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PubMed1996

Effect of digitalis on conduction dysfunction in Pelizaeus-Merzbacher disease.

We studied the effect of digitalis on nerve conduction dysfunction in Pelizaeus-Merzbacher disease (PMD). The patients were three Japanese boys with PMD, aged 7-10 years. Digitalis was administered orally in a daily dose of 0.06 mg/kg for 2 consecutive months, and the obtained serum concentrations ranged from 0.33 to 0.55 ng/ml. The digitalis therapy induced slight improvement of severe dysarthria and cognitive dysfunction in the two older patients. Electrophysiological examinations revealed the following results: In brainstem auditory evoked potentials (BAEPs), while waves II (or III) to V were absent before treatment, on treatment all waves of BAEPs except a wave IV were restored in all patients. While visual evoked potentials (VEPs) in response to transient flash stimulation showed markedly prolonged latencies before treatment, digitalis produced a mild, although not statistically significant, shortening of the latency of N160. There were also no significant changes in inter-peak amplitudes of VEPs. Transcranial cortical magnetic stimulation continued to fail to elicit motor evoked potentials of the first dorsal interosseous muscles in all patients. Thus, although the serum concentrations were insufficient to elicit favorable therapeutic effects, digitalis therapy provided slight relief of clinical symptoms with evidence of improvement of conduction dysfunction. It is suggested that patients with PMD may respond to symptomatic treatment modulating nerve conduction.

Child↗

PubMed2003

Regulatory issues in vascular dementia: a European perspective.

In many studies vascular dementia (VaD) is the second most frequent cause of organic acquired cognitive dysfunction; accounting for 10% to 50% of the cases, depending on the geographical area, patient population, and diagnostic criteria used. There is growing evidence that VaD does not include only multi-infarct dementia (MID) but relates to complex interactions of different etiologies (risk factors, cerebrovascular disease), structural changes in the brain, host factors and cognition. This resulted in reconceptualization of VaD to emphasize the differences from Alzheimer's disease (AD). However, the diagnostic criteria used (DSM-IV, ICD-10, NINDS-AIREN, or ADDTC) are based on the experience with AD and as such have their limitations and are not interchangeable. From a regulatory point of view, therefore, future research is needed to better define VaD in general and possible subtypes of VaD as targets for drug trials. Methodological issues in VaD trials, as opposed to AD, will be emphasized. The European Medicinal Products Evaluation Agency (EMEA) has adopted a guideline for trials of symptomatic treatments of dementia, particularly in AD. There is no explicit guideline for VaD trials; however, many of the recommendations for AD are already applicable to VaD for drugs aiming at alleviating symptoms of dementia. On the other hand, VaD may be potentially preventable, underscoring the importance of primary and secondary prevention as in other cerebrovascular disorders. Large long-term trials are necessary to study the importance of different risk factors and possible intervention strategies with special reference to VaD.

Aged↗

PubMedDate not supplied

[Psychiatric manifestations as the only clinical sign of hypothyroidism. Apropos of a case].

This article intends to demonstrate, by presenting a clinical case, the importance of the thyroid examination in psychiatric practice. After a brief presentation of the evolution of the conceptions regarding the relation between thyroid insufficiency and psychiatric pathology, a clinical case is reported. This 63 years old man was admitted in a psychiatric ward because of his persecutive delusions and behavioral disorders (agitation, agressivity). Cognitive (namely memory) impairment was also present at the time of admission. The endocrine investigation has documented, in spite of the absence of any suggestive physical signs, a thyroid insufficiency. After the replacement treatment, all symptoms but the cognitive dysfunction disappeared. The patient's evolution is presented clinically, also rated on MMSE and MADRS scales, and biologically (TSH and T4 determination) for a 4 months period. The absence of any pathognomonical psychiatric finding, the possibility of the absence of other signs and symptoms (namely physical) in the hypothyroid state, the presence of potentially irreversible cognitive deterioration, as well as the inocuity and sensibility of thyroid hormones examination justify the systematic thyroid evaluation for all new psychiatric patients.

Cognition Disorders↗

PubMed2005

[Interest of the Mini Mental State Examination to detect cognitive defects after cardiac surgery].

INTRODUCTION: Cognitive defects are frequently described after cardiac surgery. They occur in 30 to 79% cases. They might be related to the use of a cardiopulmonary bypass (CPB). They are poorly evaluated in clinical practice. OBJECTIVES: To evaluate the usefulness of the Mini Mental State Examination (MMSE) to screen patients scheduled for cardiac surgery. STUDY DESIGN: Prospective, open study. PATIENTS AND METHODS: 100 consecutive patients undergoing coronary artery bypass or valvular replacement under CPB were enrolled in the study. The MMSE was performed the day before surgery and five days later. Patients exhiting a postoperative defect> or =4 points were compared to those without changes or with improved results. RESULTS: 73 patients completed both tests. The mean score decreased postoperatively in 12 patients (15%). They were older (70+/-8 years), had longer CBP durations (128+/-50 min) and the lowest temperatures (30 degrees C+/-3) compared to the other patients. At the opposite, five patients (9%) improved their scores. CONCLUSION: These results entourage to carry out a more strict follow-up for the oldest patients in cardiac surgery. The MMSE could be systematically integrated to the pre and postoperative screening. The detection of cognitive dysfunction should lead to address the patient to a geriatrician for a prolonged follow-up.

Aged↗

PubMed2003

Cognitive syndrome(s) in preclinical and clinical vascular dementia.

It is still a challenge to identify typical features of cognitive function in vascular dementia (VaD) in clinical as well as in preclinical stages. Selective empirical findings are described to illuminate degrees of cognitive decline. In predementia stages, speeded performance (motor and mental) and executive functions may be affected as demonstrated by CADASIL subjects and stroke survivors. In dementia stages, motor and mental speed as well as executive functions is commonly affected in addition to typical cognitive dysfunction in dementia (memory, verbal, and visuospatial). To summarize characteristics during preclinical and clinical stages, VaD appears to be associated with impairment in motor and mental speed as well as in executive function.

Aged↗

PubMed2000

Nithsdale Schizophrenia Surveys. 20. Cognitive function in a catchment-area-based population of patients with schizophrenia.

BACKGROUND: Cognitive deficits are a core aspect of schizophrenia but there has been no study of cognitive function in a catchment-area-based population of patients with schizophrenia. AIMS: To assess cognitive function in a population of patients with schizophrenia, and relate it to community functioning. METHOD: All patients with schizophrenia in Nithsdale, south-west Scotland, were identified (n = 182). Measures of assessment were: National Adult Reading Test (NART), Mini-Mental State Examination (MMSE), Rivermead Behavioural Memory Test (RBMT), Executive Interview (EXIT), FAS Verbal Fluency and Health of the Nation Outcome Scales (HoNOS). RESULTS: We assessed 138 patients, mean age 48 years (standard deviation (s.d.) 15). Only 14% were in-patients. The mean premorbid IQ as assessed by NART was 98 (s.d. 14); 15% of patients had significant global cognitive impairment (MMSE); 81% had impaired memory (RBMT); 25% had executive dyscontrol (EXIT); and 49% had impaired verbal fluency (FAS). Scores on the functional impairment sub-scale of HoNOS correlated with all measures of cognitive impairment. CONCLUSIONS: Cognitive dysfunction is pervasive in a community-based population of patients with schizophrenia.

Adult↗

PubMed1997

Intrahippocampal injections of the beta-amyloid 1-28 fragment induces behavioral deficits in rats.

beta-amyloid (beta A) deposition is a key event in the etiopathogenesis of Alzheimer's disease (AD), contributing to neuronal degeneration and cognitive impairment in AD patients. Both neurotrophic and neurotoxic actions of beta A have been demonstrated in experimental conditions. In order to further characterize the effects of brain beta A deposits on behavioral processes, we evaluated psychomotor activity (PMA), psychomotor coordination (PMC) and learning in a passive avoidance task (PAL) in rats with unilateral or bilateral 2 microliters injections of beta-amyloid (1-28) protein (beta A; 1.5 nmol/microliter) or vehicle (water; W) into the hippocampus, 1 and 4 weeks after neurosurgery. The extent of neuronal loss in the lateral blade of the gyrus dentatus (LBGD) and the area percentage occupied by APP immunoreactivity in neurons of the CA3c subfield of the hippocampus were also measured in animals with unilateral beta A implants. PMA levels were similar in water- and beta A-injected animals 1 and 4 weeks after recovery. As compared to water-injected rats, beta A animals showed reduced PMC values 1 week, but not 4 weeks, after injections. beta A also impaired learning acquisition in a passive avoidance task, reducing the number of avoidances and mean latency per trial at both 1 and 4 weeks postsurgery in rats with unilateral or bilateral beta A implants. The extent of neuronal loss in the LBGD) was not different in rats receiving water or beta A injections. Hippocampal APP expression tended to increase in beta A-implanted rats and showed a negative correlation with cognitive performance at the 4-week period. According to these results it seems that beta A implants into the hippocampus reduce psychomotor coordination performance in a transient manner, with no effect on psychomotor activity, and induce durable learning impairment in rats, and that changes in cognitive performance correlate with histochemical parameters such as APP expression. In conclusion, the present results contribute to a better understanding of beta A-induced behavioral alterations and to the identification of potential molecular mechanisms involved in cognitive dysfunctions in this animal model of neurodegeneration.

Alzheimer Disease↗

PubMed2006

Galantamine and donepezil attenuate pharmacologically induced deficits in prepulse inhibition in rats.

Acetylcholinesterase inhibitors (AChEIs) are currently being evaluated as adjunctive therapy for the cognitive dysfunction of schizophrenia. This core symptom of schizophrenia has often been attributed to impaired attention and abnormal sensory motor gating, features that are also found in Huntington's Disease, autism, and several other psychiatric and neurological disorders. The ability to improve prepulse inhibition (PPI) of the acoustic startle response may predict the efficacy of compounds as cognitive enhancers. In this study, PPI was disrupted in Wistar rats in three pharmacologic models: dopamine receptor agonism by apomorphine, NMDA receptor antagonism by MK801, or muscarinic acetylcholine receptor antagonism by scopolamine. We then evaluated the commonly used AChEIs, donepezil (0.5, 1.0, or 2.0mg/kg) and galantamine (0.3, 1.0, or 3.0mg/kg) for the capacity to improve PPI in each model. Under vehicle conditions, the prepulse stimuli (75, 80 and 85dB) inhibited the startle response to a 120dB auditory stimulus in a graded fashion. Galantamine (depending on dose) improved PPI deficits in all three PPI disruption models, whereas donepezil ameliorated PPI deficits induced by scopolamine and apomorphine, but was not effective in the MK801 model. These results indicate that some AChEIs may have the potential to improve cognition in schizophrenia by improving auditory sensory gating.

Acoustic Stimulation↗

PubMed2003

Neuropsychological outcome after fractionated stereotactic radiotherapy (FSRT) for base of skull meningiomas: a prospective 1-year follow-up.

PURPOSE: The purpose of this study was to evaluate the cognitive outcome after fractionated stereotactic radiotherapy (FSRT) in patients with base of skull meningiomas. METHODS AND MATERIAL: A total of 40 patients with base of skull meningiomas were neuropsychologically evaluated before, after the first fraction (1.8 Gy), at the end of FSRT (n=37), 6 weeks (n=24), 6 (n=18) and 12 months (n=14) after FSRT. A comprehensive test battery including assessment of general intelligence, attention and memory functions was used. Alternate forms were used and current mood state was controlled. RESULTS: After the first fraction a transient decline in memory function and simultaneous improvements in attention functions were observed. No cognitive deteriorations were seen during further follow-up, but increases in attention and memory functions were observed. Mood state improved after the first fraction, at the end of radiotherapy and 6 weeks after radiotherapy. CONCLUSION: The present data support the conclusion that the probability for the development of permanent cognitive dysfunctions appears to be very low after FSRT. The transient memory impairments on day 1 are interpreted as most likely related to an increase of a preexisting peritumoral edema, whereas the significant acute improvements in attention functions are interpreted as practice effects. An analysis of localization specific effects of radiation failed to show clear hemisphere specific cognitive changes.

Adult↗

PubMed2003

Increased concentrations of homocysteine and asymmetric dimethylarginine and decreased concentrations of nitric oxide in the plasma of patients with Alzheimer's disease.

Vascular risk factors increase the risk of developing Alzheimer's disease. Increased concentrations of circulating homocysteine are associated with an increased risk of both vascular disease and Alzheimer's disease. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase. There is an increase in the concentration of ADMA in the circulation in vascular disease. We measured the concentrations of homocysteine, ADMA and nitric oxide (as nitrate and nitrite) in the plasma of 25 patients with Alzheimer's disease and 25 control subjects. There was a highly significant increase in the plasma concentration of homocysteine (P<0.001) and ADMA (P<0.0001) and a highly significant decrease in the plasma concentration of nitric oxide (P<0.0001) among the Alzheimer's patients. In the combined patient and control groups a highly significant positive correlation was found between the plasma concentrations of homocysteine and ADMA (r=0.782, P<0.0001). In addition, significant negative correlations were detected between the plasma concentration of nitric oxide and the plasma concentration of homocysteine (r=-0.592, P<0.0001) and ADMA (r=-0.789, P<0.0001). These significant correlations were found to persist, even when they were restricted to the Alzheimer's patients. The inhibition of endothelial nitric oxide synthesis by ADMA impairs cerebral blood flow, which may contribute to the development of Alzheimer's disease. Endothelial dysfunction is also associated with atherosclerosis and stroke, which are important risk factors for Alzheimer's disease. Inflammation plays an important role in Alzheimer's disease and the inhibition of endothelial nitric oxide by ADMA may increase the concentration of inflammatory mediators in the brain. The inhibition of neuronal nitric oxide synthesis by ADMA may cause cognitive dysfunction in Alzheimer's disease.

Aged↗

PubMed1998

A review of longitudinal studies of cognitive functions in schizophrenia patients.

Even though the idea that schizophrenia is a neurobehavioral syndrome has become a mainstream position, there is no consensus on the precise nature of the cognitive and neuropsychological impairment. Research on cognitive dysfunctions in schizophrenia has been directed toward discriminating stable dysfunctions (traits) from symptom-linked (state) deficits. A longitudinal study design is the only one that can provide answers to the question of the stability of psychological functions. This article reviews 15 studies with a followup of at least a year. The main conclusion drawn from these studies is that after the onset of schizophrenia, cognitive deficits are relatively stable over long periods. No support for a decline in cognitive functions is found. Thus, schizophrenia does not appear to be a degenerative process, but rather a static encephalopathy. Whether or not the cognitive deficits found in schizophrenia can be remediated is still an open question that needs to be examined.

Cognition Disorders↗

PubMed1994

Behavior and affect in Alzheimer's disease.

The behavioral symptoms associated with AD are a critical aspect of the disease. They provide an additional avenue not only for understanding AD but for implementing interventions. The nature of behavioral disorders in AD is complicated by a number of factors that interact and contribute to the development of problematic behavior. It is difficult to determine whether the behavior is the result of neurodegeneration, cognitive dysfunction, previous experiences, current stressors, independently coexisting psychopathology, or a combination of these factors. In any case, behavioral disturbances need to be more clearly defined and objectively measured. To understand and treat behavioral disturbances in AD, all biopsy-chosocial factors must be examined simultaneously. Currently, there is little that can be done to treat the cognitive components of AD. Consequently, our most successful and beneficial interventions may focus on the remediable behavioral manifestations of the disease. The most valuable treatment approach for patients with AD and their caregivers interweaves medications, psychosocial services, environmental strategies, and caregiver education.

Affect↗

PubMed2000

Accelerated dysfunction among the very oldest-old in nursing homes.

BACKGROUND: The population aged 65 and older is often analyzed in three categories: young-old (65-74), middle-old (75-84), and oldest-old (> or = 85). This may blind heterogeneity within the oldest category. New, large data sets allow examination of the very oldest-old (e.g., aged > or = 95) and contrasts with those who are younger. METHODS: We determined the annual change of prevalence of physical and cognitive function, and of disease problems in the old to very oldest-old, using data from existing Resident Assessment Instrument records from nursing homes in seven states during 1992-1994. We used data from 193,467 unique residents aged 80 or older, including 6,556 residents aged 100 or older. We computed the prevalence, by age, of selected conditions: physical and cognitive function, diseases, problem behavior, mood disturbance, restraint use, falls, weight loss, eating less, body mass index, chewing and swallowing problems, incontinence (bowel and bladder), catheter use, and selected diagnoses. RESULTS: Prevalence of all measures of physical and cognitive dysfunction increased most rapidly with each year of age among the very oldest-old. Most of the slope changes occurred from 95 to 100 years of age. Such changes are less pronounced or not seen in measures of disease prevalence. CONCLUSIONS: Accelerated change in prevalence of dysfunction seen in the nursing home population may suggest a change in the mechanisms of aging that occur after the mid-nineties. Examination of the very oldest-old may provide new insight into the nature of the aging process.

Activities of Daily Living↗

PubMed1997

Magnetic resonance imaging and behavioral analysis of immature rats with kaolin-induced hydrocephalus: pre- and postshunting observations.

The motor and cognitive dysfunction associated with hydrocephalus remains a clinical problem in children. We hypothesized that young rats with hydrocephalus should exhibit similar dysfunction and that the dysfunction should be reversible by shunting. Hydrocephalus was induced in 3-week-old rats by injection of kaolin into the cisterna magna. Rats were assessed by T2-weighted images obtained with a 7-T magnetic resonance device and by repeated behavioral testing including ability to traverse a narrow beam and ability to find a hidden platform in a water pool. Some of the rats underwent a shunting procedure 1 or 4 weeks after kaolin injection. Magnetic resonance images were used to measure ventricle size. They clearly demonstrated increased signal in periventricular white matter, which corresponded to increased brain water content. A flow-void phenomenon was observed in the cerebral aqueduct. Ability to traverse the beam did not correlate with the degree of ventriculomegaly. Ability to swim to the hidden platform demonstrated a progressive impairment of learning function which may have been accentuated by motor disability. When rats were shunted after 1 week, the behavioral dysfunction was prevented. Late shunting after 4 weeks was associated with gradual recovery of the behavioral disability which was not complete after 4 weeks. We conclude that early shunting is superior to late shunting with regard to behavioral dysfunction. High-resolution MR imaging shows features in hydrocephalic rats similar to those found in hydrocephalic humans.

Animals↗

PubMed2001

Nutritional status and chewing capacity in nursing home residents.

Chronically ill elderly persons sustain a high risk for protein-energy malnutrition (PEM). In this study we explored some of the complex associations between nutritional status, dental health and cognitive and physical function in 192 nursing home residents (mean age 84+/-8 years, 80% female). Nutrition-related data from the Resident Assessment Instrument (RAI) were compiled into a Nutrition Score (NuSc; 0-1 = non-PEM, 2 = risk for PEM, and 3-7 = PEM). Chewing capacity, according to number and condition of occlusal contacts, was determined by a Clinical Dental Functionality score (CDF). The Cognitive Performance Scale (CPS) and activities of daily living (ADL) were determined according to the RAI. Fifty percent of the residents had NuSc > or = 2, and 25% had NuSc > or = 3. One third did not have the dental prerequisites for chewing. i.e., < 4 occlusal contacts. Almost half of the residents had severe cognitive dysfunction, and over two thirds were severely limited in their ADL activities. Subjects with > or = 4 occlusal contacts, i.e., technical chewing capacity, had better NuSc (1.5+/-1.4) than those not able to chew (2.4+/-1.6, p=0.0005). In univariate logistic regression, the odds for NuSc > or = 2 increased with reduced ADL functions. inability to chew and poor cognition. In multivariate logistic regression, ADL and chewing capacity were significantly related to NuSc > or = 2. When NuSc > or = 3 was chosen as cut-off, only ADL was related to malnutrition. In conclusion, half of this group of nursing home residents appeared to be malnourished, or were at risk for PEM. Reduced physical function was the strongest predictor of PEM, while impaired chewing capacity was associated with risk for PEM.

Activities of Daily Living↗

PubMed1996

D-amphetamine challenge effects on Wisconsin Card Sort Test. Performance in schizotypal personality disorder.

The authors assessed the effects on Wisconsin Card Sort (WCST) performance and psychiatric symptoms of 30 mg d-amphetamine, a dopamine and norepinephrine agonist, vs placebo in nine patients with schizotypal personality disorder (SPD). Patients, particularly those who made more perseverative errors, demonstrated amphetamine-associated improvement on WCST performance. The data in this preliminary study suggest that some of the cognitive dysfunction present in SPD may improve with amphetamine challenge.

Adult↗

PubMed2005

Treating attention in mild aphasia: evaluation of attention process training-II.

UNLABELLED: This study examined whether attention processing training-II [Sohlberg, M. M., Johnson, L., Paule, L., Raskin, S. A., & Mateer, C. A. (2001). Attention Process Training-II: A program to address attentional deficits for persons with mild cognitive dysfunction (2nd ed.). Wake Forest, NC: Lash & Associates.; APT-II], when applied in the context of a multiple baseline ABA design, would improve the attention abilities of RW, a patient with mild conduction aphasia and concomitant attention and working memory deficits. We also explored whether APT-II training would enhance RW's auditory comprehension, other cognitive abilities such as memory, and his and his spouse's perceptions of his daily attention and communication difficulties. With treatment, RW improved on trained attention tasks and made modest gains on standardized tests and probes that evaluated cognitive skills related to treatment activities. Nominal change in auditory comprehension and untrained attention and memory functions was observed, and neither RW nor his spouse reported noticeable improvements in his daily attention or communication abilities. These and previous findings indicate that structured attention retraining may enhance specific attention skills, but that positive changes in broader attention and untrained functions are less likely. LEARNING OUTCOMES: As a result of reading this article, the participant will be able to: (1) summarize the previous literature regarding attention impairments and treatment approaches for patients with aphasia. (2) describe how Attention Processing Training-II affected the attention, auditory comprehension, and other cognitive abilities of the patient in this study.

Aphasia, Wernicke↗

PubMed2004

High utilizers of medical care: a crucial subgroup among somatizing patients.

OBJECTIVE: Patients with somatoform disorders (SFD) are likely to overutilize healthcare services. This study investigates (a) whether extraordinarily high medical costs can be predicted from patient characteristics or psychopathology, and (b) whether high-utilizing patients respond differently to cognitive-behavioral treatment. METHODS: We compared 42 SFD high utilizers with 53 SFD average utilizers and 29 patients suffering from other than SFD mental disorders. High utilization was defined by healthcare expenditures of > or = 2500 euros during the past 2 years. Costs were computed from medical and billing records of health insurance companies. Somatization distress, hypochondriasis, depression, dysfunctional cognitions related to bodily symptoms, general psychopathology, personality profiles, and psychosocial disabilities were assessed before treatment. RESULTS: High utilizers had higher levels of self- and observer-rated illness behavior, self-perceived bodily weakness, and psychosocial disabilities. Although they did not report more somatization symptoms, their subjective symptom distress was higher. There were no differences between high and average utilizers concerning general psychopathology, DSM-IV comorbidity, and personality profiles. Treatment improvements were similar. CONCLUSION: High- and average-utilizing somatizers represent distinguishable subgroups. The results emphasize the importance of mechanisms specifically related to SFD and may enhance the early detection of patients who are likely to develop overutilization.

Cognitive Behavioral Therapy↗