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Memory performance used to detect radiation effects on cognitive functioning.

Although radiotherapy remains a necessary and frequently used treatmentfor brain tumors, uncertainty remains about the nature and severity of neurocognitive morbidity. We show that verbal-semantic memory (free recall of word list) is sensitive to damaging radiation effects in 20 patients with low-grade, supratentorial, primary brain tumors who received moderate doses of partial-brain irradiation. We previously reported that verbal-semantic memory is dissociated from visual memory (acquisition and recall) during the same phase ofradiation effects, indicating that memory is differentially affected by radiation. In this study, we provide evidence of the nature of the iatrogenic radiation effect on memory by testing collateral cognitive functions that might explain the specific memory impairment. We found that the verbal-semantic recall impairment was not associated with impairments in auditory attention, auditory processing speed, auditory-verbal working memory, or in the temporal coding or subjective organization of word-list recall. These findings focus damaging radiation effects on primary retrievalprocesses, rather than on earlier cognitive processes or executive processes affecting recall. Knowledge of the specific patterns of change in cognition would guide the differential diagnosis and rehabilitation of survivors of brain tumors whose conditions are complicated by tumors with multiple treatments.

Adult↗

Effects of neonatal stimulation on later cognitive function and hippocampal nerve growth factor.

This study examined the behavioural and physiological effects of chronic mild stress on neonatally handled and non-handled rats. Neonatally handled and non-handled rats were exposed to chronic mild stress from weaning time to 6 months of age. They were behaviourally tested at 6 months of age, and sacrificed for analysis of nerve growth factor (NGF) in the hippocampus and hypothalamus. In contrast to the reported deleterious effect of acute strong stress, mild stress appeared to stimulate production of NGF in the hippocampus and improve spatial learning in both handled and nonhandled rats. Because neonatal handling produces neuroanatomical changes in the rat hippocampus and enhances cognitive function throughout the rats life span, these results implicate hippocampal NGF in the neuroprotective effects of handling.

Aging↗

Is apathy in late-life depressive illness related to age-at-onset, cognitive function or vascular risk?

BACKGROUND: Apathy has been shown to be an important feature of degenerative, vascular or traumatic brain disorder. Its presence is associated with high depression scores, higher age, low performance on frontal tasks, and more severe deep white matter hyperintensities. In late-life depression, lack of interest or motivation are often more prominent than depressed mood, especially in the late-onset type. It was hypothesized that in a heterogeneous sample of elderly depressed patients, apathy is associated with late-onset type of depression, cognitive dysfunction or vascular risk factors. METHOD: The Apathy Evaluation Scale (AES) was administered to twenty-nine elderly (> or = 60 years) inpatients with a DSM-IV major depression or dysthymic disorder. The severity of the depression was measured with the Montgomery-Asberg Depression Rating Scale (MADRS) and cognitive function with the Mini-mental State Examination (MMSE). The presence of vascular risk factors was traced in the patient's medical records. RESULTS: Apathy was found in 86% of the patients. The AES-score was correlated with the negative symptom score, but not with total MADRS or MMSE-score. No difference in AES-score between early-onset depressed (n = 16) and late-onset depressed (n = 13) patients was found, and between patients with or without vascular risk. CONCLUSION: Apathy is a main feature of moderate to severe depressive illness in elderly patients and related to the negative symptoms of the disorder. Further studies should include less severely depressed patients and investigate the relation between depression severity and apathy.

Age of Onset↗

[Drinking water hardness and chronic degenerative diseases. III. Tumors, urolithiasis, fetal malformations, deterioration of the cognitive function in the aged and atopic eczema].

For several decades a causal relation has been hypothesised between drinking water hardness and cardiovascular and other chronic degenerative diseases in humans. Only recently some epidemiological studies also investigated the association between the concentration of the minerals responsible for the hardness of drinking water (calcium and magnesium) and other chronic diseases. Some case-control studies carried out in Taiwan using aggregated data showed a possible protective effect of water hardness toward the risk of dying from various neoplasms, though more research is needed on the issue, possibly based on individual data, to draw definitive conclusions. There is a substantial evidence that consumption of water with high levels of calcium does not increase, and maybe reduces the risk of developing urinary stones of the most common type in developed countries (calcium oxalate), on the contrary, there is no conclusive evidence on the relation between water hardness and foetal malformations, cognitive functions in old men, diabetes and eczema.

Aged↗

The cognitive functions of language.

This paper explores a variety of different versions of the thesis that natural language is involved in human thinking. It distinguishes amongst strong and weak forms of this thesis, dismissing some as implausibly strong and others as uninterestingly weak. Strong forms dismissed include the view that language is conceptually necessary for thought (endorsed by many philosophers) and the view that language is de facto the medium of all human conceptual thinking (endorsed by many philosophers and social scientists). Weak forms include the view that language is necessary for the acquisition of many human concepts and the view that language can serve to scaffold human thought processes. The paper also discusses the thesis that language may be the medium of conscious propositional thinking, but argues that this cannot be its most fundamental cognitive role. The idea is then proposed that natural language is the medium for nondomain-specific thinking, serving to integrate the outputs of a variety of domain-specific conceptual faculties (or central-cognitive "quasimodules"). Recent experimental evidence in support of this idea is reviewed and the implications of the idea are discussed, especially for our conception of the architecture of human cognition. Finally, some further kinds of evidence which might serve to corroborate or refute the hypothesis are mentioned. The overall goal of the paper is to review a wide variety of accounts of the cognitive function of natural language, integrating a number of different kinds of evidence and theoretical consideration in order to propose and elaborate the most plausible candidate.

Cognition↗

Parallel distributed processing and neural networks: origins, methodology and cognitive functions.

Parallel Distributed Processing (PDP), a computational methodology with origins in Associationism, is used to provide empirical information regarding neurobiological systems. Recently, supercomputers have enabled neuroscientists to model brain behavior-relationships. An overview of supercomputer architecture demonstrates the advantages of parallel over serial processing. Histological data provide physical evidence of the parallel distributed nature of certain aspects of the human brain, as do corresponding computer simulations. Whereas sensory networks follow more sequential neural network pathways, in vivo brain imaging studies of attention and rudimentary language tasks appear to involve multiple cortical and subcortical areas. Controversy remains as to whether associative models or Artificial Intelligence symbolic models better reflect neural networks of cognitive functions; however, considerable interest has shifted towards associative models.

Artificial Intelligence↗

Effects of environmental enrichment on cognitive function and hippocampal NGF in the non-handled rats.

In this study we examine whether exposure to differential housing after weaning would counteract the effects of postnatal handling (H) or nonhandling (NH) treatment by affecting learning and memory processes in young rats. In addition, we seek to determine if experience in enriched environment would alter hippocampal nerve growth factor (NGF) levels which is one of the factors known to be involved in the regulation of the survival and differentiation of developing basal forebrain neurones. Rats were either exposed to handling treatment, or left undisturbed starting day 1 after birth through day 21. After weaning on day 22, we exposed half of the H rats and half of the NH rats to environmental enrichment for 60 days. The other respective half of the rats was housed in isolated environmental condition (IC). Behavioural measures were taken in open field test, and spatial water maze test. Exposure to enriched environment following postnatal handling and nonhandling increased hippocampal NGF levels, and improved cognitive function in the both groups, with NH rats being more responsive to the effects of enrichment. Our results suggest that environmental enrichment has the potential to prevent or reduce the cognitive and neurochemical deficits in the adult animals associated with nonhandling.

Animals↗

[Aspects of cognitive functioning in the aged. A transversal study].

In the context of a WHO study on psychosocial needs of the elderly, a sample of 519 subjects from the region of Louvain was psychometrically tested. This sample consisted of men and woman between 55 and 94 years of age, most of them living at home. The test battery was composed of ten verbal and nonverbal tests and tasks currently used in psychogeriatric clinical practice but lacking validation and normative data for those aged populations. This study (psychometric testing took place in 1979-1980) was intended as a first step in a follow up program to gather more definite information about mental deterioration. Up to now it can be considered however as a cross-sectional study, providing normative data for the assessment of cognitive functioning in aged individuals up to 94 years. The decline in performances, found on all these tests, reflect generation as well as aging effects; the increasing proportions of aged subjects failing on the tests however, seem to indicate a high occurrence of partial or global cognitive deficits in elderly people beyond the eighth decade.

Aged↗

The recovery of cognitive function after remifentanil-nitrous oxide anesthesia is faster than after an isoflurane-nitrous oxide-fentanyl combination in elderly patients.

UNLABELLED: We tested the hypothesis that remifentanil-nitrous oxide (N(2)O) anesthesia shortens postoperative emergence and recovery compared with an isoflurane-N(2)O-fentanyl combination in elderly patients undergoing spinal surgery. A total of 60 patients (>65 yr old) were randomly assigned to one of two groups for maintenance of anesthesia. After the induction with 3.6 +/- 1.2 mg/kg IV thiopental and endotracheal intubation facilitated with 1.4 +/- 0.5 mg/kg succinylcholine, patients were maintained with either 0.5%-1.5% isoflurane, 70% N(2)O, and up to 7 microg/kg fentanyl (iso/fent group) or 48 +/- 11 microg/kg remifentanil and 70% N(2)O (remi group). A mini-mental status examination was used to assess cognitive ability preoperatively, at 15, 30, and 60 min after arrival at the postanesthesia care unit and again 12-24 h postoperatively. The time from the conclusion of anesthesia to spontaneous respiration was similar in both groups. Times to eye opening (4.8 +/- 2.6 vs 2.3 +/- 1.1 min), extubation (6.8 +/- 3.8 vs 3.2 +/- 2.1 min), and verbalization (9.9 +/- 6.2 vs 3.9 +/- 2.6 min) were significantly shorter for the remi group (P < 0.05). Postoperative mini-mental status examination scores were significantly lower in the iso/fent group at 15 (16.3 +/- 5.8 vs 23. 7 +/- 3.3), 30 (20.2 +/- 5.2 vs 26.3 +/- 2.7), and 60 min (23.5 +/- 4.4 vs 27.5 +/- 2.0) (P < 0.001); however, the scores equalized after 12 h. Requirements for postoperative analgesics were similar in the two groups. More patients in the remi group were treated with antiemetics (21 vs 7, P = 0.06). Use of remifentanil-N(2)O for maintenance did not shorten the overall length of stay in the postanesthesia care unit; a stay is often related to multiple administrative issues, rather than cognitive recovery. IMPLICATIONS: Maintenance of anesthesia with remifentanil-nitrous oxide (N(2)O), compared with isoflurane-N(2)O-fentanyl, can safely shorten postoperative recovery of cognitive function in a geriatric population. Earlier recovery may facilitate postoperative neurological assessment. Use of remifentanil-N(2)O for maintenance did not shorten the overall length of stay in the postanesthesia care unit, a stay often related to multiple administrative issues, rather than cognitive recovery.

Aged↗

Novel effects of estradiol and estrogen receptor alpha and beta on cognitive function.

Estrogen influences the development of memory function in humans and rodents and can modulate memory in adults. In these studies we examined the role of the estrogen receptors alpha (ERalpha) and beta (ERbeta) in mediating performance on a hippocampal-dependent, hormone-sensitive task, inhibitory avoidance (IA). Ovariectomized (OVX) estrogen receptor-alpha-knockout (ERalphaKO) mice displayed impaired performance on the IA task and OVX heterozygotic (HET) mice exhibited performance that was intermediate between ERalphaKO and wild-type (WT) mice. Impaired performance by ERalphaKO mice was rescued by E(2) treatment. The ER antagonist, tamoxifen, did not block enhancement of retention by E(2) suggesting that E(2) mediated modulation of memory is not caused by known genomic receptor mechanisms. In contrast to ERalphaKO mice, IA performance by OVX estrogen receptor-beta-knockout (ERbetaKO) mice was not compromised. The results indicate an important role for ERalpha, relative to ERbeta, in the establishment of cognitive function and suggest that E(2) modulates memory function via a novel estrogenic mechanism.

Animals↗

Improving influence of insulin on cognitive functions in humans.

Insulin receptors have been identified in limbic brain structures, but their functional relevance is still unclear. In order to characterize some of their effects, we evaluated auditory evoked brain potentials (AEP) in a vigilance task, behavioral measures of memory (recall of words) and selective attention (Stroop test) during infusion of insulin. The hormone was infused at two different rates (1.5 mU/kg x min, "low insulin", and 15 mU/kg x min, "high insulin"), inducing respectively serum levels of 543 +/- 34 and 24,029 +/- 1,595 pmol/l. This experimental design allowed to compare cognitive parameters under two conditions presenting markedly different insulin levels, but with minimal incidence on blood glucose concentrations since these were kept constant by glucose infusion. A "no insulin treatment" group was not included in order to avoid leaving patients infused with glucose without insulin treatment. Measures were taken during a baseline phase preceding insulin infusion and every 90 min during the 360 min of insulin infusion. Compared with "low insulin", "high insulin" induced a slow negative potential shift in the AEP over the frontal cortex (average amplitude, high insulin: 0.27 +/- 0.48 microV; low insulin: 1.87 +/- 0.48 microV, p < 0.005), which was paralleled by enhanced memory performance (words recalled, high insulin: 22.04 +/- 0.93; low insulin: 19.29 +/- 0.92, p < 0.05). Also, during "high insulin" subjects displayed enhanced performance on the Stroop test (p < 0.05) and expressed less difficulty in thinking than during "low insulin" (p < 0.03). Results indicate an improving effect of insulin on cognitive function, and may provide a frame for further investigations of neurobehavioral effects of insulin in patients with lowered or enhanced brain insulin, i.e., patients with Alzheimer's disease or diabetes mellitus.

Adult↗

Relationship of cognitive functioning, whole brain volumes, and T2-weighted hyperintensities in neurofibromatosis-1.

Using quantitative magnetic resonance imaging morphometry, we report that the whole brain volumes of patients with neurofibromatosis-1 are significantly larger than normal, confirm the prevalence of macrocephaly as about 50%, and report that macrocephaly in patients with neurofibromatosis-1 does not appear to be related to the familial or sporadic origin of the neurofibromatosis-1 or to the presence or absence of T2-weighted hyperintensities. No strong relationship emerged between the extent of neurofibromatosis-1-associated impairment of cognitive functions and degree of macrocephaly; however, the macrocephalic neurofibromatosis-1 group did have a significant verbal impairment relative to the nonmacrocephalic neurofibromatosis-1 group in vocabulary (P < .009).

Adolescent↗

The use of an interactive computer terminal in the assessment of cognitive function in elderly psychiatric patients.

The use of a teaching machine is the assessment of mental function has been described by Gredye and his colleagues. This report concerns its use in testing 56 elderly patients suffering from functional psychiatric disorders of dementia. After a diagnostic interview patients were tested on the teaching machine as well as on the Mill Hill, Progressive Matrices, Paired Associate Learning Test and Digit Copying Test. After a fixed period all tests were repeated and clincal progress rated. Results showed a significant correlation (P less than 0.01) between teaching-machine scores and those on the standard psychological tests. The correlation between the machine scores on the two occasions was high (r equals 0.58) but this was complicated by practice effects and by low 'ceiling' of the test. It is concluded that the test provided a relatively reliable and valid measure of cognitive function but that its value would be increased by providing a parallel form and by extending its level of difficulty.

Age Factors↗

Relations between aging sensory/sensorimotor and cognitive functions.

Recent evidence is reviewed to examine relations among sensory, sensorimotor, and cognitive aging. Age-heterogeneous cross-sectional data sets show substantial covariation among sensory, sensorimotor and intellectual abilities, and an increase in covariation from adulthood to old and very old age. Recent longitudinal analyses suggest that changes in sensory and intellectual functioning are interrelated. Experimental studies investigate the interdependence between cognitive and sensory/sensorimotor aging by examining the effects of simulated sensory loss on cognitive performance, or the effects of cognitive load manipulations on sensory or motor performance. Generally, both types of manipulations hinder older adults' performance more than that of younger adults. Theoretically, the age-associated intensification of the links among sensory, sensorimotor and cognitive functions observed both correlationally and experimentally may point to (a). common causes influencing all three functions; (b). an increase in resource overlap, cross-domain resource competition, and compensatory tradeoffs; and (c). a combination of the two. Future research aiming at discerning the relative import of these possibilities would profit from an integration of experimental and correlational research strategies.

Aging↗

Age-related losses of cognitive function and motor skills in mice are associated with oxidative protein damage in the brain.

The hypothesis that age-associated impairment of cognitive and motor functions is due to oxidative molecular damage was tested in the mouse. In a blind study, senescent mice (aged 22 months) were subjected to a battery of behavioral tests for motor and cognitive functions and subsequently assayed for oxidative molecular damage as assessed by protein carbonyl concentration in different regions of the brain. The degree of age-related impairment in each mouse was determined by comparison to a reference group of young mice (aged 4 months) tested concurrently on the behavioral battery. The age-related loss of ability to perform a spatial swim maze task was found to be positively correlated with oxidative molecular damage in the cerebral cortex, whereas age-related loss of motor coordination was correlated with oxidative molecular damage within the cerebellum. These results support the view that oxidative stress is a causal factor in brain senescence. Furthermore, the findings suggest that age-related declines of cognitive and motor performance progress independently, and involve oxidative molecular damage within different regions of the brain.

Aging↗

Preoperative EEG predicts memory and selective cognitive functions after temporal lobe surgery.

Preoperative and postoperative cognitive and memory functions, psychiatric outcome, and EEGs were evaluated in 32 epileptic patients who underwent temporal lobe surgery. The presence and location of preoperative slow wave focus in routine EEG predicted memory functions of the non-resected side after surgery. Neuropsychological tests of the function of the frontal lobes also showed improvement. Moreover, psychiatric ratings showed that seizure free patients had significantly less affective symptoms postoperatively than those who were still exhibiting seizures. After temporal lobectomies, successful outcome in postoperative memory functions can be achieved in patients with unilateral slow wave activity in preoperative EEGs. This study suggests a new role for routine EEG in preoperative evaluation of patients with temporal lobe epilepsy.

Adolescent↗

Development of cortical circuitry and cognitive function.

Recent functional and anatomical studies in nonhuman primates have elucidated the basic neural circuitry underlying delayed-response function in adult nonhuman primates. Thus circuitry includes connections of the principal sulcus with other areas of parietal association and limbic cortex and projections to the caudate nucleus, superior colliculus, and other premotor centers. Anatomical tracing in primate fetuses and in monkeys at various stages of postnatal development indicates that these various classes of cortical connections begin to form by the second trimester of pregnancy. Electromicroscopic studies of the principal sulcus and other areas of cerebral cortex show that the number and density of synapses in the cortex increase rapidly, reaching and maintaining higher than normal adult values between 2 and 4 months postnatally, before slowly declining over a period of years to stable adult levels. The capacity to perform delayed-response and/or AB at short delays emerges around 4 months of age, coinciding with the end of the period of highest synaptic density in the principal sulcus. These findings suggest that a critical mass of cortical synapses is important for the emergence of this cognitive function, and that fully mature capacity may depend upon the elimination of excess synapses that occurs during adolescence and young adulthood. Knowledge of the neural basis of normal cognitive development may prove useful both to social and educational purposes as well as to understanding developmental disorders of cognition.

Animals↗

Methylphenidate improves prefrontal cortical cognitive function through alpha2 adrenoceptor and dopamine D1 receptor actions: Relevance to therapeutic effects in Attention Deficit Hyperactivity Disorder.

BACKGROUND: Methylphenidate (MPH) is the classic treatment for Attention Deficit Hyperactivity Disorder (ADHD), yet the mechanisms underlying its therapeutic actions remain unclear. Recent studies have identified an oral, MPH dose regimen which when given to rats produces drug plasma levels similar to those measured in humans. The current study examined the effects of these low, orally-administered doses of MPH in rats performing a delayed alternation task dependent on prefrontal cortex (PFC), a brain region that is dysfunctional in ADHD, and is highly sensitive to levels of catecholamines. The receptor mechanisms underlying the enhancing effects of MPH were explored by challenging the MPH response with the noradrenergic alpha2 adrenoceptor antagonist, idazoxan, and the dopamine D1 antagonist, SCH23390. RESULTS: MPH produced an inverted U dose response whereby moderate doses (1.0-2.0 mg/kg, p.o.) significantly improved delayed alternation performance, while higher doses (2.0-3.0 mg/kg, p.o.) produced perseverative errors in many animals. The enhancing effects of MPH were blocked by co-administration of either the alpha2 adrenoceptor antagonist, idazoxan, or the dopamine D1 antagonist, SCH23390, in doses that had no effect on their own. CONCLUSION: The administration of low, oral doses of MPH to rats has effects on PFC cognitive function similar to those seen in humans and patients with ADHD. The rat can thus be used as a model for examination of neural mechanisms underlying the therapeutic effects of MPH on executive functions in humans. The efficacy of idazoxan and SCH23390 in reversing the beneficial effects of MPH indicate that both noradrenergic alpha2 adrenoceptor and dopamine D1 receptor stimulation contribute to cognitive-enhancing effects of MPH.

Journal Article↗