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Magnesium and ketamine attenuate cognitive dysfunction following experimental brain injury.

We evaluated the therapeutic effects of two noncompetitive antagonists of the N-methyl-D-aspartate (NMDA) receptor, MgCl2 and ketamine, both individually and together, on cognitive dysfunction observed following parasagittal fluid-percussion (FP) brain injury in the rat. Using a modified Morris water maze technique, we found significant attenuation of post-traumatic memory dysfunction in animals treated with either MgCl2 (125 mumol) or ketamine (4 mg/kg) (P < 0.005). Combined MgCl2 and ketamine treatment also preserved memory function (P < 0.005), with no apparent additive effect.

Amnesia, Retrograde↗

The influence of different error estimates in the detection of post-operative cognitive dysfunction using reliable change indices with correction for practice effects.

The reliable change index (RCI) expresses change relative to its associated error, and is useful in the identification of post-operative cognitive dysfunction (POCD). This paper examines four common RCIs that each account for error in different ways. Three rules incorporate a constant correction for practice effects and are contrasted with the standard RCI that had no correction for practice. These rules are applied to 160 patients undergoing coronary artery bypass graft (CABG) surgery who completed neuropsychological assessments preoperatively and 1 week post-operatively using error and reliability data from a comparable healthy non-surgical control group. The rules all identify POCD in a similar proportion of patients, but the use of the within subject standard deviation, expressing the effects of random error, as an error estimate is a theoretically appropriate denominator when a constant error correction, removing the effects of systematic error, is deducted from the numerator in a RCI.

Aged↗

Cognitive dysfunction in adult survivors of allogeneic marrow transplantation: relationship to dose of total body irradiation.

Bone marrow transplant (BMT) patients are exposed to several potential sources of neurologic damage including the neurotoxicity of pre-BMT preparative regimens. The latter generally include a combination of total body irradiation (TBI) and high-dose chemotherapy. Cognitive functioning in 30 adult allogeneic BMT patients (mean of 47 months post-BMT) treated for either acute or chronic leukemia was assessed by two standardized self-report questionnaires. Consistent with hypothesis, results of both univariate and multivariate analyses indicated that increased dose of TBI was associated with increased cognitive dysfunction. Furthermore, this relationship remained even after the impact of psychological distress upon cognitive functioning was accounted for. TBI-related cognitive impairment primarily involved slowed reaction time, reduced attention and concentration, and difficulties in reasoning and problem-solving. These results complement previous findings of an inverse association between dose of TBI and self-perceptions of health and physical functioning in BMT survivors and indicate the importance of including quality of life measures in clinical trials of therapeutic innovations in the field of BMT.

Adolescent↗

Donepezil treatment of topiramate-related cognitive dysfunction.

Six migraine patients experienced significant topiramate-related cognitive and language dysfunction that improved with donepezil treatment and allowed uninterrupted topiramate use. These patients represent the first report of topiramate-related cognitive and language dysfunction that improved with a cholinesterase inhibitor. Although, the mechanism responsible for this effect is uncertain, cholinesterase inhibition resulting in cholinergic augmentation and enhanced cognition probably account for some if not most of the improvement.

Adult↗

The relationship between depressive symptoms and cognitive dysfunction in multiple sclerosis.

INTRODUCTION: Although it has been well established that otherwise healthy persons with depression experience various neuropsychological deficits, such a relationship has not been robustly supported in the initial investigations using the multiple sclerosis (MS) population. The relative inability to discover a significant relationship between depression and cognitive dysfunction may be due to methodological difficulties in previous studies (e.g., use of correlational analysis; use of neuropsychological measures that are generally not affected by depression). METHODS: The present study examined a control group and 17 MS subjects who reported relatively low (BDI h 9) or high (BDI S 16) depression levels on a variety of neurocognitive measures that were (i.e., PASAT, Digit Span Backward subtest of the WAIS-R, and a modified version of the Buschke Selective Reminding Test; SRT) or were not (i.e., Similarities, Vocabulary, and Digit Span Forward subtests of the WAIS-R) hypothesised to be associated with depression symptomatology. RESULTS: These results support our hypotheses that depressed individuals with MS evidence greater neuropsychological dysfunction relative to their nondepressed counterparts. CONCLUSION: Findings are discussed in terms of the specific cognitive impairments evidenced by depressed subjects with MS. This research may have significant implications with regard to the expected effects of antidepressant and cognitive therapies on neuropsychological functioning in MS.

Journal Article↗

Sub-regional hippocampal vulnerability in various animal models leading to cognitive dysfunction.

Various animal models, involving different brain insults, lead to memory deficits, which can be measured using behavioral tests. In numerous studies, using five different experimental models in rats, we have found that cognitive dysfunction is invariably accompanied by hippocampal CA1 and CA3 pyramidal cells degeneration. However, of these two, the most affected area changes from one model to the other. The present manuscript describes and compares the morphological alterations within the hippocampus in the following experimental models: normal aging, hypoxia, prolonged corticosterone administration, brain ischemia and cholinesterase (ChE) inhibition. In all the above, many hippocampal neurons were severely damaged, however, CA3 pyramidal cells were mostly affected in normal aging and following hypobaric hypoxia, whereas CA1 cells were especially affected following corticosterone administration, global ischemia and ChE inhibition. Several mechanisms, which might be involved in the diverse courses of the lesions are being considered: cerebral oxygen and glucose, glutamate neurotoxicity and calcium involvement. It is anticipated that elucidation of the specific role of CA1 and CA3 hippocampal sub-fields in the various experimental models might help in understanding processes such as age-related neuronal degeneration and assist in their prevention.

Aging↗

Huperzine A attenuates cognitive dysfunction and neuronal degeneration caused by beta-amyloid protein-(1-40) in rat.

Huperzine A, a promising therapeutic agent for Alzheimer's disease, was examined for its potential to antagonize the deleterious neurochemical, structural, and cognitive effects of infusing beta-amyloid protein-(1-40) into the cerebral ventricles of rats. Daily intraperitoneal administration of huperzine A for 12 consecutive days produced significant reversals of the beta-amyloid-induced deficit in learning a water maze task. This treatment also reduced the loss of choline acetyltransferase activity in cerebral cortex, and the neuronal degeneration induced by beta-amyloid protein-(1-40). In addition, huperzine A partly reversed the down-regulation of anti-apoptotic Bcl-2 and the up-regulation of pro-apoptotic Bax and P53 proteins and reduced the apoptosis that normally followed beta-amyloid injection. The present findings confirm that huperzine A can alleviate the cognitive dysfunction induced by intracerebroventricular infusion of beta-amyloid protein-(1-40) in rats. The beneficial effects are not confined to the cholinergic system, but also include favorable changes in the expression of apoptosis-related proteins and in the extent of apoptosis in widespread regions of the brain.

Alkaloids↗

Sleep apnea and cognitive dysfunction in myasthenia gravis.

19 middle-aged patients with myasthenia gravis (MG) and 10 age, sex and education-matched controls underwent overnight polysomnography and neuropsychological testing, in order to test the hypothesis of whether cognitive dysfunction and REM-sleep disturbance in MG are related to nocturnal respiratory problems or caused by CNS-involvement. We observed in 60% of the myasthenics central type of sleep apneas and hypopneas with resulting oxygen desaturations occurring during REM-sleep, but no decrease of REM sleep. In neuropsychological testing, we found normal vigilance performance but decreased memory function in the myasthenics. In comparison with patients without sleep apnea, myasthenics with sleep apneas had an impaired memory function.

Adult↗

Fragile X premutation carriers: characteristic MR imaging findings of adult male patients with progressive cerebellar and cognitive dysfunction.

BACKGROUND AND PURPOSE: Our purpose was to characterize the findings of MR imaging of the brain of adult male fragile X premutation carriers with a recently identified disorder characterized by ataxia, tremor, rigidity, and cognitive dysfunction. METHODS: MR imaging studies of the brain of 17 male patients were characterized for signal intensity and for size of ventricles, cerebral and cerebellar sulci, and brain stem. Comparison was made with age- and sex-matched control participants. Southern blot and/or polymerase chain reaction methods were used to analyze CGG trinucleotide repeats in the fragile X mental retardation 1 gene. RESULTS: Fifteen of 17 patients showed symmetrically decreased T1 and increased T2 signal intensity in cerebellar white matter lateral, superior, and inferior to the dentate nuclei. Fourteen of 17 had similar signal intensity alterations in the middle cerebellar peduncles. Cerebellar cortical atrophy was present in 16 of 17 and cerebral atrophy in 17 of 17. Evan's Index as a measure of ventricular size averaged 0.35 (range, 0.25-0.46), with that for age-matched control participants averaging 0.28 (range, 0.24-0.31) (P <.005). The mean third ventricle width was 11 mm (for control participants, 6 mm; P <.01). Corpus callosum was thinned in 14 of 16 participants. Middle cerebellar peduncles were atrophic when compared with those of control participants (P <.005). Pontine transverse dimension was 25 mm (for control participants, 31 mm; P <.005), and rostral-caudal length averaged 26 mm (for control participants, 29 mm; P <.005). CGG repeats clustered in the low to mid premutation range (86 +/- 10 CGG repeats) in the 17 patients. CONCLUSION: MR imaging findings in symptomatic male fragile X premutation carriers are characteristic of this disorder. Recognition of these alterations may support a specific diagnosis and may have implications for the potential occurrence of fragile X syndrome in the children of reproductive age female relatives.

Aged↗

Cognitive dysfunction in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune-mediated collagen disease that results in multiorgan failure. It is the collagen disease most frequently associated with neuropsychiatric symptoms, which have been hypothesized to stem from certain types of cognitive dysfunction. Subjects were 21 patients with SLE (one man, 20 women; aged 16-55 years; mean age, 35.1+/-10.7 years) who were undergoing treatment in the rheumatology unit of a general hospital, and 17 healthy control subjects matched to the patient group with respect to age and gender (two men, 15 women; mean age, 35.9+/-6.3 years). They were administered various tests of cognitive function including verbal reasoning, non-verbal reasoning, verbal memory, non-verbal memory, attention and mental flexibility, psychomotor speed and frontal lobe function. In addition, the SLE patients were tested for antiphospholipid antibodies. The SLE patients performed worse than the control group on immediate, delayed and interference of the Rey verbal test and paired associate tests of Wechsler Memory Scale, and their reaction time was slower in Trail A and Trail B tests. Moreover, these findings were more pronounced in the group with major neuropsychiatric symptoms. However, no relationship was apparent between these deficits in cognitive function and the presence or absence of antiphospholipid antibodies. The results suggest that verbal memory and psychomotor speed underlie the neuropsychiatric symptoms seen in SLE patients.

Adolescent↗

Apolipoprotein E genotype and cognitive dysfunction after noncardiac surgery.

BACKGROUND: Apolipoprotein E is important in recovery after neuronal damage. The epsilon4 allele of the apolipoprotein E gene has been shown as a risk factor for Alzheimer disease, poor outcome after cerebral injury, and accelerated cognitive decline with normal aging. The authors hypothesized that patients with the epsilon4 allele would have an increased risk of postoperative cognitive dysfunction (POCD) after noncardiac surgery. METHODS: In a multicenter study, a total of 976 patients aged 40 yr and older undergoing noncardiac surgery were tested preoperatively and 1 week and 3 months after surgery with a neuropsychological test battery comprising seven subtests. POCD was defined as a decline in test performance of more than 2 SD from the expected. Apolipoprotein E genotypes were determined by blood sample analysis at a central laboratory. Multivariate logistic regression analysis with POCD as the dependent variable assessed presence of the epsilon4 allele (yes/no) and other possible risk factors. RESULTS: The epsilon4 allele was found in 272 patients. One week after surgery, the incidence of POCD was 11.7% in patients with the epsilon4 allele and 9.9% in patients without the epsilon4 allele (P = 0.41). Three months later, POCD was found in 10.3% of patients with the epsilon4 allele and in 8.4% of patients without the epsilon4 allele (P = 0.40). Multivariate logistic regression analysis did not identify the epsilon4 allele as a risk factor at 1 week (P = 0.33) or 3 months (P = 0.57). CONCLUSIONS: The authors were unable to show a significant association between apolipoprotein E genotype and POCD, but statistical power was limited because of a lower incidence of POCD than expected.

Adult↗

Self-assessed cognitive dysfunction and objective performance in outpatients with schizophrenia participating in a rehabilitation program.

OBJECTIVE: To explore the pattern of associations between self-assessed and objective neuropsychological performance in a sample of outpatients with schizophrenia participating in a rehabilitation program. METHOD: The Subjective Scale to Investigate Cognition in Schizophrenia (SSTICS) [Compr. Psychiatry 44 (2003) 331] was used to assess cognitive complaints in 73 subjects with schizophrenia. Visuo-spatial tests of the Cambridge Neuropsychological Test Automated Battery (CANTAB) [Cogn. Neuropsychiatry 3 (1998) 45] were administered as objective measures. RESULTS: Cognitive complaints in several cognitive domains were mainly correlated with a true difficulty in memory. Higher SSTICS attention scores, i.e. increased complaints, were associated with poorer CANTAB explicit visual memory and planning performances. Higher SSTICS executive functioning scores were associated with poorer CANTAB explicit visual memory scores. CONCLUSION: These findings suggest that outpatients with schizophrenia express some cognitive difficulties. However, the cognitive nature of these subjective complaints does not strictly correspond with objective performances. These results also suggest that theoretical constructs of cognitive functions do not always have ecological validity. Thus, subjective cognitive complaints should be taken into account in assessment of patient well-being, but cannot be used as a substitute to objective cognitive measures. The simultaneous use of subjective and objective measures of cognitive dysfunction may provide a more complete picture of individual rehabilitation targets in patients with schizophrenia.

Adult↗

[Cognitive dysfunction in 32 diffuse axonal injury cases].

In acute stage of traumatic brain injury, it is not easy to diagnose diffuse axonal injury (DAI) by computer imaging. Even in chronic stage, DAIs occasionally show no remarkable abnormality by ordinal CT or MRI images. We retrospectively studied 32 DAI cases by the Functional Independence Measure (FIM), a battery of neuropsychological tests and CT or MRI films of acute and chronic phase. The result showed decrease of cognitive function in 32 DAI cases. The degree of enlargement of the ventricles in chronic stage did not correlate with cognitive dysfunction.

Adult↗

The role of negative symptoms and cognitive dysfunction in schizophrenia outcome.

Schizophrenia is a lifelong illness, with symptoms beginning in late adolescence/early adulthood and persisting throughout the rest of the patient's life. Positive psychotic symptoms may fluctuate during the course of the illness, but negative symptoms, especially primary negative symptoms, and cognitive dysfunction are relatively constant. The negative symptoms of schizophrenia are both primary (associated with the illness) and secondary (due to depression, neuroleptic-induced parkinsonism or acute psychosis). While secondary negative symptoms may be reduced by treating the causative agent, primary negative symptoms are viewed as enduring, persisting between psychotic episodes. Conventional antipsychotics treat the positive symptoms of schizophrenia, but they have little effect on primary negative and cognitive symptoms. Primary negative symptoms are often associated with poor premorbid function, the male sex, and low IQ (Intelligence Quotient). In addition, most studies find that negative symptoms are associated with a poor overall outcome. Several studies, including our own, have suggested that primary negative symptoms are functionally localized to the frontal and parietal cortices. These kinds of data raise the possibility that primary negative symptoms may have a pathophysiological basis distinct from positive psychosis. Cognitive impairment also appears to be a relatively independent aspect of schizophrenia. Impairment may be evident in a subtle form from early childhood, and often precedes the development of psychotic symptoms. Additional impairment accrues with the onset of psychotic illness with little evidence, in the vast majority of cases, of progression over the course of the illness. Cognitive impairment is only modestly related to psychotic symptom severity and type. However, the extent, and perhaps specific types of cognitive impairment, appear to be predictive of functional outcome.

Adolescent↗

Cognitive dysfunctions in patients with obsessive-compulsive disorder compared to the patients with schizophrenia patients: relation to overvalued ideas.

OBJECTIVE: The clinical overlaps between schizophrenia and obsessive-compulsive disorder (OCD) seem to be related to thought disorders involving obsessions, overvalued ideas, and delusions. Overvalued ideas are beliefs falling in between obsessions and delusions and are stronger than obsessions but weaker than delusions. The goal of the present study was to compare patients with OCD to those with schizophrenia in terms of cognitive functions and to relate cognition and overvalued ideas in OCD. METHODS: Twenty three patients with OCD (free of depression), 24 patients with schizophrenia, and 22 healthy subjects matched to patients in age, gender, education, and hand dominance were included in the study. All subjects were administered neurocognitive tests assessing verbal learning-memory, executive functions, verbal fluency, attention and verbal working memory. RESULTS: Patients with schizophrenia showed worse performance on cognitive tests than the OCD and control groups. The severity of overvalued ideas was significantly correlated to cognitive functions in the OCD group. There were no significant differences in cognitive functions between schizophrenia group and the OCD patients who had higher scores on the Overvalued Ideas Scale (OVIS). CONCLUSION: Overvalued ideas in OCD may be related to cognitive dysfunctions in OCD and this subtype of OCD may have similar characteristics to schizophrenia in terms of cognition.

Adult↗

Psychiatric symptoms and cognitive dysfunction caused by Epstein-Barr virus-induced encephalitis.

Epstein-Barr virus (EBV) encephalitis is rare and shows a wide range of clinical manifestations. We report an immunocompromised patient with EBV encephalitis diagnosed by EBV-specific PCR and antibody testing in the cerebrospinal fluid who presented with psychiatric symptoms and cognitive dysfunction in the absence of any neurological impairments or infectious signs. Clinical recovery and clearance of cerebrospinal fluid EBV DNA appeared following ganciclovir treatment within 6 weeks.

Antiviral Agents↗

Cognitive dysfunction in advanced heart failure and prospective cardiac assist device patients.

BACKGROUND: Extended periods of hypoperfusion in an advanced heart failure (HF) places patients at high risk for neurobehavioral compromise, which has not been studied systematically. It is also not clear how intravenous inotropic therapy and mechanical cardiac assist devices (MCAD) affect cognitive function. METHODS: This prospective cross-sectional cognitive preliminary study evaluated 252 potential heart transplant candidates assessing functions in memory, motor, and processing speed. Patients were divided into three HF groups based on severity of disease: group 1 outpatients (n = 113), group 2 in-patients requiring inotropic infusion (n = 83), and group 3 inpatients likely requiring MCAD support (n = 56). Aggregate z-scores for memory, motor, and processing speed and independent samples t tests assessed intergroup differences on 13 cognitive measures. RESULTS: A broad pattern of cognitive impairment was observed within the advanced HF group; fewer deficits were found in group 1 outpatients and more severe deficits in group 3 MCAD subjects. A difference in motor functions was observed as the earliest abnormality, with group 3 showing significant changes compared with group 1. The most dramatic changes were seen in domain mental processing speed along with specific verbal and visual memory functions, which were slower in group 3 compared with groups 1 and 2. CONCLUSIONS: Cognitive deficits are common in advanced HF and worsen with increasing severity of HF. Appropriately designed and randomized studies will be needed to demonstrate if earlier MCAD implantation is warranted to arrest cognitive dysfunction and better postimplantation adaptation.

Adult↗

Continuing the search for cholinergic factors in cognitive dysfunction.

The objective of the experiments reported here was to explore three hypotheses regarding cholinergic processes underlying the development of progressive degenerative dementia (PDD). One possibility involved the downregulation of muscarinic receptors (mAChR) with aging, thus reducing the capability of the cholinergic system to support normal memory and other cognitive functions. The results of downregulation to 10% of normal produced only a temporary effect, the system having the capability to repair the damage. A second hypothesis predicted that a chronic hypocholinergic state can produce structural changes that are reflected in persisting cognitive dysfunctions. Chronic administration of a false cholinergic transmitter in the diets of weanling rats mimicked such a state which, if maintained for a protracted period, produced many of the features of PDD in humans. When the diet was returned to normal, biochemical and physiological processes recovered fully. However, memory impairment continued. This suggested the possibility that the behavioral losses were mediated by persisting morphological changes in the CNS. The third hypothesis proposes that these changes may be due to cell loss resulting from impaired phospholipid metabolism. Changes in sphingomyelin, one of the two major Ch-containing lipids in cell membranes, could increase amounts of ceramide, an inducer of programmed cell death (apoptosis). Tests of this hypothesis are nearing completion.

Animals↗