for adult dogs. Following a wash-in period, the dogs were tested on a series of problems, in which reward was obtained when the animal responded selectively to the object closest to a thin wooden block, which served as a landmark. In Experiment 1, dogs were first trained to respond to a landmark placed directly on top of coaster, landmark 0 (L0). In the next phase of testing, the landmark was moved at successively greater distances (1, 4 or 10 cm) away from the reward object. Learning varied as a function of age group, food group, and task. The young dogs learned all of the tasks more quickly than the old dogs. The aged dogs on the enriched food learned L0 significantly more rapidly than aged dogs on control food. A higher proportion of dogs on the enriched food learned the task, when the distance was increased to 1cm. Experiment 2 showed that accuracy decreased with increased distance between the reward object and landmark, and this effect was greater in old animals. Experiment 3 showed stability of performance, despite using a novel landmark, and new locations, indicating that dogs learned the landmark concept. Experiment 4 found age impaired long-term retention of the landmark task. These results indicate that allocentric spatial learning is impaired in an age-dependent manner in dogs, and that age also affects performance when the distance between the landmark and target is increased. In addition, these results both support a role of oxidative damage in the development of age-associated cognitive dysfunction and indicate that short-term administration of a food enriched with supplemental antioxidants and mitochondrial cofactors can partially reverse the deleterious effects of aging on cognition.

Age Factors↗

Cognitive function in adult cardiothoracic transplant candidates and recipients.

Innovative surgical and medical techniques have prolonged the life span of cardiothoracic (CT) transplant recipients and made transplantation an option for many older patients. Cognitive function is a key determinant of the CT transplant recipient's ability to manage the complex treatment regimen and experience optimum benefit of the procedure. As the CT population ages, risk of cognitive dysfunction due to normal aging is compounded by the physical and mental changes associated with end-stage organ disease, comorbid conditions, and transplant-related complications. Cognitive abilities consist of (a) receptive functions (ability to select, acquire, classify, and integrate information); (b) memory and learning (ability to store and retrieve information); (c) thinking (ability to mentally organize and reorganize information; and (d) expressive functions (ability to communicate or act upon information). Although each of these functions represents a distinct type of behavior, they are interdependent. The purpose of this article is to (a) discuss the literature regarding cognitive function before and after adult heart, lung, and heart-lung transplantation; (b) identify methodological problems associated with the studies done to date; and (c) make recommendations for future research in this area.

Adaptation, Psychological↗

Strategies for improving adherence to second-generation antipsychotics in patients with schizophrenia by increasing ease of use.

Despite the advances in the treatment of patients with schizophrenia that have occurred since the introduction of the second-generation (atypical) antipsychotic agents, a leading cause of suboptimal outcome is poor patient adherence to oral medication. Partial adherence can be attributed to a number of factors, including lack of insight, cognitive dysfunction, a complicated treatment regimen, drug-related side effects, patient attitude, lack of patient education, and cultural factors. A number of strategies, including psychosocial interventions, cognitive-behavioral techniques, strategies that minimize side effects, and pharmacological approaches that increase ease of medication use, can be employed to support adherence and improve long-term outcomes. This article focuses on strategies for increasing ease of use of antipsychotics in the treatment of patients with schizophrenia. These strategies include using monotherapy rather than polypharmacy, simplifying the medication regimen, and using a long-acting antipsychotic formulation. The goal of these strategies is to improve adherence and help prevent relapse by ensuring continuous antipsychotic coverage. Strategies that optimize ease of use of medication treatment for schizophrenia and thus improve adherence to treatment are likely to promote the attainment of new treatment goals and improved patient outcomes.

Antipsychotic Agents↗

The spectrum from BCECTS to LKS: The Rolandic EEG trait-impact on cognition.

The laboratory hallmark of BCECTS is the rolandic discharge (RD) in the EEG of patients, occurring in a characteristic topographical, vigilance-related, event-related, and age-related pattern, disappearing during puberty. RDs are present in 2% of healthy children. About 8% of children with RDs have epilepsy. An increased prevalence rate of RDs is found in children with cognitive and behavioral disorders, with headaches and some genetic syndromes. In some patients, the cognitive disorders are transient but in others they are progressive, resulting in stable mental retardation after puberty. A recent study of 36 BCECTS patients addressed the following questions. (1) the possible relationship between the severity of RDs and the neuropsychological deficits; (2) the profile of neuropsychological deficits; (3) changes of cognition related to EEG changes; and (4) effects of therapy. No correlation was found between global IQ and the severity of the RDs. All the children had at least one specific learning disorder (sometimes long-lasting). When the children were treated, a correlation between cognitive and EEG improvement could not be demonstrated. Recently, 21 patients without epilepsy but with attention deficit and hyperactivity and/or learning disorders were studied: an open treatment trial with sulthiame resulted in improved sustained and selective attention. The neurobiology of RDs and their relationship to cognitive dysfunction and epilepsy requires further study.

Attention Deficit Disorder with Hyperactivity↗

Recovery after stroke: cognition, ADL function and return to work.

OBJECTIVES: To examine the recovery of cognitive function, activities of daily living (ADL) ability and vocational situation after stroke. MATERIALS AND METHODS: Subjects below 65 years of age were included. Cognitive function and personal and instrumental ADL were assessed at discharge and at 1 year. Pre-stroke vocational situation was recorded at baseline and at 1 and 3 years after discharge. RESULTS: Fifty-eight patients participated. During the first year after discharge, cognitive function and ADL ability improved. At 1 year after discharge, 83% still had cognitive dysfunction, 20% were dependent in ADL and few had returned to work. Only 20% returned to gainful employment 3 years later. CONCLUSIONS: There was a recovery of cognition and ADL function after stroke but few persons returned to work. Good neurological status was found to be a significant factor and recovery of cognitive function a near-significant factor for return to work.

Activities of Daily Living↗

The effect of previous alcohol abuse on cognitive function in HIV infection.

OBJECTIVE: The authors' goal was to study the potential effect on cognitive function of an interaction of HIV infection and a history of alcohol abuse. METHOD: The subjects were 30 HIV-negative and 50 HIV-positive men with and without a past history of alcohol abuse. Thirty-three of the men (12 HIV negative and 21 HIV positive) had a past history of alcohol abuse, and 47 (18 HIV negative and 29 HIV positive) had never abused alcohol. Each subject's history of alcohol use was obtained by using a syndromal approach based on the Structured Clinical Interview for DSM-III-R and a quantitative approach. Each subject was given a battery of neuropsychological tests assessing verbal reasoning, reaction time, intelligence, memory, and dexterity. The subjects were then compared on a summary neuropsychological impairment rating. RESULTS: There were no significant differences in CD4 level, age, education, depression, anxiety, or other drug abuse history between the HIV-positive and HIV-negative groups with and without a history of alcohol abuse. Significant effects on cognitive function were found for past alcohol abuse and HIV infection, with significant interactions in verbal reasoning, auditory processing, and reaction time. This demonstrates that HIV infection and a history of alcohol abuse have independent effects on some aspects of higher cognitive function but may have synergistic effects on other cognitive domains. In the HIV-negative subjects there were no differences in cognitive function between subjects with and without a history of alcohol abuse. Among the HIV-positive subjects, those with a history of alcohol abuse performed more poorly on tests of verbal IQ, verbal reasoning, and reaction time. CONCLUSIONS: There are both additive and interactive effects of previous alcohol abuse and HIV infection on cognition. Individuals with a history of past alcohol abuse may be at greater risk for cognitive dysfunction in the context of HIV infection.

Adult↗

Cognitive impairment in patients with brain tumors: assessment and intervention in the clinic setting.

Cognitive impairment is the most common neurologic problem associated with brain tumors and is present in many people with brain tumors from the time of diagnosis. Treatment of primary brain tumors with surgery, radiation, chemotherapy, and adjunctive medications such as corticosteroids results in further adverse effects on cognitive function. To plan the best care for patients with brain tumors, healthcare providers must initiate systematic and accurate assessment of cognitive functioning at the first clinic visit and extend assessment throughout the course of illness. This article outlines the range of cognitive dysfunction that may be seen in patients with primary brain tumors and offers information for clinicians seeking to develop their skills and implement a systematic approach to cognitive screening. The use of cognitive screening to guide timely intervention, such as referral to a neuropsychologist and the provision of anticipatory guidance to people with brain tumors and their families, is discussed.

Brain Neoplasms↗

Cognitive function after systemic therapy for breast cancer.

An underinvestigated area of breast cancer survivorship involves the possible impairment of cognitive function following adjuvant chemohormonal therapy. Numerous reports of disturbing and disruptive changes in short- and long-term memory, attention span, concentration, and language skills have been made by breast cancer patients who have received chemotherapy. This article reviews the four published studies that have documented cognitive dysfunction following adjuvant chemohormonal therapies commonly used in breast cancer. The studies describe a subset of approximately one-third of participants who experienced long-term cognitive impairment. Patient- and treatment-related factors that may influence cognitive function are outlined. The impact of these cognitive impairments on the individual breast cancer survivor's quality of life is discussed, as is the potential overall impact of this research on future adjuvant therapy. The need for a prospective longitudinal study documenting the neuropsychological sequelae of adjuvant chemohormonal therapy is emphasized.

Adult↗

Periventricular cerebral white matter lesions predict rate of cognitive decline.

The prospect of declining cognitive functions is a major fear for many elderly persons. Cerebral white matter lesions, as commonly found with magnetic resonance imaging, have been associated with cognitive dysfunction in cross-sectional studies. Only a few longitudinal studies using small cohorts confirmed these findings. We examined the relation between severity of white matter lesions and cognitive decline over a nearly 10-year period in 563 elderly subjects sampled from the general nondemented Dutch population. Severity of white matter lesions was scored for periventricular and subcortical regions separately using an extensive semiquantitative scale. Cognitive function was measured by the Mini-Mental State Examination at regular time intervals during 1990 to 2000, and magnetic resonance imaging scans were made in 1995 to 1996. More severe white matter lesions were associated with more rapid cognitive decline over a mean follow-up period of 7.3 years (standard deviation, 1.5). After adjusting for age, gender, educational level, measures of depression, and brain atrophy and infarcts, subjects with severe periventricular white matter lesions experienced cognitive decline nearly three times as fast (0.28 Mini-Mental State Examination points/year [95% confidence interval, 0.20-0.36]) as the average (0.10 points/year [95% confidence interval, 0.09-0.11]). There was no independent relationship between severity of subcortical white matter lesions and rate of cognitive decline.

Aged↗

Analysis of cognitive and psychological deficits in systemic lupus erythematosus patients without overt central nervous system disease.

OBJECTIVE: To examine cognitive and psychological functioning in relation to antiribosomal P protein autoantibodies in patients with systemic lupus erythematosus (SLE) who had no previous history of central nervous system disease (non-CNS SLE). METHODS: Comprehensive neuropsychological and psychological tests were administered to 51 non-CNS SLE patients, 29 rheumatoid arthritis (RA) patients, and 27 healthy controls. RESULTS: Twenty-nine percent of the non-CNS SLE patients, 31% of the RA patients, and 11% of the control subjects were classified as cognitively impaired. Similar reductions in intelligence, attention, and fluency were detected in the non-CNS SLE and RA patients compared with controls. The non-CNS SLE patients showed a distinct deficit in learning compared with the RA and control groups. Forty-two percent of the non-CNS SLE patients demonstrated psychological distress, compared with 7% of the RA patients and 6% of the controls. In the patient groups, neither cognitive dysfunction nor psychological distress was associated with disease activity or prednisone dosage. Elevated serum levels of autoantibodies to ribosomal P protein were not associated with either psychological or cognitive abnormalities. CONCLUSION: These results suggest that certain cognitive deficits in non-CNS SLE patients may not be specific to the immunopathology of SLE. In contrast, it is possible that deficits in learning, as well as psychological distress without major psychiatric pathology, may be subtle manifestations of CNS lupus.

Adult↗